Compliance to Adjuvant Chemotherapy of Patients Who Underwent Surgery for Rectal Cancer: Report from a Multi-institutional Research Network.

INTRODUCTION: Adjuvant chemotherapy for locally advanced rectal cancer is associated with improved overall survival. However, recent evidence from randomized trials showed a compliance rate of 43 to 73%, which may affect efficacy. The aim of this multicenter retrospective analysis was to investigate the compliance rate to adjuvant treatment for patients who underwent rectal surgery for cancer. METHODS: Patients who underwent surgery with curative intent for rectal cancer in six Italian colorectal centers between January 2013 and December 2017 were retrospectively reviewed. Exclusion criteria were age less than 18 years, palliative or emergency surgery, and stage IV disease. Parameters of interest were patients' characteristics, preoperative tumor stage, neo-adjuvant chemoradiation therapy, intra-operative and postoperative outcomes. Although the participating centers referred to the same treatment guidelines for treatment, the chemotherapy regiment was not standardized across the institutions. Reasons for not starting adjuvant chemotherapy when indicated, interruption, and modification of drug regimen were collected to investigate compliance. RESULTS: A total of 572 patients were included in the analysis. Two hundred and fifty-two (44.1%) patients received neo-adjuvant chemoradiation therapy. All patients underwent high anterior rectal resection, low anterior rectal resection, or Miles' procedure. Of 399 patients with an indication to adjuvant chemotherapy, 176 (44.1%) completed the treatment as planned. Compliance for patients who started chemotherapy was 56% (95% CI 50.4-61.6%). Sixty-six patients interrupted the treatment, 76 patients significantly reduced the drug dose, and 41 patients had to switch to other therapeutic regimens. CONCLUSIONS: The present multicenter investigation reports a low compliance rate to adjuvant chemotherapy after rectal resection for cancer. Multidisciplinary teams should focus on future effort to improve compliance for these patients.

Combined hepatocellular-cholangiocarcinoma: a population-level analysis of an uncommon primary liver tumor.

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare primary liver cancer. Our aims were to analyze the demographic, clinical, and pathological characteristics of cHCC-CC at a population level and to investigate the effects of these features as well as different management strategies on the prognosis. The Surveillance, Epidemiology, and End Results (SEER) database was analyzed for 1988-2009. Data analyses were performed with chi-square tests, analyses of variance, Kaplan-Meier curves, and Cox proportional hazards regression. Four hundred sixty-five patients with cHCC-CC, 52,825 patients with hepatocellular carcinoma (HCC), and 7181 patients with cholangiocarcinoma (CC) were identified. cHCC-CC was more common in patients who were white, male, and older than 65 years. Treatment was more frequently nonsurgical/interventional. Patients with cHCC-CC, HCC, and CC had 5-year overall survival (OS) and disease-specific survival rates of 10.5%, 11.7%, and 5.7% (P < 0.001) and 17.8%, 21.0%, and 11.9% (P < 0.001), respectively. For cHCC-CC patients, an increasing invasiveness of the therapeutic approach was significantly associated with prolonged survival (P < 0.001). In a multivariate model, black race, a distant SEER stage, and a tumor size of 5.0 to 10.0 cm were independently associated with lower survival for cHCC-CC patients; a year of diagnosis after 1995 and surgical treatment with minor hepatectomy, major hepatectomy (MJH), or liver transplantation (LT) were independently associated with better survival for cHCC-CC patients. Patients diagnosed with cHCC-CC, HCC, and CC and treated with LT had 5-year OS rates of 41.1%, 67.0%, and 29.0%, respectively (P < 0.001). In conclusion, cHCC-CC patients appear to have intermediate demographic, clinical, and survival characteristics in comparison with HCC and CC patients. cHCC-CC patients undergoing LT showed inferior survival in comparison with HCC patients, and the role and indications for LT in cHCC-CC have yet to be defined. At this time, MJH may be considered the best therapeutic approach for such patients.

Intraperitoneal ropivacaine nebulization for pain management after laparoscopic cholecystectomy: a comparison with intraperitoneal instillation.

BACKGROUND: Studies evaluating intraperitoneal local anesthetic instillation for pain relief after laparoscopic procedures have reported conflicting results. In this randomized, double-blind study we assessed the effects of intraperitoneal local anesthetic nebulization on pain relief after laparoscopic cholecystectomy. METHODS: Patients undergoing elective laparoscopic cholecystectomy were randomly assigned to receive either instillation of ropivacaine 0.5%, 20 mL after induction of the pneumoperitoneum, or nebulization of ropivacaine 1%, 3 mL before and after surgery. Anesthetic and surgical techniques were standardized. Degree of pain at rest and on deep breathing, incidence of shoulder pain, morphine consumption, unassisted walking time, and postoperative nausea and vomiting were evaluated at 6, 24, and 48 hours after surgery. RESULTS: Of the 60 patients included, 3 exclusions occurred for conversion to open surgery. There were no differences between groups in pain scores or in morphine consumption. No patients in the nebulization group presented significant shoulder pain in comparison with 83% of patients in the instillation group (absolute risk reduction -83, 95% CI -97 to -70, P<0.001). Nineteen (70%) patients receiving nebulization walked without assistance within 12 hours after surgery in comparison with 14 (47%) patients receiving instillation (absolute risk reduction -24, 95% CI -48 to 1, P=0.04). One (3%) patient in the instillation group vomited in comparison with 6 (22%) patients in the nebulization group (absolute risk reduction -19%, 95% CI -36 to -2, P=0.03). CONCLUSIONS: Intraperitoneal ropivacaine nebulization was associated with reduced shoulder pain and unassisted walking time but with an increased incidence of postoperative vomiting after laparoscopic cholecystectomy.

Should radical surgery for rectal cancer be offered to elderly population? A propensity-matching analysis on short- and long-term outcomes.

Elderly patients with rectal tumor are often undertreated if compared to younger ones. The reasons for this attitude are not fully clear.The aim of this study was to determine the feasibility of radical treatments for rectal cancer in subjects with an age ≥ 75 years (group 1) and to compare short- and long-term outcomes of these patients with patients with an age of less that 75 years (group 2). 311 consecutive patients who underwent radical surgery for rectal cancer were evaluated. A propensity-matching analysis on short- and long-term outcomes was conducted to compare older and younger patients. Overall postoperative complication rate was 23.8% (19/80) in the group 2 and 33.8% (27/80) in group 1 (p = 0.162). OS at 1, 3 and 5 years was 96.2%, 88.4% and 75.9% in under 75 and 92.5%, 64.3% and 50.6% in over 75 group, respectively (p = 0.001). However, TSS was considered, no significant difference was found. Major complications were comparable within groups: 10 (12.5%) versus 11 (13.8%) in groups 2 and 1, respectively (p = 0.633). This study suggests that major rectal cancer surgery with curative intent should not be denied to an elderly population on the basis of age alone. Specific oncologic features and comorbidities are better long-term mortality predictors than aging.

Creation of a rectal cancer registry in Italy by the Advanced International Mini-Invasive Surgery (AIMS) academy clinical research network.

Background: The management of rectal cancer is multimodal and involves a multidisciplinary team of cancer specialists with expertise in medical oncology, surgical oncology, radiation oncology and radiology. It is crucial for highly specialized centers to collaborate via networks that aim to maintain uniformity in every aspect of treatment and rigorously gather patients' data, from the first clinical evaluation to the last follow-up visit. The Advanced International Mini-Invasive Surgery (AIMS) academy clinical research network aims to create a rectal cancer registry. This will prospectively collect the data of patients operated on for non-metastatic rectal cancer in high volume colorectal surgical units through a well design pre-fashioned database for non-metastatic rectal cancer, in order to take all multidisciplinary aspects into consideration. Methods/Design: The protocol describes a multicenter prospective observational cohort study, investigating demographics, frailty, cancer-related features, surgical and radiological parameters, and oncological outcomes among patients with non-metastatic rectal cancer who are candidates for surgery with curative intent. Patients enrolled in the present registry will be followed up for 5 years after surgery. Discussion: Standardization and centralization of data collection for neoplastic diseases is a virtuous process for patient care. The creation of a register will allow the control of the quality of treatments provided and permit prospective and retrospective studies to be carried out on complete and reliable high quality data. Establishing data collection in a prospective and systematic fashion is the only possibility to preserve the enormous resource that each patient represents.

Post-prandial anorexigenic gut peptide, appetite and glucometabolic responses at different eating rates in obese patients undergoing laparoscopic sleeve gastrectomy.

Although different hypotheses have been proposed, the underlying mechanism(s) of the weight loss induced by laparoscopic sleeve gastrectomy (LSG) is still unknown. The aim of this study was to determine whether eating the same meal at different rates (fast vs. slow feeding) evokes different post-prandial anorexigenic gut peptide responses in ten obese patients undergoing LSG. Circulating levels of GLP-1, PYY, glucose, insulin and triglycerides were measured before and 3 months after LSG. Visual analogue scales were used to evaluate the subjective feelings of hunger and satiety. Irrespective of the operative state, either fast or slow feeding did not stimulate GLP-1 release (vs. 0 min); plasma levels of PYY were increased (vs. 0 min) by fast and slow feeding only after LSG. There were no differences in post-prandial levels of GLP-1 when comparing fast to slow feeding or pre-to-post-operative state. Plasma levels of PYY after fast or slow feeding were higher in post, rather than pre-operative state, with no differences when comparing PYY release after fast and slow feeding. Hunger and satiety were decreased and increased, respectively, (vs. 0 min) by food intake. Fast feeding evoked a higher satiety than slow feeding in both pre- and post-operative states, with no differences in hunger. In both pre- and post-operative states, there were similar responses for hunger and satiety after food intake. Finally, LSG improved insulin resistance after either fast or slow feeding. These (negative) findings would suggest a negligible contribution of the anorexigenic gut peptide responses in LSG-induced weight loss.

Intraoperative ultrasound: a review on its role in liver surgery for primitive and metastatic tumors.

Intra-operative ultrasound is an invaluable tool in hepatic surgery, either for restaging either as a guidance during resection of liver neoplasms. Nowadays, intraoperative ultrasound is still considered the most accurate diagnostic technique for detecting focal liver lesions in both hepatocellular carcinoma and colorectal liver metastases, which represent the most frequent indication for liver resection. Moreover, the use of ultrasound guidance is mandatory for planning the surgical strategy, deciding the exact resection plane and during the parenchymal transection, in order to respect the surrounding vessels and biliary structures. Every surgical procedure performed on the liver is strictly dependent from the knowledge of the liver anatomy and from the ultrasounds; definitely in liver surgery the ultrasounds represent the link between the surgical anatomy and the surgical intervention. To maximize the benefit, intraoperative ultrasound should be carried out by the surgeon himself in the perspective of surgical guidance. Here is presented an updated and extensive review of the role of ultrasounds in liver surgery, describing and analyzing the possible applications of this invaluable tool from the surgeon's point of view. Technical aspects, principles of intraoperative re-staging and ultrasound-guided liver resection, application and possible advantages of laparoscopic ultrasound and new perspective in intraoperative study of the liver are discussed.

Hepatic resection beyond barcelona clinic liver cancer indication: When and how.

Hepatocellular carcinoma (HCC) is the main common primary tumour of the liver and it is usually associated with cirrhosis. The barcelona clinic liver cancer (BCLC) classification has been approved as guidance for HCC treatment algorithms by the European Association for the Study of Liver and the American Association for the Study of Liver Disease. According to this algorithm, hepatic resection should be performed only in patients with small single tumours of 2-3 cm without signs of portal hypertension (PHT) or hyperbilirubinemia. BCLC classification has been criticised and many studies have shown that multiple tumors and large tumors, as wide as those with macrovascular infiltration and PHT, could benefit from liver resection. Consequently, treatment guidelines should be revised and patients with intermediate/advanced stage HCC, when technically resectable, should receive the opportunity to be treated with radical surgical treatment. Nevertheless, the surgical treatment of HCC on cirrhosis is complex: The goal to be oncologically radical has always to be balanced with the necessity to minimize organ damage. The aim of this review was to analyze when and how liver resection could be indicated beyond BCLC indication. In particular, the role of multidisciplinary approach to assure a proper indication, of the intraoperative ultrasound for intra-operative restaging and resection guidance and of laparoscopy to minimize surgical trauma have been enhanced.

Long-term sympathoinhibitory effects of surgically induced weight loss in severe obese patients.

Weight loss improves insulin sensitivity and exerts sympathomodulatory effects. No data, however, are available on the effects of the weight loss induced by vertical sleeve gastrectomy on sympathetic neural drive, insulin sensitivity, and their reciprocal cross talks. In 10 severe obese hypertensives (age, 54.0±2.3 years [mean±SEM]), we measured sphygmomanometric blood pressure, heart rate, body mass index, homeostatic model assessment index, plasma leptin, muscle sympathetic nerve traffic (microneurography), and baroreflex sensitivity (vasoactive drug technique). Measurements were performed 2 to 3 days before surgery and repeated 6 and 12 months after the procedure. Ten matched hypertensive obeses not undergoing gastrectomy served as controls. Six months after bariatric surgery, a significant (P<0.05) reduction in body mass index (-9.1±1.4 kg/m(2)), sphygmomanometric systolic blood pressure (-10.2±4.5 mm Hg), heart rate (-11.0±2.4 bpm), homeostatic model assessment index (-3-3±1.3 AU), plasma leptin (-53.6±8.8 µg/L), and muscle sympathetic nerve traffic (-15.0±3.4 bursts/100 heart beats) was observed. The weight loss, the plasma leptin reduction, and the sympathetic inhibition were maintained after 12 months, whereas homeostatic model assessment index showed a tendency to return toward presurgery values. A significant improvement in baroreflex control of sympathetic nerve traffic was observed both 6 (+32.1%; P<0.05) and 12 months (+60.7%; P<0.01) after gastrectomy. No significant changes in the above-mentioned variables were detected in the control group. These data provide evidence that massive weight loss induced by sleeve gastrectomy triggers profound sympathoinhibitory effects, associated with a stable and significant reduction in plasma leptin levels, whereas the improvement in insulin sensitivity was attenuated with time and unrelated to the sympathoinhibition.