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.

IMMUNOREACT 6: weak immune surveillance characterizes early-onset rectal cancer.

BACKGROUND: Colon cancer in young patients is often associated with hereditary syndromes; however, in early-onset rectal cancer, mutations of these genes are rarely observed. The aim of this study was to analyse the features of the local immune microenvironment and the mutational pattern in early-onset rectal cancer. METHODS: Commonly mutated genes were analysed within a rectal cancer series from the University Hospital of Padova. Mutation frequency and immune gene expression in a cohort from The Cancer Genome Atlas ('TCGA') were compared and immune-cell infiltration levels in the healthy rectal mucosa adjacent to rectal cancers were evaluated in the IMMUNOlogical microenvironment in REctal AdenoCarcinoma Treatment 1 and 2 ('IMMUNOREACT') series. RESULTS: In the authors' series, the mutation frequency of BRAF, KRAS, and NRAS, as well as microsatellite instability frequency, were not different between early- and late-onset rectal cancer. In The Cancer Genome Atlas series, among the genes with the most considerable difference in mutation frequency between young and older patients, seven genes are involved in the immune response and CD69, CD3, and CD8ß expression was lower in early-onset rectal cancer. In the IMMUNOlogical microenvironment in REctal AdenoCarcinoma Treatment 1 and 2 series, young patients had a lower rate of CD4+ T cells, but higher T regulator infiltration in the rectal mucosa. CONCLUSION: Early-onset rectal cancer is rarely associated with common hereditary syndromes. The tumour microenvironment is characterized by a high frequency of mutations impairing the local immune surveillance mechanisms and low expression of immune editing-related genes. A constitutively low number of CD4 T cells associated with a high number of T regulators indicates an imbalance in the immune surveillance mechanisms.

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.

Preoperative Prognostic Nutritional Index was not predictive of short-term complications after laparoscopic resection for rectal cancer.

BACKGROUND AND AIM: Prognostic Nutritional Index (PNI) is a useful tool to predict short-term results in patients undergoing surgery for gastrointestinal cancer. Few studies have addressed this issue in colorectal cancer or specifically in rectal cancer. We evaluated the prognostic relevance of preoperative PNI on morbidity of patients undergoing laparoscopic curative resection for rectal cancer (LCRRC). METHODS: PNI data and clinico-pathological characteristics of LCRRC patients (June 2005-December 2020) were evaluated. Patients with metastatic disease were excluded. Postoperative complications were evaluated using the Clavien-Dindo classification. RESULTS: A total of 182 patients were included in the analysis. Median preoperative PNI was 36.5 (IQR 32.8-41.2). Lower PNI was associated with females (p=0.02), older patients (p=0.0002), comorbidity status (p<0.0001), and those who did not receive neoadjuvant treatment (p=0.01). Post-operative complications occurred in 53 patients (29.1%), by the Clavien-Dindo classification: 40 grades I-II and 13 grades III-V. Median preoperative PNI was 35.0 (31.8-40.0) in complicated patients and 37.0 (33.0-41.5) in uncomplicated patients (p=0.09). PNI showed poor discriminative performance regarding postoperative morbidity (AUC 0.57) and was not associated with postoperative morbidity (OR 0.97) at multivariable analysis. CONCLUSIONS: Preoperative PNI was not associated with postoperative morbidity after LCRRC. Further research should focus on different nutritional indicators or hematological/immunological biomarkers.

Synthetic molecular motor activates drug delivery from polymersomes.

The design of stimuli-responsive systems in nanomedicine arises from the challenges associated with the unsolved needs of current molecular drug delivery. Here, we present a delivery system with high spatiotemporal control and tunable release profiles. The design is based on the combination of an hydrophobic synthetic molecular rotary motor and a PDMS-b-PMOXA diblock copolymer to create a responsive self-assembled system. The successful incorporation and selective activation by low-power visible light (λ = 430 nm, 6.9 mW) allowed to trigger the delivery of a fluorescent dye with high efficiencies (up to 75%). Moreover, we proved the ability to turn on and off the responsive behavior on demand over sequential cycles. Low concentrations of photoresponsive units (down to 1 mol% of molecular motor) are shown to effectively promote release. Our system was also tested under relevant physiological conditions using a lung cancer cell line and the encapsulation of an Food and Drug Administration (FDA)-approved drug. Similar levels of cell viability are observed compared to the free given drug showing the potential of our platform to deliver functional drugs on request with high efficiency. This work provides an important step for the application of synthetic molecular machines in the next generation of smart delivery systems.

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.

IMMUNOREACT 5: female patients with rectal cancer have better immune editing mechanisms than male patients - a cohort study.

BACKGROUND: Studies evaluating sex differences in colorectal cancer (CRC) tumor microenvironment are limited, and no previous study has focused on rectal cancer patients' constitutive immune surveillance mechanisms. The authors aimed to assess gender-related differences in the immune microenvironment of rectal cancer patients. METHODS: A systematic review and meta-analysis were conducted up to 31 May 2021, including studies focusing on gender-related differences in the CRC tumor microenvironment. Data on the mutational profile of rectal cancer were extracted from the Cancer Genome Atlas (TCGA). A subanalysis of the two IMMUNOREACT trials (NCT04915326 and NCT04917263) was performed, aiming to detect gender-related differences in the immune microenvironment of the healthy mucosa in patients with early (IMMUNOREACT 1 cohort) and locally advanced rectal cancer following neoadjuvant therapy (IMMUNOREACT 2 cohort). In the retrospective IMMUNOREACT 1 cohort (therapy naive), the authors enrolled 442 patients (177 female and 265 male), while in the retrospective IMMUNOREACT 2 cohort (patients who had neoadjuvant therapy), we enrolled 264 patients (80 female and 184 male). In the prospective IMMUNOREACT 1 cohort (therapy naive), the authors enrolled 72 patients (26 female and 46 male), while in the prospective IMMUNOREACT 2 cohort (patients who had neoadjuvant therapy), the authors enrolled 105 patients (42 female and 63 male). RESULTS: Seven studies reported PD-L1 expression in the CRC microenvironment, but no significant difference could be identified between the sexes. In the TGCA series, mutations of SYNE1 and RYR2 were significantly more frequent in male patients with rectal cancer. In the IMMUNOREACT 1 cohort, male patients had a higher expression of epithelial cells expressing HLA class I, while female patients had a higher number of activated CD4+Th1 cells. Female patients in the IMMUNOREACT 2 cohort showed a higher infiltration of epithelial cells expressing CD86 and activated cytotoxic T cells (P=0.01). CONCLUSIONS: Male patients have more frequent oncogene mutations associated with a lower expression of T-cell activation genes. In the healthy mucosa of female patients, more Th1 cells and cytotoxic T cells suggest a potentially better immune response to the tumor. Sex should be considered when defining the treatment strategy for rectal cancer patients or designing prognostic scores.

Laparoscopic right hemicolectomy with 2D or 3D video system technology: systematic review and meta-analysis.

BACKGROUND: Standard laparoscopic colorectal surgery relies on 2D image systems in most centers. However, 3D vision has gained popularity and is used nowadays in a constantly rising number of units. Right hemicolectomy with intracorporeal anastomosis and lymph node dissection represents a surgical procedure that may benefit the most from 3D vision. The aim of the study was to summarize the available literature on the use of 2D vs. 3D video imaging in patients undergoing laparoscopic right hemicolectomy. METHODS: A comprehensive literature review was conducted including Medline/PubMed, Embase, and Scopus (PROSPERO registration number CRD 42022344764) through October 2022. The systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The risk of bias was evaluated using the ROBINS-I tool. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines and GRADEpro to develop a summary of evidence tables. Random-effects meta-analyses were conducted. RESULTS: Five observational retrospective studies (496 patients, 275 2D and 216 3D) were included. One study was rated as having a critical risk of bias; the remaining had low to moderate risk. 2D laparoscopic right hemicolectomy patients showed longer anastomotic time in 3/3 studies (MD = 3.32; 95%CI, 1.58-5.05; p = 0.002) and an upward trend in operative time in 4/5 studies (MD = 9.98; 95%CI, -1.42, 21.37; p = 0.086) compared to 3D. The two image video systems had similar short-term outcomes, including the number of lymph nodes harvested (MD = -0.67; 95%CI, -2.47, 1.13; p = 0.47), morbidity (OR post-operative complications = 1.12; 95%CI, 0.71-1.77; p = 0.62), and length of stay (MD = 0.27; 95%CI, -0.59, 1.13; p = 0.9). CONCLUSIONS: 2D and 2D laparoscopic right hemicolectomy had similar complications rate, with a shorter anastomotic time along with a downward trend in overall operative time for 3D. Larger prospective randomized trials are awaited before definitive conclusions can be drawn.

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.

Prognostic role of platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte, and lymphocyte-to-monocyte ratio in operated rectal cancer patients: systematic review and meta-analysis.

BACKGROUND: Inflammation plays an important role in tumor growth. Novel serum blood biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), have been proposed as useful prognostic indexes in cancer patients. However, their role in rectal cancer is controversial. METHODS: A comprehensive literature review was conducted including MEDLINE/Pubmed, EMBASE, SCOPUS, and the Cochrane Database of Systematic Reviews through May 2022. The systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Quality was appraised with the Methodological Index for Non-Randomized Studies (MINORS) tool. Aim of the study was to summarize available literature on PLR, NLR, and LMR in patients with rectal cancer undergoing resection. RESULTS: Forty-seven observational studies (14,205 patients) were included; there were 42 retrospective and 5 prospective cohort studies with an average MINORS score of 14.6 (range: 12-18). Worse overall survival was associated with high NLR (HR 1.81; 95%CI 1.52-2.15; p < 0.001), high PLR (HR 1.24; 95%CI 1.06-1.46; p = 0.009), and low LMR (HR 0.67; 95%CI 0.49-0.91; p = 0.01). High NLR and low LMR were also associated with disease-free-survival (HR 1.68; 95%CI 1.35-2.08; p < 0.001 and HR 0.71; 95%CI 0.58-0.87; p < 0.001, respectively). CONCLUSIONS: NLR, PLR, and LMR are independent clinical predictors for overall survival in patients with rectal cancer treated with curative surgery. NLR and LMR are also good predictors for disease free survival. These biomarkers, which are readily available, appear optimal prognostic indexes and may help clinicians predict the prognosis of rectal cancer and develop individualized treatment strategies.

Does 3D laparoscopic video technology affect long-term survival in right hemicolectomy for cancer compared to standard 2D? A propensity score study.

BACKGROUND: There are few studies focused on the short-term results of laparoscopic right hemicolectomy performed with 2D (two-dimension) or 3D (three-dimension) video technology and none on the oncologic effects. The aim of the study was to assess the long-term results of laparoscopic right hemicolectomy (LRH) with intracorporeal anastomosis using 3D or 2D video in patients with right colon cancer with at least three years of oncologic follow-up. METHODS: Data from patients undergoing laparoscopic right hemicolectomy (LRH) with intracorporeal anastomosis for cancer in an 11-year period (June 2008-June 2019) and ≥ 3 years of follow-up were prospectively collected. Surgical procedures were performed by two expert laparoscopic surgeons. RESULTS: 111 patients were included in the study: 56 (50.5%) in the 3D group and 55 (49.5%) in the 2D group. Tumor stage and number of lymph nodes harvested were similar. Overall and disease-free survival were not different in the two groups. Local recurrence occurred in none of the patients, and distant metachronous metastases were similar in the two groups. A propensity score weighting approach was used to account for potential confounding related to patients' nonrandom allocation to the 2 groups. The effects of the intervention on postoperative outcomes were assessed with a weighted regression approach. CONCLUSIONS: Laparoscopic 3D technology allows similar oncological results as 2D vision in LRH with intracorporeal anastomosis. Larger prospective randomized studies might confirm these results in the long-term follow-up.

Missing the main actor: Intra-operative diagnosis of agenesis of the gallbladder - When late is not 'too' late.

Agenesis of the gallbladder (AGB) without extrahepatic biliary atresia is a rare congenital disease. Ultrasound (US) examination can be misleading and reveal a contracted shrunken gallbladder when there is not any and the patient in most cases is taken to the OR for a standard cholecystectomy. We describe the case of a 54-year-old female with colicky right upper abdominal pain with nausea. US revealed a contracted scleroatrophic gallbladder and the patient was listed for laparoscopic cholecystectomy. At laparoscopy, despite careful search, the gallbladder was never visualised, and the suspicion of AGB was raised. An intra-operative cholangiography confirmed the hypothesis. The post-operative recovery was uneventful, and abdominal computed tomography scan failed to show the presence of gallbladder, therefore confirming the diagnosis of AGB. Lack of awareness of this condition among radiologists and surgeons is the main reason for unnecessary operations and potentially damages to the biliary tract.

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.

Two-Dimensional Triblock Peptide Assemblies for the Stabilization of Pickering Emulsions with pH Responsiveness.

A variety of two-dimensional (2D) nanomaterials, including graphene oxide and clays, are known to stabilize Pickering emulsions to fabricate structures for functions in sensors, catalysts, and encapsulation. We introduce here a novel Pickering emulsion using self-assembled amphiphilic triblock oligoglycine as the emulsifier. Peptide amphiphiles are more responsive to environmental changes (e.g., pH, temperature, and ionic strength) than inorganic 2D materials, which have a chemically rigid, in-plane structure. Noncovalent forces between the peptide molecules change with the environment, thereby imparting responsiveness. We provide new evidence that the biantennary oligoglycine, Gly4-NH-C10H20-NH-Gly4, self-assembles into 2D platelet structures, denoted as tectomers, in solution at a neutral buffered pH using small-angle X-ray scattering and molecular dynamics simulations. The molecules are stacked in the platelets with a linear conformation, rather than in a U-shape. We discovered that the lamellar oligoglycine platelets adsorbed at an oil/water interface and stabilized oil-in-water emulsions. This is the first report of 2D oligoglycine platelets being used as a Pickering stabilizer. The emulsions showed a strong pH response in an acidic environment. Thus, upon reducing the pH, the protonation of the terminal amino groups of the oligoglycine induced disassembly of the lamellar structure due to repulsive electrostatic forces, leading to emulsion destabilization. To demonstrate the application of the material, we show that a model active ingredient, ß-carotene, in the oil is released upon decreasing the pH. Interestingly, in pH 9 buffer, the morphology of the oil droplets evolved over time, as the oligoglycine stabilizer created progressively a thicker interfacial layer. This demonstration opens a new route to use self-assembled synthetic peptide amphiphiles to stabilize Pickering emulsions, which can be significant for biomedical and pharmaceutical applications.

Reminder for the clinician: abdominal manifestations of type 1 neurofibromatosis are not so uncommon.

We describe the case of a woman in her 50s with abdominal pelvic masses suspected to be an ovarian lesion with metastases. At laparoscopy, it appeared as a possible abdominal location of neurofibromatosis type 1 (NF-1). A 50 cm of small bowel was resected to remove multiple nodular lesions. On histopathology, small bowel lesions (n=14) were all classified as GISTs. Clinicians should recognise and consider gastrointestinal manifestations of NF-1 in the diagnostic flow chart. Surgical treatment may resolve symptomatic cases and prevent local infiltration or malignant degeneration of abdominal neoplasms occurring in patients with NF-1.

Chemoradiation vs. local excision in the management of early squamous cell carcinoma of the anus: a systematic review.

PURPOSE: Squamous cell carcinoma of the anus (SCCA) suffers a constant increase each year in the last decades. Recent studies suggested the possibility of local excision (LE) as an option for early-stage SCAC patients. This systematic review aims to summarize the available evidence on the comparison of LE vs. chemoradiotherapy (CRT) in the treatment of early SCCA patients. METHODS: We conducted a literature review including MEDLINE/PubMed, EMBASE, SCOPUS, clinicaltrials.gov, and the Cochrane Database of Systematic Reviews through June 2022. MOOSE guidelines were followed. We used the methodological index for non-randomized studies (MINORS) tool to assess quality. Data on survival and procedure-associated costs were extracted. RESULTS: Four retrospective studies including 3323 patients were included. They were all comparative retrospective cohort studies (three were registry-based studies, either NCDB or SEER) with a MINORS score of 16-19 points. Overall survival (OS) was comparable between LE and CRT patients in three studies, with a 5-year OS of 85.3-100% in LE patients and 85-91.6% in CRT patients. One study investigated cancer-specific survival (CSS) and reported similar 5-year CSS in LE (98%) and CRT patients (96%). One investigated progression-free survival (PFS) and did not report any statistically significant difference in 5-year PFS between LE (91%) and CRT patients (83%). Only one study considered the mean costs associated with the two approaches (29,210 USD with LE and 46,350 USD with CRT). CONCLUSIONS: LE may potentially be considered a valid alternative to CRT for patients with early-stage SCAA. Results of prospective randomized long-term trials comparing LE with CRT are warranted to draw definitive conclusions and consider LE as a true cost-effective strategy for T1N0 SCCA with similar oncologic results offered by CRT, which-to date-remains the "gold standard." PROSPERO REGISTRATION: CRD42022338750.

Rivaroxaban vs placebo for extended antithrombotic prophylaxis after laparoscopic surgery for colorectal cancer.

The clinical benefit of extended prophylaxis for venous thromboembolism (VTE) after laparoscopic surgery for cancer is unclear. The efficacy and safety of direct oral anticoagulants for this indication are unexplored. PROphylaxis of venous thromboembolism after LAParoscopic Surgery for colorectal cancer Study II (PROLAPS II) was a randomized, double-blind, placebo-controlled, investigator-initiated, superiority study aimed at assessing the efficacy and safety of extended prophylaxis with rivaroxaban after laparoscopic surgery for colorectal cancer. Consecutive patients who had laparoscopic surgery for colorectal cancer were randomized to receive rivaroxaban (10 mg once daily) or a placebo to be started at 7 ± 2 days after surgery and given for the subsequent 3 weeks. All patients received antithrombotic prophylaxis with low-molecular-weight heparin from surgery to randomization. The primary study outcome was the composite of symptomatic objectively confirmed VTE, asymptomatic ultrasonography-detected deep vein thrombosis (DVT), or VTE-related death at 28 ± 2 days after surgery. The primary safety outcome was major bleeding. Patient recruitment was prematurely closed due to study drug expiry after the inclusion of 582 of the 646 planned patients. A primary study outcome event occurred in 11 of 282 patients in the placebo group compared with 3 of 287 in the rivaroxaban group (3.9 vs 1.0%; odds ratio, 0.26; 95% confidence interval [CI], 0.07-0.94; log-rank P = .032). Major bleeding occurred in none of the patients in the placebo group and 2 patients in the rivaroxaban group (incidence rate 0.7%; 95% CI, 0-1.0). Oral rivaroxaban was more effective than placebo for extended prevention of VTE after laparoscopic surgery for colorectal cancer without an increase in major bleeding. This trial was registered at www.clinicaltrials.gov as #NCT03055026.

Fully Laparoscopic Pancreas-Preserving Resection of the Third and Fourth Portion of the Duodenum for Adenocarcinomas and Gastrointestinal Stromal Tumors: Technical Report on a Case Series.

Background: Infra-ampullary duodenal lesions are rare and surgical management is controversial. The commonly accepted treatment, which allows radical resection, is pancreaticoduodenectomy, but segmental duodenal resection has been considered as alternative. Aim of the study was to describe the effectiveness of minimally invasive resection of the third/fourth portion of the duodenum for both benign and malignant lesions, with pancreas preservation and reconstruction through end-to-side duodenojejunostomy. Methods: Data from patients undergoing elective laparoscopic curative duodenal resection with pancreas preservation between June 2005 and June 2019 were prospectively collected. Results: A total of 5 patients were identified (3M/2F), median age 73 years (range: 54-83). Lesions were all located in the third or fourth portion of the duodenum and were adenocarcinoma in 2 patients (pT2N0 and pT3N2, both 3 cm in diameter) and gastrointestinal stromal tumor in 3 patients (two pT1N0 and one pT2N0, low-risk according to Miettinen, of 3, 2, and 5 cm in diameter, respectively). The operations lasted a median of 225 minutes (range: 180-300). Digestive continuity was restored with fully laparoscopic side-to-side duodenojejunostomy in all cases. One patient developed pneumonia after surgery (20%) and required also postoperative blood transfusions. Reoperation and mortality rate was nil. Median postoperative stay was 11 days (range: 10-13). The median follow-up was 30 months. Conclusions: Fully laparoscopic pancreas-preserving duodenal resection with duodenojejunal reconstruction can be a safe and feasible option for both benign and malignant lesions of the third and fourth portion of the duodenum. It brings good oncological results, but it needs to be validated with larger number of patients.