Francesco Brunetti

Potential of fecal microbiota for early-stage detection of colorectal cancer

Several bacterial species have been implicated in the development of colorectal carcinoma (CRC), but CRC‐associated changes of fecal microbiota and their potential for cancer screening remain to be explored. Here, we used metagenomic sequencing of fecal samples to identify taxonomic markers that distinguished CRC patients from tumor‐free controls in a study population of 156 participants. Accuracy of metagenomic CRC detection was similar to the standard fecal occult blood test (FOBT) and when both approaches were combined, sensitivity improved > 45% relative to the FOBT, while maintaining its specificity. Accuracy of metagenomic CRC detection did not differ significantly between early‐ and late‐stage cancer and could be validated in independent patient and control populations (N = 335) from different countries. CRC‐associated changes in the fecal microbiome at least partially reflected microbial community composition at the tumor itself, indicating that observed gene pool differences may reveal tumor‐related host–microbe interactions. Indeed, we deduced a metabolic shift from fiber degradation in controls to utilization of host carbohydrates and amino acids in CRC patients, accompanied by an increase of lipopolysaccharide metabolism.

Hepatic Vascular Exclusion With Preservation of the Caval Flow for Liver Resections

OBJECTIVE To report the technique and results of an alternative method of vascular clamping during liver resections. BACKGROUND Most liver resections require vascular clamping to avoid excessive blood loss. Portal triad clamping is often sufficient, but it does not suppress backflow bleeding, which can be prevented only by hepatic vascular exclusion. The latter method adds clamping of the inferior vena cava, which results in hypotension, requiring invasive anesthetic management. There is growing evidence that intermittent clamping is better tolerated than continuous clamping, especially in the presence of underlying liver disease. METHODS Hepatic vascular exclusion with preservation of the caval flow (HVEPC) involved conventional inflow clamping associated with outflow control by clamping the major hepatic veins, thus avoiding caval occlusion. HVEPC was used in 40 patients undergoing major or complex liver resection, including 16 with underlying liver disease. HVEPC was total (clamping of the porta hepatis and all major hepatic veins) in 20 cases and partial (clamping of the porta hepatis and the hepatic veins of the resected territory) in 20. Clamping was continuous in 22 cases and intermittent in 18. Resections included 12 hemihepatectomies, 12 extended hepatectomies, 3 central hepatectomies, and 13 uni- or bisegmentectomies. RESULTS Hemodynamic tolerance of clamping was excellent in all cases, without the need for therapeutic adjustment. Median red cell transfusion requirements were 0 units, and 28 patients (70%) did not receive any transfusions during the hospital stay. There were no deaths, and the morbidity rate was 17.5%. Median hospital stay was 10 days. CONCLUSION HVEPC is a safe and effective procedure applicable to liver tumors without invasion to the inferior vena cava. It offers the advantages of conventional hepatic vascular exclusion without its hemodynamic drawbacks, and it can be applied intermittently or partially.

Anatomical Bi- and Trisegmentectomies as Alternatives to Extensive Liver Resections

Objective To assess the technical and oncologic results of anatomic hepatic bi- and trisegmentectomies. Summary Background Data Regardless of their size, some tumors require extensive hepatectomy only because they are located centrally or in the vicinity of major portal pedicles or hepatic veins. Anatomic bi- and trisegmentectomy might represent an alternative to extensive hepatectomies in such cases. Methods Of 435 liver resections, 32 cases (7%) included 2 or 3 adjacent segments (left lateral sectionectomies, ie, bisegmentectomies 2–3, excluded). There were 16 central hepatectomies (segments 4, 5, and 8), 7 right posterior sectionectomies (segments 6 and 7) and 2 central anterior (segments 4b and 5), 1 central posterior (segments 4a and 8), 2 right superior (segments 7 and 8), 3 right inferior (segments 5 and 6), and 1 left anterior (segments 3 and 4b) bisegmentectomies. Indications were malignant disease in 29 patients, including 15 with cirrhosis and 2 with benign tumors. External landmarks, selective devascularization, and intraoperative ultrasound were used to achieve anatomic resection. Results Mortality, transfusion, and morbidity rates were 0%, 26%, and 19%, respectively. Mean section margin was 9 mm (range, 1-40 mm). Isolated intrahepatic recurrence occurred in 7 patients (24%) and 3 (43%) underwent repeat hepatectomy. Conclusion Anatomic bi- or trisegmentectomy is a safe alternative to extensive liver resection in selected patients, avoiding unnecessary sacrifice of functional parenchyma and enhancing the opportunity to perform repeat resections in cases of recurrence.

Safety of selective vascular clamping for major hepatectomies

BACKGROUND Although hepatic vascular clampings are widely used during major hepatic resections, they may not always be necessary. Selective vascular clamping, which only controls the afferent blood flow of the resected liver, could be a valuable alternative, provided that blood loss is not increased because the opposite liver remains perfused. STUDY DESIGN The aim of the study was to assess the safety of selective vascular clamping in 43 patients who underwent 36 right hepatectomies and 7 left hepatectomies for lesions located peripherally within the liver. Blood transfusions, hepatic tests, morbidity, mortality, and hospital stay were evaluated. RESULTS Selective vascular clamping was efficient in 34 of the 43 attempts (79%), but bleeding from the contralateral liver required conversion to portal triad damping in 9 patients (21%). Median blood transfusions were 0 units (range 0 to 4 U), and 28 patients (65%) did not require transfusions. Postoperative laboratory tests showed that larger changes occurred at day 1 and tended to return to preoperative values at the end of the first postoperative week. Median time of hospitalization was 10 days (range 7 to 28 days). Postoperative course was uneventful in 35 patients (81%). Nonlethal complications occurred in 7 patients (16.3%). One patient (2%) with massive hepatic steatosis died of liver failure after right hepatectomy. CONCLUSIONS Selective vascular clamping is a safe alternative to total inflow occlusion for major hepatectomies applicable in 80% of selected patients with peripheral liver tumors.

Aberrant methylation of NPY, PENK, and WIF1 as a promising marker for blood-based diagnosis of colorectal cancer

BackgroundDNA methylation is a well-known epigenetic mechanism involved in epigenetic gene regulation. Several genes were reported hypermethylated in CRC, althought no gene marker was proven to be individually of sufficient sensitivity or specificity in routine clinical practice. Here, we identified novel epigenetic markers and assessed their combined use for diagnostic accuracy.MethodsWe used methylation arrays on samples from several effluents to characterize methylation profiles in CRC samples and controls, as established by colonoscopy and pathology findings, and selected two differentially methylated candidate epigenetic genes (NPY, PENK). To this gene panel we added WIF, on the basis of being reported in literature as silenced by promoter hypermethylation in several cancers, including CRC. We measured their methylation degrees by quantitative multiplex-methylation specific PCR (QM-MSP) on 15 paired carcinomas and adjacent non-cancerous colorectal tissues and we subsequently performed a clinical validation on two different series of 266 serums, subdivided in 32 CRC, 26 polyps, 47 other cancers and 161 with normal colonoscopy. We assessed the results by receiver operating characteristic curve (ROC), using cumulative methylation index (CMI) as variable threshold.ResultsWe obtained CRC detection on tissues with both sensitivity and specificity of 100%. On serum CRC samples, we obtained sensitivity/specificity values of, e.g., 87%/80%, 78%/90% and 59%/95%, and negative predictive value/positive predictive value figures of 97%/47%, 95%/61% and 92%/70%. On serum samples from other cancers we obtained sensitivity/specificity of, e.g, 89%/25%, 43%/80% and 28%/91%.ConclusionsWe showed the potential of NPY, PENK, and WIF1 as combined epigenetic markers for CRC diagnosis, both in tissue and serum and tested their use as serum biomarkers in other cancers. We optimized a QM-MSP for simultaneously quantifying their methylation levels. Our assay can be an effective blood test for patients where CRC risk is present but difficult to assess (e.g. mild symptoms with no CRC family history) and who would therefore not necessarily choose to go for further examination. This panel of markers, if validated, can also be a cost effective screening tool for the detection of asymptomatic cancer patients for colonoscopy.

2016 WSES guidelines on acute calculous cholecystitis

Acute calculus cholecystitis is a very common disease with several area of uncertainty. The World Society of Emergency Surgery developed extensive guidelines in order to cover grey areas. The diagnostic criteria, the antimicrobial therapy, the evaluation of associated common bile duct stones, the identification of “high risk” patients, the surgical timing, the type of surgery, and the alternatives to surgery are discussed. Moreover the algorithm is proposed: as soon as diagnosis is made and after the evaluation of choledocholitiasis risk, laparoscopic cholecystectomy should be offered to all patients exception of those with high risk of morbidity or mortality. These Guidelines must be considered as an adjunctive tool for decision but they are not substitute of the clinical judgement for the individual patient.

Pathologic Outcomes of Laparoscopic vs Open Mesorectal Excision for Rectal Cancer: A Systematic Review and Meta-analysis

Importance Rectal resection with mesorectal excision is the mainstay treatment for rectal cancer. Objective To review and analyze the evidence concerning the pathologic outcomes of laparoscopic (LRR) vs open (ORR) rectal resection for rectal cancer. Data Sources The Cochrane Central Register of Controlled Trials, MEDLINE (through PubMed), EMBASE, Scopus databases, and clinicaltrials.gov were searched for randomized clinical trials (RCTs) comparing LRR vs ORR. Study Selection Only RCTs published in English from January 1, 1995, to June 30, 2016, that compared LRR with ORR for histologically proven rectal cancer in adult patients and reported pathologic outcomes (eg, positive circumferential resection margin, and complete mesorectal excision) were eligible for inclusion. Of 369 records screened, 14 RCTs were selected for the qualitative and quantitative analyses. Data Extraction and Synthesis Two independent reviewers performed the study selection and quality assessment. Random-effects models were used to summarize the risk ratio (RR) and mean differences. Main Outcomes and Measures The rate of positive circumferential resection margin (CRM), defined as 1 mm or less from the closest tumor to the cut edge of the tissue, and the quality of mesorectal excision (complete, nearly complete, or incomplete). Results The meta-analysis included 14 unique RCTs with 4034 unique patients. Of 2989 patients undergoing rectal resection, a positive CRM was found in 135 (7.9%) of 1697 patients undergoing LRR and 79 (6.1%) of 1292 patients undergoing ORR (RR, 1.17; 95% CI, 0.89-1.53; P = .26; I2 = 0%) in 9 studies. A noncomplete (nearly complete and incomplete) mesorectal excision was reported in 179 (13.2%) of 1354 patients undergoing LRR and 104 (10.4%) of 998 patients undergoing ORR (RR, 1.31; 95% CI, 1.05-1.64; P = .02; I2 = 0%) in 5 studies. The distal resection margin involvement (RR, 1.12; 95% CI, 0.34-3.67; P = .86), the mean number of lymph nodes retrieved (mean difference, 0.05; 95% CI, −0.77 to 0.86; P = .91), the mean distance to the distal margin (mean difference, 0.01 cm; 95% CI, −0.12 to 0.15 cm; P = .87), and the mean distance to radial margins (mean difference, −0.67 mm; 95% CI, −2.16 to 0.83 mm; P = .38) were not significantly different between LRR and ORR. The risk for bias was assessed as low in 10 studies, high in 3, and unknown in 1. The overall quality of the evidence emerging from the literature was rated as high. Conclusions and Relevance Based on the available evidence, the risk for achieving a noncomplete mesorectal excision is significantly higher in patients undergoing LRR compared with ORR. These findings question the oncologic safety of laparoscopy for the treatment of rectal cancer. However, long-term results of the ongoing RCTs are awaited to assess whether these pathologic results have an effect on disease-free and overall patient survival.

Comparison between open and laparoscopic reversal of Hartmann’s procedure for diverticulitis

AIM To compare the open and laparoscopic Hartmanns reversal in patients first treated for complicated diverticulitis. METHODS Forty-six consecutive patients with diverticular disease were included in this retrospective, single-center study of a prospectively maintained colorectal surgery database. All patients underwent conventional Hartmanns procedures for acute complicated diverticulitis. Other indications for Hartmanns procedures were excluded. Patients underwent open (OHR) or laparoscopic Hartmanns reversal (LHR) between 2000 and 2010, and received the same pre- and post-operative protocols of cares. Operative variables, length of stay, short- (at 1 mo) and long-term (at 1 and 3 years) post-operative complications, and surgery-related costs were compared between groups. RESULTS The OHR group consisted of 18 patients (13 males, mean age ± SD, 61.4 ± 12.8 years), and the LHR group comprised 28 patients (16 males, mean age 54.9 ± 14.4 years). The mean operative time and the estimated blood loss were higher in the OHR group (235.8 ± 43.6 min vs 171.1 ± 27.4 min; and 301.1 ± 54.6 mL vs 225 ± 38.6 mL respectively, P = 0.001). Bowel function returned in an average of 4.3 ± 1.7 d in the OHR group, and 3 ± 1.3 d in the LHR group (P = 0.01). The length of hospital stay was significantly longer in the OHR group (11.2 ± 5.3 d vs 6.7 ± 1.9 d, P < 0.001). The 1 mo complication rate was 33.3% in the OHR (6 wound infections) and 3.6% in the LHR group (1 hemorrhage) (P = 0.004). At 12 mo, the complication rate remained significantly higher in the OHR group (27.8% vs 10.7%, P = 0.03). The anastomotic leak and mortality rates were nil. At 3 years, no patient required re-intervention for surgical complications. The OHR procedure had significantly higher costs (+56%) compared to the LHR procedure, when combining the surgery-related costs and the length of hospital stay. CONCLUSION LHR appears to be a safe and feasible procedure that is associated with reduced hospitality stays, complication rates, and costs compared to OHR.

Confocal Laser Endomicroscopy in Gastrointestinal and Pancreatobiliary Diseases: A Systematic Review and Meta-Analysis

Confocal laser endomicroscopy (CLE) is an endoscopic-assisted technique developed to obtain histopathological diagnoses of gastrointestinal and pancreatobiliary diseases in real time. The objective of this systematic review is to analyze the current literature on CLE and to evaluate the applicability and diagnostic yield of CLE in patients with gastrointestinal and pancreatobiliary diseases. A literature search was performed on MEDLINE, EMBASE, Scopus, and Cochrane Oral Health Group Specialized Register, using pertinent keywords without time limitations. Both prospective and retrospective clinical studies that evaluated the sensitivity, specificity, or accuracy of CLE were eligible for inclusion. Of 662 articles identified, 102 studies were included in the systematic review. The studies were conducted between 2004 and 2015 in 16 different countries. CLE demonstrated high sensitivity and specificity in the detection of dysplasia in Barretts esophagus, gastric neoplasms and polyps, colorectal cancers in inflammatory bowel disease, malignant pancreatobiliary strictures, and pancreatic cysts. Although CLE has several promising applications, its use has been limited by its low availability, high cost, and need of specific operator training. Further clinical trials with a particular focus on cost-effectiveness and medicoeconomic analyses, as well as standardized institutional training, are advocated to implement CLE in routine clinical practice.

Traitement laparoscopique d'une duplication gastrique chez l'adulte

We hereby report the case of a 24 years old woman with an adult gastric duplication cyst, a very rare congenital disease. Diagnosis was established on preoperative imaging tests. Complete resection of the duplication cyst was undertaken laparoscopically. To the best of our knowledge, this is the first report of laparoscopic resection of an adult gastric duplication cyst.