IMMUNOREACT 7: Regular aspirin use is associated with immune surveillance activation in colorectal cancer.

BACKGROUND: Long-term daily use of aspirin reduces incidence and mortality due to colorectal cancer (CRC). This study aimed to analyze the effect of aspirin on the tumor microenvironment, systemic immunity, and on the healthy mucosa surrounding cancer. METHODS: Patients with a diagnosis of CRC operated on from 2015 to 2019 were retrospectively analyzed (METACCRE cohort). Expression of mRNA of immune surveillance-related genes (PD-L1, CD80, CD86, HLA I, and HLA II) in CRC primary cells treated with aspirin were extracted from Gene Expression Omnibus-deposited public database (GSE76583). The experiment was replicated in cell lines. The mucosal immune microenvironment of a subgroup of patients participating in the IMMUNOREACT1 (ClinicalTrials.gov NCT04915326) project was analyzed with immunohistochemistry and flow cytometry. RESULTS: In the METACCRE Cohort, 12% of 238 patients analyzed were aspirin users. Nodal metastasis was significantly less frequent (p = .008) and tumor-infiltrating lymphocyte infiltration was higher (p = .02) among aspirin users. In the CRC primary cells and selected cell lines, CD80 mRNA expression was increased following aspirin treatment (p = .001). In the healthy mucosa surrounding rectal cancer, the ratio of CD8/CD3 and epithelial cells expressing CD80 was higher in aspirin users (p = .027 and p = .034, respectively). CONCLUSIONS: These data suggested that regular aspirin use may have an active role in enhancing immunosurveillance against CRC.

Which video technology brings the higher cognitive burden and motion sickness in laparoscopic colorectal surgery: 3D, 2D-4 K or 3D-4 K? a propensity score study.

BACKGROUND: Technological development has offered laparoscopic colorectal surgeons new video systems to improve depth perception and perform difficult task in limited space. The aim of this study was to assess the cognitive burden and motion sickness for surgeons during 3D, 2D-4 K or 3D-4 K laparoscopic colorectal procedures and to report post-operative data with the different video systems employed. METHODS: Patients were assigned to either 3D, 2D-4 K or 3D-4 K video and two questionnaires (Simulator Sickness Questionnaire-SSQ- and NASA Task Load Index -TLX) were used during elective laparoscopic colorectal resections (October 2020-August 2022) from two operating surgeons. Short-term results of the operations performed with the three different video systems were also analyzed. RESULTS: A total of 113 consecutive patients were included: 41 (36%) in the 3D Group (A), 46 (41%) in the 3D-4 K Group and 26 (23%) in the 2D-4 K Group (C). Weighted and adjusted regression models showed no significant difference in cognitive load amongst the surgeons in the three groups of video systems when using the NASA-TLX. An increased risk for slight/moderate general discomfort and eyestrain in the 3D-4 K group compared with 2D-4 K group (OR = 3.5; p = 0.0057 and OR = 2.8; p = 0.0096, respectively) was observed. Further, slight/moderate difficulty focusing was lower in both 3D and 3D-4 K groups compared with 2D-4 K group (OR = 0.4; p = 0.0124 and OR = 0.5; p = 0.0341, respectively), and higher in the 3D-4 K group compared with 3D group (OR = 2.6; p = 0.0124). Patient population characteristics, operative time, post-operative staging, complication rate and length of stay were similar in the three groups of patients. CONCLUSIONS: 3D and 3D-4 K systems, when compared with 2D-4 K video technology, have a higher risk for slight/moderate general discomfort and eyestrain, but show lower difficulty focusing. Short post-operative outcomes do not differ, whichever imaging system is used.

Role of Immune Microenvironment in Pancreatic Ductal Adenocarcinoma: Could It Be Considered a Predictor of Prognosis?

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a highly immunosuppressive tumor microenvironment (TME). The aim of this study is to determine the potential significant TME immune markers of long-term survival. METHODS: We retrospectively included patients with a diagnosis of resectable PDAC having undergone upfront surgery. Immunohistochemical (IHC) staining using tissue microarray for PD-L1, CD3, CD4, CD8, FOXP3, CD20, iNOS and CD163 was performed in order to characterize the TME. The primary endpoint was long-term survival, defined as the Overall Survival > 24 months from surgery. RESULTS: A total of 38 consecutive patients were included, and 14 (36%) of them were long-term survivors. Long-term survivors showed a higher density of CD8+ lymphocytes intra- and peri-acinar (p = 0.08), and a higher CD8/FOXP3 intra- and peri-tumoral ratio (p = 0.05). A low density of intra- and peri-tumoral FOXP3 infiltration is a good predictor of long-term survival (p = 0.04). A significant association of the low density of intra- and peri-tumoral tumor-associated macrophages (TAMs) iNOS+ with long-term survival was detected (p = 0.04). CONCLUSIONS: Despite the retrospective nature and small sample size, our study showed that the high infiltration of CD8+ lymphocytes and low infiltration of FOXP3+ and TAMs iNOS+ are predictors of good prognosis. A preoperative assessment of these potential immune markers could be useful and determinant in the staging process and in PDAC management.

Skeletal Muscle Mass and Surgical Morbidity After Laparoscopic Rectal Cancer Resection.

Background: Sarcopenia is a useful tool in predicting short-term results in patients undergoing surgery for gastrointestinal cancer. However, there are few studies addressing this issue in colorectal cancer, and even less specifically focused on rectal cancer. We evaluated the prognostic relevance of preoperative skeletal mass index on postoperative morbidity in patients undergoing laparoscopic curative resection for rectal cancer. Methods: Skeletal mass index data and clinicopathological characteristics of rectal cancer patients in a 15-year period (June 2005-December 2020) were evaluated; patients with metastatic disease at surgery were excluded; postoperative complications within 30 days were evaluated using the Clavien-Dindo classification. Results: A total of 166 patients were included in the study. The overall prevalence of sarcopenia was 60%. BMI, Hb, or albumin were not associated with sarcopenia. Hospital stay was not correlated with sarcopenia. Postoperative complications occurred in 51 patients (31%); by the Clavien-Dindo classification 31 (61%) grade I, 10 (14.5%) grade II, and 10 (14.5%) grade III. Overall complications were not significantly different in sarcopenic and nonsarcopenic patients (P = .10). Considering only patients with complications, sarcopenia was found to be a predictor of more severe postoperative morbidity (odds ratio 12.7, P = .021). On multivariable analysis, sarcopenia was not associated with postoperative morbidity. Conclusions: Skeletal muscle status in rectal cancer patients undergoing curative resection was not associated with overall postoperative morbidity, although there was a correlation between sarcopenia and more severe complications. Further studies in a larger cohort of patients are needed before conclusions can be drawn on the relationship between muscular depletion and surgical outcomes in rectal cancer patients.

Prognostic effect of sarcopenia in patients undergoing laparoscopic rectal cancer resection.

BACKGROUND: The importance of body composition, in particular skeletal muscle mass, as risk factor affecting survival of cancer patients has recently gained increasing attention. The relationship between sarcopenia and oncological outcomes has become a topic of research in particular in patients with gastrointestinal cancer. However, there are few studies addressing this issue in colorectal cancer, and even less specifically focused on rectal cancer, in particular in Western countries. The aim of this study was to evaluate the prognostic relevance of preoperative skeletal mass index (SMI) on long-term outcomes in patients undergoing laparoscopic curative resection for rectal cancer. METHODS: SMI data and clinicopathological characteristics of rectal cancer patients in a 15-year period (June 2005-December 2020) were evaluated; patients with metastatic disease at surgery were excluded; overall and disease-free survival as well as recurrence were evaluated. RESULTS: Hundred and sixty-five patients were included in the study. Sarcopenia was identified in 30 (18%) patients. Multivariate analysis identified sarcopenia (HR = 3.28, CI = 1.33-8.11, P = 0.015), along with age (HR = 1.06, CI = 1.02-1.10, P = 0.002) and stage III (HR = 2.63, CI = 1.13-6.08, P < 0.03) as independent risk factors for overall survival. CONCLUSION: Long-term results of rectal cancer patients undergoing curative resection are affected by their preoperative skeletal muscle status. Larger studies including comprehensive data on muscle strength along with SMI are awaited to confirm these results on both Eastern and Western rectal cancer patient populations before strategies to reverse muscle depletion can be extensively applied.

Laparoscopic Welti's Maneuver: A Single-Center Experience.

Purpose: Left hemicolectomy is the standard surgical operation for a variety of colonic diseases, both benign and malignant. When colonic resection is extended, relocation of the small bowel loops can be difficult. Several techniques have been described to reposition the small intestine. Welti's technique consists in the passage of the entire small bowel to the left side of the abdomen, below the descending colon that is positioned on the right side. Methods: We retrospectively evaluated 23 patients who underwent extended left hemicolectomy and reconstruction according to the Welti's technique at our hospital. We assessed the recovery of intestinal function and the length of hospital stay; in the mid-term follow-up we searched for episodes of acute or chronic intestinal obstruction. Results: Median operative time was 215 minutes; median resumption of gas and stool emission were, respectively, 3 days (interquartile range [IQR]: 2-6) and 4 days (IQR: 2-9) after surgery. Median hospital stay was 8 (IQR: 5-37) day. After a median follow-up of 15 months (IQR: 3-132) we did not observe any episode of acute or chronic bowel obstruction. Conclusions: Welti's technique is safe and does not cause a delay in resumption of bowel functions or a delayed hospital discharge; it is a useful technique that the colorectal surgeon can use when needed.

Impact of Age on Short- and Long-Term Outcomes after Pancreatoduodenectomy for Periampullary Neoplasms.

BACKGROUND: Although mortality and morbidity of pancreatoduodenectomy (PD) have improved significantly over the past years, the impact of age for patients undergoing PD is still debated. This study is aimed at analyzing short- and long-term outcomes of PD in elderly patients. METHODS: 124 consecutive patients who have undergone PD for pancreas neoplasms in our center between 2012 and 2017 were analyzed. Patients were divided into two groups: group I (<75 years) and group II (≥75 years). Demographic features and intraoperative and clinical-pathological data were collected. Primary endpoints were perioperative morbidity and mortality; complications were classified according to the Clavien-Dindo Score. Secondary endpoints included feasibility of adjuvant treatment and overall survival rates. RESULTS: A total of 106 patients were included in this study. There were 73 (68.9%) patients in group I and 33 (31.1%) in group II. Perioperative deceases were 4 (3.6%), and postoperative pancreatic fistulas were 34 (32.1%). Significant difference between two groups was demonstrated for the ASA Score (p = 0.004), Karnofsky Score (p = 0.025), preoperative jaundice (p = 0.004), and pulmonary complications (p = 0.034). No significance was shown for diabetes, radicality of resection, stage of disease, operative time, length of stay, postoperative complications according to the Clavien-Dindo Score, postoperative mortality, pancreatic fistula, and reoperation rates. 69.9% of the patients in group I underwent adjuvant treatment vs. 39.4% of the older ones (p = 0.012). Mean overall survival was 28.5 months in group I vs. 22 months in group II (p = 0.909). CONCLUSION: PD can be performed safely in elderly patients. Advanced age should not be an absolute contraindication for PD, even if greater frailty should be considered. The outcome of elderly patients who have undergone PD is similar to that of younger patients, even though adjuvant treatment administration is significantly lower, demonstrating that surgery remains the main therapeutic option.