Ondansetron for Low Anterior Resection Syndrome (LARS): A Double-Blind, Placebo-Controlled, Cross-Over, Randomized Study.

OBJECTIVE: The aim of the study was to examine the efficacity and safety of ondansetron, a serotonin receptor antagonist, to treat patients with low anterior resection syndrome (LARS). BACKGROUND: LARS after rectal resection is common and debilitating. Current management strategies include behavioral and dietary modifications, physiotherapy, antidiarrheal drugs, enemas, and neuromodulation, but the results are not always satisfactory. METHODS: This is a randomized, multicentric, double-blinded, placebo-controlled, and cross-over study. Patients with LARS (LARS score >20) no longer than 2 years after rectal resection were randomized to receive either 4 weeks of ondansetron followed by 4 weeks of placebo (O-P group) or 4 weeks of placebo followed by 4 weeks of ondansetron (P-O group). The primary endpoint was LARS severity measured using the LARS score; secondary endpoints were incontinence (Vaizey score) and irritable bowel syndrome quality of life (IBS-QoL questionnaire). Patients' scores and questionnaires were completed at baseline and after each 4-week treatment period. RESULTS: Of 46 randomized patients, 38 were included in the analysis. From baseline to the end of the first period, in the O-P group, the mean (SD) LARS score decreased by 25% [from 36.6 (5.6) to 27.3 (11.5)] and the proportion of patients with major LARS (score >30) went from 15/17 (88%) to 7/17 (41%), ( P =0.001). In the P-O group, the mean (SD) LARS score decreased by 12% [from 37 (4.8) to 32.6 (9.1)], and the proportion of major LARS went from 19/21 (90%) to 16/21 (76%). After crossover, LARS scores deteriorated again in the O-P group receiving placebo, but further improved in the P-O group receiving ondansetron. Mean Vaizey scores and IBS QoL scores followed a similar pattern. CONCLUSIONS: Ondansetron is a safe and simple treatment that appears to improve both symptoms and QoL in LARS patients.

Robotic versus laparoscopic liver resections: propensity-matched comparison of two-center experience.

BACKGROUND: The advantages of the robotic approach in minimally invasive liver surgery (MILS) are still debated. This study compares the short-term outcomes between laparoscopic (LLR) and robotic (RLR) liver resections in propensity score matched cohorts. METHODS: Data regarding minimally invasive liver resections in two liver surgery units were retrospectively reviewed. A propensity score matched analysis (1:1 ratio) identified two groups of patients with similar characteristics. Intra- and post-operative outcomes were then compared. The difficulty of MILS was based on the IWATE criteria. RESULTS: Two hundred sixty-nine patients underwent MILS between January 2014 and December 2021 (LLR = 192; RLR = 77). Propensity score matching identified 148 cases (LLR = 74; RLR = 74) consisting of compensated cirrhotic patients (100%) underwent non-anatomic resection of IWATE 1-2 class (90.5%) for a solitary tumor < 5 cm in diameter (93.2%). In such patients, RLRs had shorter operative time (227 vs. 250 min, p = 0.002), shorter Pringle's cumulative time (12 vs. 28 min, p < 0.0001), and less blood loss (137 vs. 209 cc, p = 0.006) vs. LLRs. Conversion rate was nihil (both groups). In RLRs compared to LLRs, R0 rate (93 vs. 96%, p > 0.71) and major morbidity (4.1 vs. 5.4%, p > 0.999) were similar, without post-operative mortality. Hospital stay was shorter in the robotic group (6.2 vs. 6.6, p = 0.0001). CONCLUSION: This study supports the non-inferiority of RLR over LLR. In compensated cirrhotic patients underwent resection of low-to-intermediate difficulty for a solitary nodule < 5 cm, RLR was faster, with less blood loss despite the shorter hilar clamping, and required shorter hospitalization compared to LLR.

Minimally-invasive versus open pancreatic enucleation: systematic review and metanalysis of short-term outcomes.

BACKGROUND: Minimally Invasive Pancreatic Enucleation, either laparoscopic or robot-assisted, is rarely performed. The aim of this study was to offer the current available evidence about the outcomes of minimally invasive pancreatic enucleations and explore the possible advantage of this approach over traditional surgery. METHODS: PubMed (MEDLINE), Cochrane Library and Embase (ELSEVIER) medical databases were searched for articles published from January 1990 to March 2022. Studies which included more than 10 cases of minimally-invasive pancreatic enucleation were included. Data on the outcomes were synthetized and meta-analyzed when appropriate. RESULTS: Twenty studies published between 2009 and 2022 with a total of 552 patients were included in the systematic review: three hundred fifty-one patients (63.5%) had a laparoscopic intervention, two hundred and one (36.5%) robot-assisted with a cumulative incidence of conversion rate of 5%. Minimally-invasive surgery was performed in 63% of cases on the body/tail of the Pancreas and in 37% of the cases on the head/uncinate process of the Pancreas. The cumulative post-operative 30 days - mortality rate was 0.2% and the major postoperative morbidity (Clavien-Dindo III-IV-V) 35%. Clinically relevant pancreatic fistula was observed in 17% of the patients. Compared with the standardized open approach (n: 366 patients), mean length of hospital stay was significantly reduced in patients undergoing minimally invasive pancreatic enucleation (2.45 days, p = 0.003) with a favorable trend for post-operative major morbidity (Clavien-Dindo III-IV) (- 24% RR, p: 0.13). Operative time, blood loss and clinically relevant pancreatic fistula rate were comparable between the two groups. One hundred and fourteen robot-assisted enucleations entered in a subgroup analysis with comparable results to open surgery. CONCLUSION: Minimally-Invasive approach for pancreatic enucleation is safe, feasible and offers short-term clinical outcomes comparable with open surgery. The potential benefit of robotic surgery will need to be verified in further studies.

Transanal (TaTME) vs. laparoscopic total mesorectal excision for mid and low rectal cancer: a propensity score-matched analysis of early and long-term outcomes.

PURPOSE: Transanal total mesorectal excision (TaTME) has been proposed as an alternative to laparoscopic total mesorectal excision (LapTME) in distal rectal tumors. Despite encouraging reports, mid- and long-term oncological results are limited. In this study, we aimed at comparing TaTME versus LapTME in patients with mid and low rectal cancer. METHODS: From January 2012 to December 2019, all patients undergoing either TaTME or LapTME for rectal adenocarcinoma ≤ 12 cm from the anal verge were included. Demographic, clinical, and follow-up data were retrieved from a prospective and audited database, and a propensity score-matched analysis was performed. RESULTS: A total of 144 patients were included, 38 underwent TaTME, and 106 LapTME. The median age was 68.0 (60.2-75.8) years, and 96 (66.7%) patients were male. Median follow-up was 30.6 (20.2-39.8) months in the TaTME group and 49.5 (22.6-68.5) months in the LapTME group. There was one (2.6%) local recurrence in the TaTME group and two (1.9%) in the LapTME group (p = 0.788). There was no difference in the 3-year disease-free survival between groups both in the primary (93% vs. 86%, p = 0.274) and the propensity score-matched analyses (93% vs. 81%, p = 0.132). Conversion to open surgery was less frequent in the TaTME group (none vs. 4 (11.4%), p = 0.041). Intra- and postoperative complications, length of stay, specimen quality, and resection margins were similar between groups. CONCLUSIONS: In our experience, TaTME was associated with a less frequent conversion to open surgery but otherwise had similar post-operative results compared to LapTME. Local recurrence and 3-year survival rates were similar.

Bowel function recovery after laparoscopic transverse colectomy within an ERAS program: a comparison to right and left colectomy.

BACKGROUND: It is known that functional recovery of the bowel is slower after right colectomy (RC) compared to left colectomy (LC), but very little has been reported on transverse colectomy (TC). OBJECTIVES: The aim of this study was to compare the clinical and early functional outcomes of TC, a more infrequent operation, to RC, and LC for colorectal cancer. METHODS: Between December 2011 and December 2017, all patients undergoing elective colon resection in our institution were treated according to a standardized ERAS protocol and entered in a prospective database. We included in the study patients undergoing laparoscopic TC, RC, or LC for cancer with curative intent. The primary endpoint was prolonged postoperative ileus (PPOI), defined as need to insert a nasogastric tube, or refractory nausea VAS > 4 on or after the third postoperative day. Secondary endpoints were postoperative morbidity and length of hospital stay (LoS). RESULTS: Out of 286 patients, 126 met the inclusion criteria: 20 underwent TC, 65 RC, and 41 LC. Patients in LC group were younger than in TC and RC groups; other baseline demographics were similar. PPOI was observed in 5 (25%), 26 (40%), and 10 (24%) patients in TC, RC, and LC groups, respectively (p = 0.417). In single group comparisons, the incidence of PPOI in the TC group was significantly lower in comparison to the RC group (OR for RC: 4.255, 95% CI 1.092-16.667, p = 0.037) and similar to the LC group. No significant differences in terms of postoperative complications or LoS stay were observed. CONCLUSION: The incidence of PPOI after segmental laparoscopic colectomy for cancer within an ERAS program appears as infrequent in TC as in LC and lower than after RC. It may be reasonable to consider a slower oral intake after RC, as it represents an independent predictor of PPOI.

COVID-free surgical pathways for treating patients with acute calculous cholecystitis: a retrospective comparative study.

Introduction: During the Sars-Cov-2 crisis, some of the resources committed to emergency surgery services were transiently reallocated to the care of patients with severe COVID-19, preserving immediate treatment of mostly non-deferrable conditions. Moreover, the fear of contracting infections or hindering the treatment of critical COVID-19 patients has caused many individuals to defer seeking emergency care. This situation has then possibly modified the standard of care of some common surgical conditions and the relative outcomes. Our aims was to highlight any difference in surgical outcomes in patients treated for acute cholecystitis before and during the COVID-19 outbreak. Method: This is a retrospective study on a prospectively collected database that included all consecutive patients treated for acute cholecystitis from March 2019 to February 2021 at the Lugano Regional Hospital, a COVID-free hospital for general surgery patients. Patients were divided into pre-and post-COVID-19 outbreak groups. We collected thorough clinical characteristics and intra-and postoperative outcomes. Results: We included 124 patients, of which 60 and 64 were operated on before and after the COVID-19 outbreak respectively. The two groups resulted similar in terms of patients' clinical characteristics (age, gender, body mass index, ASA score, and comorbidities). Patients in the post-outbreak period were admitted to the hospital 0.7 days later than patients in the pre-outbreak period (3.8 ± 6.0 days vs. 3.1 ± 4.1 days, p = 0.453). Operative time, recovery room time, complications, and reoperations resulted similar between groups. More patients in the post-outbreak period received postoperative antibiotic therapy (63.3% vs. 37.5%, p = 0.004) and for a longer time (6.9 ± 5.1 days vs. 4.5 ± 3.9 days, p = 0.020). No significant histopathological difference was found in operatory specimens. Discussion: Despite more frequent antibiotic therapy that suggests eventually worse inflammatory local status, our results showed similar outcomes for patients treated for acute cholecystitis before and during the COVID-19 pandemic. The local COVID management, reallocating resources, and keeping COVID-free hospitals was key to offering patients a high standard of treatment.

Preoperative chemotherapy in upfront resectable colorectal liver metastases: New elements for an old dilemma?

The use of preoperative or "neoadjuvant" chemotherapy (NAC) has long been controversial for resectable colorectal liver metastases (CRLM). The European Society of Medical Oncology (ESMO) 2023 guidelines on metastatic colorectal cancer (CRC) indicate a combination of surgical/technical and oncologic/prognostic criteria as the two determinants for allocating patients to NAC or upfront hepatectomy. However, surgical and technical criteria have evolved, and oncologic prognostic criteria date from the pre-modern chemotherapy era and lack prospective validation. The traditional literature is interpreted as not supporting the use of NAC because several studies fail to demonstrate a benefit in overall survival (OS) compared to upfront surgery; however, OS may not be the most appropriate endpoint to consider. Moreover, the commonly quoted studies against NAC contain many limitations that may explain why NAC failed to demonstrate its value. The query of the recent literature focused primarily on other aspects than OS, such as surgical technique, the impact of side effects of chemotherapy, the histological growth pattern of metastases, or the detection of circulating tumor DNA, shows data that support a more widespread use of NAC. These should prompt a critical reappraisal of the use of NAC, leading to a more precise selection of patients who could benefit from it.

Concomitant training in robotic and laparoscopic liver resections of low-to-intermediate difficulty score: a retrospective analysis of the learning curve.

In the setting of minimally invasive liver surgery (MILS), training in robotic liver resections (RLR) usually follows previous experience in laparoscopic liver resections (LLR). The aim of our study was to assess the learning curve of RLR in case of concomitant training with LLR. We analyzed consecutive RLRs and LLRs by a surgeon trained simultaneously in both techniques (Surg1); while a second surgeon trained only in LLRs was used as control (Surg2). A regression model was used to adjust for confounders and a Cumulative Sum (CUSUM) analysis was carried out to assess the learning phases according to operative time and difficulty of the procedures (IWATE score). Two-hundred-forty-five procedures were identified (RobSurg1, n = 75, LapSurg1, n = 102, LapSurg2, n = 68). Mean IWATE was 4.0, 4.3 and 5.8 (p < 0.001) in each group. The CUSUM analysis of the adjusted operative times estimated the learning phase in 40 cases (RobSurg1), 40 cases (LapSurg1), 48 cases (LapSurg2); for IWATE score it was 38 cases (RobSurg1), 33 cases (LapSurg1), 38 cases (LapSurg2) respectively. Our preliminary experience showed a similar learning curve of 40 cases for low and intermediate difficulty RLR and LLR. Concomitant training in both techniques was safe and may be a practical option for starting a MILS program.

Neo-Adjuvant Treatment in Primary Resectable Pancreatic Cancer: A Systematic Review and PRISMA-Compliant Updated Metanalysis of Oncological Outcomes.

BACKGROUND: Despite advances in treatment, the prognosis of resectable pancreatic adenocarcinoma remains poor. Neoadjuvant therapy (NAT) has gained great interest in hopes of improving survival. However, the results of available studies based on different treatment approaches, such as chemotherapy and chemoradiotherapy, showed contrasting results. The aim of this systematic review and meta-analysis is to clarify the benefit of NAT compared to upfront surgery (US) in primarily resectable pancreatic adenocarcinoma. METHODS: A PRISMA literature review identified 139 studies, of which 15 were finally included in the systematic review and meta-analysis. All data from eligible articles was summarized in a systematic summary and then used for the meta-analysis. Specifically, we used HR for OS and DFS and risk estimates (odds ratios) for the R0 resection rate and the N+ rate. The risk of bias was correctly assessed according to the nature of the studies included. RESULTS: From the pooled HRs, OS for NAT patients was better, with an HR for death of 0.80 (95% CI: 0.72-0.90) at a significance level of less than 1%. In the sub-group analysis, no difference was found between patients treated with chemoradiotherapy or chemotherapy exclusively. The meta-analysis of seven studies that reported DFS for NAT resulted in a pooled HR for progression of 0.66 (95% CI: 0.56-0.79) with a significance level of less than 1%. A significantly lower risk of positive lymph nodes (OR: 0.45; 95% CI: 0.32-0.63) and an improved R0 resection rate (OR: 1.70; 95% CI: 1.23-2.36) were also found in patients treated with NAT, despite high heterogeneity. CONCLUSIONS: NAT is associated with improved survival for patients with resectable pancreatic adenocarcinoma; however, the optimal treatment strategy has yet to be defined, and further studies are required.

Imaging based body composition profiling and outcomes after oncologic liver surgery.

Body composition profiling is gaining attention as a pre-operative factor that can play a role in predicting the short- and long- term outcomes of patients undergoing oncologic liver surgery. Existing evidence is mostly limited to retrospective and single-institution series and in many of these studies, the evaluation of body composition is based on parameters which are derived from CT-scan imaging. Among body composition phenotypes, sarcopenia is the most well studied but this is only one of the possible profiles which can impact the outcomes of oncologic hepatic surgery. Interest has recently grown in studying the effect of sarcopenic obesity, central obesity, or visceral fat amount, myosteatosis, and bone mineral density on -such patients. The objective of this review is to summarize the current evidence on whether imaging-based parameters of body composition have an impact on the outcome of patients undergoing liver surgery for each of the most frequent indications for liver resection in clinical practice: hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and colorectal liver metastases (CRLM).

A Pilot, Prospective, Observational Study to Investigate the Value of NGS in Liquid Biopsies to Predict Tumor Response After Neoadjuvant Chemo-Radiotherapy in Patients With Locally Advanced Rectal Cancer: The LiBReCa Study.

Introduction: Circulating tumor DNA (ctDNA) correlates with the response to therapy in different types of cancer. However, in patients with locally advanced rectal cancer (LARC), little is known about how ctDNA levels change with neoadjuvant chemoradiation (Na-ChRT) and how they correlate with treatment response. This work aimed to explore the value of serial liquid biopsies in monitoring response after Na-ChRT with the hypothesis that this could become a reliable biomarker to identify patients with a complete response, candidates for non-operative management. Materials and Methods: Twenty-five consecutive LARC patients undergoing long-term Na-ChRT therapy were included. Applying next-generation sequencing (NGS), we characterized DNA extracted from formalin-fixed paraffin embedded diagnostic biopsy and resection tissue and plasma ctDNA collected at the following time points: the first and last days of radiotherapy (T0, Tend), at 4 (T4), 7 (T7) weeks after radiotherapy, on the day of surgery (Top), and 3-7 days after surgery (Tpost-op). On the day of surgery, a mesenteric vein sample was also collected (TIMV). The relationship between the ctDNA at those time-points and the tumor regression grade (TRG) of the surgical specimen was statistically explored. Results: We found no association between the disappearance of ctDNA mutations in plasma samples and pathological complete response (TRG1) as ctDNA was undetectable in the majority of patients from Tend on. However, we observed that the poor (TRG 4) response to Na-ChRT was significantly associated with a positive liquid biopsy at the Top. Conclusions: ctDNA evaluation by NGS technology may identify LARC patients with poor response to Na-ChRT. In contrast, this technique does not seem useful for identifying patients prone to developing a complete response.