Radiofrequency Combined with Intratumoral Immunotherapy: Preclinical Results and Safety in Metastatic Colorectal Carcinoma.

Radiofrequency ablation (RFA) of cancer induces an anti-tumor immunity, which is insufficient to prevent recurrences. In mice, RFA-intratumoral immunotherapy by granulocyte-macrophage colony-stimulating factor (GM-CSF) and Bacillus Calmette-Guerin resulted in complete metastases regression. Infectious risk in human needs replacement of live vaccines. Intratumoral purified protein derivatives (PPD) have never been tested in digestive cancers, and the safety of intratumoral immunotherapy after RFA has not yet been validated in human models. We investigated the therapeutic efficacy of combined radiofrequency ablation (RFA) and intratumoral immunotherapy (ITI) using an immune-muco-adherent thermogel (IMT) in a mouse model of metastatic colorectal cancer (CRC) and the safety of this approach in a pig model. Intratumoral stability of the immunogel was assessed using magnetic resonance imaging (MRI) and bioluminescent imaging. Seventy-four CT26 tumor-bearing female BALB/c mice were treated with RFA either alone or in combination with intratumoral IMT. Regression of distant metastasis and survival were monitored for 60 days. Six pigs that received liver radiofrequency and intralesional IMT injections were followed for 15 days. Experimental gel embolisms were treated using an intravascular approach. Pertinent rheology of IMT was confirmed in tumors, by the signal stability during 3 days in MRI and 7 days in bioluminescence imaging. In mice, the abscopal effect of RFA-intratumoral immunotherapy resulted in regression of distant lesions completed at day 16 vs. a volume of 350 ± 99.3 mm3 in the RFA group at day 25 and a 10-fold survival rate at 60 days. In pigs, injection of immunogel in the liver RFA area was safe after volume adjustment without clinical, hematological, and liver biology disorder. Flow cytometry showed an early increase in CD3 TCRγδ+T cells at D7 (p < 0.05) and a late decrease in CD29+-CD8 T cells at D15 (p < 0.05), reflecting the inflammation status changes. Systemic GM-CSF release was not detectable. Experimental caval and pulmonary thermogel embolisms were treated by percutaneous catheterism and cold serum infusion. RFA-intratumoral immunotherapy as efficient and safe mini-invasive interventional oncology is able to improve ablative treatment of colorectal liver metastases.

Pathogenic alterations in PIK3CA and KMT2C are frequent and independent prognostic factors in anal squamous cell carcinoma treated with salvage abdominoperineal resection.

The management of anal squamous cell carcinoma (ASCC) has yet to experience the transformative impact of precision medicine. Conducting genomic analyses may uncover novel prognostic biomarkers and offer potential directions for the development of targeted therapies. To that end, we assessed the prognostic and theragnostic implications of pathogenic variants identified in 571 cancer-related genes from surgical samples collected from a homogeneous, multicentric French cohort of 158 ASCC patients who underwent abdominoperineal resection treatment. Alterations in PI3K/AKT/mTOR, chromatin remodeling, and Notch pathways were frequent in HPV-positive tumors, while HPV-negative tumors often harbored variants in cell cycle regulation and genome integrity maintenance genes (e.g., frequent TP53 and TERT promoter mutations). In patients with HPV-positive tumors, KMT2C and PIK3CA exon 9/20 pathogenic variants were associated with worse overall survival in multivariate analysis (Hazard ratio (HR)KMT2C = 2.54, 95%CI = [1.25,5.17], P value = .010; HRPIK3CA = 2.43, 95%CI = [1.3,4.56], P value = .006). Alterations with theragnostic value in another cancer type was detected in 43% of patients. These results suggest that PIK3CA and KMT2C pathogenic variants are independent prognostic factors in patients with ASCC with HPV-positive tumors treated by abdominoperineal resection. And, importantly, the high prevalence of alterations bearing potential theragnostic value strongly supports the use of genomic profiling to allow patient enrollment in precision medicine clinical trials.

Contemporary Outcomes for the Curative Treatment of Colorectal Cancer Pulmonary Metastases.

PURPOSE: Treatment of pulmonary metastases (PM) from colorectal cancer (CRC) is the standard of care by several guidelines from Europe and the USA, but the validity of this strategy has been recently questioned, and the available evidence supporting this strategy is weak. We report the outcomes of a curative intent strategy in a very recent and homogenous series of patients. METHODS: We did a retrospective review of all curative intent surgical or ablative treatment of PM from CRC performed consecutively in 3 French institutions from January 2015 to December 2019. Demographics, clinicopathological, and molecular characteristics were evaluated. Cox regression models were used to identify prognostic factors related to local recurrence and disease-free survival. RESULTS: Records from 152 patients were reviewed. One-hundred thirty-five patients (88%) had surgical metastasectomy. Median age was 67 years. Most of the patients had a single lesion (66%), and 16% had synchronous PM. Eighty-one patients (53%) experienced recurrence, and the thorax was the most common site of recurrence. Median disease-free survival and overall survival were 35 months and 78 months after PM treatment. At the end of the study, only 17% of the patients died. Pulmonary tumor burden was correlated with disease-free survival in univariate analysis, but multivariate analysis did not find any prognostic factor independently associated with local recurrence or survival. CONCLUSION: Our finds corroborate existing recommendation for the invasive treatment of PM from CRC in selected patients.

Rational testing for gene fusion in colorectal cancer: MSI and RAS-BRAF wild-type metastatic colorectal cancer as target population for systematic screening.

Gene fusions provide access to new therapeutic opportunities for patients treated for a colorectal cancer (CRC). However, they do not excess 1% of patients. A better identification of patients in whom gene fusions are highly prevalent is a major issue in a therapeutic and medico-economics perspective. This study assesses the rates of gene fusions in CRC patients with MSI/RAS-BRAFWT in our routine practice detected with a commercially available NGS-based fusion panel. Among the 130 MSI CRC tumors, 43 (33%) were KRAS-NRAS-BRAFWT. A gene fusion was detected in 7 (25.9%) of the 27 MSI/RAS-BRAFWT samples, which had RNA suitable for analysis after quality control. These fusions involved mainly NTRK1/3 (n = 5), as well as ALK (n = 1) and BRAF (n = 1). In the present study, we confirm that patients with MSI/RAS-BRAFWT CRCs represent a subpopulation in which targetable gene fusions are overrepresented. Our results support the use of a two-step algorithm for molecular screening, in which metastatic CRC patients would have routine MSI and RAS/BRAF testing, and then only those with MSI/RAS-BRAFWT would be screened with dedicated NGS RNA panel for gene fusions.

Incidence and risk factors for Chyle leak after pancreatic surgery for cancer: A comprehensive systematic review.

BACKGROUND: Chyle leak (CL) is a clinically relevant complication after pancreatectomy. Its incidence and the associated risk factors are ill defined, and various treatments options have been described. There is no consensus, however, regarding optimal management. The present study aims to systematically review the literature on CL after pancreatectomy. METHODS: A systematic review from PubMed, Scopus and Embase database was performed. Studies using a clear definition for CL and published from January 2000 to January 2021 were included. The PRISMA guidelines were followed during all stages of this systematic review. The MINORS score was used to assess methodological quality. RESULTS: Literature search found 361 reports, 99 of which were duplicates. The titles and abstracts of 262 articles were finally screened. The references from the remaining 181 articles were manually assessed. After the exclusions, 43 articles were thoroughly assessed. A total of 23 articles were ultimately included for this review. The number of patients varied from 54 to 3532. Incidence of post pancreatectomy CL varied from 1.3% to 22.1%. Main risk factors were the extent of the surgery and early oral or enteral feeding. CL dried up spontaneously or after conservative management within 14 days in 53% to 100% of the cases. CONCLUSIONS: The extent of surgery is the most common predictor of risk of CL. Conservative treatment has been shown to be effective in most cases and can be considered the treatment of choice. We propose a management algorithm based on the current available evidence.

Safeness of Simultaneous Colonic Resection and Hepatic Radiofrequency Ablation.

Background and Objectives: Previous reports showed an increased risk of infectious complications when liver radiofrequency ablation (RFA) is performed simultaneously to colorectal resection. The aim of this study was to compare early and long-term outcomes of simultaneous versus staged strategy. Methods: Data from colorectal cancer liver metastases consecutively treated by surgery of the primary tumor with an associated liver RFA procedure between January 1, 2010 and January 31, 2020. Patients were divided into two groups: RFA performed during colorectal surgery (simultaneous) or in a different moment (staged). Patients were manually matched (1:1) to minimize influence of known covariates. Results: Seventy-two patients were included. After matching, there was no difference between the two groups in morbidity or mortality. Hospital stay was 2 days shorter in the simultaneous group. Conclusions: Early or long-term outcomes were identical between the two strategies. The simultaneous strategy was associated with a shorter duration of hospitalization although not significant. Simultaneous colorectal resection and liver RFA is safe and must be included in surgeons' armamentarium.

Five-Year Survival Outcomes of Hybrid Minimally Invasive Esophagectomy in Esophageal Cancer: Results of the MIRO Randomized Clinical Trial.

Importance: Available data comparing the long-term results of hybrid minimally invasive esophagectomy (HMIE) with that of open esophagectomy are conflicting, with similar or even better results reported for the minimally invasive esophagectomy group. Objective: To evaluate the long-term, 5-year outcomes of HMIE vs open esophagectomy, including overall survival (OS), disease-free survival (DFS), and pattern of disease recurrence, and the potential risk factors associated with these outcomes. Design, Setting, and Participants: This randomized clinical trial is a post hoc follow-up study that analyzes the results of the open-label Multicentre Randomized Controlled Phase III Trial, which enrolled patients from 13 different centers in France and was conducted from October 26, 2009, to April 4, 2012. Eligible patients were 18 to 75 years of age and were diagnosed with resectable cancer of the middle or lower third of the esophagus. After exclusions, patients were randomized to either the HMIE group or the open esophagectomy group. Data analysis was performed on an intention-to-treat basis from November 19, 2019, to December 4, 2020. Interventions: Hybrid minimally invasive esophagectomy (laparoscopic gastric mobilization with open right thoracotomy) was compared with open esophagectomy. Main Outcomes and Measures: The primary end points of this follow-up study were 5-year OS and DFS. The secondary end points were the site of disease recurrence and potential risk factors associated with DFS and OS. Results: A total of 207 patients were randomized, of whom 175 were men (85%), and the median (range) age was 61 (23-78) years. The median follow-up duration was 58.2 (95% CI, 56.5-63.8) months. The 5-year OS was 59% (95% CI, 48%-68%) in the HMIE group and 47% (95% CI, 37%-57%) in the open esophagectomy group (hazard ratio [HR], 0.71; 95% CI, 0.48-1.06). The 5-year DFS was 52% (95% CI, 42%-61%) in the HMIE group vs 44% (95% CI, 34%-53%) in the open esophagectomy group (HR, 0.81; 95% CI, 0.55-1.17). No statistically significant difference in recurrence rate or location was found between groups. In a multivariable analysis, major intraoperative and postoperative complications (HR, 2.21; 95% CI, 1.41-3.45; P < .001) and major pulmonary complications (HR, 1.94; 95% CI, 1.21-3.10; P = .005) were identified as risk factors associated with decreased OS. Similarly, multivariable analysis of DFS identified overall intraoperative and postoperative complications (HR, 1.93; 95% CI, 1.28-2.90; P = .002) and major pulmonary complications (HR, 1.85; 95% CI, 1.19-2.86; P = .006) as risk factors. Conclusions and Relevance: This study found no difference in long-term survival between the HMIE and open esophagectomy groups. Major postoperative overall complications and pulmonary complications appeared to be independent risk factors in decreased OS and DFS, providing additional evidence that HMIE may be associated with improved oncological results compared with open esophagectomy primarily because of a reduction in postoperative complications. Trial Registration: ClinicalTrials.gov Identifier: NCT00937456.

Nutrition and physical activity: French intergroup clinical practice guidelines for diagnosis, treatment and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, AFC, SFP-APA, SFNCM, AFSOS).

This document is a summary of the French intergroup guidelines regarding the nutrition and physical activity (PA) management in digestive oncology. This collaborative work was produced under the auspices of all French medical and surgical societies involved in digestive oncology, nutrition and supportive care. It is based on published guidelines, recent literature review and expert opinions. Recommendations are graded according to the level of evidence. Malnutrition affects more than half of patients with digestive cancers and is often underdiagnosed. It has multiple negative consequences on survival, quality of life and risk of treatment complications. Consequently, in addition to anticancer treatments, supportive care including nutritional support and PA plays a central role in the management of digestive cancers. It is crucial to detect malnutrition (diagnostic criteria updated in 2019) early, to prevent it and to act against it at all stages of the cancer and at all times of the care pathway. In this context, we proposed recommendations for the evaluation and management in nutrition and PA in digestive oncology for each stage of the disease (perioperative setting, during radiation therapy, during systemic treatments, at the palliative phase, after cancer). Guidelines for nutrition and PA management aim at increasing awareness about malnutrition in oncology. They are continuously evolving and need to be regularly updated.

Nutrition and physical activity professional education in gastrointestinal oncology: a national multidisciplinary survey.

OBJECTIVES: Sarcopenia, present in more than 50% of digestive oncology patients, has a negative impact on clinical outcomes. Nutrition and adapted physical activity are two major interventions for the management of sarcopenia. However, young hepato-gastroenterologists, oncologists and surgeons in France have limited awareness on these topics. We aimed to evaluate the need for training programmes of physicians (residents and senior doctors) involved in digestive oncology on nutrition and adapted physical activity. METHODS: A 42-question survey was developed, by a working group of clinicians, dieticians and adapted physical activity teachers, to assess five areas related to demographics of respondents, nutrition practices, nutrition training, adapted physical activity practices and adapted physical activity training. The national survey was undertaken between April and July of 2019. RESULTS: 230 physicians participated in the survey; 34% were hepato-gastroenterologists, 31% were oncologists, 23% were surgeons and 40% were residents. Sixty-one per cent of participants had received training in nutrition and only 21% in adapted physical activity. Ninety per cent of the physicians expressed their desire for more effective training on these two topics. Disparities in clinical practices were observed between hepato-gastroenterologists, oncologists and surgeons. CONCLUSIONS: More initial and continuing training on nutrition and adapted physical activity is needed for French physicians in the current digestive oncology clinical practice.

Right Colectomy with Absorbable Mesh Repair as a Salvage Solution for the Management of Giant Incisional Hernia with Loss of Domain: Results of a Bicentric Study.

BACKGROUND: Incisional hernia (IH) may occur in 20% of patients after laparotomy. The hernia sac volume may be of significance, with reintegration of visceral contents potentially leading to repair failure or abdominal compartment syndrome. The present study aimed to evaluate a two-step surgical strategy comprising right colectomy for hernia reduction with synchronous absorbable mesh repair followed by definitive non-absorbable mesh repair in recurrence. METHODS: Patients operated between 2012 and 2017 at two university centers were retrospectively included. Volumetric evaluation of the IH was performed by CT imaging. RESULTS: Eleven patients were included. The mean BMI was 43 kg/m2 (23-52 kg/m2). Progressive preoperative pneumoperitoneum was performed in 82% of patients, with complications in 22%. The mean volumetric ratio of the volume of the hernia to the volume of the abdominal cavity was 70% (48-100%). The first parietal repair was performed using an synthetic absorbable mesh (36%), a biologic mesh (27%), or a slowly absorbable mesh (36%). No patients died as a result of the procedure. Seven (64%) patients developed grade III-IV complications, including one case of an anastomotic fistula. Recurrence occurred in eight (73%) patients after the first repair. Of these, four (50%) patients were reoperated using a non-absorbable mesh, leading to solid repair in 75% of cases. After 27 ± 18 months of follow-up, the residual IH rate was 46%. CONCLUSIONS: Right colectomy for volume reduction in IH with loss of domain potentially represents an appropriate salvage option, supporting bowel reintegration and temporary hernia repair with absorbable material.

Health-related Quality of Life Following Hybrid Minimally Invasive Versus Open Esophagectomy for Patients With Esophageal Cancer, Analysis of a Multicenter, Open-label, Randomized Phase III Controlled Trial: The MIRO Trial.

BACKGROUND: Hybrid minimally invasive esophagectomy (HMIE) has been shown to reduce major postoperative complications compared with open esophagectomy (OE) for esophageal cancer. OBJECTIVES: The aim of this study was to compare short- and long-term health-related quality of life (HRQOL) following HMIE and OE within a randomized controlled trial. METHODS: We performed a multicenter, open-label, randomized controlled trial at 13 study centers between 2009 and 2012. Patients aged 18 to 75 years with resectable cancers of the middle or lower third of the esophagus were randomized to undergo either transthoracic OE or HMIE. Patients were followed-up every 6 months for 3 years postoperatively and global health assessed with EORTC-QLQC30 and esophageal symptoms assessed with EORTC-OES18. RESULTS: The short-term reduction in global HRQOL at 30 days specifically role functioning [-33.33 (HMIE) vs -46.3 (OE); P = 0.0407] and social functioning [-16.88 (HMIE) vs -35.74 (OE); P = 0.0003] was less substantial in the HMIE group. At 2 years, social functioning had improved following HMIE to beyond baseline (+5.37) but remained reduced in the OE group (-8.33) (P = 0.0303). At 2 years, increases in pain were similarly reduced in the HMIE compared with the OE group [+6.94 (HMIE) vs +14.05 (OE); P = 0.018]. Postoperative complications in multivariate analysis were associated with role functioning, pain, and dysphagia. CONCLUSIONS: Esophagectomy has substantial effects upon short-term HRQOL. These effects for some specific parameters are, however, reduced with HMIE, with persistent differences up to 2 years, and maybe mediated by a reduction in postoperative complications.

Multicenter phase III randomized trial comparing laparoscopy and laparotomy for colon cancer surgery in patients older than 75 years: the CELL study, a Fédération de Recherche en Chirurgie (FRENCH) trial.

BACKGROUND: Several multicenter randomized controlled trials comparing laparoscopy and conventional open surgery for colon cancer have demonstrated that laparoscopic approach achieved the same oncological results while improving significantly early postoperative outcomes. These trials included few elderly patients, with a median age not exceeding 71 years. However, colon cancer is a disease of the elderly. More than 65% of patients operated on for colon cancer belong to this age group, and this proportion may become more pronounced in the coming years. In current practice, laparoscopy is underused in this population. METHODS: The CELL (Colectomy for cancer in the Elderly by Laparoscopy or Laparotomy) trial is a multicenter, open-label randomized, 2-arm phase III superiority trial. Patients aged 75 years or older with uncomplicated colonic adenocarcinoma or endoscopically unresectable colonic polyp will be randomized to either colectomy by laparoscopy or laparotomy. The primary endpoint of the study is overall postoperative morbidity, defined as any complication classification occurring up to 30 days after surgery. The secondary endpoints are: 30-day and 90-day postoperative mortality, 30-day readmission rate, quality of surgical resection, health-related quality of life and evolution of geriatric assessment. A 35 to 20% overall postoperative morbidity rate reduction is expected for patients operated on by laparoscopy compared with those who underwent surgery by laparotomy. With a two-sided α risk of 5% and a power of 80% (ß = 0.20), 276 patients will be required in total. DISCUSSION: To date, no dedicated randomized controlled trial has been conducted to evaluate morbidity after colon cancer surgery by laparoscopy or laparotomy in the elderly and the benefits of laparoscopy is still debated in this context. Thus, a prospective multicenter randomized trial evaluating postoperative outcomes specifically in elderly patients operated on for colon cancer by laparoscopy or laparotomy with curative intent is warranted. If significant, such a study might change the current surgical practices and allow a significant improvement in the surgical management of this population, which will be the vast majority of patients treated for colon cancer in the coming years. TRIAL REGISTRATION: ClinicalTrials.gov NCT03033719 (January 27, 2017).

Does A Longer Waiting Period After Neoadjuvant Radio-chemotherapy Improve the Oncological Prognosis of Rectal Cancer?: Three Years' Follow-up Results of the Greccar-6 Randomized Multicenter Trial.

OBJECTIVE: The aim of this study was to report the 3-year survival results of the GRECCAR-6 trial. SUMMARY BACKGROUND DATA: Current data on the effect of an extended interval between radiochemotherapy (RCT) and resection for rectal cancer on the rate of complete pathological response (pCR = ypT0N0) is controversial. Furthermore, its effect on oncological outcomes is unknown. METHODS: The GRECCAR-6 trial was a phase III, multicenter, randomized, open-label, parallel-group, controlled trial. Patients with cT3/T4 or TxN+ tumors of the mid or lower rectum who had received RCT (45-50 Gy with 5-fluorouracil or capecitabine) were included and randomized into a 7- or 11-week waiting period. Primary endpoint was the pCR rate. Secondary endpoints were 3-year overall (OS), disease-free survival (DFS), and recurrence rates. RESULTS: A total of 265 patients from 24 participating centers were enrolled. A total of 253 patients underwent a mesorectal excision. Overall pCR rate was 17% (43/253). Mean follow-up from surgical resection was 32 ±â€Š8 months. Twenty-four deaths occurred with an 89% OS at 3 years. DFS was 68.7% at 3 years (75 recurrences). Three-year local and distant recurrences were 7.9% and 23.8%, respectively. The randomization group had no impact on the 3-year OS (P = 0.8868) or DFS (P = 0.9409). Distant (P = 0.7432) and local (P = 0.3944) recurrences were also not influenced by the waiting period. DFS was independently influenced by 3 factors: circumferential radial margin (CRM) ≤1 mm [hazard ratio (HR) = 2.03; 95% confidence interval (CI), 1.17-3.51], ypT3-T4 (HR = 2.69; 95% CI, 1.19-6.08) and positive lymph nodes (HR = 3.62; 95% CI, 1.89-6.91). CONCLUSION: Extending the waiting period by 4 weeks following RCT has no influence on the oncological outcomes of T3/T4 rectal cancers.

Can we classify ampullary tumours better? Clinical, pathological and molecular features. Results of an AGEO study.

BACKGROUND: Ampullary adenocarcinoma (AA) originates from either intestinal (INT) or pancreaticobiliary (PB) epithelium. Different prognostic factors of recurrence have been identified in previous studies. METHODS: In 91 AA patients of the AGEO retrospective multicentre cohort, we evaluated the centrally reviewed morphological classification, panel markers of Ang et al. including CK7, CK20, MUC1, MUC2 and CDX2, the 50-gene panel mutational analysis, and the clinicopathological AGEO prognostic score. RESULTS: Forty-three (47%) of the 91 tumours were Ang-INT, 29 (32%) were Ang-PB, 18 (20%) were ambiguous (Ang-AMB) and one could not be classified. Among these 90 tumours, 68.7% of INT tumours were Ang-INT and 78.2% of PB tumours were Ang-PB. MUC5AC expression was detected in 32.5% of the 86 evaluable cases. Among 71 tumours, KRAS, TP53, APC and PIK3CA were the most frequently mutated genes. The KRAS mutation was significantly more frequent in the PB subtype. In multivariate analysis, only AGEO prognostic score and tumour subtype were associated with relapse-free survival. Only AGEO prognostic score was associated with overall survival. CONCLUSIONS: Mutational analysis and MUC5AC expression provide no additional value in the prognostic evaluation of AA patients. Ang et al. classification and the AGEO prognostic score were confirmed as a strong prognosticator for disease recurrence.

Local immunomodulation combined to radiofrequency ablation results in a complete cure of local and distant colorectal carcinoma.

Radiofrequency ablation (RFA) of colorectal liver metastases activates a specific T-cell response that is ineffective in avoiding recurrence. Recently, local immunomodulation garnered interests as a way to improve the immune response. We were interested in improving the RFA immune response priming to propose a curative treatment of colorectal cancer (CRC) based on antitumor immunity. First, we demonstrated that the RFA did not increase the tumor infiltrating lymphocytes in secondary distant tumors of patients and in mice model and could not avoid relapse. Remarkably, RFA and in situ immunomodulation with GM-CSF-BCG hydrogel induced complete cure of microscopic secondary lesions in mice, related to a strong specific immune response. Then, we demonstrated that the immune escape of large secondary lesions was reversed by addition of the systemic PD-1 blockade to the in situ immunomodulation. The lack of an effective distant immune response in patients treated with RFA confirmed the relevance of this new combination strategy. Increasing the in situ priming response of radiofrequency ablation provides effective adjuvants to induce an abscopal effect. In the case of large lesions, synergy between PD1 blockade inhibitor, ineffective alone or after single RFA, with in situ immunomodulation, could lead to reconsideration of the use of checkpoint inhibition in metastatic MSS CRC.

Hybrid Minimally Invasive Esophagectomy for Esophageal Cancer.

BACKGROUND: Postoperative complications, especially pulmonary complications, affect more than half the patients who undergo open esophagectomy for esophageal cancer. Whether hybrid minimally invasive esophagectomy results in lower morbidity than open esophagectomy is unclear. METHODS: We performed a multicenter, open-label, randomized, controlled trial involving patients 18 to 75 years of age with resectable cancer of the middle or lower third of the esophagus. Patients were randomly assigned to undergo transthoracic open esophagectomy (open procedure) or hybrid minimally invasive esophagectomy (hybrid procedure). Surgical quality assurance was implemented by the credentialing of surgeons, standardization of technique, and monitoring of performance. Hybrid surgery comprised a two-field abdominal-thoracic operation (also called an Ivor-Lewis procedure) with laparoscopic gastric mobilization and open right thoracotomy. The primary end point was intraoperative or postoperative complication of grade II or higher according to the Clavien-Dindo classification (indicating major complication leading to intervention) within 30 days. Analyses were done according to the intention-to-treat principle. RESULTS: From October 2009 through April 2012, we randomly assigned 103 patients to the hybrid-procedure group and 104 to the open-procedure group. A total of 312 serious adverse events were recorded in 110 patients. A total of 37 patients (36%) in the hybrid-procedure group had a major intraoperative or postoperative complication, as compared with 67 (64%) in the open-procedure group (odds ratio, 0.31; 95% confidence interval [CI], 0.18 to 0.55; P<0.001). A total of 18 of 102 patients (18%) in the hybrid-procedure group had a major pulmonary complication, as compared with 31 of 103 (30%) in the open-procedure group. At 3 years, overall survival was 67% (95% CI, 57 to 75) in the hybrid-procedure group, as compared with 55% (95% CI, 45 to 64) in the open-procedure group; disease-free survival was 57% (95% CI, 47 to 66) and 48% (95% CI, 38 to 57), respectively. CONCLUSIONS: We found that hybrid minimally invasive esophagectomy resulted in a lower incidence of intraoperative and postoperative major complications, specifically pulmonary complications, than open esophagectomy, without compromising overall and disease-free survival over a period of 3 years. (Funded by the French National Cancer Institute; ClinicalTrials.gov number, NCT00937456 .).

Ventral hernia surgery in morbidly obese patients, immediate or after bariatric surgery preparation: Results of a case-matched study.

BACKGROUND: Obesity is a risk factor for the development of ventral hernia and increases the risk of recurrence and surgical site infection after hernia repair (HR). OBJECTIVES: We tested the hypothesis that bariatric surgery (BS) before HR would decrease these risks in patients with morbid obesity. SETTING: University hospital, France. METHODS: We retrospectively compared 2 groups of patients with morbid obesity in a case-matched study; 1 underwent immediate HR surgery (control), and the other initially underwent BS and then HR after weight loss (case). Patients were individually matched at a 2:1 ratio according to defect size (<7 or ≥7 cm), obesity grade (<40 or ≥40 kg/m²), American Society of Anesthesiologists score, sex, smoker status, and presence of chronic obstructive pulmonary disease. RESULTS: From 2000 to 2017, 41 patients underwent BS, in association with herniorrhaphy in 14 cases (34%). Initial body mass index was higher in the BS group (46.7 ± 6.4 versus 42.4 ± 7.2, P < .0001) but had decreased by the time of HR (34.1 ± 6.5 versus 42.3 ± 7.2, P < .0001). Prosthetic HR was performed after 21.5 months (range, 7-87); however, 7 patients did not receive HR at this time due to insufficient weight loss. Postoperative morbidity was similar in the 2 groups. Hospital stay was shorter in the BS group (6.2 ± 2.6 versus 10.7 ± 9.3 d, P = .002). After a median follow-up of 4.6 ± 4.1 years, the recurrence rate was lower in the BS group (2/30, 6.7%) than in the control group (12/50, 24%; P = .048). CONCLUSION: For morbidly obese patients with ventral hernia, BS before HR surgery can decrease recurrence without increasing morbidity.

Association of IL-36γ with tertiary lymphoid structures and inflammatory immune infiltrates in human colorectal cancer.

IL-1 family cytokines play a dual role in the gut, with different family members contributing either protective or pathogenic effects. IL-36γ is an IL-1 family cytokine involved in polarizing type-1 immune responses. However, its function in the gut, including in colorectal cancer pathogenesis, is not well appreciated. In a murine model of colon carcinoma, IL-36γ controls tertiary lymphoid structure formation and promotes a type-1 immune response concurrently with a decrease in expression of immune checkpoint molecules in the tumor microenvironment. Here, we demonstrate that IL-36γ plays a similar role in driving a pro-inflammatory phenotype in human colorectal cancer. We analyzed a cohort of 33 primary colorectal carcinoma tumors using imaging, flow cytometry, and transcriptomics to determine the pattern and role of IL-36γ expression in this disease. In the colorectal tumor microenvironment, we observed IL-36γ to be predominantly expressed by M1 macrophages and cells of the vasculature, including smooth muscle cells and high endothelial venules. This pattern of IL-36γ expression is associated with a CD4+ central memory T cell infiltrate and an increased density of B cells in tertiary lymphoid structures, as well as with markers of fibrosis. Conversely, expression of the antagonist to IL-36 signaling, IL-1F5, was associated with intratumoral expression of checkpoint molecules, including PD-1, PD-L1, and CTLA4, which can suppress the immune response. These data support a role for IL-36γ in the physiologic immune response to colorectal cancer by sustaining inflammation within the tumor microenvironment.

[Colorectal cancer surgery in the elderly]. / Chirurgie du cancer colorectal chez la personne âgée.

Colorectal cancer risk factors increase with age, comorbidities, delayed diagnosis, obstruction, emergency and frailty. Surgery is the standard treatment as the survival rate for this pathology is the same as in young patients. It would appear that there is an excess morbidity and mortality of colorectal cancer surgery in the elderly. Early rehabilitation is to be favoured during the postoperative period.