Patients with advanced gastric cancer (AGC) with peritoneal carcinomatosis (PC) usually have poor outcomes and high mortality risk, even with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). This study analyzed the prognostic factors of AGC with PC and evaluated laparoscopic HIPEC (LHIPEC) plus neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) as a conversion surgery for AGC patients with PC with a poor initial prognosis. Patient and Methods. We retrospectively evaluated 127 patients with AGC and PC from January 1, 2012, to March 1, 2020. After the exclusion of 32 ineligible patients, the conversion group comprised 34 patients who underwent LHIPEC + NIPS as a conversion surgery followed by CRS plus HIPEC. The CRS + HIPEC group included 15 patients who underwent CRS with HIPEC alone. Additionally, the C/T group comprised 23 patients who received systemic chemotherapy, and the palliative group comprised 23 patients who received only conservative therapy or palliative gastrectomy.

The conversion group demonstrated a significantly better mean overall survival compared to the CRS + HIPEC, C/T, and palliative groups (p < 0.001). Patients in the conversion group who underwent LHIPEC + NIPS had significantly decreased peritoneal cancer index (PCI) scores (p < 0.001) and ascites (p=0.003). Malignant ascites amount also significantly decreased after treatment in the LHIPEC + NIPS group (p < 0.001).

LHIPEC + NIPS can significantly improve the overall survival, the PCI score, and malignant ascites amount in peritoneal cytology-positive gastric cancer with PC, and an initially high PCI score. Therefore, it may be a feasible conversion strategy for AGC patients with PC.

Introduction: Gastric cancer is the fourth/fifth most common malignancy worldwide, with only a quarter of patients achieving a 5-year survival rate. It has been estimated that 15-50% or more of patients have peritoneal disease upon surgical exploration. Until the early 1990s, peritoneal metastasis was considered as terminal stage of the disease; in the late 1990s, selected patients with peritoneal metastasis were recategorized as local disease. Over the past two decades, the treatment of peritoneal involvement has transformed, and cytoreductive surgery plus intraperitoneal therapy have drastically altered the natural course of several malignancies. Areas covered: We performed a review of studies available on PubMed from 1 January 2014 to 31 July 2019 and the analysis of their reference citations. We describe the most current intraperitoneal chemotherapy opportunities in the treatment of gastric cancer: hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC), laparoscopic hyperthermic intraperitoneal chemotherapy (LHIPEC), neoadjuvant intraperitoneal and systemic chemotherapy (NIPS), LHIPEC + NIPS, extensive intraoperative peritoneal lavage (EIPL), early postoperative intraperitoneal chemotherapy (EPIC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC). Expert opinion: Comprehensive treatment consisting of CRS combined with perioperative intraperitoneal/systemic chemotherapy can, today, be considered an effective strategy to improve the long-term survival of gastric cancer patients with peritoneal metastasis.

Gastric Cancer (GC) with Peritoneal Carcinomatosis (PC) has long been regarded as a terminal disease. Over the past two decades, cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has changed the traditional concept of peritoneal metastases from being a systemic disease, to being considered a locoregional dissemination.

A prospective study was performed at a high-volume Carcinomatosis Center to evaluate survival, morbi-mortality and prognostic factors for survival in a cohort of patients with GC and PC treated with CRS + HIPEC between June 2006 and December 2016.

Thirty-five patients were included in the study. Median follow-up was 54 months. Postoperative major complications (>grade IIIa) occurred in 25.7% of patients, including 2 deaths (mortality 5.7%). The median overall survival (OS) was 16 months and the 1-, 3- and 5-year OS rates were 70.8%, 21.3% and 21.3% %, respectively. The median OS for patients with PCI ≤6 was 19 months, in contrast to 12 months for the 19 patients with PCI >6. Three patients were included with only a positive cytology and their median OS was not reached. Perineural invasion was the only factor that had a negative influence in prognosis (HR 18.8) in multivariate analysis.

Although GC with PC still has a poor prognosis, survival has improved in selected patients with CRS + HIPEC and perioperative systemic chemotherapy. Patients with isolated positive cytology or peritoneal carcinomatosis with PCI less than 6 had encouraging survival rates.

Endolichenic fungi are microbes that inhabit the thalli of lichens and produce various unique chemicals that can be used for pharmaceutical purposes.

This study screened a library of endolichenic fungal extracts to identify novel anticancer agents capable of suppressing the tumorigenicity of human cancer cells.

Active compounds were isolated from extracts of endolichenic fungi by column chromatography and reverse-phase HPLC. The anticancer effects of the extracts on cell viability was assessed with the use of MTT assay, Western blotting, fluorescence labeling of apoptotic cell, and flow cytometric analysis; and cell motility with the use of migration, invasion and soft agar colony-formation assay in vitro; and on skin and intraperitoneal mouse xenograft tumors in vivo were investigated. The therapeutic effects of the extract alone or in combination with the conventional chemoreagent docetaxel were analyzed by sulforhodamine B assay.

Acetone extracts of EL002332, isolated from Endocarpon pusillum collected in the China desert in 2010, showed selective cytotoxicity against AGS human gastric cancer cells and CT26 mouse colon cancer cells. An active pure compound named myC was isolated from mycelium acetone extracts in a liquid culture system and showed more potent cytotoxicity than crude extracts in the AGS cell line. Especially, myC greatly increased the apoptotic cell population at the IC₅₀ concentration and activated apoptotic signaling by regulating Bcl2 family protein expression and caspase pathway activity. EL002332 crude extracts and myC decreased AGS cell motility at sub-lethal concentrations. In vivo skin and intraperitoneal xenograft tumor experiments showed that the size of tumors and the tumor score were significantly smaller in EL002332 crude extract-treated groups than in control groups. EL002332 crude extracts showed synergistic effects with docetaxel on the AGS and TMK1 cell lines.

The endolichenic fungus EL002332 has potential anticancer activity in gastric cancer and peritoneal carcinomatosis.

Peritoneal carcinomatosis in colorectal cancer is an advanced stage of the disease where improved survival can be attained whenever the resection associated with hyperthermic intreperitoneal chemotherapy is possible. In unresectable cases, systemic chemotherapy is administered to obtain conversion to resectability but results have not yet been clearly evaluated. Local chemotherapy in this setting has been proven useful in several similar situations. The aim of the present pilot study was to evaluate the feasibility of pre-operative intraperitoneal chemotherapy with oxaliplatin in these patients.

Six patients with unresectable peritoneal disease of colorectal origin were included in the study. An intraperitoneal implantable chamber catheter was inserted during the laparotomy that evaluated the extent of the peritoneal disease (peritoneal carcinomatosis index 25 to 39). Patients then underwent intraperitoneal chemotherapy with oxaliplatin 85 mg/m² in combination with systemic chemotherapy (FOLFIRI or simplified LV5FU) and a targeted therapy every 2 weeks.

Two catheter perfusion incidents were reported due to the abdominal wall thickness. Two patients completed the four intraperitoneal (IP) chemotherapy cycles without major toxicity. One patient developed grade 3 or 4 diarrhea requiring a short intensive care unit (ICU) stay, though it is not clear whether the event was induced by intravenous irinotecan, IP oxaliplatin or the combination of both. Grade 3 fatigue and abdominal pain were also recorded. For one patient with aggressive disease, best supportive care was initiated after the first course of chemotherapy.

Our study is the first to assess intraperitoneal oxaliplatin-based chemotherapy in the preoperative setting for patients with unresectable peritoneal metastases. The tolerance was acceptable for 85 mg/m² IP oxaliplatin combined with systemic therapy in these patients. Our results justify carrying on with a phase I/II trial to determine the recommended dose of oxaliplatin in this clinical context and its efficacy.

Gastric cancer associated peritoneal carcinomatosis (GCPC) has a poor prognosis with a median survival of less than one year. Systemic chemotherapy including targeted agents has not been found to significantly increase the survival in GCPC. Since recurrent gastric cancer remains confined to the abdominal cavity in many patients, regional therapies like aggressive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been investigated for GCPC. HIPEC has been used for three indications in GC- as an adjuvant therapy after a curative surgery, HIPEC has been shown to improve survival and reduce peritoneal recurrences in many randomised trials in Asian countries; as a definitive treatment in established PC, HIPEC along with CRS is the only therapeutic modality that has resulted in long-term survival in select groups of patients; as a palliative treatment in advanced PC with intractable ascites, HIPEC has been shown to control ascites and reduce the need for frequent paracentesis. While the results of randomised trials of adjuvant HIPEC from western centres are awaited, the role of HIPEC in the treatment of GCPC is still evolving and needs larger studies before it is accepted as a standard of care.

Owing to the risks of serious and sustained toxicity, anticancer drugs such as cisplatin and irinotecan cannot be readily administered to patients with gastric cancer and severe peritoneal metastasis. Therefore, a standard chemotherapy regimen has yet to be established for these types of patients. This randomized study investigated the utility of sequential methotrexate and 5-fluorouracil therapy vs. 5-fluorouracil continuous infusion for gastric cancer with peritoneal metastasis.

Eligible patients had radiologically confirmed peritoneal metastasis with intestinal stenosis, peritoneal tumor or ascites. Treatment with 5-fluorouracil continuous infusion (800 mg/m(2)/day, ci, d1-5, q4w) or methotrexate and 5-fluorouracil therapy (methotrexate, 100 mg/m(2), bolus infusion, followed 3 h later by 5-fluorouracil, 600 mg/m(2), bolus infusion, with leucovorin rescue, q1w) was continued until disease progression or unacceptable toxicity. The projected sample size was 236, providing 80% power to detect a 40% increase in median overall survival in methotrexate and 5-fluorouracil therapy with a one-sided α of 0.05.

All 237 randomized patients were included in the primary analysis. The methotrexate and 5-fluorouracil therapy arm was not superior to the 5-fluorouracil continuous infusion arm (median survival time, 9.4 months in the 5-fluorouracil continuous infusion arm, 10.6 months in the methotrexate and 5-fluorouracil therapy arm; hazard ratio, 0.94; 95% confidence interval, 0.72-1.22; one-sided P = 0.31). Frequencies of Grade 3 or higher neutropenia, Grade 3 or higher anorexia and treatment-related deaths were 0.9, 27.4 and 1.7%, respectively, in the 5-fluorouracil continuous infusion arm, and 31.9, 33.6 and 0.9%, respectively, in the methotrexate and 5-fluorouracil therapy arm.

Methotrexate and 5-fluorouracil therapy is not suitable for use as standard therapy for advanced gastric cancer with peritoneal metastasis.

This study was aimed to analyze the contrast-enhanced CT features of gastrohepatic ligament (GHL) involvement in gastric carcinoma (GC) and to evaluate the influence of GHL on the spread of GC correlating with the anatomic bases.

CT scans of 41 patients known to have GC and GHL involvement were reviewed retrospectively for the primary tumor and the GHL abnormalities, as well as the role GHL played in the spread of GC. Emphasis was placed on direct invasion, lymph node metastasis, and GHL seeding. The relationship between the accompanying ascites and the different pattern of the GHL involvement were also evaluated statistically.

CT features of the GHL abnormalities caused by GC could be summarized as follows: (a) direct invasion (34.1%, 14 of 41), which was visualized as a regional (nine of 14) or diffuse mass (five of 14) in the GHL; (b) GHL seeding (26.8%, 11 of 41), which consists of ''smudged'' appearance (eight of 11), nodular infiltration (two of 11) and "GHL caking" (one of 11); (c) lymph node metastasis (63.4%, 26 of 41), including enlargement of lymph nodes (22 of 26) and cystic lesion (four of 26). We also found direct extension of GC into the transverse fissure and/or the liver via the GHL in three patients. Ascites, which was found in ten patients, seemed to be associated with the pattern of seeding involvement.

GHL can be invaded by GC through several patterns and contrast-enhanced CT scan plays an important role in detecting GHL involvement in GC, which has a variety of CT manifestations. GHL may also serve as a potential conduit for the predictable spread of GC into the neighboring organs such as the liver.

The aim of this study was to evaluate the efficacy and toxicity of low dose of docetaxel in combination with standard dose of S-1 for patients with advanced or recurrent gastric cancer and to investigate whether the protein expression level of dihydropyrimidine dehydrogenase is a predictive factor of toxicities or responses.

Between March 2010 and December 2011, 61 patients from the Department of Medical Oncology of Shanghai Zhong Shan Hospital, Fudan University, were enrolled in the study. Patients with advanced or recurrent gastric adenocarcinoma were treated with docetaxel of 40 mg/m(2) intravenously on day 1 and S-1 of 80 mg/m(2) orally on days 1-14 every 3 weeks as first-line chemotherapy. The chemotherapeutic effects were evaluated following every 3 cycles of chemotherapy using the Response Evaluation Criteria In Solid Tumors (RECIST). The serum of peripheral blood was obtained at the start of the study and at each evaluation point to analyze the protein expression level of DPD, which was estimated using an enzyme-linked immunosorbent assay. All the patients were followed-up until the time of progression, death, or the censor time, to calculate progression-free survival and overall survival (OS) time.

In total, 61 patients [median age 60 years (range 28-76 years)] received a total of 318 treatment cycles [median 5 (range 2-9)], and 94 cycles of single S-1 maintenance treatment. One complete response (CR) and 25 partial responses (PR) were observed, with an overall response rate of 42.6%. A total of 29 patients (47.5%) had stable disease (SD) and 6 patients (9.8%) had progressive disease (PD). The disease control rate (DCR, CR + PR + SD) was 90.2%. Median overall survival was 13.0 months [95% confidence interval (CI) 10.76-15.24 months], and median PFS was 6.0 months (95% CI 4.61-7.39 months). Progression-free survival was far longer in peritoneal metastatic patients than that in patients with other metastases (7.3 ± 2. 6 vs. 5.4 ± 2.8 months; P < 0.05); however, this was not the case for OS. Grade 3-4 neutropenia was well controlled and grade 4 non-hematologic toxicities did not occur. Baseline expression level of DPD was not associated with efficacy. Lower expression level of DPD was correlated with high grade of toxicities (P < 0.05).

This combination of standard dose of S-1 and low dose of docetaxel is effective and well tolerated in patients with advanced or recurrent gastric cancer. Peritoneal metastasis is treated more effectively by this regimen than other forms of metastases. Baseline DPD expression level in the serum is associated with toxicity, but not tumor response.

Two patients with gastric carcinoma underwent CT colonography (CTC) for preoperative work-up. Although no obvious peritoneal nodules were seen on axial CT images, colonic wall deformities were noted on three-dimensional (3D) air images. Multiplanar-reformatted images revealed corresponding colonic wall thickening at the deformities, and in addition, dense cordlike structures connecting the primary gastric cancer and colonic wall thickening were also observed. In one patient, cordlike indurations consistent with peritoneal invasion were found to connect the primary gastric cancer, gastrocolic ligament, and transverse mesocolon during exploratory surgery, and in the other, colonic scars consistent with peritoneal invasion after chemotherapy were observed. These observations suggest that CTC could be of potential use for the differentiation of transperitoneal colonic invasion and gastric cancer.