Oligometastatic Gastric Cancer: Clinical Data from the Meta-Gastro Prospective Register of the Italian Research Group on Gastric Cancer

Background: Interest in the field of metastatic gastric cancer has grown in recent years, and the identification of oligometastatic patients plays a critical role as it consents to their inclusion in multimodal treatment strategies, which include systemic therapy but also surgery with curative intent. To collect sound clinical data on this subject, The Italian Research Group on Gastric Cancer developed a prospective multicentric observational register of metastatic gastric cancer patients called META-GASTRO. Methods: Data on 383 patients in Meta-Gastro were mined to help our understanding of oligometastatic, according to its double definition: quantitative/anatomical and dynamic. Results: the quantitative/anatomical definition applies to single-site metastases independently from the metastatic site (p < 0.001) to peritoneal metastases with PCI ≤ 12 (p = 0.009), to 1 or 2 hepatic metastases (p = 0.024) and nodal metastases in station 16 (p = 0.002). The dynamic definition applies to a percentage of cases variable according to the metastatic site: 8%, 13.5 and 23.8% for hepatic, lymphatic and peritoneal sites, respectively. In all cases, the OS of patients benefitting from conversion therapy was similar to those of cases deemed operable at diagnosis and operated after neoadjuvant chemotherapy. Conclusions: META-GASTRO supports the two-fold definition of oligometastatic gastric cancer: the quantitative/anatomical one, which accounts for 30% of our population, and the dynamic one, observed in 16% of our cases

GZMKhigh CD8+ T effector memory cells are associated with CD15high neutrophil abundance in non-metastatic colorectal tumors and predict poor clinical outcome.

CD8(+) T cells are a major prognostic determinant in solid tumors, including colorectal cancer (CRC). However, understanding how the interplay between different immune cells impacts on clinical outcome is still in its infancy. Here, we describe that the interaction of tumor infiltrating neutrophils expressing high levels of CD15 with CD8(+) T effector memory cells (T(EM)) correlates with tumor progression. Mechanistically, stromal cell-derived factor-1 (CXCL12/SDF-1) promotes the retention of neutrophils within tumors, increasing the crosstalk with CD8(+) T cells. As a consequence of the contact-mediated interaction with neutrophils, CD8(+) T cells are skewed to produce high levels of GZMK, which in turn decreases E-cadherin on the intestinal epithelium and favors tumor progression. Overall, our results highlight the emergence of GZMK(high) CD8(+) T(EM) in non-metastatic CRC tumors as a hallmark driven by the interaction with neutrophils, which could implement current patient stratification and be targeted by novel therapeutics

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Laparoscopic total mesorectal excision after neoadjuvant chemoradiotherapy

Background: Although several authors have demonstrated that laparoscopic total mesorectal excision (TME) is feasible, safe, and has short-term benefits over open surgery, evidence about oncological outcome is lacking. Preoperative chemoradiation has been shown to improve local control in locally advanced rectal cancer. Therefore, neoadjuvant treatment followed by laparoscopic TME has become widely used. We reviewed our series of laparoscopic TME focusing on comparison between preoperative chemoradiation therapy and primary surgery. Methods: Out of 59 patients who underwent laparoscopic TME, 20 were submitted to neoadjuvant chemoradiation and represent study population. Twenty-six patients with non-metastatic rectal cancer >T1 on pathologic TNM staging who underwent primary laparoscopic surgery were considered for comparison. Results: No significant differences were found in operative time, in conversions to open surgery, in intra- and postoperative complications, and in anastomotic leakage rate between the two groups. No isolated local recurrence nor port-site metastases were detected in either group. Cumulative 3-year and 5-year survivals are also similar. Conclusion: Neoadjuvant treatment does not seem to jeopardize perioperative results of laparoscopic TME. The low incidence of local recurrence reported in both groups may be attributed to a more precise dissection allowed by the endoscopic view. Laparoscopic TME and preoperative chemoradiotherapy may significantly improve oncologic results and quality of life in patients with mid and low rectal cancer. Results should be validated by randomized trials with adequate follow-up

Stapled anopexy : postoperative course and functional outcome in 400 patients

PURPOSE: We performed a retrospective analysis of postoperative course and functional outcome after at least six months' follow-up in a series of 400 consecutive patients who underwent stapled anopexy. METHODS: All patients were evaluated at one week and one month after surgery and then according to symptoms. A clinical or telephone follow-up was obtained for all patients. The last 50 patients were prospectively evaluated with an obstructive defecation syndrome score and Wexner continence and constipation score before operation and six months after anopexy. RESULTS: There were no intraoperative complications. Postoperative bleeding that requires reoperation was observed in 11 patients, most cases (9/11) occurring in the early experience (first 50 patients). After a median follow-up of 6.1 years, four patients required reoperation. After anopexy, we observed an improvement in patients who present disturbance in defecation. The difference between the median obstructive defecation syndrome score before and after operation was statistically significant. Wexner score showed improvement without significant difference. CONCLUSIONS: Treatment of hemorrhoids with circular stapler seems to be effective with low morbidity and high satisfaction rate because of reduced postoperative pain and rapid recovery. This technique also allows improvement of obstructive defecation symptoms, which are seldom studied in patients with hemorrhoids

Nissen fundoplication after failure of endoluminal fundoplication: short term results

Background: Endoluminal fundoplcation (ELF) with EsophyX\u2122 is a new attractive investigational procedure for the control of gastroesophageal reflux disease (GERD). The aim of this work is to evaluate the short-term results of Nissen fundoplication (NF) after failure of ELF. Method: During the period April 2007-January 2010, nine patients previously treated with ELF for GERD were submitted to laparoscopic NF for persistent reflux. Results: All patients were symptomatic for GERD, had a pathological esophageal acid exposure at multichannel intraluminal impedance (MII pH/24 h), and all of them were on proton pump inhibitor. Mean duration of the NF was 85 min (range, 56-104). There were no intraoperative complications. One patient had a postoperative mild peritoneal bleeding treated conservatively. After a mean follow-up of 24.9 months (4-34), all patients are asymptomatic for reflux. Two patients have a mild or moderate dysphagia at follow-up. Five patients underwent MII pH/24 h 1 year after surgery. Mean total reflux time was 0.3%, and acid reflux percent time was 0. Conclusions: Patients with persistent symptomatic reflux after a failing ELF can still undergo NF with good results; the endoluminal procedure does not seem to modify the results of the laparoscopic procedure, although an increased incidence of dysphagia pos-NF may be observed

Assessment of HER2 status in patients with gastroesophageal adenocarcinoma treated with epirubicin-based chemotherapy: heterogeneity-related issues and prognostic implications

Background: HER2 and topoisomerase 2 alpha (TOP2A) genomic status was previously reported to predict benefit from anthracyclines in breast cancer. We sought to define the prognostic impact and possible pitfalls related to these biomarkers in resectable gastroesophageal adenocarcinoma. Methods: HER2 and TOP2A gene amplification by fluorescent in situ hybridization and HER2 protein expression by immunohistochemistry (IHC) were assessed on whole tissue sections from 101 patients receiving peri- or postoperative epirubicin-based chemotherapy. In a subgroup of patients, at least two matched tumor blocks, originating either from surgical procedures (n = 88) or diagnostic biopsies (n = 32), were available for HER2 analyses by IHC. Results: Eighteen of 101 patients (17.8 %) were HER2 positive, whereas TOP2A was amplified in 4 of 84 patients (4.7 %). HER2 positivity was significantly associated with improved disease-free survival [HR = 0.47 (95 % CI 0.22\u20130.99), P = 0.046] and overall survival [HR = 0.33 (95 % CI 0.13\u20130.83), P < 0.018], independent of clinical-pathologic features. HER2 expression in matched tumor blocks from the same resection specimen was discordant in up to 11.8 % of pairs, while this rate increased up to 27.2 % when diagnostic biopsies and paired surgical samples were compared. Conclusions: HER2 status is an independent prognostic biomarker in gastroesophageal adenocarcinomas receiving epirubicin-based chemotherapy. Compared to diagnostic biopsies, HER2 assessment in multiple resection specimens might lower the risk of sampling errors. These findings have several implications with respect to the optimal choice of the sample to be submitted to IHC testing of HER2

Open versus laparoscopic versus robotic gastric gastrointestinal stromal tumour resections: A multicentre cohort study

Purpose: To present the outcomes of gastric gastrointestinal stromal tumour (GIST) resection from five Italian centres, focussing the analysis on the comparison among open (OG), laparoscopic (LG) and robotic (RG) approaches. Methods: All consecutive gastric wedge resections for GIST between 2009 and 2019 were included. Results: In total 101 (OG = 14, LG = 63 and RG = 24) were included. No differences were seen in the preoperative characteristics among the groups. Robotic procedures were longer (RG 180 min vs. LG 100 vs. OG 110; p &lt; 0.0001). Time-to-first flatus and length of hospital stay were significantly longer in the OG group. Complication rates were similar among the groups. A sub-analysis on minimally invasive (RG = 19 vs. LG = 20) wedge resections and hand/robot-sewn suture showed that operative time was longer in the RGs (p = 0.007). No conversions were recorded in the RG group versus three in the LG group (p = 0.231). Safety-related factors were similar. Conclusions: Gastric GIST can be safely treated with a minimally invasive approach which is also associated with improved postoperative outcomes

Intraoperative use of fluorescence with indocyanine green reduces anastomotic leak rates in rectal cancer surgery: an individual participant data analysis

Background: Fluorescence imaging by means of Indocyanine green (ICG) has been applied to intraoperatively determine the perfusion of the anastomosis. The purpose of this Individual Participant Database meta-analysis was to assess the effectiveness in decreasing the incidence of anastomotic leak (AL) after rectal cancer surgery. Methods: We searched PubMed, Embase, Cochrane Library and ClinicalTrial.gov, EU Clinical Trials and ISRCTN registries on September 1st, 2019. We considered eligible those studies comparing the assessment of anastomotic perfusion during rectal cancer surgery by intraoperative use of ICG fluorescence compared with standard practice. We defined as primary outcome the incidence of AL at 30&nbsp;days after surgery. The studies were assessed for quality by means of the ROBINS-I and the Cochrane risk tools. We calculated odds ratios (ORs) using the Individual patient data analysis, restricted to rectal lesions, according to original treatment allocation. Results: The review of the literature and international registries produced 15 published studies and 5 ongoing trials, for 9 of which the authors accepted to share individual participant data. 314 patients from two randomized trials, 452 from three prospective series and 564 from 4 non-randomized studies were included. Fluorescence imaging significantly reduced the incidence of AL (OR 0.341; 95% CI 0.220\u20130.530; p &lt; 0.001), independent of age, gender, BMI, tumour and anastomotic distance from the anal verge and neoadjuvant therapy. Also, overall morbidity and reintervention rate were positively influenced by the use of ICG. Conclusions: The incidence of AL may be reduced when ICG fluorescence imaging is used to assess the perfusion of a colorectal anastomosis. Limitations relate to the consistent number of non-randomized studies included and their heterogeneity in defining and assessing AL. Ongoing large randomized studies will help to determine the exact role of routine ICG fluorescence imaging may decrease the incidence of AL in surgery for rectal cancer