|
1
|
Gundavda K, Chopde A, Pujari A, Reddy B, Pawar A, Ramaswamy A, Ostwal V, Patkar S, Bhandare M, Shrikhande SV, Chaudhari VA. Prognostic Impact of Para-Aortic Lymph Node Metastasis in Resected Non-Pancreatic Periampullary Cancers. Ann Surg Oncol 2024; 31:7052-7063. [PMID: 39031265 PMCID: PMC11413064 DOI: 10.1245/s10434-024-15847-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 07/02/2024] [Indexed: 07/22/2024]
Abstract
BACKGROUND Surgery remains debatable in para-aortic lymph node (PALN, station 16b1) metastasis in non-pancreatic periampullary cancer (NPPAC). This study examined the impact of PALN metastasis on outcomes following pancreaticoduodenectomy (PD) in NPPAC. METHODS A retrospective analysis of patients with NPPAC who were explored for PD with PALN dissection was performed. Based on the extent of nodal involvement on final histopathology, they were stratified as node-negative (N0), regional node involved (N+) and metastatic PALN (N16+) and their outcomes were compared. RESULTS Between 2011 and 2022, 153/887 PD patients underwent a PALN dissection, revealing N16+ in 42 patients (27.4%), of whom 32 patients underwent resection. The 3-years overall survival (OS) for patients with N16+ was 28% (95% confidence interval [CI] 13-60%), notably lower than the 67% (95% CI 53-83.5%; p = 0.007) for those without PALN metastasis. Stratified by nodal involvement, the median OS for N+ and N16+ patients was similar (28.4 months and 26.2 months, respectively). The N0 subgroup had a significantly longer 3-years OS of 87.5% (95% CI 79-96.7%; p = 0.0051). Interestingly, 10 patients not offered resection following N16+ identified on frozen section had a median survival of only 9 months. The perioperative morbidity and mortality in patients undergoing PD with PALN dissection were similar to standard resections. CONCLUSION In a select group of patients with NPPAC, PD in isolated PALN metastasis was associated with improved OS. The survival in this group of patients was comparable with regional node-positive patients and significantly better than palliative treatment alone.
Collapse
Affiliation(s)
- Kaival Gundavda
- Division of Gastrointestinal and HPB Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Amit Chopde
- Division of Gastrointestinal and HPB Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Avinash Pujari
- Division of Gastrointestinal and HPB Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Bhaskar Reddy
- Division of Gastrointestinal and HPB Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Akash Pawar
- Department of Biostatistics, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Anant Ramaswamy
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Vikas Ostwal
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Shraddha Patkar
- Division of Gastrointestinal and HPB Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Manish Bhandare
- Division of Gastrointestinal and HPB Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Shailesh V Shrikhande
- Division of Gastrointestinal and HPB Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Vikram A Chaudhari
- Division of Gastrointestinal and HPB Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India.
| |
Collapse
|
|
2
|
Bhatti ABH, Dar FS, Ahmed IN. Pancreaticoduodenectomy with Para-aortic Lymph Node Dissection for Periampullary Cancer. Indian J Surg Oncol 2024; 15:338-343. [PMID: 38817990 PMCID: PMC11133244 DOI: 10.1007/s13193-023-01866-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 12/11/2023] [Indexed: 06/01/2024] Open
Abstract
There is no consensus on the utility of para-aortic lymph node dissection (PALND) in patients undergoing pancreaticoduodenectomy (PD) for periampullary cancer. The objective of this study was to assess survival in patients who underwent PD with PALND for pancreatic (PAC) and non-pancreatic (non-PAC) adenocarcinoma. All patients who underwent PD and PALND between 2011 and 2019 were reviewed (n = 114). We looked at the impact of tumor type (PAC versus non-PAC) and pathologically confirmed PALN metastasis (PALNM) on overall survival (OS). Out of 114 patients, PALNM were pathologically confirmed in 17(14.9%) patients. Without PALND, pathological staging would be pN0 in1(0.8%), pN1 in 3(2.5%), and pN2 in 13(11.2%) patients. The 30-day mortality was 3(2.6%) and 65(57%) patients received adjuvant treatment. The 4-year OS for PAC and non-PAC was 9% and 39% (P = 0.001). Advanced nodal involvement (pN2) was seen in 14/17(82.4%) and 21/97(21.6%) patients with and without PALNM, respectively (P < 0.001). For PAC, 4-year OS for patients with pN0-N1, pN2, and PALNM was 12%, 8%, and not reached (P = 0.067). For non-PAC, 4-year OS was 45%, 19%, and 12% (P = 0.006). In patients with non-PAC, despite metastatic involvement of PALN, acceptable long-term survival can be achieved with curative resection. For PAC, survival benefit with curative resection remains questionable.
Collapse
Affiliation(s)
- Abu Bakar Hafeez Bhatti
- Department of HPB Surgery and Liver Transplantation, Shifa International Hospital, Islamabad, Pakistan
- Department of Pathology, Shifa International Hospital, Islamabad, Pakistan
| | - Faisal Saud Dar
- Department of HPB Surgery and Liver Transplantation, Shifa International Hospital, Islamabad, Pakistan
| | - Imran Nazer Ahmed
- Department of Pathology, Shifa International Hospital, Islamabad, Pakistan
| |
Collapse
|
|
3
|
Kazami Y, Oba A, Ono Y, Sato T, Inoue Y, Saiura A, Takahashi Y, Ito H. Intraoperative paraaortic lymph node sampling during resection for pancreatic cancer: evolving role in the modern chemotherapy era. HPB (Oxford) 2023; 25:1169-1178. [PMID: 37357111 DOI: 10.1016/j.hpb.2023.05.366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 05/15/2023] [Accepted: 05/31/2023] [Indexed: 06/27/2023]
Abstract
BACKGROUND The role of paraaortic lymph node (PALN) sampling for pancreatic cancer (PC) remains controversial. This study aimed to assess the yield of PALN sampling and its impact on long-term outcomes. METHODS Patients treated from 2005 to 2018 were included. Since 2015, patients with borderline resectable or unresectable (BR/UR) tumours received standardized neoadjuvant therapy (NAT), whereas patients with resectable tumours underwent upfront resection. RESULTS Among 771 patients with PALN excision, metastasis was confirmed in 76 patients (10%) and 59 proceeded to planned resection. PALN metastasis was associated with early recurrence and shorter survival after upfront resection (1-year recurrence-free rate: 23% vs 57% for resectable tumours, P < 0.001, 9% vs 52% for BR/UR tumours, P = 0.006; median overall survival (OS): 19 vs 31 months for resectable tumours, P < 0.001, 17 vs 23 months for BR/UR tumours, P = 0.057). In contrast, they were both similar between patients with/without PALN metastasis following NAT for BR tumours (1-year recurrence-free rate, 50% vs 58%, P = 0.88; median OS, 28 vs 35 months, P = 0.45, respectively). CONCLUSIONS Occult metastasis to PALNs is not uncommon in patients with potentially resectable PC. Its prognostic impact depends on the treatment strategy, and the intraoperative decision for resection should be individualized.
Collapse
Affiliation(s)
- Yusuke Kazami
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Atsushi Oba
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yoshihiro Ono
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takafumi Sato
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yosuke Inoue
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Akio Saiura
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan; Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Yu Takahashi
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Hiromichi Ito
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
| |
Collapse
|
|
4
|
Sillesen M, Hansen CP, Burgdorf SK, Dencker EE, Krohn PS, Gisela Kollbeck SL, Stender MT, Storkholm JH. Impact of para aortic lymph node removal on survival following resection for pancreatic adenocarcinoma. BMC Surg 2023; 23:214. [PMID: 37528360 PMCID: PMC10394933 DOI: 10.1186/s12893-023-02123-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 07/24/2023] [Indexed: 08/03/2023] Open
Abstract
INTRODUCTION For PDAC patients undergoing resection, it remains unclear whether metastases to the paraaortic lymph nodes (PALN+) have any prognostic significance and whether metastases should lead to the operation not being carried out. Our hypothesis is that PALN + status would be associated with short overall survival (OS) compared with PALN-, but longer OS compared with patients undergoing surgical exploration only (EXP). METHODS Patients with registered PALN removal from the nationwide Danish Pancreatic Cancer Database (DPCD) from May 1st 2011 to December 31st 2020 were assessed. A cohort of PDAC patients who only had explorative laparotomy due to non-resectable tumors were also included (EXP group). Survival analysis between groups were performed with cox-regression in a multivariate approach including relevant confounders. RESULTS A total of 1758 patients were assessed, including 424 (24.1%) patients who only underwent explorative surgery leaving 1334 (75.8%) patients for further assessment. Of these 158 patients (11.8%) had selective PALN removal, of whom 19 patients (12.0%) had PALN+. Survival analyses indicated that explorative surgery was associated with significantly shorter OS compared with resection and PALN + status (Hazard Ratio 2.36, p < 0.001). No difference between PALN + and PALN- status could be demonstrated in resected patients after controlling for confounders. CONCLUSION PALN + status in patients undergoing resection offer improved survival compared with EXP. PALN + should not be seen as a contraindication for curative intended resection.
Collapse
Affiliation(s)
- Martin Sillesen
- Department of Organ Surgery and Transplantation, Copenhagen University Hospital, Rigshospitalet Blegdamsvej 9, Copenhagen, 2100, Denmark.
- Center for Surgical Translation and Artificial Intelligence Research (CSTAR), Copenhagen University Hospital, Rigshospitalet, Denmark.
- Institute of Clinical Medicine, University of Copenhagen, København, Denmark.
| | - Carsten Palnæs Hansen
- Department of Organ Surgery and Transplantation, Copenhagen University Hospital, Rigshospitalet Blegdamsvej 9, Copenhagen, 2100, Denmark
| | - Stefan Kobbelgaard Burgdorf
- Department of Organ Surgery and Transplantation, Copenhagen University Hospital, Rigshospitalet Blegdamsvej 9, Copenhagen, 2100, Denmark
| | - Emilie Even Dencker
- Department of Organ Surgery and Transplantation, Copenhagen University Hospital, Rigshospitalet Blegdamsvej 9, Copenhagen, 2100, Denmark
- Center for Surgical Translation and Artificial Intelligence Research (CSTAR), Copenhagen University Hospital, Rigshospitalet, Denmark
| | - Paul Suno Krohn
- Department of Organ Surgery and Transplantation, Copenhagen University Hospital, Rigshospitalet Blegdamsvej 9, Copenhagen, 2100, Denmark
| | - Sophie Louise Gisela Kollbeck
- Department of Organ Surgery and Transplantation, Copenhagen University Hospital, Rigshospitalet Blegdamsvej 9, Copenhagen, 2100, Denmark
- Center for Surgical Translation and Artificial Intelligence Research (CSTAR), Copenhagen University Hospital, Rigshospitalet, Denmark
| | | | - Jan Henrik Storkholm
- Department of Organ Surgery and Transplantation, Copenhagen University Hospital, Rigshospitalet Blegdamsvej 9, Copenhagen, 2100, Denmark
- Dep. of Surgery, Imperial College NHS trust, Hammersmith Hospital, London, UK
| |
Collapse
|
|
5
|
Kim JS, Hwang HK, Lee WJ, Kang CM. Unexpected Para-aortic Lymph Node Metastasis in Pancreatic Ductal Adenocarcinoma: a Contraindication to Resection? J Gastrointest Surg 2020; 24:2789-2799. [PMID: 31792906 DOI: 10.1007/s11605-019-04483-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Accepted: 11/17/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND Margin-negative resection is the only cure for pancreatic cancer. However, para-aortic lymph node metastasis is considered a contraindication to curative resection in pancreatic cancer. To determine if there are long-term survival differences according to the presence or absence of para-aortic lymph node metastasis in patients undergoing pancreatectomy, we evaluated oncologic outcomes in resected pancreatic cancer with unexpected para-aortic lymph node metastasis confirmed on intraoperative frozen section biopsy. METHODS We retrospectively investigated 362 patients with pathologically confirmed pancreatic ductal adenocarcinoma who underwent pancreatectomy between 1996 and 2016. RESULTS Patients with a metastatic para-aortic lymph node had the poorest median disease-specific survival [hazard ratio 14, 95% confidence interval 10-19]. However, after chemotherapy, patients with a metastatic para-aortic lymph node had a much higher disease-specific survival rate (para-aortic lymph node+/postoperative chemotherapy- versus para-aortic lymph node+/postoperative chemotherapy+, P = 0.0003, adjusted P = 0.0015). Patients with a metastatic para-aortic lymph node who underwent postoperative chemotherapy had a similar survival benefit to patients with metastatic regional lymph node without para-aortic lymph node metastasis, regardless of postoperative chemotherapy (para-aortic lymph node+/postoperative chemotherapy+ versus regional lymph node+/postoperative chemotherapy-, P = 0.3047, adjusted P > 0.9999; para-aortic lymph node+/postoperative chemotherapy+ versus regional lymph node+/postoperative chemotherapy+, P = 0.0905, adjusted P = 0.4525). CONCLUSIONS Unexpected para-aortic lymph node metastasis on frozen section biopsy may no longer be a contraindication to curative resection in "resectable" pancreatic ductal adenocarcinoma, as long as postoperative adjuvant chemotherapy can be administered.
Collapse
Affiliation(s)
- Ji Su Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, #50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea
| | - Ho Kyoung Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, #50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea
- Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, Korea
| | - Woo Jung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, #50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea
- Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, Korea
| | - Chang Moo Kang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, #50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.
- Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, Korea.
| |
Collapse
|
|
6
|
Para-aortic lymph node metastasis detected intraoperatively by systematic frozen section examination in pancreatic head adenocarcinoma: is resection improving the prognosis? HPB (Oxford) 2020; 22:1604-1612. [PMID: 32179009 DOI: 10.1016/j.hpb.2020.02.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 01/16/2020] [Accepted: 02/18/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND This study aimed to evaluate the controversial benefit of a pancreaticoduodenectomy (PD) in patients with PALN metastasis intraoperatively detected by systematic frozen section examination in pancreatic adenocarcinoma. METHODS PALN intraoperative examination by frozen section was systematically performed from January 2006 to February 2018 prior to performing PD for pancreatic adenocarcinoma. Until June 2012, PALN + patients still underwent PD (PALN+/PD group) in the framework of a prospective study. Since July 2012, PALN+ was considered as contraindicating the planned PD (PALN+/No-PD group). Post-operative morbidity and survival were compared between these two groups. RESULTS Of the 32 PALN + patients intraoperatively detected, the first 13 underwent a PD, while the last 19 did not undergo resection. Seven patients (54%) among 13 PALN+/PD patients developed a post-operative complication against 3 (16%) among 19 PALN+/No-PD patients (p = 0.049). The median length of stay was 5 days longer for PALN+/PD patients (p = 0.001). The median survival did not differ between PALN+/No-PD and PALN+/PD groups (respectively 13.4 months (95%CI:7.6-19.3) and 11.5 months (95%CI:5.9-17.1), p = 0.471). No patient was alive 4 years after surgery in both the PALN+/No-PD or PALN+/PD groups. CONCLUSION In case of PALN detected intraoperatively in pancreatic adenocarcinoma, PD does not improve survival compared to current palliative treatment.
Collapse
|
|
7
|
Zhou Y, Zhou G, Gao X, Xu C, Wang X, Xu P. Apparent diffusion coefficient value of mass-forming intrahepatic cholangiocarcinoma: a potential imaging biomarker for prediction of lymph node metastasis. Abdom Radiol (NY) 2020; 45:3109-3118. [PMID: 32107582 DOI: 10.1007/s00261-020-02458-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE To compare the differences of MR features between mass-forming intrahepatic cholangiocarcinoma (IMCC) with and without lymph node metastasis (LNM) and to search for new imaging biomarkers for predicting LNM. MATERIALS AND METHODS The study included 91 patients with histopathologically confirmed single IMCC (20 patients with LNM and 71 patients without LNM). Findings of preoperative MR imaging including diffusion-weighted imaging (DWI) (b value 0, 500 mm2/s) were analyzed and apparent diffusion coefficient (ADC) values (b = 500 mm2/s) were calculated. Logistic regression analysis was performed to identify independent predictors of LNM. The diagnostic performance of independent predictors was assessed by receiver operating characteristic (ROC) and area under the curve (AUC) was compared. RESULTS Larger tumor size (p = 0.001), diameter of largest lymph node (LN) > 1 cm (p < 0.001), higher ADC value of primary IMCC lesion (ADCIMCC value) (p = 0.001), and positive CA19-9 level (p = 0.018) were correlated with LNM. Multivariate logistic regression analysis demonstrated that ADCIMCC value (odds ratio, 3.347; p = 0.001) and diameter of largest LN > 1 cm (odds ratio, 7.571; p = 0.004) were independent predictors of LNM. The AUCs for ADCIMCC value, diameter of largest LN > 1 cm,and combined method (the combination of ADCIMCC value and diameter of largest LN > 1 cm) were 0.782, 0.701,and 0.857, respectively. The AUC for combined method was significantly higher than that of diameter of largest LN > 1 cm (p = 0.033). CONCLUSION ADCIMCC value can be a potential imaging biomarker for predicting LNM of IMCC, especially in combination with diameter of largest LN > 1 cm.
Collapse
Affiliation(s)
- Yang Zhou
- Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Guofeng Zhou
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Xuan Gao
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Chen Xu
- Department of Pathology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Xiaolin Wang
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Pengju Xu
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China.
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
| |
Collapse
|
|
8
|
Role of lymphadenectomy in resectable pancreatic cancer. Langenbecks Arch Surg 2020; 405:889-902. [PMID: 32902706 DOI: 10.1007/s00423-020-01980-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 08/31/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Pancreatic cancer (PC) remains one of the most devastating malignant diseases, predicted to become the second leading cause of cancer-related death by 2030. Despite advances in surgical techniques and in systemic therapy, the 5-year relative survival remains a grim 9% for all stages combined. The extent of lymphadenectomy has been discussed intensively for decades, given that even in early stages of PC, lymph node (LN) metastasis can be detected in approximately 80%. PURPOSE The primary objective of this review was to provide an overview of the current literature evaluating the role of lymphadenectomy in resected PC. For this, we evaluated randomized controlled studies (RCTs) assessing the impact of extent of lymphadenectomy on OS and studies evaluating the prognostic impact of anatomical site of LN metastasis and the impact of the number of resected LNs on OS. CONCLUSIONS Lymphadenectomy plays an essential part in the multimodal treatment algorithm of PC and is an additional therapeutic tool to increase the chance for surgical radicality and to ensure correct staging for optimal oncological therapy. Based on the literature from the last decades, standard lymphadenectomy with resection of at least ≥ 15 LNs is associated with an acceptable postoperative complication risk and should be recommended to obtain local radicality and accurate staging of the disease. Although radical surgery including appropriate lymphadenectomy of regional LNs remains the only chance for long-term tumor control, future studies specifically assessing the impact of neoadjuvant therapy on extraregional LNs are warranted.
Collapse
|
|
9
|
Pranger BK, Tseng DSJ, Ubels S, van Santvoort HC, Nieuwenhuijs VB, de Jong KP, Patijn G, Molenaar IQ, Erdmann JI, de Meijer VE. How to Approach Para-Aortic Lymph Node Metastases During Exploration for Suspected Periampullary Carcinoma: Resection or Bypass? Ann Surg Oncol 2020; 27:2949-2958. [PMID: 32157526 PMCID: PMC7334266 DOI: 10.1245/s10434-020-08304-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Indexed: 01/08/2023]
Abstract
Background Intraoperative para-aortic lymph node (PALN) sampling during surgical exploration in patients with suspected pancreatic head cancer remains controversial. Objective The aim of this study was to assess the value of routine PALN sampling and the consequences of different treatment strategies on overall patient survival. Methods A retrospective, multicenter cohort study was performed in patients who underwent surgical exploration for suspected pancreatic head cancer. In cohort A, the treatment strategy was to avoid pancreatoduodenectomy and to perform a double bypass procedure when PALN metastases were found during exploration. In cohort B, routinely harvested PALNs were not examined intraoperatively and pancreatoduodenectomy was performed regardless. PALNs were examined with the final resection specimen. Clinicopathological data, survival data and complication data were compared between study groups. Results Median overall survival for patients with PALN metastases who underwent a double bypass procedure was 7.0 months (95% confidence interval [CI] 5.5–8.5), versus 11 months (95% CI 8.8–13) in the pancreatoduodenectomy group (p = 0.049). Patients with PALN metastases who underwent pancreatoduodenectomy had significantly increased postoperative morbidity compared with patients who underwent a double bypass procedure (p < 0.001). In multivariable analysis, severe comorbidity (ASA grade 2 or higher) was an independent predictor for decreased survival in patients with PALN involvement (hazard ratio 3.607, 95% CI 1.678–7.751; p = 0.001). Conclusion In patients with PALN metastases, pancreatoduodenectomy was associated with significant survival benefit compared with a double bypass procedure, but with increased risk of complications. It is important to weigh the advantages of resection versus bypass against factors such as comorbidities and clinical performance when positive intraoperative PALNs are found. Electronic supplementary material The online version of this article (10.1245/s10434-020-08304-0) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Bobby K Pranger
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Dorine S J Tseng
- Department of Hepatopancreatobiliary Surgery, Regional Academic Cancer Center Utrecht, St. Antonius Hospital Nieuwegein and University Medical Center Utrecht, Utrecht, The Netherlands
| | - Sander Ubels
- Department of Surgery, Isala Clinics Zwolle, Zwolle, The Netherlands
| | - Hjalmar C van Santvoort
- Department of Hepatopancreatobiliary Surgery, Regional Academic Cancer Center Utrecht, St. Antonius Hospital Nieuwegein and University Medical Center Utrecht, Utrecht, The Netherlands
| | | | - Koert P de Jong
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Gijs Patijn
- Department of Surgery, Isala Clinics Zwolle, Zwolle, The Netherlands
| | - I Quintus Molenaar
- Department of Hepatopancreatobiliary Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Joris I Erdmann
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Vincent E de Meijer
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
| |
Collapse
|
|
10
|
Zhou Y, Zhou G, Gao X, Xu C, Wang X, Xu P. Apparent diffusion coefficient value of mass-forming intrahepatic cholangiocarcinoma: a potential imaging biomarker for prediction of lymph node metastasis. ABDOMINAL RADIOLOGY (NEW YORK) 2020. [PMID: 32107582 DOI: 10.1007/s00261-020-02458-x.pmid:] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 09/29/2022]
Abstract
PURPOSE To compare the differences of MR features between mass-forming intrahepatic cholangiocarcinoma (IMCC) with and without lymph node metastasis (LNM) and to search for new imaging biomarkers for predicting LNM. MATERIALS AND METHODS The study included 91 patients with histopathologically confirmed single IMCC (20 patients with LNM and 71 patients without LNM). Findings of preoperative MR imaging including diffusion-weighted imaging (DWI) (b value 0, 500 mm2/s) were analyzed and apparent diffusion coefficient (ADC) values (b = 500 mm2/s) were calculated. Logistic regression analysis was performed to identify independent predictors of LNM. The diagnostic performance of independent predictors was assessed by receiver operating characteristic (ROC) and area under the curve (AUC) was compared. RESULTS Larger tumor size (p = 0.001), diameter of largest lymph node (LN) > 1 cm (p < 0.001), higher ADC value of primary IMCC lesion (ADCIMCC value) (p = 0.001), and positive CA19-9 level (p = 0.018) were correlated with LNM. Multivariate logistic regression analysis demonstrated that ADCIMCC value (odds ratio, 3.347; p = 0.001) and diameter of largest LN > 1 cm (odds ratio, 7.571; p = 0.004) were independent predictors of LNM. The AUCs for ADCIMCC value, diameter of largest LN > 1 cm,and combined method (the combination of ADCIMCC value and diameter of largest LN > 1 cm) were 0.782, 0.701,and 0.857, respectively. The AUC for combined method was significantly higher than that of diameter of largest LN > 1 cm (p = 0.033). CONCLUSION ADCIMCC value can be a potential imaging biomarker for predicting LNM of IMCC, especially in combination with diameter of largest LN > 1 cm.
Collapse
Affiliation(s)
- Yang Zhou
- Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.,Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Guofeng Zhou
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China.,Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Xuan Gao
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Chen Xu
- Department of Pathology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Xiaolin Wang
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Pengju Xu
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China. .,Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
| |
Collapse
|
|
11
|
Hempel S, Oehme F, Müssle B, Aust DE, Distler M, Saeger HD, Weitz J, Welsch T. Prognostic impact of para-aortic lymph node metastases in non-pancreatic periampullary cancer. World J Surg Oncol 2020; 18:16. [PMID: 31964383 PMCID: PMC6975057 DOI: 10.1186/s12957-020-1783-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Accepted: 12/31/2019] [Indexed: 11/29/2022] Open
Abstract
Background Resection of the para-aortic lymph node (PALN) group Ln16b1 during pancreatoduodenectomy remains controversial because PALN metastases are associated with a worse prognosis in pancreatic cancer patients. The present study aimed to analyze the impact of PALN metastases on outcome after non-pancreatic periampullary cancer resection. Methods One hundred sixty-four patients with non-pancreatic periampullary cancer who underwent curative pancreatoduodenectomy or total pancreatectomy between 2005 and 2016 were retrospectively investigated. The data were supplemented with a systematic literature review on this topic. Results In 67 cases, the PALNs were clearly assigned and could be histopathologically analyzed. In 10.4% of cases (7/67), tumor-infiltrated PALNs (PALN+) were found. Metastatic PALN+ stage was associated with increased tumor size (P = 0.03) and a positive nodal stage (P < 0.001). The median overall survival (OS) of patients with metastatic PALN and non-metastatic PALN (PALN–) was 24.8 and 29.5 months, respectively. There was no significant difference in the OS of PALN+ and pN1 PALN patients (P = 0.834). Patients who underwent palliative surgical treatment (n = 20) had a lower median OS of 13.6 (95% confidence interval 2.7–24.5) months. Including the systematic literature review, only 23 cases with PALN+ status and associated OS could be identified; the average survival was 19.8 months. Conclusion PALN metastasis reflects advanced tumor growth and lymph node spread; however, it did not limit overall survival in single-center series. The available evidence of the prognostic impact of PALN metastasis is scarce and a recommendation against resection in these cases cannot be given.
Collapse
Affiliation(s)
- Sebastian Hempel
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Florian Oehme
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Benjamin Müssle
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Daniela E Aust
- Institute of Pathology, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
| | - Marius Distler
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Hans-Detlev Saeger
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Jürgen Weitz
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Thilo Welsch
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
| |
Collapse
|
|
12
|
Socha J, Surdyka D, Kepka L. Nodal CTV selection according to primary tumour location and pT stage for biliary tract cancer. J Med Imaging Radiat Oncol 2019; 63:822-828. [PMID: 31402569 DOI: 10.1111/1754-9485.12937] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Accepted: 07/14/2019] [Indexed: 11/30/2022]
Abstract
INTRODUCTION/PURPOSE To assist radiation oncologists in determining the elective nodal CTV for biliary tract cancer, we aimed to provide the rules for selection of the CTV for each subsite of biliary tract with respect to the pT stage, based on the analysis of the incidence and location of metastatic lymph nodes. METHODS Systematic review and meta-analysis was performed to determine the rate of pathological nodal involvement of each individual lymph node station (LNS) as a function of the primary tumour pT stage (pT1-2 vs. pT3-4) separately for right intrahepatic cholangiocarcinoma (rIHC), left/hilar intrahepatic cholangiocarcinoma l/hIHC), proximal extrahepatic cholangiocarcinoma (pEHC), middle extrahepatic cholangiocarcinoma (mEHC), distal extrahepatic cholangiocarcinoma (dEHC) and gall bladder cancer (GBC). A 5% or higher risk of involvement was assumed to justify inclusion of the LNS in the CTV. RESULTS Coeliac LNS, which is usually included in the CTV in clinical practice, has a low risk of involvement and can presumably be omitted for pT1-2 GBC, for dEHC irrespective of pT stage and for mEHC. Para-aortic and superior mesenteric artery (SMA) LNS that are usually omitted have a high risk of involvement. Para-aortic LNS should be considered for inclusion for all the subsites except for pT1-2 dEHC, and SMA LNS for all the subsites except for pT1-2 dEHC, pT1-2 GBC and pEHC. Left gastric artery, lesser curvature and paracardial LNS should be considered for inclusion for l/hIHC. CONCLUSION This systematic review provides an evidence-based strategy for nodal CTV selection in biliary tract cancer according to primary tumour location and pT stage.
Collapse
Affiliation(s)
- Joanna Socha
- Radiation Oncology Department, Military Institute of Medicine, Warsaw, Poland.,Radiation Oncology Department, Regional Oncology Center, Czestochowa, Poland
| | - Dariusz Surdyka
- Radiation Oncology Department, Cancer Center of the Lublin Region, Lublin, Poland
| | - Lucyna Kepka
- Radiation Oncology Department, Military Institute of Medicine, Warsaw, Poland
| |
Collapse
|
|
13
|
Schwarz L, Tortajada P, Pittau G, Di Fiore F, Sefrioui D, Bridoux V, Laurenzi A, Tuech JJ, Sa Cunha A. “Laparoscopic Para-Aortic Lymph Node Sampling” First Approach for Pancreatic Adenocarcinoma as an Oncological Practice. J Laparoendosc Adv Surg Tech A 2019; 29:900-904. [DOI: 10.1089/lap.2018.0775] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Affiliation(s)
- Lilian Schwarz
- Department of Digestive Surgery, Rouen University Hospital, Rouen, France
- Department of Genomic and Personalized Medicine in Cancer and Neurological Disorders, UNIROUEN, UMR 1245 INSERM, Rouen University Hospital, Normandie University, Rouen, France
| | - Pauline Tortajada
- Department of Digestive Surgery, Rouen University Hospital, Rouen, France
- Department of HPB Surgery and Transplantation, Hôpital Paul Brousse, Aphp, Villejuif, France
| | - Gabriella Pittau
- Department of HPB Surgery and Transplantation, Hôpital Paul Brousse, Aphp, Villejuif, France
| | - Frederic Di Fiore
- Department of Genomic and Personalized Medicine in Cancer and Neurological Disorders, UNIROUEN, UMR 1245 INSERM, Rouen University Hospital, Normandie University, Rouen, France
- Department of Digestive Oncology, Rouen University Hospital, Rouen, France
| | - David Sefrioui
- Department of Genomic and Personalized Medicine in Cancer and Neurological Disorders, UNIROUEN, UMR 1245 INSERM, Rouen University Hospital, Normandie University, Rouen, France
- Department of Digestive Oncology, Rouen University Hospital, Rouen, France
| | - Valérie Bridoux
- Department of Digestive Surgery, Rouen University Hospital, Rouen, France
| | - Andrea Laurenzi
- Department of HPB Surgery and Transplantation, Hôpital Paul Brousse, Aphp, Villejuif, France
| | - Jean-Jacques Tuech
- Department of Digestive Surgery, Rouen University Hospital, Rouen, France
- Department of Genomic and Personalized Medicine in Cancer and Neurological Disorders, UNIROUEN, UMR 1245 INSERM, Rouen University Hospital, Normandie University, Rouen, France
| | - Antonio Sa Cunha
- Department of HPB Surgery and Transplantation, Hôpital Paul Brousse, Aphp, Villejuif, France
| |
Collapse
|
|
14
|
Zhang X, Zhang J, Fan H, Liu Y, He Q. Risk factors related to metastasis of para-aortic lymph nodes in pancreatic ductal adenocarcinoma: A retrospective observational study. Medicine (Baltimore) 2018; 97:e12370. [PMID: 30290595 PMCID: PMC6200498 DOI: 10.1097/md.0000000000012370] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
This study was designed to explore the risk factors related to metastasis of para-aortic lymph node (PALN).Clinicopathologic data of 241 patients with resectable or borderline resectable pancreatic cancer who underwent pancreaticoduodenectomy with extended lymphadenectomy between January 2008 and December 2015 were collected, potential factors related to metastasis of PALN were analyzed.Positive rate of PALN was 19.5% (47/241). Univariate analysis showed that back pain (P = .028), preoperative CA19-9 level (P < .001), tumor size (P < .001), portal vein (PV)/superior mesenteric vein (SMV) invasion (P < .001), superior mesenteric artery (SMA) invasion (P < .001), and diameter > 1.0 cm were in correlation with PALN involvement, multivariate analysis revealed that preoperative CA19-9 level, PV/SMV invasion, SMA invasion and diameter > 1.0 cm were independent risk factors to metastasis of PALN. Patients with LN8+ had a higher positive rate of PALN than with LN8- (38.1% vs 15.6%, P = .001), similar results could be found when LN12+ (35.8% vs 13.2%, P < .001) and LN14+ (41.2% vs 11.0%, P < .001), multivariate analysis showed that LN8+ and LN14+ were closely in correlation with PALN metastasis.Several factors were related to the status of PALN, preoperative CA19-9 level, PV/SMV invasion, SMA invasion and diameter > 1.0 cm were 4 independent risk factors to PALN metastasis. LN8+ and LN14+ were 2 strong predictors of PALN metastasis. A comprehensive analysis covering all possible risk factors related to metastasis of PALN should be given before design of treatment plan whenever involvement of PALN was suspected.
Collapse
Affiliation(s)
- Xingmao Zhang
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital
| | - Jie Zhang
- The First Hospital of Combination of the Western Medicine and Traditional Chinese Medicine, Xiaozhuang Hospital, Capital Medical University, Beijing, China
| | - Hua Fan
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital
| | - Yu Liu
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital
| | - Qiang He
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital
| |
Collapse
|
|
15
|
Outcomes of pancreatic adenocarcinoma that was not resected because of isolated para-aortic lymph node involvement. J Visc Surg 2018; 156:97-101. [PMID: 30026012 DOI: 10.1016/j.jviscsurg.2018.06.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
PURPOSE Survival appears to be poor in cases of pancreatic ductal adenocarcinoma (PDAC) with para-aortic lymph node involvement (PALN+). However, resection is still performed in these cases because the prognostic impact of PALN+remains controversial. METHODS PALN+was intraoperatively found in 14 patients (4.8%) with resectable PDAC who consequently did not undergo pancreatectomy. RESULTS The median overall survival time after laparotomy was 21 months. The 1- and 3-year overall survival rates were 58.3% and 25%, respectively. CONCLUSIONS We support the advisability of reconsidering pancreatectomy in patients with intraoperatively detected PALN+because the reported survival of such patients who undergo pancreatectomy is poorer than the survival observed for patients in our series.
Collapse
|
|
16
|
Jun SY, Sung YN, Lee JH, Park KM, Lee YJ, Hong SM. Validation of the Eighth American Joint Committee on Cancer Staging System for Distal Bile Duct Carcinoma. Cancer Res Treat 2018; 51:98-111. [PMID: 29510611 PMCID: PMC6333967 DOI: 10.4143/crt.2017.595] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2017] [Accepted: 03/01/2018] [Indexed: 12/31/2022] Open
Abstract
PURPOSE T category of the eighth edition of the American Joint Committee on Cancer (AJCC) staging system for distal bile duct carcinoma (DBDC) was changed to include tumor invasion depth measurement, while the N category adopted a 3-tier classification system based on the number of metastatic nodes. Materials and Methods To validate cancer staging, a total of 200 surgically resected DBDCs were staged and compared according to the seventh and eighth editions. RESULTS T categories included T1 (n=37, 18.5%), T2 (n=114, 57.0%), and T3 (n=49, 24.5%). N categories included N0 (n=133, 66.5%), N1 (n=50, 25.0%), and N2 (n=17, 8.5%). Stage groupings included I (n=33, 16.5%), II (n=150, 75.0%), and III (n=17, 8.5%). The overall 5-year survival rates (5-YSRs) of T1, T2, and T3 were 59.3%, 42.4%, and 12.2%, respectively. T category could discriminate patient survival by both pairwise (T1 and T2, p=0.011; T2 and T3, p < 0.001) and overall (p < 0.001) comparisons. The overall 5-YSRs of N0, N1, and N2 were 47.3%, 17.0%, and 14.7%, respectively. N category could partly discriminate patient survival by both pairwise (N0 and N1, p < 0.001; N1 and N2, p=0.579) and overall (p < 0.001) comparisons. The overall 5-YSRs of stages I, II, and III were 59.0%, 35.4%, and 14.7%, respectively. Stages could distinguish patient survival by both pairwise (I and II, p=0.002; II and III, p=0.015) and overall (p < 0.001) comparisons. On multivariate analyses, T and N categories (p=0.014 and p=0.029) and pancreatic invasion (p=0.006) remained significant prognostic factors. CONCLUSION The T andNcategories of the eighth edition AJCC staging system for DBDC accurately predict patient prognosis.
Collapse
Affiliation(s)
- Sun-Young Jun
- Department of Pathology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea
| | - You-Na Sung
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jae Hoon Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kwang-Min Park
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-Joo Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seung-Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| |
Collapse
|
|
17
|
Yamada T, Nakanishi Y, Okamura K, Tsuchikawa T, Nakamura T, Noji T, Asano T, Tanaka K, Kurashima Y, Ebihara Y, Murakami S, Shichinohe T, Mitsuhashi T, Hirano S. Impact of serum carbohydrate antigen 19-9 level on prognosis and prediction of lymph node metastasis in patients with intrahepatic cholangiocarcinoma. J Gastroenterol Hepatol 2018; 33:1626-1633. [PMID: 29427472 DOI: 10.1111/jgh.14124] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2017] [Revised: 01/30/2018] [Accepted: 01/31/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIM Lymph node metastasis is an important prognostic factor for intrahepatic cholangiocarcinoma (ICC), but accurate preoperative diagnosis is difficult. The aim of this study was to measure the concentration of serum carbohydrate antigen 19-9 (s-CA19-9) as a preoperative predictor of lymph node metastasis. METHODS In our department, curative-intent hepatectomy for ICC has been performed only once the absence of metastases in para-aortic lymph nodes (PALN) has been confirmed from intraoperative frozen-section pathological examinations. The present study included 13 non-resected ICC patients with PALN metastasis (PALN group) and 44 resected ICC patients without PALN metastasis (non-PALN group). S-CA19-9 was examined to evaluate predictive performance for PALN metastasis and regional lymph node metastasis (pN1) from analysis of the receiver operating characteristic curve. In the non-PALN group, univariate and multivariate analyses for survival were performed on clinicopathological variables. RESULTS From receiver operating characteristic curve analysis, s-CA19-9 showed good diagnostic accuracy for PALN metastasis (68%; cut-off, 200 U/mL) and pN1 (77%; cut-off, 100 U/mL). In univariate analysis, age (<65 years), s-CA19-9 (≥100 U/mL), portal vein resection, pN1, and positive resection margin (R1) were all identified as significant negative prognostic factors. Five-year survival rates of patients with high s-CA19-9 and pN1 were 6.9% and 7.3%, respectively. In multivariate analysis, high s-CA19-9 and R1 represented independent predictors of poor prognosis. CONCLUSIONS Preoperative s-CA19-9 appears useful as a biomarker in patients with ICC, for predicting not only lymph node metastasis but also prognosis after surgical resection with curative intent.
Collapse
Affiliation(s)
- Toru Yamada
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Japan
- Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan
| | - Yoshitsugu Nakanishi
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Japan
| | - Keisuke Okamura
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Japan
| | - Takahiro Tsuchikawa
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Japan
| | - Toru Nakamura
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Japan
| | - Takehiro Noji
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Japan
| | - Toshimichi Asano
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Japan
| | - Kimitaka Tanaka
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Japan
| | - Yo Kurashima
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Japan
| | - Yuma Ebihara
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Japan
| | - Soichi Murakami
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Japan
| | - Toshiaki Shichinohe
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Japan
| | - Tomoko Mitsuhashi
- Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan
| | - Satoshi Hirano
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Japan
| |
Collapse
|
|
18
|
Sperti C, Gruppo M, Blandamura S, Valmasoni M, Pozza G, Passuello N, Beltrame V, Moletta L. Para-aortic node involvement is not an independent predictor of survival after resection for pancreatic cancer. World J Gastroenterol 2017; 23:4399-4406. [PMID: 28706422 PMCID: PMC5487503 DOI: 10.3748/wjg.v23.i24.4399] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2017] [Revised: 02/21/2017] [Accepted: 05/19/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To analyze the importance of para-aortic node status in a series of patients who underwent pancreaticoduodenectomy (PD) in a single Institution. METHODS Between January 2000 and December 2012, 151 patients underwent PD with para-aortic node dissection for pancreatic adenocarcinoma in our Institution. Patients were divided into two groups: patients with negative PALNs (PALNs-), and patients with metastatic PALNs (PALNs+). Pathologic factors, including stage, nodal status, number of positive nodes and lymph node ratio, invasion of para-aortic nodes, tumor's grading, and radicality of resection were studied by univariate and multivariate analysis. Survival curves were constructed with Kaplan-Meier method and compared with Log-rank test: significance was considered as P < 0.05. RESULTS A total of 107 patients (74%) had nodal metastases. Median number of pathologically assessed lymph nodes was 26 (range 14-63). Twenty-five patients (16.5%) had para-aortic lymph node involvement. Thirty-three patients (23%) underwent R1 pancreatic resection. One-hundred forty-one patients recurred and died for tumor recurrence, one is alive with recurrence, and 9 are alive and free of disease. Overall survival was significantly influenced by grading (P = 0.0001), radicality of resection (P = 0.001), stage (P = 0.03), lymph node status (P = 0.04), para-aortic nodes metastases (P = 0.02). Multivariate analysis showed that grading was an independent prognostic factor for overall survival (P = 0.0001), while grading (P = 0.0001) and radicality of resection (P = 0.01) were prognostic parameters for disease-free survival. Number of metastatic nodes, node ratio, and para-aortic nodes involvement were not independent predictors of disease-free and overall survival. CONCLUSION In this experience, lymph node status and para-aortic node metastases were associated with poor survival at univariate analysis, but they were not independent prognostic factors.
Collapse
|
|
19
|
Holzapfel K, Gaa J, Schubert EC, Eiber M, Kleeff J, Rummeny EJ, Loos M. Value of diffusion-weighted MR imaging in the diagnosis of lymph node metastases in patients with cholangiocarcinoma. Abdom Radiol (NY) 2016; 41:1937-41. [PMID: 27271285 DOI: 10.1007/s00261-016-0791-y] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
PURPOSE To evaluate diffusion-weighted MR imaging (DWI) in the diagnosis of lymph node metastases in patients with cholangiocarcinoma. METHODS In 24 patients with cholangiocarcinoma, MR imaging of the upper abdomen was performed prior to surgery at 1.5 T using a respiratory-triggered single-shot echo-planar imaging (SSEPI) sequence (b values: 50, 300, and 600 s/mm(2)). ADC (apparent diffusion coefficient) values and diameters of regional lymph nodes (LN) were determined. Subsequently, in all patients, surgical exploration and/or resection of the primary tumor and regional LN dissection were performed. Imaging results were correlated with results of histopathologic analysis. ADC values and diameters of benign and malignant LN were compared using the Mann-Whitney U test. In addition, a ROC (receiver operating characteristic curve) analysis was performed. RESULTS The mean ADC value (×10(-3) mm(2)/s) of metastatic LN (1.21 ± 0.15) was significantly lower than that of benign LN (1.62 ± 0.33, p < 0.001) while there was no significant difference in the mean diameter of malignant (16.8 ± 5.4 mm) and benign LN (14.1 ± 4.0 mm; p = 0.09). Using an ADC value of 1.25 × 10(-3) mm(2)/s as threshold, 91.4% of LN were correctly classified as benign or malignant with a sensitivity/specificity of 83.3%/92.8% and a positive/negative predictive value of 66.7%/96.7%. The area under the ROC curve was 0.93. CONCLUSION DWI using a respiratory-triggered SSEPI sequence, according to our preliminary experience, is a promising imaging modality in the differentiation of benign and malignant LN in patients with cholangiocarcinoma.
Collapse
Affiliation(s)
- Konstantin Holzapfel
- Department of Radiology, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675, Munich, Germany.
| | - Jochen Gaa
- Department of Radiology, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675, Munich, Germany
| | - Elaine C Schubert
- Department of Radiology, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675, Munich, Germany
| | - Matthias Eiber
- Department of Nuclear Medicine, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675, Munich, Germany
| | - Joerg Kleeff
- Department of Surgery, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675, Munich, Germany
| | - Ernst J Rummeny
- Department of Radiology, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675, Munich, Germany
| | - Martin Loos
- Department of Surgery, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675, Munich, Germany
| |
Collapse
|
|
20
|
El Hajj II, Eloubeidi M. Sampling para-aortic lymph nodes in pancreatic and biliary cancers with EUS-guided FNA: diagnostic, clinical, and therapeutic implications. Gastrointest Endosc 2016; 84:476-8. [PMID: 27530480 DOI: 10.1016/j.gie.2016.05.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Accepted: 05/04/2016] [Indexed: 02/08/2023]
Affiliation(s)
- Ihab I El Hajj
- Division of Gastroenterology and Hepatology, Indiana University, Indianapolis, Indiana, USA
| | | |
Collapse
|
|
21
|
Lin JY, Zhang XM, Kou JT, Fa H, Zhang XX, Dai Y, He Q. Analysis of prognostic factors for pancreatic head cancer according to para-aortic lymph node. Cancer Med 2016; 5:2701-2707. [PMID: 27541833 PMCID: PMC5083722 DOI: 10.1002/cam4.853] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2016] [Revised: 07/07/2016] [Accepted: 07/15/2016] [Indexed: 12/29/2022] Open
Abstract
This study was designed to investigate the relationship between prognosis of pancreatic head cancer and status of para-aortic lymph node (PALN). A total of 233 patients with pancreatic head cancer who underwent surgical resection between February 2008 and October 2015 were enrolled in this study. Univariate and multivariate analyses were used to reveal the prognostic factors. Prognostic factors for patients with and without metastasis of PALN were analyzed, respectively. The 5-year overall survival (OS) rate was 19.0% for all patients, and the positive rate of PALN metastasis was 18.9% (44/233). The 1-, 2-, 3-, and 5-year OS rates in patients without metastasis of PALN were 79.4%, 54.8%, 36.4%, and 22.9%, respectively, whereas the 1-, 2-, and 3-year survival rates were 54.0%, 14.8%, and 0%, respectively, in patients with metastasis of PALN. Preoperative CA19-9 level, tumor size, T status, N status, and adjuvant therapy were independent prognostic factors for all patients confirmed by multivariate analysis. For patients without PALN metastasis, back pain, tumor size, T status, N status, portal or superior mesenteric vein invasion, and adjuvant therapy were independent prognostic factors, while the only one influence factor for 2-year OS was adjuvant therapy for patients with metastasis of PALN. Metastasis of PALN was associated with poor prognosis for patients with pancreatic head cancer. Patients with and without metastasis of PALN had different prognostic factors, and adjuvant therapy was the only prognostic factor for patients with metastasis of PALN.
Collapse
Affiliation(s)
- Jian-Yu Lin
- Comprehensive Department, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Xing-Mao Zhang
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Jian-Tiao Kou
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Hua Fa
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Xin-Xue Zhang
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Yang Dai
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Qiang He
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
| |
Collapse
|
|
22
|
Agalianos C, Gouvas N, Papaparaskeva K, Dervenis C. Positive para-aortic lymph nodes following pancreatectomy for pancreatic cancer. Systematic review and meta-analysis of impact on short term survival and association with clinicopathologic features. HPB (Oxford) 2016; 18:633-41. [PMID: 27485057 PMCID: PMC4972380 DOI: 10.1016/j.hpb.2016.04.007] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2016] [Revised: 04/21/2016] [Accepted: 04/22/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND The relation between para-aortic lymph nodes (PALN) involvement and pancreatic ductal adenocarcinoma (PDAC) survival, along with the optimal handling of this particular lymph node station remain unclear. A systematic review and meta-analysis was performed to assess this. METHODS A search of Medline, Embase, Ovid and Cochrane databases was performed until July 2015 to identify studies reporting on the relation of PALN involvement and PDAC outcomes and a meta-analysis was performed following data extraction. RESULTS Ten retrospective studies and two prospective non randomized studies (2467 patients) were included. Patients with positive PALN had worse one (p < 0.00001) and two year (p < 0.00001) survival when compared with patients with negative PALN. Even when comparing only patients with positive lymph nodes (N1), patients with PALN involvement presented with a significant lower one (p = 0.03) and two (p = 0.002) year survival. PALN involvement was associated with an increased possibility of positive margin (R1) resection (p < 0.00001), stations' 12, 14 and 17 malignant infiltration (p < 0.00001), but not with tumour stage (p = 0.78). DISCUSSION Involvement of PALN is associated with decreased survival in pancreatic cancer patients. However, existence of long term survivors among this subgroup of patients should be further evaluated, in order to identify factors associated with their favourable prognosis.
Collapse
Affiliation(s)
- Christos Agalianos
- Athens Naval and Veterans Hospital, Department of Surgery, Athens, Greece,Correspondence Christos Agalianos, Department of General Surgery, Athens Naval & Veterans Hospital, 70 Dinokratous Str., GR-11521 Athens, Greece. Tel: +30 6932399731.Department of General SurgeryAthens Naval & Veterans Hospital70 Dinokratous Str.AthensGR-11521Greece
| | - Nikolaos Gouvas
- “Konstantopouleio” Hospital of Athens, Department of Surgery, Athens, Greece
| | - Kleo Papaparaskeva
- “Konstantopouleio” Hospital of Athens, Department of Pathology, Athens, Greece
| | - Christos Dervenis
- “Konstantopouleio” Hospital of Athens, Department of Surgery, Athens, Greece
| |
Collapse
|
|
23
|
Gu J, Xia L, Xu B, Lu T, Halmurat O, Wang J, Zhang J, Ding Y, Xia Q. Clinical prognostic significance of regional and extended lymphadenectomy for biliary cancer with para-aortic lymph node metastasis: A systematic review and meta-analysis. Dig Liver Dis 2016; 48:717-25. [PMID: 27094254 DOI: 10.1016/j.dld.2016.03.019] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2015] [Revised: 03/21/2016] [Accepted: 03/29/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND The aim of our study was to evaluate clinical prognostic significance of regional and extended lymphadenectomy for biliary cancer with para-aortic lymph node metastasis. METHODS A thorough literature search was performed in PubMed/Medline, Cochrane Central Register, Embase, ISI Web of Science and Google Scholar between January 1965 and May 2014 with restricted articles for the English language. Data were processed for a meta-analysis by RevMan 5 software. RESULTS Altogether 10 retrospective studies were finally enrolled in our study. For positive para-aortic lymph node group irrespective of regional lymph node metastasis, the overall 1-, 3-, 5-yr pooled RR estimates of survival rates were 2.30, 1.70, and 1.42. There were significant differences between positive para-aortic lymph node group and negative group. For positive para-aortic lymph node group in the setting of regional lymph node metastasis, the overall 1-, 3-, 5-yr pooled RR estimates of survival rates were 1.57, 1.29, and 1.11, respectively. The long-term outcomes referred to 5-yr survival rate were similar between para-aortic lymph node metastasis and regional lymph node metastasis only. DISCUSSION Radical resection with extended lymphadenectomy should be caution in terms of the results of an intraoperative sampling biopsy of para-aortic lymph node, which requires a well-designed, prospective controlled study in the future.
Collapse
Affiliation(s)
- Jinyang Gu
- Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Lei Xia
- Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Biyun Xu
- Department of Biostatistics, Affiliated DrumTower Hospital of Nanjing University Medical School, Nanjing, China
| | - Tianfei Lu
- Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Obulkasim Halmurat
- Department of Hepatobiliary Surgery, Affiliated DrumTower Hospital of Nanjing University Medical School, Nanjing, China
| | - Jun Wang
- Department of Hepatobiliary Surgery, Affiliated DrumTower Hospital of Nanjing University Medical School, Nanjing, China
| | - Jianjun Zhang
- Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yitao Ding
- Department of Hepatobiliary Surgery, Affiliated DrumTower Hospital of Nanjing University Medical School, Nanjing, China
| | - Qiang Xia
- Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
| |
Collapse
|
|
24
|
Komo T, Murakami Y, Kondo N, Uemura K, Hashimoto Y, Nakagawa N, Urabe K, Takahashi S, Sueda T. Prognostic Impact of Para-Aortic Lymph Node Micrometastasis in Pancreatic Ductal Adenocarcinoma. Ann Surg Oncol 2016; 23:2019-27. [PMID: 26856722 DOI: 10.1245/s10434-016-5120-8] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Indexed: 01/07/2023]
Abstract
BACKGROUND It is still unclear whether micrometastasis of para-aortic lymph nodes (PALNs) in pancreatic ductal adenocarcinoma (PDAC) is tantamount to PALN metastasis detected by hematoxylin and eosin (HE) staining. METHODS A total of 242 patients with PDAC who underwent radical pancreatectomy with PALN dissection were eligible for this study. Micrometastasis in PALNs was evaluated by CAM 5.2 immunohistochemistry. The relationship between PALN status and overall survival (OS) was analyzed. RESULTS Of the 242 enrolled patients, 25 (10 %) had PALN metastasis detected by HE (PALN HE-positive), and 21 (9 %) had PALN micrometastasis not detected by HE but identified by CAM 5.2 immunohistochemistry. Univariate analysis revealed that patients with PALN micrometastasis (p = .004) and PALN HE positivity (p = .003) had a significantly shorter OS than those without PALN metastasis, whereas no significant difference was observed between the two former groups (p = .874). In multivariate analysis, lack of adjuvant chemotherapy (hazard ratio [HR] 2.43, p < .001), PALN micrometastasis (HR 1.89; p = .046), and PALN HE-positivity (HR 1.89, p = .023) were identified as independent risk factors for poor prognosis. Within a subset of 46 patients with PALN HE-positivity or micrometastasis, lack of adjuvant chemotherapy was independently associated with poor OS (HR 2.58. p = .029). CONCLUSIONS The prognosis of patients with PALN micrometastasis was extremely poor as well as HE-positive PALNs. However, postoperative adjuvant chemotherapy may contribute to improving the prognosis of PDAC patients with PALN metastasis.
Collapse
Affiliation(s)
- Toshiaki Komo
- Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yoshiaki Murakami
- Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
| | - Naru Kondo
- Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kenichiro Uemura
- Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yasushi Hashimoto
- Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Naoya Nakagawa
- Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kazuhide Urabe
- Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Shinya Takahashi
- Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Taijiro Sueda
- Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| |
Collapse
|
|
25
|
Paiella S, Sandini M, Gianotti L, Butturini G, Salvia R, Bassi C. The prognostic impact of para-aortic lymph node metastasis in pancreatic cancer: A systematic review and meta-analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2016; 42:616-624. [PMID: 26916137 DOI: 10.1016/j.ejso.2016.02.003] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Revised: 01/26/2016] [Accepted: 02/02/2016] [Indexed: 12/12/2022]
Abstract
PURPOSE To evaluate by a meta-analytic approach the long-term prognostic impact of para-aortic lymph node (PALN) involvement in resected ductal adenocarcinoma of the pancreas. METHODS MEDLINE, Embase, PubMed and the Cochrane Library were searched from January 1990 to June 2015. Trials reporting Kaplan-Meier curves and comparing overall long-term survival of negative and metastatic PALN in patients who underwent resection for pancreatic cancer were included. Lymph nodes were classified according to the Japan Pancreatic Society rules and identified using hematoxylin and eosin staining. Hazard ratios (HRs) and 95%CI were estimated for each trial and pooled in a meta-analysis. RESULTS Thirteen eligible studies including 2141 patients (364 positive PALN; 1777 negative PALN) were identified. Most of the studies were retrospective. Heterogeneity among trials was high (I(2) = 98.7%; p < .001). PALN metastasis was associated with increased mortality when compared with patients with negative PALN regardless regional nodal status [HR 1.85, 95%CI 1.48-2.31; p < .001]. Median survival was significantly decreased in patients with positive PALN (WMD = -4.92 months 95%CI -6.40; -3.43; p < .001). Moreover, metastatic PALN affected mortality also when regional lymph nodes were positive [HR 1.67, 95%CI 1.34-2.08; p < .001]. No publication bias was detected. CONCLUSIONS PALN metastasis appears to correlate with poor prognosis in patients with pancreatic adenocarcinoma. The assessment of PALN status may be considered for a more accurate staging of the disease and appropriated subgroup survival reporting. However, the definitive avoidance of the resection in case of intraoperative metastatic PALN needs further investigation.
Collapse
Affiliation(s)
- S Paiella
- Unit of General Surgery B, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy.
| | - M Sandini
- Department of Surgery and Translational Medicine, Milano Bicocca University, Monza, Italy
| | - L Gianotti
- Department of Surgery and Translational Medicine, Milano Bicocca University, Monza, Italy
| | - G Butturini
- Unit of General Surgery B, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - R Salvia
- Unit of General Surgery B, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - C Bassi
- Unit of General Surgery B, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| |
Collapse
|
|
26
|
Nappo G, Borzomati D, Perrone G, Valeri S, Amato M, Petitti T, Coppola R. Incidence and prognostic impact of para-aortic lymph nodes metastases during pancreaticoduodenectomy for peri-ampullary cancer. HPB (Oxford) 2015; 17:1001-8. [PMID: 26335256 PMCID: PMC4605339 DOI: 10.1111/hpb.12497] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Accepted: 07/16/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND Standard lymphadenectomy during pancreaticoduodenectomy (PD) for peri-ampullary cancer does not include the routine removal of para-aortic lymph nodes (PALN) (station 16, according to the JPS staging system). The aim of this study was to report the incidence and the prognostic value of PALN metastases in patients undergoing PD for peri-ampullary cancer. MATERIALS AND METHODS One hundred thirty-five consecutive patients who underwent PD and PALN dissection for peri-ampullary cancer were prospectively evaluated. The relationship between clinicopathological factors, including PALN metastases and survival was evaluated at univariate and multivariate analysis. RESULTS PALN metastases (N16+) were found in 11.1% of cases. At univariate analysis, R1 resection, metastatic nodes different from para aortic (N1) and N16+ significantly affected patients' prognosis. Compared with N16+, the median overall survival (OS) of N0 patients was significantly longer (32 versus 69 months, respectively; P < 0.05), whereas no difference was found between N16+ and N1 patients (32 versus 34 months, respectively) (P > 0.05). At multivariate analysis, only R1 resection reached statistical significance and was confirmed an independent prognostic factor. CONCLUSIONS Neoplastic involvement of PALN in peri-ampullary cancer is frequent and, so, their removal during PD could be justified. Moreover, PALN metastases should be not considered an absolute contraindication to radical surgery.
Collapse
Affiliation(s)
- Gennaro Nappo
- Department of General Surgery, Campus Bio-Medico University of RomeRome, Italy
| | - Domenico Borzomati
- Department of General Surgery, Campus Bio-Medico University of RomeRome, Italy
| | - Giuseppe Perrone
- Unit of Pathology, Campus Bio-Medico University of RomeRome, Italy
| | - Sergio Valeri
- Department of General Surgery, Campus Bio-Medico University of RomeRome, Italy
| | - Michela Amato
- Unit of Pathology, Campus Bio-Medico University of RomeRome, Italy
| | | | - Roberto Coppola
- Department of General Surgery, Campus Bio-Medico University of RomeRome, Italy
| |
Collapse
|
|
27
|
Paiella S, Malleo G, Maggino L, Bassi C, Salvia R, Butturini G. Pancreatectomy with Para-Aortic Lymph Node Dissection for Pancreatic Head Adenocarcinoma: Pattern of Nodal Metastasis Spread and Analysis of Prognostic Factors. J Gastrointest Surg 2015; 19:1610-1620. [PMID: 26160322 DOI: 10.1007/s11605-015-2882-4] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2015] [Accepted: 06/23/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND This study investigated the prognostic impact of the exact location of nodal metastases in a subgroup of patients who underwent pancreatectomy with extended lymphadenectomy for head adenocarcinoma, with a special focus on station 16b1. METHODS Clinical, pathologic, and follow-up details were extracted from our database and analyzed retrospectively. Survival analysis was performed using univariate and multivariate models. We also performed a matched case-control analysis with resected patients who did not receive extended lymphadenectomy and with locally advanced patients. RESULTS The study population consisted of 67 patients. The rate of station 16b1 metastases was 20.9%. Station 14a-b metastases (OR = 4.28), G3 tumors (OR = 4.03), and number of PLN ≥ 8 (OR = 4.46) were independently associated with station 16b1 involvement. Among pN1 patients, station 14a-b (HR = 2.60) and station 16b1 metastases (HR = 2.40) were predictors of survival. The median disease-specific survival of 16b1+ patients was 17 months (95% CI 8.47-25.52). In the matched case-control analysis, the survival rates of resected 16b1+ patients was in between pN1/16b1- patients and locally advanced patients. CONCLUSIONS Metastases to station 16b1 are associated with a decreased survival in comparison with pN1/16b1- patients, yet longer than in matched locally advanced patients. Station 14 can be considered as a "junctional node" to station 16b1.
Collapse
Affiliation(s)
- Salvatore Paiella
- Unit of General and Pancreatic Surgery, The Pancreas Institute, G.B. Rossi Hospital, University of Verona Hospital Trust, P. Le L.A. Scuro 10, 37134, Verona, Italy,
| | | | | | | | | | | |
Collapse
|
|
28
|
Azagra JS, Arru L, Estévez S, Silviu-Tiberiu MP, Poulain V, Goergen M. Pure laparoscopic pancreatoduodenectomy with initial approach to the superior mesenteric artery. Wideochir Inne Tech Maloinwazyjne 2015; 10:450-7. [PMID: 26649095 PMCID: PMC4653251 DOI: 10.5114/wiitm.2015.54040] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 06/05/2015] [Accepted: 07/15/2015] [Indexed: 12/23/2022] Open
Abstract
INTRODUCTION The "artery-first approach" (AFA) to the superior mesenteric artery allows an early assessment of resectability of pancreatic tumours and could improve the benefits of laparoscopy, reducing invasiveness, especially for unresectable tumours. AIM To describe our technique of pure laparoscopic pancreatoduodenectomy (PLPD) with the AFA, and to report the surgical outcomes of this procedure in a small series of 12 patients through a retrospective analysis of a prospectively collected database. MATERIAL AND METHODS Twelve selected patients underwent elective full laparoscopic pancreatoduodenectomy with the AFA. The technical aspects of the procedure are described in detail and the included images facilitate the understanding of the procedure. RESULTS The mean operative time was 300 min (range: 250-540 min). No intraoperative complications were observed. No conversion to laparotomy was necessary. The mean postoperative hospital stay was 18 days (range: 8-42). Mortality was null. There were 3 major complications at the 3rd post-operative month follow-up: 2 patients reporting a grade A pancreatic fistula and one biliary fistula. CONCLUSIONS Our work shows that pure laparoscopic pancreatoduodenectomy (PLPD) with the AFA is feasible, in selected patients. The AFA could improve on the advantages of laparoscopy in the identification of unresectable patients, and it also allows early control of vascular structures.
Collapse
Affiliation(s)
- Juan Santiago Azagra
- Centre Hospitalier de Luxembourg, Service de Chirurgie Générale et Mini-invasive, Luxembourg City, Luxembourg GD
| | - Luca Arru
- Centre Hospitalier de Luxembourg, Service de Chirurgie Générale et Mini-invasive, Luxembourg City, Luxembourg GD
| | - Sergio Estévez
- Centre Hospitalier de Luxembourg, Service de Chirurgie Générale et Mini-invasive, Luxembourg City, Luxembourg GD
| | - Makkai-Popa Silviu-Tiberiu
- Centre Hospitalier de Luxembourg, Service de Chirurgie Générale et Mini-invasive, Luxembourg City, Luxembourg GD
| | - Virginie Poulain
- Centre Hospitalier de Luxembourg, Service de Chirurgie Générale et Mini-invasive, Luxembourg City, Luxembourg GD
| | - Martine Goergen
- Centre Hospitalier de Luxembourg, Service de Chirurgie Générale et Mini-invasive, Luxembourg City, Luxembourg GD
| |
Collapse
|
|
29
|
Ouaissi M, Frasconi C, Mege D, Panicot-Dubois L, Boiron L, Dahan L, Debourdeau P, Dubois C, Farge D, Sielezneff I. Impact of venous thromboembolism on the natural history of pancreatic adenocarcinoma. Hepatobiliary Pancreat Dis Int 2015; 14:436-42. [PMID: 26256090 DOI: 10.1016/s1499-3872(15)60397-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Few studies have analyzed the effect of venous thromboembolism (VTE) events on the prognosis of pancreatic cancer, but their results were conflicting. The present study was undertaken to determine the effect of VTE on pancreatic adenocarcinoma (PA) outcomes. METHODS All consecutive patients diagnosed with PA from May 2004 to January 2012 in a single oncology center were retrospectively studied. Clinical, radiological and histological data at time of diagnosis or within the first 3 months after surgery, including the presence (+) or absence (-) of VTE were collected. VTE was defined as radiological evidence of either pulmonary embolism (PE), deep venous thrombosis without infection or catheter-related thrombosis. PA with and without PE was compared for survival using the Kaplan-Meier method to estimate overall survival. RESULTS Among 162 PA patients with a median follow-up of 15 (3-92) months after diagnosis, 28 demonstrated VTE (+). PA patients with and without PE were similar for age, American Society of Anesthesiologist score, body mass index, and history of treatment. The distribution of cancer stages was similar between the two groups VTE (+) and VTE (-). The median duration of survival was significantly worse in the VTE (+) group vs VTE (-) (12 vs 18 months, P=0.010). In multivariate analysis, the presence of VTE and surgical treatment were independent prognostic factors for overall survival. CONCLUSION VTE (+) at time of diagnosis or within the first 3 months after surgery during treatment is an independent factor of poor prognosis in PA.
Collapse
Affiliation(s)
- Mehdi Ouaissi
- Departments of Digestive Surgery, Timone Hospital, Aix-Marseille University, Marseille, France; Atelier Provencale d'Ecriture Medicale, Faculte de Medecine de Marseille; Groupe Francophone Thrombose et Cancer, Hopital ST Louis, 1 avenue Claude Vellefaux, Paris, France. mehdi.ouaissi@ mail.ap-hm.fr
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
30
|
Pedrazzoli S. Extent of lymphadenectomy to associate with pancreaticoduodenectomy in patients with pancreatic head cancer for better tumor staging. Cancer Treat Rev 2015; 41:577-87. [PMID: 26045226 DOI: 10.1016/j.ctrv.2015.04.013] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Revised: 04/28/2015] [Accepted: 04/29/2015] [Indexed: 01/14/2023]
Abstract
OBJECTIVES To define the extent of lymphadenectomy to associate with surgery for pancreatic head cancer. BACKGROUND Pancreaticoduodenectomy with extended lymphadenectomy fails to prolong patient survival. METHODS Prospective randomized and nonrandomized controlled trials (RCTs and NRCTs), meta-analyses, retrospective reviews, consensus conferences and pre- and intraoperative diagnoses of lymph node (LN) metastases were retrieved. Standard and extended lymphadenectomies were reviewed, including their effects on postoperative complications, mortality rate and long-term survival. The minimum total number of LN examined (TNLE) for adequate tumor staging, and the incidence of metastasis to each LN station were also considered. A pros and cons analysis was performed on the removal of each LN station. RESULTS Eleven retrospective studies (2514 patients), five prospective NRCTs (545 patients), and five prospective RCTs (586 patients) described different lymphadenectomies, which obtained similar long-term results. Five meta-analyses showed they did not influence long-term survival. However, N status is an important component of tumor staging. The recommended minimum TNLE is 15. The percent incidence of metastasis to each LN station was calculated considering at least 385 and up to 3725 patients. Preoperative imaging and intraoperative exploration frequently fail to identify metastatic nodes. A pros and cons analysis suggests that lymph node status is better established removing the following LN stations: 6, 8a-p, 12a-b-c, 13a-b, 14a-b-c-d, 16b1, 17a-b. Metastasis to 16b1 LNs significantly worsens prognosis. Their removal and frozen section examination, before proceeding with resection, may contraindicate resection. CONCLUSION A standard lymphadenectomy demands an adequate TNLE and removal of the LN stations metastasizing more frequently, without increasing the surgical risk.
Collapse
|
|
31
|
Macchia G, Sainato A, Talamini R, Boz G, Bacigalupo A, Caravatta L, Fiore M, Friso ML, Fusco V, Lupattelli M, Mantello G, Mattiucci GC, Slim N, Sciacero P, Turri L, Valentini V, Morganti AG, Genovesi D. Patterns of radiotherapy practice for pancreatic cancer: Results of the Gastrointestinal Radiation Oncology Study Group multi-institutional survey. Oncol Rep 2015; 34:382-90. [PMID: 25955190 DOI: 10.3892/or.2015.3955] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2014] [Accepted: 01/05/2015] [Indexed: 11/06/2022] Open
Abstract
No information is currently available regarding pancreatic cancer (PC) pattern of care in Italy. In the present study, a nationwide survey using a questionnaire was performed to enquire the local standards for PC diagnosis and radiotherapy treatment. Fifty-seven percent of 140 Italian centres completed questionnaire. The main causes of no radiotherapy indication were poor general condition (45%) and lack of guidelines (25%). Physicians (38%) employed neoadjuvant therapy in locally advanced PC patients, while in other centres (62%) adjuvant chemoradiation was administered. Adjuvant gemcitabine-based chemotherapy was selected as the treatment of choice by 59% of centres. Patients were treated mostly with doses of 50-54.9 Gy on the tumour (or bed) plus lymph nodes. A 3D-CRT technique was used in 81.2% of centres, while IMRT and IGRT were available in 61.2 and 48.7% of cases, respectively. Extensive variation exists with regard to patterns of care for PC in Italy. Nevertheless, cooperative studies emerging from this survey appeared beneficial.
Collapse
Affiliation(s)
- Gabriella Macchia
- Radiation Oncology Unit, Research and Care Foundation 'Giovanni Paolo II', Catholic University of Sacred Heart, Campobasso, Italy
| | - Aldo Sainato
- Radiation Oncology Unit, University Hospital, Pisa, Italy
| | - Renato Talamini
- Epidemiology and Biostatistics Unit, Oncological Referral Center, Aviano, Italy
| | - Giovanni Boz
- Radiation Oncology Department, Oncological Referral Center, Aviano, Italy
| | - Almalina Bacigalupo
- Radiation Oncology Unit, AOU IRCCS San Martino, IST National Cancer Research Institute, Genoa, Italy
| | - Luciana Caravatta
- Radiation Oncology Department, 'A. Businco' Regional Oncological Hospital, Cagliari, Italy
| | - Michele Fiore
- Radiation Oncology Unit, Campus Bio-Medico University Hospital, Rome, Italy
| | - Maria Luisa Friso
- Radiotherapy and Nuclear Medicine Unit, Veneto Institute of Oncology-IRCCS, Padua, Italy
| | - Vincenzo Fusco
- Radiation Oncology Unit, IRCCS CROB, Rionero in Vulture, Potenza, Italy
| | - Marco Lupattelli
- Radiation Oncology Unit, 'S. Maria della Misericordia' Hospital, Perugia, Italy
| | | | - Gian Carlo Mattiucci
- Radiation Oncology Department, 'A. Gemelli' Hospital, Catholic University of Sacred Heart, Rome, Italy
| | - Najla Slim
- Radiation Oncology Unit, 'San Raffaele' Hospital, Milan, Italy
| | - Piera Sciacero
- Radiation Oncology Unit, ASL TO4, General Hospital, Ivrea, Italy
| | - Lucia Turri
- Radiation Oncology Unit, 'Maggiore della Carità' Hospital, Novara, Italy
| | - Vincenzo Valentini
- Radiation Oncology Department, 'A. Gemelli' Hospital, Catholic University of Sacred Heart, Rome, Italy
| | - Alessio Giuseppe Morganti
- Radiation Oncology Unit, Research and Care Foundation 'Giovanni Paolo II', Catholic University of Sacred Heart, Campobasso, Italy
| | - Domenico Genovesi
- Radiation Oncology Unit, 'SS Annunziata' Hospital, 'G. D'Annunzio' University, Chieti, Italy
| |
Collapse
|
|
32
|
|
|
33
|
Pancreatic cancer: diagnosis and treatments. Tumour Biol 2015; 36:1375-84. [PMID: 25680410 DOI: 10.1007/s13277-015-3223-7] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2014] [Accepted: 02/03/2015] [Indexed: 12/12/2022] Open
Abstract
Pancreatic cancer is one of the deadliest cancers, with exceptionally high mortality. Despite the relatively low incidence rate (10th), it is the fourth leading cause of cancer-related deaths in most developed countries. To improve the early diagnosis of pancreatic cancer and strengthen the standardized comprehensive treatment are still the main focus of pancreatic cancer research. Here, we summarized the rapid developments in the diagnosis and treatments of pancreatic cancer. Regarding diagnosis, we reviewed advances in medical imaging technology, tumor markers, molecular biology (e.g., gene mutation), and proteomics. Moreover, great progress has also been made in the treatments of this disease, including surgical resection, chemotherapy, targeted radiotherapy, targeted minimally invasive treatment, and molecular targeted therapy. Therefore, we also recapitulated the development, advantages, and disadvantages of each of the treatment methods in this review.
Collapse
|
|
34
|
Caravatta L, Macchia G, Mattiucci GC, Sainato A, Cernusco NLV, Mantello G, Di Tommaso M, Trignani M, De Paoli A, Boz G, Friso ML, Fusco V, Di Nicola M, Morganti AG, Genovesi D. Inter-observer variability of clinical target volume delineation in radiotherapy treatment of pancreatic cancer: a multi-institutional contouring experience. Radiat Oncol 2014; 9:198. [PMID: 25199768 PMCID: PMC4261525 DOI: 10.1186/1748-717x-9-198] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2014] [Accepted: 08/31/2014] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND An observational multi-institutional study has been conducted aimed to evaluate the inter-observer variability in clinical target volume (CTV) delineation among different radiation oncologists in radiotherapy treatment of pancreatic cancer. METHODS A multi-institutional contouring dummy-run of two different cases of pancreatic cancer treated by postoperative and preoperative radiotherapy (RT) was performed. Clinical history, diagnostics, and planning CT imaging were available on AIRO website (http://www.radioterapiaitalia.it). Participants were requested to delineate CTVs according to their skills and knowledge. Aiming to quantify interobserver variability of CTVs delineations, the total volume, craniocaudal, laterolateral, and anteroposterior diameters were calculated. Descriptive statistic was calculated. The 95% Confidence Interval (95% CI) for coefficient of variation (CV) was estimated. The Dice Similarity Index (DSI) was used to evaluate the spatial overlap accuracy of the different CTVs compared with the CTVs of a national reference Centre considered as a benchmark. The mean DSI (mDSI) was calculated and reported. RESULTS A total of 18 radiation oncologists from different Institutes submitted the targets. Less variability was observed for the Elective CTV rather than the Boost CTV, in both cases. The estimated CV were 28.8% (95% CI: 21.2-45.0%) and 20.0% (95% CI: 14.9-30.6%) for the Elective CTV, in adjuvant (Case 1) and neoadjuvant (Case 2) case, respectively. The mDSI value was 0.68 for the Elective CTVs in both cases (range 0.19-0.79 in postoperative vs range 0.35-0.79 in preoperative case). The mDSI was increased to 0.71 (Case 1) and 0.72 (Case 2) if the observers with a worse agreement have been excluded. On the other hand, a CV of 42.4% (95% CI: 30.1-72.4%) and 63.8% (95% CI: 43.9-119.2%) with a mDSI value of 0.44 and 0.52, were calculated for the Boost CTV in Case 1 and Case 2, respectively. CONCLUSIONS The CV and mDSI obtained values for Elective CTVs showed an acceptable agreement among participants either in postoperative as well in preoperative setting. Additional strategies to reduce the variability in Boost CTV delineation need to be found and promoted.
Collapse
Affiliation(s)
- Luciana Caravatta
- />Radiation Oncology Department, “San Francesco” Hospital, Via Mannironi, 1, 08110 Nuoro, Italy
| | - Gabriella Macchia
- />Radiation Oncology Department, Fondazione di Ricerca e Cura “Giovanni Paolo II”, Università Cattolica del S. Cuore, Campobasso, Italy
| | | | - Aldo Sainato
- />Radiotherapy Unit, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy
| | - Nunzia LV Cernusco
- />Radiotherapy Unit, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy
| | | | - Monica Di Tommaso
- />Department of Radiotherapy, “SS Annunziata” Hospital, “G. D’Annunzio” University, Chieti, Italy
| | - Marianna Trignani
- />Department of Radiotherapy, “SS Annunziata” Hospital, “G. D’Annunzio” University, Chieti, Italy
| | - Antonino De Paoli
- />Department of Radiation Oncology Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy
| | - Gianni Boz
- />Department of Radiation Oncology Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy
| | - Maria L Friso
- />Radiotherapy and Nuclear Medicine Unit, Istituto Oncologico Veneto, IRCCS, Padova, Italy
| | - Vincenzo Fusco
- />Department of Radiation Oncology, IRCCS CROB, Rionero in Vulture, Potenza, Italy
| | - Marta Di Nicola
- />Department of Experimental and Clinical Sciences, Laboratory of Biostatistics, “G. D’Annunzio” University, Chieti, Italy
| | - Alessio G Morganti
- />Radiation Oncology Department, Fondazione di Ricerca e Cura “Giovanni Paolo II”, Università Cattolica del S. Cuore, Campobasso, Italy
- />Radiotherapy Department, Università Cattolica del S. Cuore, Roma, Italy
| | - Domenico Genovesi
- />Department of Radiotherapy, “SS Annunziata” Hospital, “G. D’Annunzio” University, Chieti, Italy
| |
Collapse
|
|
35
|
Chuong MD, Boggs DH, Patel KN, Regine WF. Adjuvant chemoradiation for pancreatic cancer: what does the evidence tell us? J Gastrointest Oncol 2014; 5:166-77. [PMID: 24982765 DOI: 10.3978/j.issn.2078-6891.2014.025] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2014] [Accepted: 05/08/2014] [Indexed: 12/12/2022] Open
Abstract
The role of adjuvant chemoradiation (CRT) for pancreas cancer remains unclear. A handful of randomized trials conducted decades of ago ignited a debate that continues today about whether CRT improves survival after surgery. The many flaws in these trials are well described in the literature, which include the use of antiquated radiation delivery techniques and suboptimal doses. Recent prospective randomized data is lacking, and we eagerly await the results the ongoing Radiation Therapy Oncology Group (RTOG) 0848 trial that is evaluating the utility of high quality adjuvant CRT in resected pancreas cancer patients. Until the results of RTOG 0848 are available we should look to other studies from the modern era to guide adjuvant treatment recommendations. Here we review the current state of the art for adjuvant pancreas CRT with respect to patient selection, radiation techniques, radiation dose, and integration with novel systemic agents.
Collapse
Affiliation(s)
- Michael D Chuong
- Department of Radiation Oncology, University of Maryland Medical Systems, Baltimore, MD 21201, USA
| | - Drexell H Boggs
- Department of Radiation Oncology, University of Maryland Medical Systems, Baltimore, MD 21201, USA
| | - Kruti N Patel
- Department of Radiation Oncology, University of Maryland Medical Systems, Baltimore, MD 21201, USA
| | - William F Regine
- Department of Radiation Oncology, University of Maryland Medical Systems, Baltimore, MD 21201, USA
| |
Collapse
|
|
36
|
Schwarz L, Lupinacci RM, Svrcek M, Lesurtel M, Bubenheim M, Vuarnesson H, Balladur P, Paye F. Para-aortic lymph node sampling in pancreatic head adenocarcinoma. Br J Surg 2014; 101:530-8. [PMID: 24633831 DOI: 10.1002/bjs.9444] [Citation(s) in RCA: 87] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/10/2014] [Indexed: 12/12/2022]
Abstract
BACKGROUND The significance of positive para-aortic nodes in patients with resectable pancreatic carcinoma is unclear. This study sought to evaluate the accuracy of intraoperative detection and prognostic significance of these lymph nodes in patients with resected adenocarcinoma of the pancreatic head. METHODS From 2000 to 2010, para-aortic node sampling was performed prospectively in all patients before pancreatoduodenectomy. Frozen sections were created and nodes categorized as positive or negative for metastases. Surgeons were blinded to the frozen-section results. This was followed by standard histopathological assessment of corresponding paraffin-embedded, haematoxylin and eosin-stained material. Nodes considered uninvolved by this analysis were examined immunohistochemically for micrometastases. RESULTS A total of 111 consecutive patients were included, with a median follow-up of 20·8 (range 1·5-126) months. The 1-, 2- and 5-year overall survival (OS) and disease-free survival (DFS) rates were 73·6, 54·0 and 24·7 per cent, and 51·8, 28·1 and 18·8 per cent respectively. Para-aortic node involvement was always associated with peripancreatic lymph node metastasis, and was detected by frozen-section analysis in 12 patients and by haematoxylin and eosin staining in 17. Sensitivity and specificity of frozen-section examination for detecting para-aortic lymph node metastases were 71 and 100 per cent respectively. Median OS for patients with and without para-aortic node involvement on frozen-section analysis was 9·7 versus 28·5 months respectively (P = 0·012), and 15·7 versus 27·2 months (P = 0·050) when assessed by haematoxylin and eosin staining. Median DFS for patients with and without para-aortic node involvement on frozen-section examination was 5·6 versus 12·9 months respectively (P = 0·041), and 8·4 versus 12·9 months (P = 0·038) for haematoxylin and eosin analysis. The presence of micrometastases in para-aortic nodes was not significantly associated with altered OS or DFS. CONCLUSION Para-aortic node sampling with frozen-section examination detects distant lymphatic involvement reliably. It should be performed systematically. When metastases are found, they should be considered a contraindication to pancreatic resection.
Collapse
Affiliation(s)
- L Schwarz
- Departments of Digestive Surgery and Marie Curie University, Paris
| | | | | | | | | | | | | | | |
Collapse
|
|
37
|
CHOI SUNGHOON, KIM SEHOON, CHOI JUNJEONG, KANG CHANGMOO, HWANG HOKYOUNG, LEE WOOJUNG. Clinical necessity of the immunohistochemical reassessment of para-aortic lymph nodes in resected pancreatic ductal adenocarcinoma. Oncol Lett 2013; 6:1189-1194. [PMID: 24179493 PMCID: PMC3813805 DOI: 10.3892/ol.2013.1539] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2013] [Accepted: 07/03/2013] [Indexed: 12/11/2022] Open
Abstract
Para-aortic lymph node (PALN) metastasis is widely regarded as a systemic disease in cancer. Undetected PALN micrometastases during routine hematoxylin and eosin (HE) staining may be a cause of poor prognosis following a potentially curative pancreatectomy for pancreatic cancer. In the present study, paraffin-embedded PALN tissue blocks from 99 patients who underwent a pancreatectomy were re-evaluated by immunohistochemical staining using cytokeratin (CK)-19. Patients with PALN metastasis were summarized according to the clinicopathological data. A total of 484 PALNs (median, 4.9 nodes per patient; range, 1-19) were evaluated. PALN metastases were revealed in eight patients (8.1%) by routine HE staining of frozen section biopsies and in one patient (1.0%) by HE staining of a permanent section. Only one patient (1.0%) demonstrated micrometastasis by IHC; this patient did not display any adverse pathological characteristics and had a relatively favorable survival period of 41 months. The present study concluded that an additional reassessment for micrometastasis in PALNs using CK-19 immunohistochemistry (IHC) is not a viable method for determining the survival outcome. A careful examination of a frozen section biopsy is sufficient for attempting curative surgery.
Collapse
Affiliation(s)
- SUNG HOON CHOI
- Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, South Korea
- Pancreaticobiliary Cancer Clinic, Institute of Gastroenterology, Severance Hospital, Seoul 120-752, South Korea
| | - SE HOON KIM
- Department of Pathology, Yonsei University College of Medicine, Seoul 120-752, South Korea
| | - JUN JEONG CHOI
- Department of Pathology, Yonsei University Wonju College of Medicine, Wonju 220-050, South Korea
| | - CHANG MOO KANG
- Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, South Korea
- Pancreaticobiliary Cancer Clinic, Institute of Gastroenterology, Severance Hospital, Seoul 120-752, South Korea
| | - HO KYOUNG HWANG
- Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, South Korea
- Pancreaticobiliary Cancer Clinic, Institute of Gastroenterology, Severance Hospital, Seoul 120-752, South Korea
| | - WOO JUNG LEE
- Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, South Korea
- Pancreaticobiliary Cancer Clinic, Institute of Gastroenterology, Severance Hospital, Seoul 120-752, South Korea
| |
Collapse
|
|
38
|
Masui T, Kubota T, Aoki K, Nakanishi Y, Miyamoto T, Nagata J, Morino K, Fukugaki A, Takamura M, Sugimoto S, Onuma H, Tokuka A. Long-term survival after resection of pancreatic ductal adenocarcinoma with para-aortic lymph node metastasis: case report. World J Surg Oncol 2013; 11:195. [PMID: 23945441 PMCID: PMC3751482 DOI: 10.1186/1477-7819-11-195] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2012] [Accepted: 08/04/2013] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer patients with para-aortic lymph node metastasis have a poor prognosis and patients living longer than 3 years are rare. We had a patient with pancreatic cancer who survived for more than 10 years after removal of the para-aortic lymph node metastasis. A 57-year-old woman was diagnosed with pancreatic head cancer and underwent a pancreaticoduodenectomy with subtotal gastric resection following Whipple reconstruction in 2000. Para-aortic lymph node metastasis was detected during the operation by intraoperative pathological diagnosis and an extended lymphadenectomy was performed with vascular skeletonization of the celiac and superior mesenteric arteries. In 2004, a low-density area was detected around the superior mesenteric artery (SMA) 5 cm from its root and she was treated with gemcitabine, and the area was undetectable after 3 years of treatment. In 2010, computed tomography showed a low-density area around the same lesion with an increased carcinoembryonic antigen level. After 4 months of gemcitabine treatment, we resected the tumor en bloc with the associated superior mesenteric vein and perineural tissue. Histopathological examination of the resected specimen revealed a well-differentiated tubular adenocarcinoma that closely resembled the original primary pancreatic cancer, indicating perineural recurrence 10 years after the initial resection. She had no recurrence around the SMA for more than one year. Although a meta-analysis has not proved the efficacy of preventive radical dissection, this case indicates that a patient with well-differentiated, chemotherapy-responsive pancreatic cancer with para-aortic lymph node metastasis could have a long survival time through extended dissection of the lymph nodes.
Collapse
|
|
39
|
Caravatta L, Sallustio G, Pacelli F, Padula GDA, Deodato F, Macchia G, Massaccesi M, Picardi V, Cilla S, Marinelli A, Cellini N, Valentini V, Morganti AG. Clinical target volume delineation including elective nodal irradiation in preoperative and definitive radiotherapy of pancreatic cancer. Radiat Oncol 2012; 7:86. [PMID: 22691275 PMCID: PMC3494529 DOI: 10.1186/1748-717x-7-86] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2012] [Accepted: 06/05/2012] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Radiotherapy (RT) is widely used in the treatment of pancreatic cancer. Currently, recommendation has been given for the delineation of the clinical target volume (CTV) in adjuvant RT. Based on recently reviewed pathologic data, the aim of this study is to propose criteria for the CTV definition and delineation including elective nodal irradiation (ENI) in the preoperative and definitive treatment of pancreatic cancer. METHODS The anatomical structures of interest, as well as the abdominal vasculature were identified on intravenous contrast-enhanced CT scans of two different patients with pancreatic cancer of the head and the body. To delineate the lymph node area, a margin of 10 mm was added to the arteries. RESULTS We proposed a set of guidelines for elective treatment of high-risk nodal areas and CTV delineation. Reference CT images were provided. CONCLUSIONS The proposed guidelines could be used for preoperative or definitive RT for carcinoma of the head and body of the pancreas. Further clinical investigations are needed to validate the defined CTVs.
Collapse
Affiliation(s)
- Luciana Caravatta
- Radiotherapy Unit, Department of Oncology, Fondazione di Ricerca e Cura “Giovanni Paolo II”, Università Cattolica del S. Cuore, Largo A. Gemelli 1, 86100, Campobasso, Italy
| | - Giuseppina Sallustio
- Radiology Unit, Fondazione di Ricerca e Cura “Giovanni Paolo II”, Università Cattolica del S. Cuore, Largo A. Gemelli 1, 86100, Campobasso, Italy
| | - Fabio Pacelli
- Surgery Unit, Department of Oncology, Fondazione di Ricerca e Cura “Giovanni Paolo II”, Università Cattolica del S. Cuore, Largo A. Gemelli 1, 86100, Campobasso, Italy
| | - Gilbert DA Padula
- Radiation Oncology Department, The Lacks Cancer Center Saint Mary’s Health Care, Grand Rapids, MI, USA
| | - Francesco Deodato
- Radiotherapy Unit, Department of Oncology, Fondazione di Ricerca e Cura “Giovanni Paolo II”, Università Cattolica del S. Cuore, Largo A. Gemelli 1, 86100, Campobasso, Italy
| | - Gabriella Macchia
- Radiotherapy Unit, Department of Oncology, Fondazione di Ricerca e Cura “Giovanni Paolo II”, Università Cattolica del S. Cuore, Largo A. Gemelli 1, 86100, Campobasso, Italy
| | - Mariangela Massaccesi
- Radiotherapy Unit, Department of Oncology, Fondazione di Ricerca e Cura “Giovanni Paolo II”, Università Cattolica del S. Cuore, Largo A. Gemelli 1, 86100, Campobasso, Italy
| | - Vincenzo Picardi
- Radiotherapy Unit, Department of Oncology, Fondazione di Ricerca e Cura “Giovanni Paolo II”, Università Cattolica del S. Cuore, Largo A. Gemelli 1, 86100, Campobasso, Italy
| | - Savino Cilla
- Physics Unit, Fondazione di Ricerca e Cura Giovanni Paolo II, Università Cattolica del S. Cuore, Campobasso, Italy
| | - Alfonso Marinelli
- Radiotherapy Unit, Department of Oncology, Fondazione di Ricerca e Cura “Giovanni Paolo II”, Università Cattolica del S. Cuore, Largo A. Gemelli 1, 86100, Campobasso, Italy
| | - Numa Cellini
- Radiotherapy Department, Università Cattolica del S. Cuore, Rome, Italy
| | | | - Alessio G Morganti
- Radiotherapy Unit, Department of Oncology, Fondazione di Ricerca e Cura “Giovanni Paolo II”, Università Cattolica del S. Cuore, Largo A. Gemelli 1, 86100, Campobasso, Italy
- Radiotherapy Department, Università Cattolica del S. Cuore, Rome, Italy
| |
Collapse
|
|
40
|
Nathanson SD, Kwon D, Kapke A, Hensley Alford S, Chitale D. The role of lymph node metastasis in the systemic dissemination of breast cancer. Indian J Surg Oncol 2010; 1:313-22. [PMID: 22695980 PMCID: PMC3372967 DOI: 10.1007/s13193-011-0063-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2009] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND.: Lymphatic invasion is necessary for regional lymph node (RLN) metastasis in breast cancer (BC), while systemic metastasis requires blood vessel (BV) invasion. The site of BV invasion could be at the primary BC site or through lymphovascular anastomoses. The vague pathologic term "lymphovascular invasion" (LVI) encourages the belief that peri/intratumoral BV invasion may be common. We investigated the relative contribution of RLN metastasis to systemic metastasis by studying the relationship among LVI and RLN and/or systemic metastasis in a population-based cohort of breast cancer patients. METHODS.: Fisher's exact test was done to assess global associations among LVI and RLN and/or systemic metastasis in a prospective database of breast cancer patients undergoing RLN biopsy. Logistic regression was used to determine multivariable contributions of LVI to metastasis when controlling for available demographic, radiologic, and pathologic variables. RESULTS.: Of 1668 patients evaluated 25.4% were RLN positive and 10.4% had LVI. RLN metastasis was predicted by tumor size (P < .0001), HER-2/neu overexpression (P = .0022) and the interaction between LVI positive and HER-2/neu positive tumors (< .0001). Patients with LVI/HER-2-neu positive were 3 times as likely to have positive RLNs compared with patients LVI/HER-2-neu negative. Systemic metastasis was significantly (P = .0013) associated with LVI/ RLN positive, but not with LVI positive/RLN negative patients (P = .137). CONCLUSIONS.: LVI predicted RLN metastasis. LVI also significantly predicted systemic metastasis, but only when the RLN was also positive. Since RLN requires lymphatic invasion, these data support the hypothesis that primary breast cancers often invade lymphatics to gain access to the systemic circulation.
Collapse
Affiliation(s)
| | - David Kwon
- Department of Surgery, Henry Ford Health System, Detroit, MI USA
| | - Alissa Kapke
- Department of Biostatistics and Research Epidemiology, Henry Ford Health System, Detroit, MI USA
| | - Sharon Hensley Alford
- Department of Biostatistics and Research Epidemiology, Henry Ford Health System, Detroit, MI USA
| | | |
Collapse
|
|
41
|
Ouaissi M, Hubert C, Verhelst R, Astarci P, Sempoux C, Jouret-Mourin A, Loundou A, Gigot JF. Vascular reconstruction during pancreatoduodenectomy for ductal adenocarcinoma of the pancreas improves resectability but does not achieve cure. World J Surg 2010; 34:2648-61. [PMID: 20607257 DOI: 10.1007/s00268-010-0699-6] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Combined vascular and pancreatic resection improves long-term survival of patients suffering from ductal adenocarcinoma of the pancreatic head. This study was designed to compare the results of surgical resection in patients with pancreatic cancer with or without vascular resection. Late 10-year disease-free survival was considered as an indicator of patients' disease cure. METHODS A total of 149 consecutive patients have undergone pancreatoduodenectomy without vascular resection (group 1: 82 patients), with isolated venous resection (group B: 67 patients), or with arterial and/or venous resection (group C: 8 patients). RESULTS The duration of surgery and blood losses were significantly more important in groups B and C compared with group A; however, postoperative morbidity and mortality rates were similar. R1 resection was significantly more frequent in groups B (42%) and C (50%) compared with group A (13%; p = 0.0002), but there were more advanced tumors in these groups, as demonstrated by a lower Karnowsky index, higher Ca 19-9 plasmatic level, greater tumor size, more advanced stage in the AJCC classification, and more tumor location in the uncinate process of the pancreas. Ten-year overall and disease-free survivals were significantly better in group A (19 and 20%) compared with group B (2.8 and 0%) and group C (0% and 0%). Multivariate analysis proved vascular resection and metastatic nodal status as being independent predictive factors of disease-free survival. CONCLUSIONS Vascular resection combined to pancreatoduodenectomy for pancreatic cancer increases local resectability without increasing mortality and morbidity rates but does not improve patients' disease cure rate.
Collapse
Affiliation(s)
- Mehdi Ouaissi
- Division of Hepato-Biliary and Pancreatic Surgery, Department of Abdominal Surgery and Transplantation, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain (UCL), Hippocrate Avenue 10, 1200, Brussels, Belgium
| | | | | | | | | | | | | | | | | |
Collapse
|
|
42
|
Murakami Y, Uemura K, Sudo T, Hashimoto Y, Yuasa Y, Sueda T. Prognostic impact of para-aortic lymph node metastasis in pancreatic ductal adenocarcinoma. World J Surg 2010; 34:1900-7. [PMID: 20376442 DOI: 10.1007/s00268-010-0577-2] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The aim of the present study was to clarify the prognostic impact of para-aortic lymph node metastasis in pancreatic ductal adenocarcinoma. METHODS Medical records of 103 consecutive patients with pancreatic ductal adenocarcinoma, who underwent pancreatic resection with regional and para-aortic lymph node dissection were reviewed retrospectively. Clinicopathological factors and survival were compared between patients with and without para-aortic lymph node metastasis. RESULTS Tumor size (p = 0.045), extrapancreatic nerve plexus invasion (p = 0.043), UICC pT factor (p = 0.026), and surgical margin status (p = 0.002) were associated significantly with para-aortic lymph node metastasis. Postoperative adjuvant chemotherapy (p < 0.001) and absence of extrapancreatic nerve plexus invasion (p = 0.041) were associated independently with longer survival, but para-aortic lymph node metastasis (p = 0.078) was not associated significantly with survival by multivariate analysis. The 2- and 5-year survival rates and median survival time of patients with and without para-aortic lymph node metastasis were 12, 0%, 12.4 months and 49, 23%, 14.5 months, respectively, and there was a significant difference in survival between the two groups by a log-rank test (p < 0.001). Postoperative adjuvant chemotherapy significantly improved the survival of patients with para-aortic lymph node metastasis (p = 0.025). CONCLUSIONS The prognosis of patients with para-aortic lymph node metastasis is poor in pancreatic ductal adenocarcinoma. However, postoperative adjuvant chemotherapy may improve survival.
Collapse
Affiliation(s)
- Yoshiaki Murakami
- Department of Surgery, Division of Clinical Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
| | | | | | | | | | | |
Collapse
|
|
43
|
Sun W, Leong CN, Zhang Z, Lu JJ. Proposing the lymphatic target volume for elective radiation therapy for pancreatic cancer: a pooled analysis of clinical evidence. Radiat Oncol 2010; 5:28. [PMID: 20398316 PMCID: PMC2859771 DOI: 10.1186/1748-717x-5-28] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2010] [Accepted: 04/15/2010] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Radiation therapy is an important cancer treatment modality in both adjuvant and definitive setting, however, the use of radiation therapy for elective treatment of regional lymph nodes is controversial for pancreatic cancer. No consensus on proper selection and delineation of subclinical lymph nodal areas in adjuvant or definitive radiation therapy has been suggested either conclusively or proposed for further investigation. This analysis aims to study the pattern of lymph node metastasis through a pooled analysis of published results after radical tumor and lymph nodal resection with histological study in pancreatic cancer. METHODS Literature search using electronic databases including MEDLINE, EMBASE, and CANCERLIT from January 1970 to June 2009 was performed, supplemented by review of references. Eighteen original researches and a total of 5954 pancreatic cancer patients underwent radical surgical resection were included in this analysis. The probability of metastasis in regional lymph nodal stations (using Japan Pancreas Society [JPS] Classification) was calculated and analyzed based on the location and other characteristics of the primary disease. RESULTS Commonly involved nodal regions in patients with pancreatic head tumor include lymph nodes around the common hepatic artery (Group 8, 9.79%), posterior pancreaticoduodenal lymph nodes (Group 13, 32.31%), lymph nodes around the superior mesenteric artery (Group 14, 15.85%), paraaortic lymph nodes (Group 16, 10.92%), and anterior pancreaticoduodenal lymph nodes (Group 17, 19.78%); The probability of metastasis in other lymph nodal regions were <9%.Commonly involved nodal regions in patients with pancreatic body/tail tumor include lymph nodes around the common hepatic artery (Group 8, 15.07%), lymph nodes around the celiac trunk (Group 9, 9.59%), lymph nodes along the splenic artery (Group 11, 35.62%), lymph nodes around the superior mesenteric artery (Group 14, 9.59%), paraaortic lymph nodes (Group 16, 16.44%), and inferior body lymph nodes (Group 18, 24.66%). The probability of metastasis in other lymph nodal regions were <9%. CONCLUSIONS Pancreatic cancer has a high propensity of regional lymphatic metastases; however, clear patterns including the site and probability of metastasis can be identified and used as a guide of treatment in patients with resectable pancreatic cancer. Further clinical investigation is needed to study the efficacy of elective treatment to CTV defined based on these patterns using high-dose conformal or intensity-modulated radiation therapy.
Collapse
Affiliation(s)
- Wenjie Sun
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Cheng N Leong
- Department of Radiation Oncology, National University Cancer Institute, National University Health System, National University of Singapore, Singapore 119074, Republic of Singapore
| | - Zhen Zhang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Jiade J Lu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Department of Radiation Oncology, National University Cancer Institute, National University Health System, National University of Singapore, Singapore 119074, Republic of Singapore
| |
Collapse
|
|
44
|
Nathanson SD, Kwon D, Kapke A, Alford SH, Chitale D. The role of lymph node metastasis in the systemic dissemination of breast cancer. Ann Surg Oncol 2010; 16:3396-405. [PMID: 19657697 DOI: 10.1245/s10434-009-0659-2] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2009] [Revised: 06/19/2009] [Accepted: 07/13/2009] [Indexed: 12/13/2022]
Abstract
BACKGROUND Lymphatic invasion is necessary for regional lymph node (RLN) metastasis in breast cancer (BC), while systemic metastasis requires blood vessel (BV) invasion. The site of BV invasion could be at the primary BC site or through lymphovascular anastomoses. The vague pathologic term "lymphovascular invasion" (LVI) encourages the belief that peri/intratumoral BV invasion may be common. We investigated the relative contribution of RLN metastasis to systemic metastasis by studying the relationship among LVI and RLN and/or systemic metastasis in a population-based cohort of breast cancer patients. METHODS Fisher's exact test was done to assess global associations among LVI and RLN and/or systemic metastasis in a prospective database of breast cancer patients undergoing RLN biopsy. Logistic regression was used to determine multivariable contributions of LVI to metastasis when controlling for available demographic, radiologic, and pathologic variables. RESULTS Of 1668 patients evaluated 25.4% were RLN positive and 10.4% had LVI. RLN metastasis was predicted by tumor size (P < .0001), HER-2/neu overexpression (P = .0022) and the interaction between LVI positive and HER-2/neu positive tumors (< .0001). Patients with LVI/HER-2-neu positive were 3 times as likely to have positive RLNs compared with patients LVI/HER-2-neu negative. Systemic metastasis was significantly (P = .0013) associated with LVI/RLN positive, but not with LVI positive/RLN negative patients (P = .137). CONCLUSIONS LVI predicted RLN metastasis. LVI also significantly predicted systemic metastasis, but only when the RLN was also positive. Since RLN requires lymphatic invasion, these data support the hypothesis that primary breast cancers often invade lymphatics to gain access to the systemic circulation.
Collapse
|
|
45
|
Imai H, Doi R, Kanazawa H, Kamo N, Koizumi M, Masui T, Iwanaga Y, Kawaguchi Y, Takada Y, Isoda H, Uemoto S. Preoperative assessment of para-aortic lymph node metastasis in patients with pancreatic cancer. Int J Clin Oncol 2010; 15:294-300. [PMID: 20232101 DOI: 10.1007/s10147-010-0066-5] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2009] [Accepted: 02/04/2010] [Indexed: 12/12/2022]
Abstract
BACKGROUND Para-aortic lymph node (PALN) metastasis is an important prognostic factor in patients with pancreatic cancer, but accurate preoperative diagnosis is difficult. The objective of this study was to assess the accuracy of diagnosis of PALN by computed tomography (CT), magnetic resonance imaging (MRI), and (18)F-fluorodeoxyglucose positron-emission tomography (FDG-PET). METHODS From August 2005 to July 2008, 119 patients with invasive ductal adenocarcinoma of the pancreas were included in this study. PALNs with a longer diameter >10 mm on CT or MRI were suspected of being involved by metastasis, whereas FDG uptake exceeding that of the adjacent normal tissue was considered to be positive for metastasis on FDG-PET studies. The imaging findings were compared with the pathological diagnosis of PALN metastasis. RESULTS PALN dissection was performed in 71 patients (60.0%). Although histopathological examination revealed metastasis in 6 patients (8.5%), none of these patients was positive in any of the preoperative imaging studies. The longer diameter, the shorter diameter, the ratio of the two diameters, and the calculated lymph node volume showed no significant differences between patients with and without PALN metastasis. CONCLUSIONS Preoperative detection of PALN metastasis in patients with pancreatic cancer is very difficult. Intraoperative histopathological examination of frozen sections is necessary if radical resection is contemplated.
Collapse
Affiliation(s)
- Hisashi Imai
- Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University, 54 Shogoinkawaracho, Sakyoku, Kyoto, 606-8507, Japan
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
46
|
Shrikhande SV, Barreto SG. Extended pancreatic resections and lymphadenectomy: An appraisal of the current evidence. World J Gastrointest Surg 2010; 2:39-46. [PMID: 21160848 PMCID: PMC2999214 DOI: 10.4240/wjgs.v2.i2.39] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2009] [Revised: 12/11/2009] [Accepted: 12/18/2009] [Indexed: 02/06/2023] Open
Abstract
Surgery remains the mainstay of treatment for pancreatic ductal adenocarcinoma and complete removal of the cancer confers a definite survival advantage, especially in early disease. However, the majority of patients do not present with early disease, thus precluding the chance of a cure by standard pancreatoduodenectomy (PD), distal pancreatectomy or total pancreatectomy. For this reason, pancreatic surgeons have attempted to push the limits of resection over the last three decades. The aim of these resections has been to determine whether obtaining a complete resection by extending the limits of conventional resection in patients with advanced disease will yield the results seen with PD alone in early disease. This article revisits the data from such studies in an attempt to determine if the available literature supports the performance of extended resections for pancreatic cancer in terms of improvement of survival.
Collapse
Affiliation(s)
- Shailesh V Shrikhande
- Shailesh V Shrikhande, Department of Hepato-Pancreato-Biliary Surgical Oncology, Tata Memorial Hospital, Mumbai 400 012, India
| | | |
Collapse
|
|
47
|
Ignat M, Aprahamian M, Lindner V, Altmeyer A, Perretta S, Dallemagne B, Mutter D, Marescaux J. Feasibility and reliability of pancreatic cancer staging using fiberoptic confocal fluorescence microscopy in rats. Gastroenterology 2009; 137:1584-92.e1. [PMID: 19632230 DOI: 10.1053/j.gastro.2009.07.045] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2008] [Revised: 06/17/2009] [Accepted: 07/10/2009] [Indexed: 01/05/2023]
Abstract
BACKGROUND & AIMS Surgical management of pancreatic cancer depends on tumor resectability and staging. This study evaluated a new in vivo technique, fiberoptic confocal fluorescence microscopy (FCFM), for detection and staging of pancreatic tumors in rats. METHODS FCFM was used with a protease-activated fluorescent marker (ProSense; VisEn Medical Inc, Woburn, MA) for in vivo imaging of solid organs (1.8-microm resolution) in a rat model of pancreatic ductal adenocarcinoma. A preliminary study described the FCFM rendering of normal and pathologic tissues. Subsequently, 2 double-blind studies compared FCFM to standard histology in (1) detection of tumors in rat models of cancer and controls and (2) detection of nodal involvement (splenic, celiac, mesenteric, and colic) 4, 5, and 6 weeks after tumor induction vs controls. RESULTS Tumor cells displayed a fluorescent ductal pattern compared with non-fluorescent normal pancreas or normal follicular pattern of lymph nodes (LNs). FCFM detected all the pancreatic tumors (1.7-mm mean diameter) and identified 23 LNs that contained metastases of 99 LNs examined. Standard histologic analyses resulted in 1 false-negative result in tumor detection and 2 false negatives in LN detection, whereas FCFM produced no false-negative results. Additional serial sectioning confirmed all tumors and 16 metastatic LNs; FCFM had a negative predictive value of 100% and a positive predictive value of 69.6%. CONCLUSIONS Real-time "virtual biopsy" using FCFM detects tumors and LN metastases with 100% sensitivity and 92.2% specificity in rats, making it a reliable technique for detection and staging of pancreatic cancer.
Collapse
|
|
48
|
Choi SB, Park SW, Kim KS, Choi JS, Lee WJ. The survival outcome and prognostic factors for middle and distal bile duct cancer following surgical resection. J Surg Oncol 2009; 99:335-42. [PMID: 19226533 DOI: 10.1002/jso.21238] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND AND OBJECTIVES The objective of this study was to analyze the survival outcome and the clinicopathological factors that influence survival and recurrence of middle and distal bile duct cancer after surgical resection. METHODS From January 2000 to June 2007, 125 patients underwent surgical resection for middle and distal bile duct cancer. The clinicopathological characteristics and survival outcomes were reviewed retrospectively. RESULTS Of the 125 patients, 31 patients underwent segmental resection of the bile duct, and 94 patients underwent pancreaticoduodenectomy (PD). Overall survival rates were 85.8% at 1 year and 38.3% at 5 years. Lymph node metastasis, noncurative resection, poorly differentiated tumor, and preoperative bilirubin level greater than 5.0 mg/dl were significant independent predictors of poor prognosis by multivariate analysis. The number of metastatic lymph nodes did not significantly affect survival. Recurrence occurred in 72 patients (61.0%). Disease-free survival rates were 74.1% at 1 year and 42.0% at 3 years. Lymph node and distant metastases and poorly differentiated tumors were found to be significant independent predictors of recurrence by multivariate analysis. CONCLUSIONS R0 resection confers a survival benefit, thus the surgeon should make an effort to achieve R0 resection. The presence of lymph node metastasis was a significant prognostic factor.
Collapse
Affiliation(s)
- Sae Byeol Choi
- Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, Korea
| | | | | | | | | |
Collapse
|
|
49
|
Jin C, Yao L, Long J, Fu DL, Yu XJ, Xu J, Yang F, Ni QX. Effect of multiple-phase regional intra-arterial infusion chemotherapy on patients with resectable pancreatic head adenocarcinoma. Chin Med J (Engl) 2009; 122:284-290. [PMID: 19236805 DOI: 10.3760/cma.j.issn.0366-6999.2009.03.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
BACKGROUND Regional intra-arterial infusion chemotherapy (RIAC) has been more valuable to improve prognosis and quality of life of patients with inoperable pancreatic adenocarcinomas, and adjuvant RIAC plays an important role in prolonging survival and reducing risk of liver metastasis after radical resection of pancreatic cancer, but the effect of preoperative or multiple-phase RIAC (preoperative combined with postoperative RIAC) for resectable pancreatic cancers has not been investigated. In this prospective study, the effect of multiple-phase RIAC for patients with resectable pancreatic head adenocarcinoma was evaluated, and its safety and validity comparing with postoperative RIAC were also assessed. METHODS Patients with resectable pancreatic head cancer were randomly assigned to two groups. Patients in group A (n=50) were treated with new therapeutic mode of extended pancreaticoduodenectomy combined with multiple-phase RIAC, and those in group B (n=50) were treated with extended pancreaticoduodenectomy combined with postoperative RIAC in the same period. The feasibility, compliance and efficiency of the new therapeutic mode were evaluated by tumor size, serum tumor markers, clinical benefit response (CBR), surgical complications, mortality and toxicity of RIAC. The disease-free survival time, median survival time, incidence of liver metastasis, survival rate at 1, 2, 3 and 5 years were also observed. Life curves were generated by the Kaplan-Meier method. RESULTS The pain relief rate and CBR in group A was 80% and 84% respectively. Serum tumor markers decreased obviously and tumors size decreased in 26% of patients after preoperative RIAC in group A. No more surgical complications, mortality or severe systemic side effects were observed in group A compared with group B. The incidence of liver metastasis in group A was 34% which was lower than 50% in group B. The disease-free survival time and median survival time in group A were 15.5 months and 18 months respectively. The 1-, 2-, 3- and 5-year survival rates were 54.87%, 34.94%, 24.51% and 12.25% respectively. There was no significant difference of survival time or survival rates between two groups. CONCLUSIONS Multiple-phase RIAC is effective in combined therapy of resectable pancreatic head carcinomas by enhancing inhibition of tumor growth and reduction of liver metastasis, without negative effect on patients' safety or surgical procedure.
Collapse
Affiliation(s)
- Chen Jin
- Pancreatic Disease Institution, Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China
| | | | | | | | | | | | | | | |
Collapse
|
|
50
|
Yamada S, Nakao A, Fujii T, Sugimoto H, Kanazumi N, Nomoto S, Kodera Y, Takeda S. Pancreatic cancer with paraaortic lymph node metastasis: a contraindication for radical surgery? Pancreas 2009; 38:e13-7. [PMID: 18797422 DOI: 10.1097/mpa.0b013e3181889e2d] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES The purpose of this study was to determine the operative indications for pancreatic cancer with paraaortic lymph node metastases (No. 16 [+]). METHODS Between July 1981 and March 2007, 335 patients with pancreatic cancer including 45 No. 16 (+) patients underwent extended radical surgery at the Department of Surgery II, Nagoya University. The overall survival rates and clinicopathological parameters were analyzed using univariate and multivariate analyses. RESULTS Although there was no significant difference in survival between the No. 16 (+) patients and the unresectable cases, there were some long-term survivors among the No. 16 (+) patients. Multivariate analysis of the No. 16 (+) patients identified age (59 years or younger), tumor size (>4 cm), and pathologically confirmed portal invasion (pPV[+]) as independent prognostic factors. The survival of No. 16 (+) patients without these factors was significantly better than the unresectable cases. The survival of patients with only 1 metastatic paraaortic lymph node also was significantly better than the unresectable cases, and tended to be better than those with more than 2 metastatic nodes. CONCLUSIONS No. 16 (+) pancreatic cancer patients with age 60 years or older, tumor size 4 cm or less, and pPV(-) may benefit from resection.
Collapse
Affiliation(s)
- Suguru Yamada
- Department of Surgery II, Graduate School and Faculty of Medicine, University of Nagoya, Nagoya, Japan
| | | | | | | | | | | | | | | |
Collapse
|