D2 procedure has been accepted in Far East as the standard treatment for both early(EGC) and advanced gastric cancer(AGC) for many decades. Recently EGC has been successfully treated with endoscopy ...by endoscopic mucosal resection or endoscopic submucosal dissection, when restricted or extended Gotoda’s criteria can be applied and D1+ surgery is offered only to patients not fitted for less invasive treatment. Furthermore, two randomised controlled trials(RCTs) have been demonstrating the non inferiority of minimally invasive technique as compared to standard open surgery for the treatment of early cases and recently the feasibility of adequate D1+ dissection has been demonstrated also for the robot assisted technique. In case of AGC the debate on the extent of nodal dissection has been open for many decades. While D2 gastrectomy was performed as the standard procedure in eastern countries, mostly based on observational and retrospective studies, in the west the Medical Research Council(MRC), Dutch and Italian RCTs have been conducted to show a survival benefit of D2 over D1 with evidence based medicine. Unfortunately both the MRC and the Dutch trials failed to show a survival benefit after the D2 procedure, mostly due to the significant increase of postoperative morbidity and mortality, which was referred to splenopancreatectomy. Only 15 years after the conclusion of its accrual, the Dutch trial could report a significant decrease of recur-rence after D2 procedure. Recently the long term survival analysis of the Italian RCT could demonstrate a benefit for patients with positive nodes treated with D2 gastrectomy without splenopancreatectomy. As nowadays also in western countries D2 procedure can be done safely with pancreas preserving technique and without preventive splenectomy, it has been suggested in several national guidelines as the recommended procedure for patients with AGC.
Background
The evidence supporting the use of the air leak test (ALT) after laparoscopic left-sided colon resection (LLCR) to test the colorectal anastomosis (CA) integrity aiming at reducing the ...rate of postoperative CA leakage (CAL) is not conclusive. The aim of this study was to challenge the use of ALT after elective LLCR.
Methods
It is a retrospective analysis of a prospectively collected database including all patients undergoing elective LLCR with primary CA and no proximal bowel diversion between January 1996 and June 2017. The decision to perform the ALT was based on the individual surgeon routine practice. A multivariate analysis was performed to identify independent risk factors for CAL.
Results
A total of 777 LLCR without proximal diversion were included in the analysis: the CA was tested in 398 patients (ALT group), while intraoperative ALT was not performed in 379 patients (No-ALT group). The two groups were similar in demographic characteristics, indication, and type of procedure. Intraoperative ALT was positive in 20 (5%) patients: a stoma was created in 14 (70%) patients, while 6 (30%) patients had a suture repair alone. Overall, postoperative CAL occurred in 32 patients (4.1%): the postoperative CAL rate was lower in ALT patients (2.5% vs. 5.8%,
p
= 0.025). A reoperation was needed in 87.5% of cases. No CAL occurred in the 20 patients with intraoperative positive ALT. Multivariate analysis showed that ASA score 3–4 (OR 5.39, 95% CI 2.53–11.51,
p
< 0.001) and male sex (OR 3.96, 95% CI 1.66–9.43,
p
= 0.002) were independent risk factors for postoperative CAL, while intraoperative ALT independently reduced the postoperative CAL rate (OR 0.40, 95% CI 0.18–0.88,
p
= 0.022).
Conclusion
Intraoperative ALT allows to detect AL defects after LLCR that can be effectively managed intraoperatively, leading to a significant lower risk of postoperative CAL.
Abstract
Complete mesocolic excision with central vascular ligation, or simply CME, includes the sharp dissection along the mesocolic visceral and parietal layers, with the ligation of the main ...vessels at their origins. To date, there is low evidence on its safety and efficacy. This is a study-protocol of a multicenter, randomized, superiority trial in patients with right-sided colon cancer. It aims to investigate whether the complete mesocolic excision improves the oncological outcomes as compared with conventional right hemicolectomy, without worsening early outcomes. Data on efficacy and safety of complete mesocolic excision are available only from a large trial recruiting eastern patients and from a low-volume single-center western study. No results on survival are still available. For this reason, complete mesocolic excision continues to be a controversial topic in daily practice, particularly in western world. This new nationwide multicenter large-volume trial aims to provide further data on western patients, concerning both postoperative and survival outcomes.
Aim
Anastomotic leakage after restorative surgery for rectal cancer shows high morbidity and related mortality. Identification of risk factors could change operative planning, with indications for ...stoma construction. This retrospective multicentre study aims to assess the anastomotic leak rate, identify the independent risk factors and develop a clinical prediction model to calculate the probability of leakage.
Methods
The study used data from 24 Italian referral centres of the Colorectal Cancer Network of the Italian Society of Surgical Oncology. Patients were classified into two groups, AL (anastomotic leak) or NoAL (no anastomotic leak). The effect of patient‐, disease‐, treatment‐ and postoperative outcome‐related factors on anastomotic leak after univariable and multivariable analysis was measured.
Results
A total of 5398 patients were included, 552 in group AL and 4846 in group NoAL. The overall incidence of leaks was 10.2%, with a mean time interval of 6.8 days. The 30‐day leak‐related mortality was 2.6%. Sex, body mass index, tumour location, type of approach, number of cartridges employed, weight loss, clinical T stage and combined multiorgan resection were identified as independent risk factors. The stoma did not reduce the leak rate but significantly decreased leak severity and reoperation rate. A nomogram with a risk score (RALAR score) was developed to predict anastomotic leak risk at the end of resection.
Conclusions
While a defunctioning stoma did not affect the leak risk, it significantly reduced its severity. Surgeons should recognize independent risk factors for leaks at the end of rectal resection and could calculate a risk score to select high‐risk patients eligible for protective stoma construction.
Many phase III trials failed to demonstrate a survival benefit from the addition of molecular therapy to conventional chemotherapy for advanced and metastatic gastric cancer, and only three agents ...were approved by the FDA. We examined the efficacy and safety of novel drugs recently investigated. PubMed, Embase and Cochrane Library were searched for phase III randomized controlled trials published from January 2016 to December 2020. Patients in the experimental arm received molecular therapy with or without conventional chemotherapy, while those in the control arm had conventional chemotherapy alone. The primary outcomes were overall and progression-free survival. The secondary outcomes were the rate of tumor response, severe adverse effects, and quality of life. Eight studies with a total of 4223 enrolled patients were included. The overall and progression-free survival of molecular and conventional therapy were comparable. Most of these trials did not find a significant difference in tumor response rate and in the number of severe adverse effects and related deaths between the experimental and control arms. The survival benefits of molecular therapies available to date for advanced and metastatic gastric cancer are rather unclear, mostly due to inaccurate patient selection, particularly concerning oncogene amplification and copy number.
Objectives
A dendritic cell‐based cancer vaccine has recently received Food and Drug Administration approval in the USA based on its ability to prolong the survival of prostate cancer patients with ...advanced disease. However, tumor‐mediated immunosuppressive mechanisms might represent an obstacle to optimal performance of this therapy. We have recently shown that monocytes from the blood of prostate cancer patients can fully mature to dendritic cells only after the tumor is removed. Here, we have tested the hypothesis that these tumor‐driven monocytes correspond to the recently described subset of CD14+HLA‐DRlow immunosuppressor cells.
Methods
Prostate cancer patients were studied before and 1 month after prostatectomy. Pre‐ and postsurgical patients with colorectal cancer were also included for comparison. Flow cytometric analysis was applied to define CD14−HLA‐DRlowCD33+CD11b+ (myeloid) and CD14+HLA‐DRlow (monocytic) suppressor cells. Interferon‐γ release was used to assess the immunocompetence of lymphocytes.
Results
In both prostate cancer and colorectal cancer patients, the percentage of CD14+HLA‐DRlow cells was several‐fold higher compared with normal subjects. This was not the case for CD14−HLA‐DRlowCD33+CD11b+ cells. Furthermore, postsurgical normalization of CD14+HLA‐DRlow cells only occurred in prostate cancer patients. In all patients, the interferon‐γ response of T lymphocytes to phorbolmyristate acetate‐ionomycin was higher compared with normal donors, but it was further increased after tumor ablation only in prostate cancer patients.
Conclusions
The direct link between CD14+HLA‐DRlow increase and presence of primary tumor suggests a distinguishing immunosuppressive profile of prostate cancer. This observation supports the principle that the appropriate setting for prostate cancer vaccine therapy is a minimal disease status.
Patient-Derived Xenografts (PDXs) are, so far, the best preclinical model to validate targets and predictors of response to therapy. While subcutaneous implantation very rarely allows metastatic ...dissemination, orthotopic implantation (Patient-Derived Orthotopic Xenograft—PDOX) increases metastatic capability. Using a modified tool to analyze model validity, we performed a systematic review of Embase, PubMed, and Web of Science up to December 2018 to identify all original publications describing gastric cancer (GC) PDOXs. We identified ten studies of PDOX model validation from January 1981 to December 2018 that fulfilled the inclusion and exclusion criteria. Most models (70%) were derived from human GC cell lines rather than tissue fragments. In 90% of studies, the implantation was performed in the subserosal layer. Tumour engraftment rate ranged from 0 to 100%, despite the technique. Metastases were observed in 40% of PDOX models implanted into the subserosal layer, employing either cell suspension or cell line-derived tumour fragments. According to our modified model validity tool, half of the studies were defined as unclear because one or more validation criteria were not reported. Available GC PDOX models are not adequate according to our model validity tool. There is no demonstration that the submucosal site is more effective than the subserosal layer, and that tissue fragments are better than cell suspensions for successful engraftment and metastatic spread. Further studies should strictly employ model validity tools and large samples with orthotopic implant sites mirroring as much as possible the donor tumour characteristics.
In patients with locally advanced rectal cancer treated by neoadjuvant chemoradiation, pathological complete response in the surgical specimen is associated with favourable long-term oncologic ...outcome. Based on this observation, nonoperative management is being explored in the subset of patients with clinical complete response. Whereas, patients with poor response have a high risk of local and distant recurrence, and appear to receive no benefit from standard neoadjuvant chemoradiation. Therefore, in order to develop alternative treatment strategies for non responding patients, predictive and prognostic factors are highly needed. Accumulating clinical observations indicate that elevated platelet count is associated with poor outcome in different type of tumors. In this study we investigated the predictive and prognostic impact of elevated platelet count on pathological response and long-term oncologic outcome in patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation.
A total of 965 patients were selected from prospectively maintained databases of seven Centers within the SICO Colorectal Cancer Network. Patients were divided into two groups based on a pre-neoadjuvant chemoradiation platelet count cut-off value of 300 × 10
/L identified by receiver operating characteristic curve considering complete pathological response as the outcome.
Complete pathological response rate was lower in patients with elevated platelet count (12.8% vs. 22.1%, p = 0.001). Mean follow-up was 50.1 months. Comparing patients with elevated platelet count with patients with not elevated platelet count, 5-year overall survival was 69.5% vs.76.5% (p = 0.016), and 5-year disease free survival was 63.0% vs. 68.9% (p = 0.019). Local recurrence rate was higher in patients with elevated platelet count (11.1% vs. 5.3%, p = 0.001), as higher was the occurrence of distant metastasis (23.9% vs. 16.4%, p = 0.007). At multivariate analysis of potential prognostic factors EPC was independently associated with worse overall survival (HR 1.40, 95% CI 1.06-1.86), and disease free survival (HR 1.37, 95% CI 1.07-1.76).
In locally advanced rectal cancer elevated platelet count before neoadjuvant chemoradiation is a negative predictive and prognostic factor which might help to identify subsets of patients with more aggressive tumors to be proposed for alternative therapeutic strategies.
Duodenal perforation consequent to prior surgery is a rare but severe complication carrying serious consequences if not promptly managed. This study aims to identify the best treatment pathway ...available to date. This is a systematic review registered to PROSPERO. The literature research was conducted on Ovid Medline, Embase, and Cochrane up to February 2022 to identify all papers reporting surgical-related duodenal perforations. Twelve articles were included. Most of these studies were case reports or case series. The most common cause of perforation was laparoscopic cholecystectomy (72.7%). The median time to symptom appearance was 2 days. Most of these perforations were severe injuries located in the first portion of the duodenum. Only one patient was treated with a non-interventional conservative management, which failed. Five patients were managed with interventional non-surgical treatments: 4 with endoscopy (50% failure) and one with a percutaneous occluder. Different surgical treatments were reported: direct suture (100% failure), direct suture and T-tube duodenostomy (75% failure), simple abdominal drainage, and suture with pyloric exclusion. Further extensive surgeries were also reported. The overall mortality rate was 13.6%, with a median hospital stay of 38.5 days. This review shows a wide spectrum of managements for patients with duodenal perforation related to prior surgery. The decision on which treatment to adopt must consider patient’s clinical setting and duodenal defect characteristics (size, site, and time to diagnosis). A tentative treatment flowchart is provided, although larger sample size studies are needed to obtain a treatment pathway based on evidence.
Purpose
The LARS score is an internationally well-accepted questionnaire to assess low anterior resection syndrome, but currently there is no formally validated Italian version. The purpose of this ...study was to test the reliability and validity of the Italian version among Italian patients submitted to sphincter-sparing surgery for rectal cancer.
Methods
The English version of the LARS score was translated into Italian following the forward-and-back translation process. A total of 147 patients filled out our version. Among them, 40 patients answered the questionnaire twice for the test-retest reliability phase. The validity of the LARS score was tested using convergent and discriminant validity indicators by correlating the EORTC QLQ-C30 and QLQ-CR29 questionnaires. The LARS score capability to differentiate groups of patients with different demographic or clinical features was also assessed.
Results
The test-retest reliability was excellent in 87.5% of patients, remained in the same LARS category in both tests. The convergent validity phase showed a relevant relationship of the LARS score with the EORTC domains, which was significant for 7 of 15 EORTC QLQ-C30 subscales, and for 14 of 29 EORTC QLQ-CR29 subscales. The LARS score was able to discriminate patients who received radiotherapy (
p
= 0.0026), TME vs. PME (
p
= 0.0060), tumour site at < 10 cm from the anal verge (
p
= 0.0030) and history of protective stoma (
p
< 0.0001).
Conclusion
The Italian version of the LARS score is a valid and reliable tool for measuring LARS in Italian patients after SSS for rectal cancer.
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