Whether rotation of a diverting loop ileostomy during rectal cancer surgery, for reducing the catastrophic effect of an anastomotic leakage, affects the incidence of small-bowel obstruction has not been fully investigated. The purpose of this study is to explore whether technical maneuvers in diverting loop ileostomy creation, including its rotation, are associated with increased incidence of small-bowel obstruction in rectal tumor surgery.
Methods
This multicenter prospective study was conducted by the Clinical Study Group of Osaka University, which comprises 24 major institutions. Patients with rectal adenocarcinoma scheduled for laparoscopic/robotic low anterior resection or intersphincteric resection with a diverting loop ileostomy were included. A total of 451 patients were prospectively enrolled between July 2015 and April 2021. The primary endpoint was the relevance of loop ileostomy rotation to the incidence of small-bowel obstruction; the secondary endpoints included the origin of the small-bowel obstruction and length of hospital stay.
Results
Small-bowel obstruction was observed in 10.8% in the nonrotated group and 12.3% in the rotated group, with no significant difference (P > .99). The only risk factor identified for small-bowel obstruction was distance from the ileocecal valve, with a significant difference in 16 patients (7.3%) with a distance of ≤30 cm and 16 patients (15.4%) in a distance of >30 cm (P = .028).
Conclusion
Rotation of the diverting loop ileostomy had no significant effect on the incidence of small-bowel obstruction.
{"title":"Influence of the rotation of the diverting loop ileostomy in rectal cancer surgery on small-bowel obstruction: A multicenter prospective study conducted by the Clinical Study Group of Osaka University, Colorectal Group","authors":"Masaaki Miyo MD, PhD , Mamoru Uemura MD, PhD , Yuki Ozato MD, PhD , Junichi Nishimura MD, PhD , Ken Nakata MD, PhD , Yozo Suzuki MD, PhD , Yoshinori Kagawa MD, PhD , Taishi Hata MD, PhD , Koji Munakata MD, PhD , Mitsuyoshi Tei MD, PhD , Genta Sawada MD, PhD , Shinichi Yoshioka MD, PhD , Yusuke Takahashi MD, PhD , Koji Oba PhD , Tsuyoshi Hata MD, PhD , Takayuki Ogino MD, PhD , Norikatsu Miyoshi MD, PhD , Hirofumi Yamamoto MD, PhD , Kohei Murata MD, PhD , Yuichiro Doki MD, PhD , Hidetoshi Eguchi MD, PhD","doi":"10.1016/j.surg.2024.09.032","DOIUrl":"10.1016/j.surg.2024.09.032","url":null,"abstract":"<div><h3>Aims</h3><div>Whether rotation of a diverting loop ileostomy during rectal cancer surgery, for reducing the catastrophic effect of an anastomotic leakage, affects the incidence of small-bowel obstruction has not been fully investigated. The purpose of this study is to explore whether technical maneuvers in diverting loop ileostomy creation, including its rotation, are associated with increased incidence of small-bowel obstruction in rectal tumor surgery.</div></div><div><h3>Methods</h3><div>This multicenter prospective study was conducted by the Clinical Study Group of Osaka University, which comprises 24 major institutions. Patients with rectal adenocarcinoma scheduled for laparoscopic/robotic low anterior resection or intersphincteric resection with a diverting loop ileostomy were included. A total of 451 patients were prospectively enrolled between July 2015 and April 2021. The primary endpoint was the relevance of loop ileostomy rotation to the incidence of small-bowel obstruction; the secondary endpoints included the origin of the small-bowel obstruction and length of hospital stay.</div></div><div><h3>Results</h3><div>Small-bowel obstruction was observed in 10.8% in the nonrotated group and 12.3% in the rotated group, with no significant difference (<em>P</em> > .99). The only risk factor identified for small-bowel obstruction was distance from the ileocecal valve, with a significant difference in 16 patients (7.3%) with a distance of ≤30 cm and 16 patients (15.4%) in a distance of >30 cm (<em>P</em> = .028).</div></div><div><h3>Conclusion</h3><div>Rotation of the diverting loop ileostomy had no significant effect on the incidence of small-bowel obstruction.</div></div>","PeriodicalId":22152,"journal":{"name":"Surgery","volume":"178 ","pages":"Article 108874"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.surg.2024.10.015
Christian T.J. Magyar MD , Luckshi Rajendran MD, MEd , Shiva Babakhani BSc , Woo Jin Choi MD, PhD , Zhihao Li MD , Roxana Bucur MD , Marco P.A.W. Claasen MD , Trevor W. Reichman MD , Chaya Shwaartz MD , Ian D. McGilvray MD , Sean P. Cleary MD, MSc, MPH , Carol-Anne E. Moulton MBBS, MEd, PhD , Stuart A. McCluskey MD, PhD , Gonzalo Sapisochin MD, PhD, MSc
Background
Postoperative acute kidney injury is associated with an increase in hospital length of stay and mortality. Intraoperative hemodynamics and fluid management may contribute to acute kidney injury. The aim of this study is to evaluate the association between intraoperative duration of hypotension with adverse events after laparoscopic liver resection.
Methods
A prospective cohort including adult patients undergoing laparoscopic liver resection between January 2010 and June 2022. Cumulative time below mean arterial blood pressure thresholds and association with major adverse events composing of postoperative acute kidney injury (≤2 days) and complications (Dindo-Clavien ≥3a) ≤30 days were assessed.
Results
In 360 patients, the median age was 61 years, 206 (57%) were male, median body mass index was 26.3, and 129 (36%) patients had hepatocellular carcinoma. Acute kidney injury was recorded in 3 (0.8%) patients as stage 1, 6 (1.7%) patients as stage 2, and 7 (1.9%) patients as stage 3. Major adverse events occurred in 31 (8.6%) patients, and the median estimated blood loss was 200 mL. On continuous analysis, a threshold <60 mmHg at ≥15 minutes was found for major adverse events. The mean arterial blood pressure <55 mmHg for ≥20 minutes was associated with an increased risk of major adverse events (odds ratio 7.72; P < .001). In patients with >15 minutes of mean arterial blood pressure <60 mmHg, higher intravenous volume was associated with increase in major adverse events (P = .045), whereas adjusted intravenous volume was not associated with major adverse events (P = .657), acute kidney injury (P = .681), or blood loss (P = .875).
Conclusions
Laparoscopic liver resection is a safe procedure with a low risk of acute kidney injury. After ≥15 minutes at mean arterial blood pressure <60 mmHg, the risk of major adverse events increases. Greater intravenous fluid infusion volume was associated with an observed risk for major adverse events, suggesting that mean arterial blood pressure should be managed by vasoactive agents.
{"title":"Impact of intraoperative hypotension during laparoscopic liver resection on postoperative complications including acute kidney injury","authors":"Christian T.J. Magyar MD , Luckshi Rajendran MD, MEd , Shiva Babakhani BSc , Woo Jin Choi MD, PhD , Zhihao Li MD , Roxana Bucur MD , Marco P.A.W. Claasen MD , Trevor W. Reichman MD , Chaya Shwaartz MD , Ian D. McGilvray MD , Sean P. Cleary MD, MSc, MPH , Carol-Anne E. Moulton MBBS, MEd, PhD , Stuart A. McCluskey MD, PhD , Gonzalo Sapisochin MD, PhD, MSc","doi":"10.1016/j.surg.2024.10.015","DOIUrl":"10.1016/j.surg.2024.10.015","url":null,"abstract":"<div><h3>Background</h3><div>Postoperative acute kidney injury is associated with an increase in hospital length of stay and mortality. Intraoperative hemodynamics and fluid management may contribute to acute kidney injury. The aim of this study is to evaluate the association between intraoperative duration of hypotension with adverse events after laparoscopic liver resection.</div></div><div><h3>Methods</h3><div>A prospective cohort including adult patients undergoing laparoscopic liver resection between January 2010 and June 2022. Cumulative time below mean arterial blood pressure thresholds and association with major adverse events composing of postoperative acute kidney injury (≤2 days) and complications (Dindo-Clavien ≥3a) ≤30 days were assessed.</div></div><div><h3>Results</h3><div>In 360 patients, the median age was 61 years, 206 (57%) were male, median body mass index was 26.3, and 129 (36%) patients had hepatocellular carcinoma. Acute kidney injury was recorded in 3 (0.8%) patients as stage 1, 6 (1.7%) patients as stage 2, and 7 (1.9%) patients as stage 3. Major adverse events occurred in 31 (8.6%) patients, and the median estimated blood loss was 200 mL. On continuous analysis, a threshold <60 mmHg at ≥15 minutes was found for major adverse events. The mean arterial blood pressure <55 mmHg for ≥20 minutes was associated with an increased risk of major adverse events (odds ratio 7.72; <em>P</em> < .001). In patients with >15 minutes of mean arterial blood pressure <60 mmHg, higher intravenous volume was associated with increase in major adverse events (<em>P</em> = .045), whereas adjusted intravenous volume was not associated with major adverse events (<em>P</em> = .657), acute kidney injury (<em>P</em> = .681), or blood loss (<em>P</em> = .875).</div></div><div><h3>Conclusions</h3><div>Laparoscopic liver resection is a safe procedure with a low risk of acute kidney injury. After ≥15 minutes at mean arterial blood pressure <60 mmHg, the risk of major adverse events increases. Greater intravenous fluid infusion volume was associated with an observed risk for major adverse events, suggesting that mean arterial blood pressure should be managed by vasoactive agents.</div></div>","PeriodicalId":22152,"journal":{"name":"Surgery","volume":"178 ","pages":"Article 108924"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The long-term survival rate of patients with pancreatic ductal adenocarcinoma has improved alongside the development of multidisciplinary treatment, and there is now demand for less invasive surgery that maintains postoperative pancreatic function. We evaluated the efficacy of pancreas-preserving distal pancreatectomy in terms of oncologic parameters and postoperative pancreatic function.
Methods
The data of 98 consecutive patients who underwent distal pancreatectomy for the treatment of pancreatic ductal adenocarcinoma between 2012 and 2022 in our institution were retrospectively analyzed. The surgical outcomes, overall survival, and postoperative pancreatic function were compared between pancreas-preserving distal pancreatectomy, in which the pancreatic stump was distal to the left margin of the portal vein on postoperative computed tomography, and conventional distal pancreatectomy.
Results
Sixteen patients (16%) underwent pancreas-preserving distal pancreatectomy. Fewer lymph nodes were dissected in the pancreas-preserving distal pancreatectomy group than the conventional distal pancreatectomy group (19 vs 31, respectively; P < .01); however, the R0 resection rate (94% vs 93%, respectively; P = 1.00), recurrence-free survival, and overall survival were similar. Similar results were obtained in an analysis limited to patients with pancreatic ductal adenocarcinoma in the pancreatic tail. Patients who underwent pancreas-preserving distal pancreatectomy were less likely to develop worsening of their diabetes than those who underwent conventional distal pancreatectomy (19% vs 39%, respectively; P = .16). Nonalcoholic fatty liver disease newly developed in 22% of the patients who underwent conventional distal pancreatectomy but in none of those who underwent pancreas-preserving distal pancreatectomy (P = .04).
Conclusion
The pancreatic transection site should be distally located to preserve postoperative pancreatic function when R0 resection can be achieved.
背景:胰腺导管腺癌患者的长期生存率随着多学科治疗的发展而提高,现在需要微创手术来维持术后胰腺功能。我们从肿瘤参数和术后胰腺功能方面评估了保留胰腺的远端胰腺切除术的疗效。方法:回顾性分析我院2012 ~ 2022年连续行胰腺远端切除术治疗胰管腺癌的98例患者资料。比较保留胰腺的远端胰腺切除术(术后计算机断层扫描显示胰腺残端位于门静脉左缘远端)和传统远端胰腺切除术的手术结果、总生存率和术后胰腺功能。结果:16例(16%)患者行远端胰腺切除术。保留胰腺的远端胰腺切除术组比传统远端胰腺切除术组清扫的淋巴结少(分别为19 vs 31;P < 0.01);然而,R0切除率分别为94%和93%;P = 1.00),无复发生存期和总生存期相似。在一项仅限于胰腺尾部胰腺导管腺癌患者的分析中也获得了类似的结果。行保留胰腺远端胰腺切除术的患者比行常规远端胰腺切除术的患者糖尿病恶化的可能性更小(分别为19% vs 39%;P = .16)。22%接受常规远端胰腺切除术的患者新发非酒精性脂肪性肝病,而没有接受保留胰腺远端胰腺切除术的患者新发非酒精性脂肪性肝病(P = 0.04)。结论:在R0切除可行的情况下,胰腺横断部位应选择远端,以保留术后胰腺功能。
{"title":"Clinical efficacy of pancreas-preserving distal pancreatectomy for the treatment of pancreatic ductal adenocarcinoma","authors":"Naoki Ikenaga MD, PhD , Kohei Nakata MD, PhD , Toshiya Abe MD, PhD , Yusuke Watanabe MD, PhD , Noboru Ideno MD, PhD , Masatoshi Murakami MD, PhD , Keijiro Ueda MD, PhD , Nao Fujimori MD, PhD , Nobuhiro Fujita MD, PhD , Kousei Ishigami MD, PhD , Yoshihiro Ogawa MD, PhD , Masafumi Nakamura MD, PhD","doi":"10.1016/j.surg.2024.108958","DOIUrl":"10.1016/j.surg.2024.108958","url":null,"abstract":"<div><h3>Background</h3><div>The long-term survival rate of patients with pancreatic ductal adenocarcinoma has improved alongside the development of multidisciplinary treatment, and there is now demand for less invasive surgery that maintains postoperative pancreatic function. We evaluated the efficacy of pancreas-preserving distal pancreatectomy in terms of oncologic parameters and postoperative pancreatic function.</div></div><div><h3>Methods</h3><div>The data of 98 consecutive patients who underwent distal pancreatectomy for the treatment of pancreatic ductal adenocarcinoma between 2012 and 2022 in our institution were retrospectively analyzed. The surgical outcomes, overall survival, and postoperative pancreatic function were compared between pancreas-preserving distal pancreatectomy, in which the pancreatic stump was distal to the left margin of the portal vein on postoperative computed tomography, and conventional distal pancreatectomy.</div></div><div><h3>Results</h3><div>Sixteen patients (16%) underwent pancreas-preserving distal pancreatectomy. Fewer lymph nodes were dissected in the pancreas-preserving distal pancreatectomy group than the conventional distal pancreatectomy group (19 vs 31, respectively; <em>P</em> < .01); however, the R0 resection rate (94% vs 93%, respectively; <em>P</em> = 1.00), recurrence-free survival, and overall survival were similar. Similar results were obtained in an analysis limited to patients with pancreatic ductal adenocarcinoma in the pancreatic tail. Patients who underwent pancreas-preserving distal pancreatectomy were less likely to develop worsening of their diabetes than those who underwent conventional distal pancreatectomy (19% vs 39%, respectively; <em>P</em> = .16). Nonalcoholic fatty liver disease newly developed in 22% of the patients who underwent conventional distal pancreatectomy but in none of those who underwent pancreas-preserving distal pancreatectomy (<em>P</em> = .04).</div></div><div><h3>Conclusion</h3><div>The pancreatic transection site should be distally located to preserve postoperative pancreatic function when R0 resection can be achieved.</div></div>","PeriodicalId":22152,"journal":{"name":"Surgery","volume":"178 ","pages":"Article 108958"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.surg.2024.10.009
Victoria Lai MD, MS
{"title":"Response to Letter to the Editor","authors":"Victoria Lai MD, MS","doi":"10.1016/j.surg.2024.10.009","DOIUrl":"10.1016/j.surg.2024.10.009","url":null,"abstract":"","PeriodicalId":22152,"journal":{"name":"Surgery","volume":"178 ","pages":"Article 108918"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
With a growing proportion of patients undergoing surgery for colorectal cancer being older adults, it is unknown whether traditional quality metrics are achieved as often compared with younger adults. This work was done with a view to understand tailoring needs of quality metrics for older adults with colorectal cancer.
Methods
This retrospective cohort study used the American College of Surgeons National Surgical Quality Improvement Program registry to identify adults (≥18 years) between 2016 and 2021 who underwent elective colorectal cancer surgery for nonmetastatic cancer. older adults was defined as adults ≥65 years. The association between older adults and attainment of consensus quality metrics were evaluated using multivariable logistic regression adjusting for patient, cancer, and treatment factors.
Results
Of 46,159 patients undergoing elective colon cancer resection, 18,592 (40.3%) were older adults. Being an older adult was independently associated with a 14% reduction in odds of harvest of ≥12 nodes and 4.3 times increase in odds of 30-day mortality. Of 9,106 patients undergoing elective rectal cancer resection 5,143 (56.5%) were older adults. Being an older adult was independently associated with a 19% reduction in odds of harvest of ≥12 nodes, 2.3 times increase in odds of 30-day mortality and a 44% reduction in odds of receiving neoadjuvant radiation. Findings were robust to sensitivity analyses of alternate methods of handling missing data and alternate analytic approaches.
Conclusion
Given unique needs of the older adult population, interpretation of disparities in quality metrics is challenging because of an inability to differentiate between patient factors, tailored care, or bias. Monitoring and reporting of quality metrics for older adults need to be re-evaluated with consideration to stratification, unique benchmarks, and older adult–specific quality metrics.
{"title":"Inequalities in quality metrics for colorectal cancer surgery in older adults: A retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program registry","authors":"Tiago Ribeiro MD, MSc , Adom Bondzi-Simpson MD, MSc , Tyler R. Chesney MD, MSc , Sami A. Chadi MD, MSc , Natalie Coburn MD, MPH , Julie Hallet MD, MSc","doi":"10.1016/j.surg.2024.09.027","DOIUrl":"10.1016/j.surg.2024.09.027","url":null,"abstract":"<div><h3>Background</h3><div>With a growing proportion of patients undergoing surgery for colorectal cancer being older adults, it is unknown whether traditional quality metrics are achieved as often compared with younger adults. This work was done with a view to understand tailoring needs of quality metrics for older adults with colorectal cancer.</div></div><div><h3>Methods</h3><div>This retrospective cohort study used the American College of Surgeons National Surgical Quality Improvement Program registry to identify adults (≥18 years) between 2016 and 2021 who underwent elective colorectal cancer surgery for nonmetastatic cancer. older adults was defined as adults ≥65 years. The association between older adults and attainment of consensus quality metrics were evaluated using multivariable logistic regression adjusting for patient, cancer, and treatment factors.</div></div><div><h3>Results</h3><div>Of 46,159 patients undergoing elective colon cancer resection, 18,592 (40.3%) were older adults. Being an older adult was independently associated with a 14% reduction in odds of harvest of ≥12 nodes and 4.3 times increase in odds of 30-day mortality. Of 9,106 patients undergoing elective rectal cancer resection 5,143 (56.5%) were older adults. Being an older adult was independently associated with a 19% reduction in odds of harvest of ≥12 nodes, 2.3 times increase in odds of 30-day mortality and a 44% reduction in odds of receiving neoadjuvant radiation. Findings were robust to sensitivity analyses of alternate methods of handling missing data and alternate analytic approaches.</div></div><div><h3>Conclusion</h3><div>Given unique needs of the older adult population, interpretation of disparities in quality metrics is challenging because of an inability to differentiate between patient factors, tailored care, or bias. Monitoring and reporting of quality metrics for older adults need to be re-evaluated with consideration to stratification, unique benchmarks, and older adult–specific quality metrics.</div></div>","PeriodicalId":22152,"journal":{"name":"Surgery","volume":"178 ","pages":"Article 108870"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.surg.2024.09.026
Ameera J.M.S. AlHasan MD, FACS , Sarah Mills MD, FRCS
{"title":"Practice makes perfect: Immersion endoscopy training in colorectal surgery focuses on quantity and quality","authors":"Ameera J.M.S. AlHasan MD, FACS , Sarah Mills MD, FRCS","doi":"10.1016/j.surg.2024.09.026","DOIUrl":"10.1016/j.surg.2024.09.026","url":null,"abstract":"","PeriodicalId":22152,"journal":{"name":"Surgery","volume":"178 ","pages":"Article 108869"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Letter to the editor: Routine use of robotics in cholecystectomy: Another brick in the wall","authors":"Dimitrios Moris MD, PhD, Piyush Gupta MD, Pejman Radkani MD, MSPH, FACS","doi":"10.1016/j.surg.2024.09.045","DOIUrl":"10.1016/j.surg.2024.09.045","url":null,"abstract":"","PeriodicalId":22152,"journal":{"name":"Surgery","volume":"178 ","pages":"Article 108906"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.surg.2024.09.043
Giulia Becherucci MD , Cesare Ruffolo MD, PhD , Melania Scarpa MS, PhD , Federico Scognamiglio MS , Astghik Stepanyan MS , Isacco Maretto MD , Andromachi Kotsafti MS, PhD , Ottavia De Simoni MD , Pierluigi Pilati MD , Boris Franzato MD , Antonio Scapinello MD , Francesca Bergamo MD , Marco Massani MD , Tommaso Stecca MD , Anna Pozza MD , Ivana Cataldo MD , Stefano Brignola MD , Valerio Pellegrini MD , Matteo Fassan MD , Vincenza Guzzardo MS , Marco Scarpa MD, PhD
Background
Transanal excision of rectal cancer can be considered the definitive surgical treatment if the depth spread is T1 or lower, and the lesion is completely included within the resection margin. This study aims to analyze the immune microenvironment in healthy rectal mucosa as a possible predictor of tumor infiltration depth, lateral tumor spread, and recurrence of rectal cancer after transanal local excision.
Methods
This study is a subanalysis of data from the IMMUNOREACT 1 and 2 trials (NCT04915326 and NCT04917263, respectively) including all the patients who underwent transanal excision of rectal cancer. This multicentric study collected healthy mucosa surrounding the neoplasms of patients with rectal cancer. A panel of immune markers was investigated at immunohistochemistry: CD3, CD4, CD8, CD8β, Tbet, FoxP3, PD-L1, MSH6, and PMS2 and CD80. Flow cytometry determined the proportion of epithelial cells expressing CD80, CD86, CD40, HLA ABC or HLA DR and the proportion of activated CD8+ T cells, CD4+ Th1 cells, and Treg.
Results
Receiver operating characteristic curve analysis for predicting deep tumor spread showed an area under the curve of 0.70 (95% confidence interval: 0.60–0.80) for CD25+FoxP3+ cell rate and 0.74 (95% confidence interval: 0.53–0.92) for CK+CD86+ cell rate. Receiver operating characteristic curve analysis for predicting lateral tumor spread showed an area under the curve of 0.82 (95% confidence interval: 0.61–0.99) for CD8+CD38+ MFI, 0.96 (95% confidence interval: 0.85–0.99) for CD8β infiltration, and 0.97 (95% confidence interval: 0.87–0.99) for CK+HLAabc+ cell rate. Receiver operating characteristic curve analysis for predicting recurrence showed an area under the curve of 0.93 (95% confidence interval: 0.76–0.99) for CD8+CD38+ MFI and 0.94 (95% confidence interval: 0.78–0.99) for CD8+CD28+ MFI. Low CD8+CD38+ MFI and low CD8+CD28+ MFI were associated with shorter disease-free survival (P = .025 and P = .021, respectively).
Conclusion
Our study showed that the association between the high proportion of epithelial cells acting as presenting cells and deep or lateral tumor spread may be explained by the presence of a greater tumor load at the site. Moreover, it showed that weak activation of CD8+ T cells within the rectal mucosa is associated with lateral tumor spread and eventually a higher recurrence rate. The mucosal level of CD8β infiltration detected at immunohistochemistry might be tested as a marker of lateral tumor spread and potentially translated into clinical practice.
{"title":"IMMUNOREACT 8: Immune markers of local tumor spread in patients undergoing transanal excision for clinically N0 rectal cancer","authors":"Giulia Becherucci MD , Cesare Ruffolo MD, PhD , Melania Scarpa MS, PhD , Federico Scognamiglio MS , Astghik Stepanyan MS , Isacco Maretto MD , Andromachi Kotsafti MS, PhD , Ottavia De Simoni MD , Pierluigi Pilati MD , Boris Franzato MD , Antonio Scapinello MD , Francesca Bergamo MD , Marco Massani MD , Tommaso Stecca MD , Anna Pozza MD , Ivana Cataldo MD , Stefano Brignola MD , Valerio Pellegrini MD , Matteo Fassan MD , Vincenza Guzzardo MS , Marco Scarpa MD, PhD","doi":"10.1016/j.surg.2024.09.043","DOIUrl":"10.1016/j.surg.2024.09.043","url":null,"abstract":"<div><h3>Background</h3><div>Transanal excision of rectal cancer can be considered the definitive surgical treatment if the depth spread is T1 or lower, and the lesion is completely included within the resection margin. This study aims to analyze the immune microenvironment in healthy rectal mucosa as a possible predictor of tumor infiltration depth, lateral tumor spread, and recurrence of rectal cancer after transanal local excision.</div></div><div><h3>Methods</h3><div>This study is a subanalysis of data from the IMMUNOREACT 1 and 2 trials (NCT04915326 and NCT04917263, respectively) including all the patients who underwent transanal excision of rectal cancer. This multicentric study collected healthy mucosa surrounding the neoplasms of patients with rectal cancer. A panel of immune markers was investigated at immunohistochemistry: CD3, CD4, CD8, CD8β, Tbet, FoxP3, PD-L1, MSH6, and PMS2 and CD80. Flow cytometry determined the proportion of epithelial cells expressing CD80, CD86, CD40, HLA ABC or HLA DR and the proportion of activated CD8+ T cells, CD4+ Th1 cells, and Treg.</div></div><div><h3>Results</h3><div>Receiver operating characteristic curve analysis for predicting deep tumor spread showed an area under the curve of 0.70 (95% confidence interval: 0.60–0.80) for CD25+FoxP3+ cell rate and 0.74 (95% confidence interval: 0.53–0.92) for CK+CD86+ cell rate. Receiver operating characteristic curve analysis for predicting lateral tumor spread showed an area under the curve of 0.82 (95% confidence interval: 0.61–0.99) for CD8+CD38+ MFI, 0.96 (95% confidence interval: 0.85–0.99) for CD8β infiltration, and 0.97 (95% confidence interval: 0.87–0.99) for CK+HLAabc+ cell rate. Receiver operating characteristic curve analysis for predicting recurrence showed an area under the curve of 0.93 (95% confidence interval: 0.76–0.99) for CD8+CD38+ MFI and 0.94 (95% confidence interval: 0.78–0.99) for CD8+CD28+ MFI. Low CD8+CD38+ MFI and low CD8+CD28+ MFI were associated with shorter disease-free survival (<em>P</em> = .025 and <em>P</em> = .021, respectively).</div></div><div><h3>Conclusion</h3><div>Our study showed that the association between the high proportion of epithelial cells acting as presenting cells and deep or lateral tumor spread may be explained by the presence of a greater tumor load at the site. Moreover, it showed that weak activation of CD8+ T cells within the rectal mucosa is associated with lateral tumor spread and eventually a higher recurrence rate. The mucosal level of CD8β infiltration detected at immunohistochemistry might be tested as a marker of lateral tumor spread and potentially translated into clinical practice.</div></div>","PeriodicalId":22152,"journal":{"name":"Surgery","volume":"178 ","pages":"Article 108902"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.surg.2024.10.017
Zhijie Xu PhD, MD , Yunfei Wu MD , Yanfeng Bai PhD, MD , Xiaoyi Chen PhD, MD , Guanghou Fu MD , Baiye Jin PhD, MD
<div><h3>Background</h3><div>Muscle-invasive bladder cancer continues to lack reliable diagnostic and prognostic biomarkers. Recently, tumor vaccines targeting specific molecules have emerged as a promising treatment in inhibiting tumor progression, which was rekindled under the background of coronavirus disease-2019 pandemic. However, the application of mRNA vaccine targeting muscle-invasive bladder cancer–specific antigens remains limited, and there has been a lack of comprehensive studies or validations to identify suitable patient subgroups for vaccination. This study aims to explore novel muscle-invasive bladder cancer antigen signatures to identify patients most likely to benefit from vaccination.</div></div><div><h3>Methods</h3><div>Gene expression profiles of muscle-invasive bladder cancer samples, along with corresponding clinical data, were retrieved from the Cancer Genome Atlas Program. The least absolute shrinkage and selection operator model was applied to develop signatures for stratifying muscle-invasive bladder cancer patients. Prognostic accuracy of each factor was assessed using receiver operating characteristic analysis. Tumor Immune Estimation Resource was employed to visualize the relationship between the proportion of antigen-presenting cells and the expression of selected genes. The CIBERSORT and WGCNA R packages were used to identify differences in immune infiltration levels across muscle-invasive bladder cancer subgroups. Additionally, the STRING database and Cytoscape were used to construct the protein-protein interaction network. CCK-8 and colony formation assays were employed in invitro experiments.</div></div><div><h3>Results</h3><div>A total of 49 potential tumor antigens were identified. Using least absolute shrinkage and selection operator Cox regression, 14 tumor antigens were selected to develop a risk evaluation signature. The risk score signature can serve as a valuable tool for predicting the outcomes of muscle-invasive bladder cancer patients. Based on differential clinical, molecular, and immune-related gene profiles, muscle-invasive bladder cancer patients were classified into 2 subtypes: the immune “cold” subtype (immune score 1) and the immune “hot” subtype (immune score 2). The immune score signature, developed using a logistic score model, effectively distinguishes between patients more likely to belong to immune score 1 or 2. Notably, patients with a high risk score exhibited a higher proportion of immune score 2 compared to those with a low risk score. Additionally, the prognostic accuracy was significantly enhanced when the risk score and immune score were combined. Different tumor subtypes displayed distinct immune landscapes and signaling pathways. Moreover, novel tumor antigens associated with oxidative stress were identified.</div></div><div><h3>Conclusion</h3><div>The risk score and immune score signatures based on tumor antigens have identified potential effective neo-antigens for the developme
{"title":"Identification of tumor-antigen signatures and immune subtypes for mRNA vaccine selection in muscle-invasive bladder cancer","authors":"Zhijie Xu PhD, MD , Yunfei Wu MD , Yanfeng Bai PhD, MD , Xiaoyi Chen PhD, MD , Guanghou Fu MD , Baiye Jin PhD, MD","doi":"10.1016/j.surg.2024.10.017","DOIUrl":"10.1016/j.surg.2024.10.017","url":null,"abstract":"<div><h3>Background</h3><div>Muscle-invasive bladder cancer continues to lack reliable diagnostic and prognostic biomarkers. Recently, tumor vaccines targeting specific molecules have emerged as a promising treatment in inhibiting tumor progression, which was rekindled under the background of coronavirus disease-2019 pandemic. However, the application of mRNA vaccine targeting muscle-invasive bladder cancer–specific antigens remains limited, and there has been a lack of comprehensive studies or validations to identify suitable patient subgroups for vaccination. This study aims to explore novel muscle-invasive bladder cancer antigen signatures to identify patients most likely to benefit from vaccination.</div></div><div><h3>Methods</h3><div>Gene expression profiles of muscle-invasive bladder cancer samples, along with corresponding clinical data, were retrieved from the Cancer Genome Atlas Program. The least absolute shrinkage and selection operator model was applied to develop signatures for stratifying muscle-invasive bladder cancer patients. Prognostic accuracy of each factor was assessed using receiver operating characteristic analysis. Tumor Immune Estimation Resource was employed to visualize the relationship between the proportion of antigen-presenting cells and the expression of selected genes. The CIBERSORT and WGCNA R packages were used to identify differences in immune infiltration levels across muscle-invasive bladder cancer subgroups. Additionally, the STRING database and Cytoscape were used to construct the protein-protein interaction network. CCK-8 and colony formation assays were employed in invitro experiments.</div></div><div><h3>Results</h3><div>A total of 49 potential tumor antigens were identified. Using least absolute shrinkage and selection operator Cox regression, 14 tumor antigens were selected to develop a risk evaluation signature. The risk score signature can serve as a valuable tool for predicting the outcomes of muscle-invasive bladder cancer patients. Based on differential clinical, molecular, and immune-related gene profiles, muscle-invasive bladder cancer patients were classified into 2 subtypes: the immune “cold” subtype (immune score 1) and the immune “hot” subtype (immune score 2). The immune score signature, developed using a logistic score model, effectively distinguishes between patients more likely to belong to immune score 1 or 2. Notably, patients with a high risk score exhibited a higher proportion of immune score 2 compared to those with a low risk score. Additionally, the prognostic accuracy was significantly enhanced when the risk score and immune score were combined. Different tumor subtypes displayed distinct immune landscapes and signaling pathways. Moreover, novel tumor antigens associated with oxidative stress were identified.</div></div><div><h3>Conclusion</h3><div>The risk score and immune score signatures based on tumor antigens have identified potential effective neo-antigens for the developme","PeriodicalId":22152,"journal":{"name":"Surgery","volume":"178 ","pages":"Article 108926"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}