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Wirth U, Schardey J, von Ahnen T, Crispin A, Kappenberger A, Zimmermann P, Florian K, D'Haese JG, Werner J, Rau B. Outcome of a 3-day vs 7-day selective digestive tract decontamination-based regimen for oral antibiotic bowel decontamination in left-sided colorectal surgery: A noninferiority study. J Gastrointest Surg 2024; 28:1665-1673. [PMID: 39098473 DOI: 10.1016/j.gassur.2024.07.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 07/29/2024] [Accepted: 07/30/2024] [Indexed: 08/06/2024]
Abstract
BACKGROUND Colorectal surgery still experiences high rates of infectious complications, such as anastomotic leakage (AL) and surgical site infections (SSIs). Therefore, oral antibiotic bowel decontamination (OABD) has experienced a renaissance. However, data on perioperative selective digestive tract decontamination (SDD)-based regimens or combined bowel preparation are inconsistent. Nonetheless, with widespread use of Enhanced Recovery After Surgery concepts, the ideal length for perioperative SDD treatment has to be reconsidered. METHODS Perioperative outcome was analyzed in a cohort of patients undergoing minimally invasive surgery for left-sided colorectal cancer in a retrospective study. Additional to usual perioperative outcome measures, including AL, SSIs, and overall infectious complications, the efficacy of a shortened 3-day perioperative OABD treatment was compared with the efficacy of a 7-day perioperative OABD treatment based on a noninferiority analysis. RESULTS Overall, 256 patients were included into analysis, of whom 84 and 172 patients were treated by 3-day and 7-day perioperative OABD regimens, respectively. AL occurred in 1.2% of patients in the 3-day group and 5.2% of patients in the 7-day group, and SSIs occurred in 3.6% of patients in the 3-day group and 5.8% of patients in the 7-day group, without significant difference. The shortened 3-day perioperative SDD-based regimen was noninferior to the regular 7-day perioperative SDD-based regimen concerning the rates of AL, SSIs, and infectious complications. CONCLUSION Our data demonstrated noninferiority of a shortened 3-day SDD-based treatment vs a 7-day SDD-based treatment for AL, SSIs, and overall infectious complications.
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Affiliation(s)
- Ulrich Wirth
- Department of General, Visceral, and Transplantation Surgery, Ludwig Maximilian University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.
| | - Josefine Schardey
- Department of General, Visceral, and Transplantation Surgery, Ludwig Maximilian University Hospital, Ludwig Maximilian University of Munich, Munich, Germany
| | - Thomas von Ahnen
- Department of General, Visceral, Vascular and Endocrine Surgery, Agatharied Hospital, Hausham, Germany
| | - Alexander Crispin
- Faculty of Medicine, Institute of Medical Data Processing, Biometry, and Epidemiology, Pettenkofer School of Public Health, Ludwig Maximilian University of Munich, Munich, Germany
| | - Alina Kappenberger
- Department of General, Visceral, and Transplantation Surgery, Ludwig Maximilian University Hospital, Ludwig Maximilian University of Munich, Munich, Germany
| | - Petra Zimmermann
- Department of General, Visceral, and Transplantation Surgery, Ludwig Maximilian University Hospital, Ludwig Maximilian University of Munich, Munich, Germany
| | - Kühn Florian
- Department of General, Visceral, and Transplantation Surgery, Ludwig Maximilian University Hospital, Ludwig Maximilian University of Munich, Munich, Germany
| | - Jan G D'Haese
- Department of General, Visceral, Vascular and Endocrine Surgery, Agatharied Hospital, Hausham, Germany
| | - Jens Werner
- Department of General, Visceral, and Transplantation Surgery, Ludwig Maximilian University Hospital, Ludwig Maximilian University of Munich, Munich, Germany
| | - Bettina Rau
- Department of Surgery, Klinikum Neumarkt, Neumarkt in der Oberpfalz, Germany
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Benedek Z, Coroş MF. The impact of sarcopenia on the postoperative outcome in colorectal cancer surgery. Med Pharm Rep 2023; 96:20-27. [PMID: 36818326 PMCID: PMC9924812 DOI: 10.15386/mpr-2483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 06/27/2022] [Accepted: 10/26/2022] [Indexed: 01/20/2023] Open
Abstract
Background and aim Malnutrition-induced sarcopenia predicts poorer clinical outcomes for patients with cancer. Postoperative complications such as wound infection, anastomotic leak (AL), cardiorespiratory events are the most frequent and devastating postoperative complications in colorectal cancer surgery and are frequently associated with malnutrition. Methods We reviewed the recent available literature to assess the relationship between the patient nutritional status and sarcopenia in colorectal surgery. The PubMed database was searched for publications. The included studies were original articles, prospective and randomized trials, clinical, systematic reviews and meta-analyses. The information was structured in a narrative review form. Results A simple method to assess malnutrition is to define the presence of sarcopenia (skeletal muscle mass reduction and modified composition) by radiological image analysis. Quantifying the material composition and quality is a novel method in patient-specific therapy. This could be a new perspective in colorectal surgery to reduce postoperative mortality, improve surgical planning, and enhance clinical outcomes. A few recent studies have objectively investigated the presence of sarcopenia in colorectal cancer and its impact on morbidity and mortality, but sometimes the results are contradictory. Conclusion There is evolving research to find the most appropriate management method, surgeons must be aware of the existence of sarcopenia to identify this risk factor in the occurrence of postoperative complications in colorectal cancer surgery.
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Affiliation(s)
- Zalán Benedek
- “G. E. Palade” University of Medicine, Pharmacy, Science and Technology of Târgu Mureş, Romania,Surgery Department, Municipal Hospital, Odorheiu Secuiesc, Romania
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Liu Y, Li B, Wei Y. New understanding of gut microbiota and colorectal anastomosis leak: A collaborative review of the current concepts. Front Cell Infect Microbiol 2022; 12:1022603. [PMID: 36389160 PMCID: PMC9663802 DOI: 10.3389/fcimb.2022.1022603] [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: 08/18/2022] [Accepted: 10/06/2022] [Indexed: 01/24/2023] Open
Abstract
Anastomotic leak (AL) is a life-threatening postoperative complication following colorectal surgery, which has not decreased over time. Until now, no specific risk factors or surgical technique could be targeted to improve anastomotic healing. In the past decade, gut microbiota dysbiosis has been recognized to contribute to AL, but the exact effects are still vague. In this context, interpretation of the mechanisms underlying how the gut microbiota contributes to AL is significant for improving patients' outcomes. This review concentrates on novel findings to explain how the gut microbiota of patients with AL are altered, how the AL-specific pathogen colonizes and is enriched on the anastomosis site, and how these pathogens conduct their tissue breakdown effects. We build up a framework between the gut microbiota and AL on three levels. Firstly, factors that shape the gut microbiota profiles in patients who developed AL after colorectal surgery include preoperative intervention and surgical factors. Secondly, AL-specific pathogenic or collagenase bacteria adhere to the intestinal mucosa and defend against host clearance, including the interaction between bacterial adhesion and host extracellular matrix (ECM), the biofilm formation, and the weakened host commercial bacterial resistance. Thirdly, we interpret the potential mechanisms of pathogen-induced poor anastomotic healing.
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Affiliation(s)
- Yang Liu
- Pancreatic and Gastrointestinal Surgery Division, HwaMei Hospital, University of Chinese Academy of Science, Ningbo, China,Ningbo Clinical Research Center for Digestive System Tumors, Ningbo, China
| | - Bowen Li
- Pancreatic and Gastrointestinal Surgery Division, HwaMei Hospital, University of Chinese Academy of Science, Ningbo, China,Department of Oncology and Laparoscopy Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yunwei Wei
- Pancreatic and Gastrointestinal Surgery Division, HwaMei Hospital, University of Chinese Academy of Science, Ningbo, China,Ningbo Clinical Research Center for Digestive System Tumors, Ningbo, China,*Correspondence: Yunwei Wei,
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Sripathi S, Khan MI, Patel N, Meda RT, Nuguru SP, Rachakonda S. Factors Contributing to Anastomotic Leakage Following Colorectal Surgery: Why, When, and Who Leaks? Cureus 2022; 14:e29964. [DOI: 10.7759/cureus.29964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/05/2022] [Indexed: 11/06/2022] Open
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Jin X, Liu Y, Yan W, Shi S, Liu L, Lin B, Guo X, Cai T, Wei Y. Gut microbiota from nCAL patients promotes colon anastomotic healing by inducing collagen synthesis in epithelial cells. J Gastroenterol Hepatol 2022; 37:1756-1767. [PMID: 35849493 DOI: 10.1111/jgh.15946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 04/23/2022] [Accepted: 07/01/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIMS Colon anastomotic leak (CAL) is considered one of the most feared and serious postoperative complications in colorectal cancer (CRC) patients, with no effective prevention strategies to date. Based on previous studies, gut microbiota is associated with anastomotic healing, but its ability to effectively promote anastomotic healing remains largely unknown. METHODS We performed a clinical study to analyze the gut microbiota profiling in CRC patients who developed CAL and those who did not (nCAL) using 16S-rRNA-based next-generation sequencing (NGS). To investigate these changes in an in vivo model, we performed fecal microbiota transplantation in a colon anastomosis rat experimental model to elucidate the causal effect between gut microbiota and anastomotic healing. Notably, RNA-seq in the anastomotic tissue of the latter experimental model was utilized to discover the potential molecular mechanism. RESULTS Our analysis implicated that gut microbiota profiling was profoundly different between CAL and nCAL patients. Strikingly, the rat experimental model transplanted with fecal microbiota derived from nCAL patients demonstrated enhanced anastomotic healing properties. Moreover, collagen synthesis, EMT, and TGF-β/Smad signaling pathways were upregulated in the same rats. Concordantly, we discovered that the better anastomotic healing profiling displayed in gut microbiota derived from nCAL patients is dependent on the TGF-β/Smad-induced EMT in vitro and in vivo. CONCLUSIONS Collectively, our clinical study identified the postoperative gut microbiota profile is associated with CAL in CRC patients. On the contrary, fecal microbiota from nCAL patients promotes anastomotic healing via TGF-β/Smad-induced EMT, with subsequent collagen synthesis and enhanced anastomosis healing.
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Affiliation(s)
- Xiangren Jin
- Department of Oncological and Endoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.,Department of Gastrointestinal Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Yang Liu
- Department of Oncological and Endoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.,Pancreatic and Gastrointestinal Surgery Division, HwaMei Hospital, University of Chinese Academy of Science, Ningbo, China.,Ningbo Clinical Research Center for Digestive System Tumors, Ningbo, China
| | - Wei Yan
- Department of Oncological and Endoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Shang Shi
- Department of Oncological and Endoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Lujia Liu
- Department of Oncological and Endoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Baiqiang Lin
- Department of Oncological and Endoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xiao Guo
- Department of Oncological and Endoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Ting Cai
- Department of Experimental Medical Science, HwaMei Hospital, University of Chinese Academy of Science, Ningbo, China.,Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China.,Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo, China
| | - Yunwei Wei
- Department of Experimental Medical Science, HwaMei Hospital, University of Chinese Academy of Science, Ningbo, China.,Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China.,Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo, China
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Kawada K, Wada T, Yamamoto T, Itatani Y, Hida K, Obama K. Correlation between Colon Perfusion and Postoperative Fecal Output through a Transanal Drainage Tube during Laparoscopic Low Anterior Resection. Cancers (Basel) 2022; 14:cancers14092328. [PMID: 35565456 PMCID: PMC9101401 DOI: 10.3390/cancers14092328] [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: 04/07/2022] [Revised: 04/30/2022] [Accepted: 05/05/2022] [Indexed: 12/10/2022] Open
Abstract
In order to prevent anastomotic leakage (AL) following rectal surgery, various solutions—such as intraoperative indocyanine green (ICG) angiography and transanal drainage tubes (TDT)—have been proposed. This study investigated the relationship between intestinal perfusion and fecal volume through TDT in laparoscopic low anterior resection (LAR). A total of 59 rectal cancer patients who underwent laparoscopic LAR with both intraoperative ICG angiography and postoperative TDT placement were retrospectively analyzed. The relationship between intestinal perfusion and fecal volume through TDT was examined. Based on the ICG fluorescence, the transection site was shifted more proximally in 20 cases (33.9%). Symptomatic AL occurred in seven patients (11.8%). The AL rate of the patients whose daily fecal volume exceeded 100 mL/day in 2 or more days was significantly higher than that of those whose daily fecal volume exceeded it in 0 or 1 day (44.4% vs. 6.0%; p < 0.01). Univariate and multivariate analyses showed that the need for a proximal shift of the transection site was significantly associated with a high fecal volume. The quantitative analysis of ICG fluorescence indicated that Fmax (the fluorescence difference between the baseline and maximum) was significantly associated with fecal volume through TDT.
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Affiliation(s)
- Kenji Kawada
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan; (T.W.); (T.Y.); (Y.I.); (K.H.); (K.O.)
- Correspondence: ; Tel.: +81-75-366-7595
| | - Toshiaki Wada
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan; (T.W.); (T.Y.); (Y.I.); (K.H.); (K.O.)
- Department of Surgery, Faculty of Medicine, Kindai University, Osaka 589-8511, Japan
| | - Takehito Yamamoto
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan; (T.W.); (T.Y.); (Y.I.); (K.H.); (K.O.)
- Department of Gastroenterological Surgery and Oncology, Kitano Hospital Medical Research Institute, Osaka 530-8480, Japan
| | - Yoshiro Itatani
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan; (T.W.); (T.Y.); (Y.I.); (K.H.); (K.O.)
| | - Koya Hida
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan; (T.W.); (T.Y.); (Y.I.); (K.H.); (K.O.)
| | - Kazutaka Obama
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan; (T.W.); (T.Y.); (Y.I.); (K.H.); (K.O.)
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Aaron DJ, Anandhi A, Sreenath GS, Sureshkumar S, Shaikh OH, Balasubramaniyan V, Kate V. Serial estimation of serum C-reactive protein and procalcitonin for early detection of anastomotic leak after elective intestinal surgeries: a prospective cohort study. Turk J Surg 2021; 37:22-27. [PMID: 34585090 DOI: 10.47717/turkjsurg.2021.5102] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Accepted: 03/05/2021] [Indexed: 02/08/2023]
Abstract
Objectives Anastomotic leak can adversely affect the outcome of surgery especially if detected late. The present study was carried out to detect the anastomotic leak early in the postoperative period using serial estimation of procalcitonin (PCT) and C-reactive protein (CRP). Material and Methods A single centre prospective cohort study was done on patients undergoing elective gastrointestinal surgery with anastomosis. Serial estimation of serum procalcitonin and C reactive protein was done on the first five postoperative days. Other parameters such as hemoglobin, total protein, albumin and WBC counts were noted perioperatively. Patients were followed up to 60th postoperative day to assess for anastomotic leak, wound infection and other septic foci. Results Eighty-four patients were included in the study. Anastomotic leak rate was 26.19% (22/84) and 3/22 patients died in the anastomotic leak group. Wound infection rate was 23.81%. The cut off value of CRP on third postoperative day in detecting anastomotic leak was 44.322 mg/dl with sensitivity of 72.73%, specificity of 66.13% and accuracy of 59.52%. The cut off value for WBC count measured perioperatively in detecting anastomotic leak was 9470 cell/mm3 with sensitivity of 72.73%, specificity of 56.45% and accuracy of 59.74%. Serum procalcitonin, haemoglobin, total protein and albumin measured were not sensitive enough to detect the anastomotic leak early. Conclusion Measuring CRP on the third postoperative day can predict anastomotic leak with a cut off value of 44.32 mg/dl. Patients with raised CRP need careful evaluation to rule out anastomotic leak before deciding on early discharge.
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Affiliation(s)
- Devarajan Jebin Aaron
- Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Amaranathan Anandhi
- Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Gubbi Shamanaa Sreenath
- Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Sathasivam Sureshkumar
- Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Oseen Hajilal Shaikh
- Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Vairrappan Balasubramaniyan
- Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Vikram Kate
- Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
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Procalcitonin and C-Reactive Protein as an Early Predictor of Infection in Elective Gastrointestinal Cancer Surgery-a Prospective Observational Study. J Gastrointest Cancer 2021; 53:605-613. [PMID: 34328613 DOI: 10.1007/s12029-021-00661-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/22/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND Postoperative infections are a common entity following elective gastrointestinal surgery among which intra-abdominal infection is notorious and life threatening. Early detection could reduce postoperative morbidity and permit safe and early discharge. This study was aimed to establish the usefulness of procalcitonin (PCT) and C-reactive protein (CRP) on postoperative day 3 as reliable markers for early detection of intra-abdominal infection and other postoperative infections following elective gastrointestinal cancer surgery. METHODS A total of 125 patients following elective gastrointestinal cancer surgery were prospectively observed until discharge from January 2018 to December 2019. The incidence of intra-abdominal infections and other postoperative infections was recorded. Serum PCT and CRP were estimated on postoperative day 3 for all the patients. ROC analysis of PCT and CRP was performed to establish their predictability in detecting these infections. Risk factors for postoperative infections were also studied. RESULTS The incidence of intra-abdominal infection (IAI) was 24%. The difference in PCT between the infected and non-infected patients was statistically significant (p = 0.001) but not in CRP (p = 0.223). On ROC analysis of CRP and PCT in detecting IAI, the areas under the curve were 0.494 and 0.615 respectively. CONCLUSION Raised serum PCT values on postoperative day 3 indicate the presence of infections and should prompt the surgeon to consider other investigations to confirm the presence of IAI and other postoperative infections and plan early intervention thus expediting the postoperative recovery. CLINICAL TRIAL REGISTRATION NUMBER CTRI/2018/12/016695.
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Janssen R, Van Workum F, Baranov N, Blok H, ten Oever J, Kolwijck E, Tostmann A, Rosman C, Schouten J. Selective Decontamination of the Digestive Tract to Prevent Postoperative Pneumonia and Anastomotic Leakage after Esophagectomy: A Retrospective Cohort Study. Antibiotics (Basel) 2021; 10:antibiotics10010043. [PMID: 33466226 PMCID: PMC7824731 DOI: 10.3390/antibiotics10010043] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 12/28/2020] [Accepted: 12/30/2020] [Indexed: 11/16/2022] Open
Abstract
Infectious complications occur frequently after esophagectomy. Selective decontamination of the digestive tract (SDD) has been shown to reduce postoperative infections and anastomotic leakage in gastrointestinal surgery, but robust evidence for esophageal surgery is lacking. The aim was to evaluate the association between SDD and pneumonia, surgical-site infections (SSIs), anastomotic leakage, and 1-year mortality after esophagectomy. A retrospective cohort study was conducted in patients undergoing Ivor Lewis esophagectomy in four Dutch hospitals between 2012 and 2018. Two hospitals used SDD perioperatively and two did not. SDD consisted of an oral paste and suspension (containing amphotericin B, colistin, and tobramycin). The primary outcomes were 30-day postoperative pneumonia and SSIs. Secondary outcomes were anastomotic leakage and 1-year mortality. Logistic regression analyses were performed to determine the association between SDD and the relevant outcomes (odds ratio (OR)). A total of 496 patients were included, of whom 179 received SDD perioperatively and the other 317 patients did not receive SDD. Patients who received SDD were less likely to develop postoperative pneumonia (20.1% vs. 36.9%, p < 0.001) and anastomotic leakage (10.6% vs. 19.9%, p = 0.008). Multivariate analysis showed that SDD is an independent protective factor for postoperative pneumonia (OR 0.40, 95% CI 0.23–0.67, p < 0.001) and anastomotic leakage (OR 0.46, 95% CI 0.26–0.84, p = 0.011). Use of perioperative SDD seems to be associated with a lower risk of pneumonia and anastomotic leakage after esophagectomy.
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Affiliation(s)
- Robin Janssen
- Department of Intensive Care Medicine, Radboud Institute for Health Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands;
- Radboud Center of Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands; (J.t.O.); (A.T.)
- Correspondence: ; Tel.: +31-629-625-745
| | - Frans Van Workum
- Department of Surgery, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands; (F.V.W.); (N.B.); (C.R.)
| | - Nikolaj Baranov
- Department of Surgery, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands; (F.V.W.); (N.B.); (C.R.)
| | - Harmen Blok
- Faculty of Medical Sciences, Radboud University, Geert Grooteplein Noord 21, 6525 EZ Nijmegen, The Netherlands;
| | - Jaap ten Oever
- Radboud Center of Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands; (J.t.O.); (A.T.)
- Department of Internal Medicine, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands
| | - Eva Kolwijck
- Department of Medical Microbiology, Jeroen Bosch Hospital, Henri Dunantstraat 1, 5223 GZ Den Bosch, The Netherlands;
| | - Alma Tostmann
- Radboud Center of Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands; (J.t.O.); (A.T.)
- Unit Hygiene and Infection Prevention, Department of Medical Microbiology, Radboud University Medical Center, Geert Grooteplein, Zuid 10, 6525 GA Nijmegen, The Netherlands
| | - Camiel Rosman
- Department of Surgery, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands; (F.V.W.); (N.B.); (C.R.)
| | - Jeroen Schouten
- Department of Intensive Care Medicine, Radboud Institute for Health Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands;
- Radboud Center of Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands; (J.t.O.); (A.T.)
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10
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Schardey HM, Wirth U, Strauss T, Kasparek MS, Schneider D, Jauch KW. Prevention of anastomotic leak in rectal cancer surgery with local antibiotic decontamination: a prospective, randomized, double-blind, placebo-controlled single center trial. Int J Colorectal Dis 2020; 35:847-857. [PMID: 32103326 DOI: 10.1007/s00384-020-03544-8] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/17/2020] [Indexed: 02/04/2023]
Abstract
PURPOSE Anastomotic leak and other infectious complications are septic complications of rectal cancer surgery caused by bacteria. Data from registry analysis show a beneficial effect of local antimicrobial administration on anastomotic leaks, but data are inconsistent in recent clinical trials. Therefore, our aim was to study the efficacy of topical antibiotic treatment on the incidence of anastomotic leaks in rectal cancer surgery. METHODS A prospective, randomized, double-blind and placebo-controlled, single center trial was conducted. Patients received either placebo and amphotericin B or decontamination with polymyxin B, tobramycin, vancomycin, and amphotericin B four times per day starting the day before surgery until postoperative day 7. If a protective ileostomy was created, a catheter was placed transanally and the medication was administered locally to the anastomotic site. All patients received an intravenous perioperative antibiotic prophylaxis. RESULTS The trial had to be stopped for ethical reasons after first interim analysis with 80 patients instead of the initially planned 280 patients. Of the 40 patients randomized to receive placebo, eight (20%) developed anastomotic leak compared to only 2 (5%) in the treatment group of 40 patients (decontamination) with significant difference in the χ2 test (p = 0.0425). Twenty percent of the placebo group and 12.5% in the treatment group developed infectious complications not associated with anastomotic leak (p = 0.5312). One patient (2.5%) in the placebo group died (p = 0.3141). CONCLUSION Local decontamination with polymyxin, tobramycin, vancomycin, and amphotericin B is safe and effective in the prevention of anastomotic leak in rectal cancer surgery.
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Affiliation(s)
- H M Schardey
- Department of General, Visceral, and Transplantion Surgery, Ludwig-Maximilians-University Munich, Marchioninistr. 15, 81377, Munich, Germany
- Department of General, Visceral and Vascular Surgery, Agatharied Hospital, Norbert-Kerkel-Platz, 83734, Hausham, Germany
| | - Ulrich Wirth
- Department of General, Visceral, and Transplantion Surgery, Ludwig-Maximilians-University Munich, Marchioninistr. 15, 81377, Munich, Germany.
| | - T Strauss
- Department of General, Visceral, and Transplantion Surgery, Ludwig-Maximilians-University Munich, Marchioninistr. 15, 81377, Munich, Germany
- AGAPLESION Diakonieklinikum Rotenburg, 27356, Rotenburg, Germany
| | - M S Kasparek
- Department of General, Visceral, and Transplantion Surgery, Ludwig-Maximilians-University Munich, Marchioninistr. 15, 81377, Munich, Germany
- Department of Visceral Surgery, Josephinum, Schönfeldstraße 16, 80539, Munich, Germany
| | - D Schneider
- Department of General, Visceral, and Transplantion Surgery, Ludwig-Maximilians-University Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - K W Jauch
- Department of General, Visceral, and Transplantion Surgery, Ludwig-Maximilians-University Munich, Marchioninistr. 15, 81377, Munich, Germany
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van Praagh JB, Luo JN, Zaborina O, Alverdy JC. Involvement of the Commensal Organism Bacillus subtilis in the Pathogenesis of Anastomotic Leak. Surg Infect (Larchmt) 2020; 21:865-870. [PMID: 32310731 DOI: 10.1089/sur.2019.345] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Background: It is now well established that microbes play a key and causative role in the pathogenesis of anastomotic leak. Yet, in patients, determining whether a cultured pathogen retrieved from an anastomotic leak site is a cause or a consequence of the complication remains a challenge. The aim of this study was to test a methodology to invoke causality between a retrieved microbe from a leak site and its role in anastomotic leak. Methods: The commensal organism Bacillus subtilis was isolated from an esophagojejunostomy leak site in a 35-year-old patient with a CDH1 mutation after a prophylactic gastrectomy whose body mass index (BMI) was 35 kg/m2. The organism was screened for its ability to degrade collagen, shift human recombinant matrix metalloprotease-9 (MMP9) to its active form, and induce a clinical anastomotic leak when introduced to anastomotic tissues of mice fed their standard diet (SD) of chow or an obesogenic Western-type diet (WD). Results: The Bacillus subtilis strain retrieved from the anastomotic leak site displayed a high degree of collagenolytic activity and was able to activate human MMP9 consistent with other pathogens expressing this characteristic "leak phenotype." Exposure of the Bacillus subtilis to the anastomotic tissues of obese mice fed a WD led to dehiscence of the anastomosis, abscess formation with peritonitis, and mortality in 50% of mice (3/6). When anastomotic healing was evaluated by a validated anastomotic healing score (AHS), substantially worse healing was observed (i.e., higher AHS) in WD-fed mice exposed to Bacillus subtilis compared to SD-fed mice (analysis of variance [ANOVA], p = 0.0006). Conclusions: Microbial strains obtained from patients' anastomotic leak sites can be evaluated for their pathogenic in the leak process by assessing their ability to produce collagenase, activate MMP9 and cause clinical leaks in mice fed a WD. These studies may aid in identifying those bacterial strains that play a causal role in patients with an anastomotic leak.
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Affiliation(s)
- Jasper B van Praagh
- Department of Surgery, University of Chicago, Pritzker School of Medicine, Chicago, Illinois, USA.,Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - James N Luo
- Department of Surgery, University of Chicago, Pritzker School of Medicine, Chicago, Illinois, USA
| | - Olga Zaborina
- Department of Surgery, University of Chicago, Pritzker School of Medicine, Chicago, Illinois, USA
| | - John C Alverdy
- Department of Surgery, University of Chicago, Pritzker School of Medicine, Chicago, Illinois, USA
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Alverdy JC, Hyman N. Bowel preparation under siege. Br J Surg 2019; 107:167-170. [PMID: 31872429 DOI: 10.1002/bjs.11454] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2019] [Accepted: 11/05/2019] [Indexed: 12/11/2022]
Abstract
An analysis of the results and conclusions from the most recent RCTs of the role of mechanical bowel preparation before colonic surgery is presented. The results indicate a wide disparity in the methods, results and conclusion of these studies, and the lack of microbial culture confirmation to advance understanding of how to move the field forward. Controversy on bowel preparation in colorectal surgery.
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Affiliation(s)
- J C Alverdy
- University of Chicago Pritzker School of Medicine, 5841 S Maryland Avenue, MC 6090, Chicago, Illinois, 60637, USA
| | - N Hyman
- University of Chicago Pritzker School of Medicine, 5841 S Maryland Avenue, MC 6090, Chicago, Illinois, 60637, USA
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Siddharthan R, Chapek M, Warren M, Martindale R. Probiotics in Prevention of Surgical Site Infections. Surg Infect (Larchmt) 2018; 19:781-784. [PMID: 30394861 DOI: 10.1089/sur.2018.231] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Despite significant improvements in peri-operative care, surgical site infections (SSIs) remain an important contributor to morbidity, cost, and death. The human gastrointestinal tract is a complex microenvironment linking host cells and the indigenous microflora or "microbiome," creating a "super-organism" that engages in macro-nutrient and micro-nutrient extraction for the host while serving as a barrier to toxins and other detrimental bacterial end-products. Maintaining a healthy microbiome in the peri-operative period may enable control of multi-drug resistance (MDR) organisms, whereas use of antibiotics simply resets the dysbiotic relation by eliminating multiple strains of bacteria. Such loss of microbial diversity or abundance can slow wound healing. Use of pro-biotics to prevent infection has been evaluated in several studies, but their utility is not yet clear. There is a clear need for randomized trials to draw firm conclusions about their efficacy and to make clinical recommendations.
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Affiliation(s)
- Ragavan Siddharthan
- Department of Surgery, Oregon Health and Science University , Portland, Oregon
| | - Michael Chapek
- Department of Surgery, Oregon Health and Science University , Portland, Oregon
| | - Malissa Warren
- Department of Surgery, Oregon Health and Science University , Portland, Oregon
| | - Robert Martindale
- Department of Surgery, Oregon Health and Science University , Portland, Oregon
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14
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Alverdy JC. Microbiome Medicine: This Changes Everything. J Am Coll Surg 2018; 226:719-729. [PMID: 29505823 PMCID: PMC5924601 DOI: 10.1016/j.jamcollsurg.2018.02.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Accepted: 02/08/2018] [Indexed: 12/13/2022]
Affiliation(s)
- John C Alverdy
- Department of Surgery, University of Chicago Pritzker School of Medicine, Chicago, IL.
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15
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Local antibiotic decontamination to prevent anastomotic leakage short-term outcome in rectal cancer surgery. Int J Colorectal Dis 2018; 33:53-60. [PMID: 29119289 DOI: 10.1007/s00384-017-2933-2] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/30/2017] [Indexed: 02/07/2023]
Abstract
PURPOSE Anastomotic leakage still presents an issue in rectal cancer surgery with rates of about 11%. As bacteria play a critical role, there is the concept of perioperative local decontamination to prevent anastomotic leakage. METHODS To ascertain the effectiveness of this treatment, we performed a retrospective analysis on 206 rectal resections with primary anastomosis and routine use of a selective decontamination of the digestive tract (SDD) regimen for local decontamination. SDD medication was administered every 8 h from the day before surgery to the seventh postoperative day. All patients were treated according to the fast-track protocol without mechanical bowel preparation; instead, a laxative was used. RESULTS Overall morbidity was 30%, overall mortality 0.5%. In our data, overall rate of anastomotic leakage (AL) was 5.8%, with 3.9% in anterior rectal resection and 6.5% in low anterior rectal resection group. In 75% of cases, anastomotic leakage was grade "C" and needed re-laparotomy. Surgical site infection rate was 19.9%. No serious adverse events were related to decontamination. CONCLUSION Local antibiotic decontamination appears to be safe and effective to decrease the rate of anastomotic leakage in rectal cancer surgery. Further focus should be on perioperative management including bowel preparation and choice of antimicrobial agents for local decontamination.
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Sind Darmbakterien an der Entstehung der Anastomoseninsuffizienz beteiligt? COLOPROCTOLOGY 2017. [DOI: 10.1007/s00053-017-0145-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
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Schardey HM, Rogers S, Schopf SK, von Ahnen T, Wirth U. Are gut bacteria associated with the development of anastomotic leaks? COLOPROCTOLOGY 2017. [DOI: 10.1007/s00053-016-0136-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Abstract
Surgery involving the gastrointestinal tract continues to prove challenging because of the persistence of unpredictable complications such as anastomotic leakage and life-threatening infections. Removal of diseased intestinal segments results in substantial catabolic stress and might require complex reconstructive surgery to maintain the functional continuity of the intestinal tract. As gastrointestinal surgery necessarily involves a breach of an epithelial barrier colonized by microorganisms, preoperative intestinal antisepsis is used to reduce infection-related complications. The current approach to intestinal antisepsis varies widely across institutions and countries with little understanding of its mechanism of action, effect on the gut microbiota and overall efficacy. Many of the current approaches to intestinal antisepsis before gastrointestinal surgery run counter to emerging concepts of intestinal microbiota contributing to immune function and recovery from injury. Here, we review evidence outlining the role of gut microbiota in recovery from gastrointestinal surgery, particularly in the development of infections and anastomotic leak. To make surgery safer and further reduce complications, a molecular, genetic and functional understanding of the response of the gastrointestinal tract to alterations in its microbiota is needed. Methods can then be developed to preserve the health-promoting functions of the microbiota while at the same time suppressing their harmful effects.
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Affiliation(s)
- Kristina Guyton
- MC-6040, Department of Surgery, University of Chicago Medicine, 5841 South Maryland Avenue, Chicago, Illinois 60637, USA
| | - John C Alverdy
- MC-6090, Department of Surgery, University of Chicago Medicine, 5841 South Maryland Avenue, Chicago, Illinois 60637, USA
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Kawada K, Sakai Y. Preoperative, intraoperative and postoperative risk factors for anastomotic leakage after laparoscopic low anterior resection with double stapling technique anastomosis. World J Gastroenterol 2016; 22:5718-5727. [PMID: 27433085 PMCID: PMC4932207 DOI: 10.3748/wjg.v22.i25.5718] [Citation(s) in RCA: 89] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2016] [Revised: 05/30/2016] [Accepted: 06/13/2016] [Indexed: 02/06/2023] Open
Abstract
Anastomotic leakage (AL) is one of the most devastating complications after rectal cancer surgery. The double stapling technique has greatly facilitated intestinal reconstruction especially for anastomosis after low anterior resection (LAR). Risk factor analyses for AL after open LAR have been widely reported. However, a few studies have analyzed the risk factors for AL after laparoscopic LAR. Laparoscopic rectal surgery provides an excellent operative field in a narrow pelvic space, and enables total mesorectal excision surgery and preservation of the autonomic nervous system with greater precision. However, rectal transection using a laparoscopic linear stapler is relatively difficult compared with open surgery because of the width and limited performance of the linear stapler. Moreover, laparoscopic LAR exhibits a different postoperative course compared with open LAR, which suggests that the risk factors for AL after laparoscopic LAR may also differ from those after open LAR. In this review, we will discuss the risk factors for AL after laparoscopic LAR.
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20
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Bosmans JWAM, Jongen ACHM, Bouvy ND, Derikx JPM. Colorectal anastomotic healing: why the biological processes that lead to anastomotic leakage should be revealed prior to conducting intervention studies. BMC Gastroenterol 2015; 15:180. [PMID: 26691961 PMCID: PMC4687306 DOI: 10.1186/s12876-015-0410-3] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2015] [Accepted: 12/10/2015] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Anastomotic leakage (AL) remains the most dreaded complication after colorectal surgery and causes high morbidity and mortality. The pathophysiology of AL remains unclear, despite numerous studies that have been conducted on animals and humans, probably due to the undetermined healing process of colorectal anastomoses. Increasing basic knowledge on this healing process may shed more light on causal factors of AL, and additionally reduce the quantity and accelerate the quality of experimental studies. In this debate article, our aim was to provide different perspectives on what is known about the colorectal healing process in relation to wound healing and AL. DISCUSSION Since knowledge on anastomotic healing is lacking, it remains difficult to conclude which factors are essential in preventing AL. This is essential information in the framework of humane animal research, where the focus should lie on Replacement, Reduction and Refinement (3Rs). While many researchers compare anastomotic healing with wound healing in the skin, there are substantial recognized differences, e.g. other collagen subtypes and different components involved. Based on our findings in literature as well as discussions with experts, we advocate stop considering anastomotic healing in the gastrointestinal tract and cutaneous healing as a similar process. Furthermore, intervention studies should at least address the anastomotic healing process in terms of histology and certain surrogate markers. Finally, the anastomotic healing process ought to be further elucidated - with modern techniques to achieve 3Rs in animal research--to provide starting points for potential interventions that can prevent AL.
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Affiliation(s)
- Joanna W A M Bosmans
- Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands. .,NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands.
| | - Audrey C H M Jongen
- Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands. .,NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands.
| | - Nicole D Bouvy
- Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands. .,NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands.
| | - Joep P M Derikx
- NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands. .,Pediatric Surgical Center Amsterdam, Emma Children's Hospital AMC/VUMC, P.O.Box 22660, 1100 DD, Amsterdam, The Netherlands.
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Krezalek MA, Umanskiy K, Hyman NH. Reoperative surgery following colorectal anastomotic leaks. SEMINARS IN COLON AND RECTAL SURGERY 2015. [DOI: 10.1053/j.scrs.2015.09.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
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