Mehdi Karoui

Laparoscopic Liver Resection for Peripheral Hepatocellular Carcinoma in Patients With Chronic Liver Disease: Midterm Results and Perspectives

Objective:Report the midterm results of laparoscopic resection for hepatocellular in chronic liver disease (CLD). Summary Background Data:Surgical resection for hepatocellular carcinoma (HCC) in chronic liver disease (CLD) remains controversial because of high morbidity and recurrence rates. Laparoscopic resection of liver tumors has recently been developed and could reduce morbidity. Methods:From 1998 to 2003, patients with HCC and CLD were considered for laparoscopic liver resection. Inclusion criteria were chronic hepatitis or Childs A cirrhosis, solitary tumor ≤5 cm in size, and location in peripheral segments of the liver. Mortality, morbidity, recurrence rates, and survival were analyzed. Results:A total of 27 patients were included. Liver resections included anatomic resection in 17 cases and non anatomic resection in 10. Seven conversions to laparotomy (26%) occurred for moderate hemorrhage in 5 cases and technical difficulties in 2 cases. Mortality and morbidity rates were 0% and 33%, respectively. Postoperative ascites and encephalopathy occurred in 2 patients (7%) who both had undergone conversion to laparotomy. Mean surgical margin was 11 mm (range, 1–47 mm). After a mean follow-up of 2 years (range, 1.1–4.7), 8 patients (30%) developed intrahepatic tumor recurrence of which one died. Treatment of recurrence was possible in 4 patients (50%), including orthotopic liver transplantation, right hepatectomy, radiofrequency ablation, and chemoembolization in 1 case each. There were no adhesions in the 2 reoperated patients. Overall and disease-free 3-year survival rates were 93% and 64%, respectively. Conclusion:Our study shows that laparoscopic liver resection for HCC in selected patients is a safe procedure with very good midterm results. This approach could have an impact on the therapeutic strategy of HCC complicating CLD as a treatment with curative intent or as a bridge to liver transplantation.

Amoxicillin plus clavulanic acid versus appendicectomy for treatment of acute uncomplicated appendicitis: an open-label, non-inferiority, randomised controlled trial

BACKGROUND Researchers have suggested that antibiotics could cure acute appendicitis. We assessed the efficacy of amoxicillin plus clavulanic acid by comparison with emergency appendicectomy for treatment of patients with uncomplicated acute appendicitis. METHODS In this open-label, non-inferiority, randomised trial, adult patients (aged 18-68 years) with uncomplicated acute appendicitis, as assessed by CT scan, were enrolled at six university hospitals in France. A computer-generated randomisation sequence was used to allocate patients randomly in a 1:1 ratio to receive amoxicillin plus clavulanic acid (3 g per day) for 8-15 days or emergency appendicectomy. The primary endpoint was occurrence of postintervention peritonitis within 30 days of treatment initiation. Non-inferiority was shown if the upper limit of the two-sided 95% CI for the difference in rates was lower than 10 percentage points. Both intention-to-treat and per-protocol analyses were done. This trial is registered with ClinicalTrials.gov, number NCT00135603. FINDINGS Of 243 patients randomised, 123 were allocated to the antibiotic group and 120 to the appendicectomy group. Four were excluded from analysis because of early dropout before receiving the intervention, leaving 239 (antibiotic group, 120; appendicectomy group, 119) patients for intention-to-treat analysis. 30-day postintervention peritonitis was significantly more frequent in the antibiotic group (8%, n=9) than in the appendicectomy group (2%, n=2; treatment difference 5·8; 95% CI 0·3-12·1). In the appendicectomy group, despite CT-scan assessment, 21 (18%) of 119 patients were unexpectedly identified at surgery to have complicated appendicitis with peritonitis. In the antibiotic group, 14 (12% [7·1-18·6]) of 120 underwent an appendicectomy during the first 30 days and 30 (29% [21·4-38·9]) of 102 underwent appendicectomy between 1 month and 1 year, 26 of whom had acute appendicitis (recurrence rate 26%; 18·0-34·7). INTERPRETATION Amoxicillin plus clavulanic acid was not non-inferior to emergency appendicectomy for treatment of acute appendicitis. Identification of predictive markers on CT scans might enable improved targeting of antibiotic treatment. FUNDING French Ministry of Health, Programme Hospitalier de Recherche Clinique 2002.

High prevalence of Foxp3 and IL17 in MMR-proficient colorectal carcinomas

Background and aims: Colorectal cancer (CRC) harbours different types of DNA alterations, including microsatellite instability (MSI). Cancers with high levels of MSI (MSI-H) are considered to have a good prognosis, probably related to lymphocyte infiltration within tumours. The aim of the present study was to characterise the intratumoural expression of markers associated with the antitumour immune response in mismatch repair (MMR)-proficient (MSS) colon cancers. Methods: Ninety human colon cancers (T) and autologous normal colon mucosa (NT) were quantified for the expression of 15 markers of the immune response with quantitiative reverse transcription-PCR (qRT-PCR). mRNA expression levels were correlated with MMR status. Immunohistochemistry (IHC) was performed using both interleukin 17 (IL17) and CD3 antibodies. Results: Expression of cytotoxic markers (FasL, granzyme B and perforin), inflammatory cytokines (IL1β, IL6, IL8, IL17 and transforming growth factor β (TGFβ)) and a marker of regulatory T cells (forkhead box P3 (Foxp3)) was significantly higher in tumours than in autologous normal tissues. Adjusting for MMR status, higher tumoural expression of both granzyme B and perforin was associated with the MSI-H phenotype, and the perforin T/NT ratio was higher in MSI-H tissues than in MSS tissues. Higher tumoural expression of Foxp3, IL17, IL1β, IL6 and TGFβ was associated with the MSS phenotype, and the IL17 T/NT ratio was higher in MSS tissues than in MSI-H tissues as assessed by both qRT-PCR and IHC. Conclusions: Immune gene expression profiling in CRC displayed different patterns according to MMR status. Higher Foxp3, IL6, TGFβ and IL17 expression is a particular determinant in MMR-proficient CRC. These may be potential biomarkers for a new prognostic “test set” in sporadic CRCs.

Laparoscopic Peritoneal Lavage or Primary Anastomosis With Defunctioning Stoma for Hinchey 3 Complicated Diverticulitis : Results of a Comparative Study

PURPOSE: This study was designed to compare postoperative outcomes of laparoscopic peritoneal lavage and open primary anastomosis with defunctioning stoma in the management of Hinchey 3 diverticulitis. METHODS: From 1994 to 2006, 35 patients underwent laparoscopic peritoneal lavage for Hinchey 3 diverticulitis in three institutions. Data prospectively collected were compared with those of a retrospective series of 24 patients matched for Hincheys classification and who underwent primary anastomosis with defunctioning stoma. RESULTS: There was no postoperative death. Postoperative morbidity was not different between the two groups. One patient in the laparoscopic peritoneal lavage group required a Hartmanns procedure because of a colonic fistula. One patient in the primary anastomosis with defunctioning stoma group underwent a reoperation for incisional dehiscence. The median hospital stay was lower in patients treated by laparoscopic peritoneal lavage (8 vs. 17 days, P < 0.0001). Twenty-five patients in the laparoscopic peritoneal lavage group underwent elective laparoscopic resection. One of them required conversion to laparotomy. All patients in the primary anastomosis with defunctioning stoma group have had their ileostomy closed. Cumulative surgical morbidity (16 vs. 37.5 percent, P = 0.0507) and hospital stay (14 vs. 23 days, P < 0.0001) were lower in the laparoscopic peritoneal lavage group. CONCLUSION: In the management of Hinchey 3 diverticulitis, laparoscopic peritoneal lavage does not result in excess morbidity or mortality, it reduces the length of hospital stay and avoids a stoma in most patients, and it is, therefore, a reasonable alternative to primary anastomosis with defunctioning stoma.

Intravoxel incoherent motion (IVIM) MR imaging of colorectal liver metastases: Are we only looking at tumor necrosis?

To determine if intra‐voxel incoherent motion diffusion‐weighted imaging (IVIM‐DWI) parameters, including free molecular‐based (D) and perfusion‐related (D*, f) diffusion parameters, correlate with the degree of tumor necrosis and viable tumor in colo‐rectal cancer (CRC) metastasis.

Right colon to rectal anastomosis (Deloyers procedure) as a salvage technique for low colorectal or coloanal anastomosis: postoperative and long-term outcomes.

BACKGROUND: After extended left colectomy, it may be difficult to take down a well-vascularized colon into the pelvis and perform a tension-free colorectal or coloanal anastomosis. The Deloyers procedure comprising complete mobilization and rotation of the right colon while maintaining the ileocolic artery may be used in this circumstance. OBJECTIVE: The aim of this study is to report postoperative and long-term outcomes after the Deloyers procedure as a salvage technique for colorectal anastomosis or coloanal anastomosis. DESIGN: From a prospective database, we retrospectively reviewed all patients who underwent a Deloyers procedure. SETTING: This study was conducted at the Colorectal Unit in a tertiary referral teaching hospital. PATIENTS: Between 1998 and 2011, 48 consecutive patients underwent a Deloyers procedure. Indications were as following: Hartmann reversal (n = 17), previous colorectal anastomosis-related complications (n = 11), diverticular disease (n = 6), left colon cancer (n = 6), ischemic colitis (n = 3), iterative colectomy for cancer (n = 3), rectal cancer local recurrence (n = 1), and synchronous colon cancer (n = 1). RESULTS: There were 38 men and 10 women (median age at surgery, 67 years). Colorectal anastomosis and coloanal anastomosis were performed in 38 and 10 patients. Thirty-one patients had defunctioning stoma. Mortality and early morbidity rate was 2% and 23%. Three patients (6%) had severe complications (Dindo ≥3). There was no anastomotic leakage. Reoperation was required in 2 patients for intra-abdominal hemorrhage. The median hospital stay was 12 days. The median follow-up was 26 months. All patients had their ileostomy closed. Twenty-three percent of patients developed late complications. The median number of bowel movements per day was 3 (range, 1–7), but 67% of patients had fewer than 3. One patient required an ileostomy refashioning because of poor functional results, and 23% of patients routinely take loperamide-based medication. LIMITATION: The retrospective nature of the study was a limitation. CONCLUSIONS: The Deloyers procedure is safe, associated with low morbidity and good long-term functional results. It represents a safe alternative to total colectomy and ileorectal anastomosis.

Primary chemotherapy with or without colonic stent for management of irresectable stage IV colorectal cancer.

AIM Management of patients with irresectable stage IV colorectal cancer is controversial. Since 2000, we have favoured primary chemotherapy with stent insertion in case of obstructive tumor. Our aim was to report the results of this strategy in an unselected consecutive series of patients. PATIENTS AND METHODS From 2000 to 2007, 68 of 115 consecutive patients admitted with stage IV colorectal cancer were considered irresectable. Data were collected prospectively. Feasibility and outcomes were analysed in an intention to treat basis. RESULTS Of 68 patients, 37 received the intended primary chemotherapy, with stent insertion in 19, 13 required surgery as initial management and 18 patients received supportive care only. Twelve patients in the primary chemotherapy group developed local complication, including bowel obstruction in 9, successfully managed by stent in 6 of them. In patients requiring surgery at presentation, mortality and morbidity were 31% and 77%, respectively. Overall, 41 patients received chemotherapy, of whom, 6 were downstaged to undergo curative resection. Median survival was 6.7 and 15.4 months for the whole series and patients treated by primary chemotherapy, respectively (p<0.0001). On multivariate analysis, age, CEA level, primary chemotherapy and secondary curative resection were independently associated with survival. CONCLUSION In unselected patients with irresectable stage IV colorectal cancer, primary chemotherapy with or without stent is feasible in more than 50% of cases and is associated with a low rate of secondary surgery for complicated primary tumor. This strategy may represent the best palliation in these patients for both duration and quality of survival.

Plasma Circulating Tumor DNA in Pancreatic Cancer Patients Is a Prognostic Marker

Purpose: Despite recent therapeutic advances, prognosis of patients with pancreatic adenocarcinoma remains poor. Analyses from tumor tissues present limitations; identification of informative marker from blood might be a promising alternative. The aim of this study was to assess the feasibility and the prognostic value of circulating tumor DNA (ctDNA) in pancreatic adenocarcinoma. Experimental Design: From 2011 to 2015, blood samples were prospectively collected from all consecutive patients with pancreatic adenocarcinoma treated in our center. Identification of ctDNA was done with next-generation sequencing targeted on referenced mutations in pancreatic adenocarcinoma and with picoliter droplet digital PCR. Results: A total of 135 patients with resectable (n = 31; 23%), locally advanced (n = 36; 27%), or metastatic (n = 68; 50%) pancreatic adenocarcinoma were included. In patients with advanced pancreatic adenocarcinoma (n = 104), 48% (n = 50) had ctDNA detectable with a median mutation allelic frequency (MAF) of 6.1%. The presence of ctDNA was strongly correlated with poor overall survival (OS; 6.5 vs. 19.0 months; P < 0.001) in univariate and multivariate analyses (HR = 1.96; P = 0.007). To evaluate the impact of ctDNA level, patients were grouped according to MAF tertiles: OS were 18.9, 7.8, and 4.9 months (P < 0.001). Among patients who had curative intent resection (n = 31), 6 had ctDNA detectable after surgery, with an MAF of 4.4%. The presence of ctDNA was associated with a shorter disease-free survival (4.6 vs.17.6 months; P = 0.03) and shorter OS (19.3 vs. 32.2 months; P = 0.027). Conclusions: ctDNA is an independent prognostic marker in advanced pancreatic adenocarcinoma. Furthermore, it arises as an indicator of shorter disease-free survival in resected patients when detected after surgery. Clin Cancer Res; 23(1); 116–23. ©2016 AACR.

Postoperative and long-term outcomes after redo surgery for failed colorectal or coloanal anastomosis: retrospective analysis of 50 patients and review of the literature.

INTRODUCTION: Redo surgery for failed colorectal or coloanal anastomosis is a surgical challenge, but despite its technical difficulties and the high associated morbidity risk, it may represent the only valuable option to improve patients’ quality of life by avoiding a permanent stoma and decreasing chronic pelvic symptoms. OBJECTIVES: This study aimed to analyze postoperative and long-term outcomes, with particular focus on functional results, in patients undergoing redo surgery in comparison with previously published studies. DESIGN: This was a retrospective review of prospectively collected data in an institutional database. SETTING: The study was conducted in the colorectal unit of a tertiary referral teaching hospital in France. PATIENTS: Consecutive patients who underwent redo surgery for failed colorectal or coloanal anastomosis from 1998 to 2011 were included. RESULTS: A total of 50 patients (23 men, 27 women) were included. The median age at redo surgery was 62 years (range, 40–84). Twenty-six patients (52%) underwent a redo colorectal anastomosis and 24 patients a redo coloanal anastomosis (48%). Indications were anastomotic stricture (n = 20), chronic pelvic sepsis (n = 14), rectovaginal fistula (n = 3), prior Hartmann’s procedure for complication of initial anastomosis (n = 8), and anastomotic cancer recurrence (n = 5). The median operative time was 435 minutes. Postoperative mortality was 0% and morbidity was 26%. No anastomotic leakage occurred. After a median follow-up of 21 (range, 1–137) months, 44 patients (88%) were evaluated for functional results. The median number of bowel movements per day was 2 (range, 1–10), with 70% of patients having fewer than 3 per day. LIMITATION: The study was limited by its retrospective nature and lack of data on quality of life. CONCLUSIONS: Redo surgery for failed colorectal or coloanal anastomosis is a valuable surgical option which allows avoidance of a permanent stoma in nearly 90% of patients. It remains a major undertaking with high intraoperative and postoperative morbidity.

Liver resection for colorectal liver metastases with peri-operative chemotherapy: oncological results of R1 resections

BACKGROUND Retrospective analysis of outcomes of R0 (negative margin) versus R1 (positive margin) liver resections for colorectal metastases (CLM) in the context of peri-operative chemotherapy. METHODS All CLM resections between 2000 and 2006 were reviewed. Exclusion criteria included: macroscopically incomplete (R2) resections, the use of local treatment modalities, the presence of extra-hepatic disease and no peri-operative chemotherapy. R0/R1 status was based on pathological examination. RESULTS Of 86 eligible patients, 63 (73%) had R0 and 23 (27%) had R1 resections. The two groups were comparable for the number, size of metastases and type of hepatectomy. The R1 group had more bilobar CLM (52% versus 24%, P = 0.018). The median follow-up was 3.1 years. Five-year overall and disease-free survival were 54% and 21% for the R0 group and 49% and 22% for the R1 group (P = 0.55 and P = 0.39, respectively). An intra-hepatic recurrence was more frequent in the R1 group (52% versus 27%, P = 0.02) and occurred more frequently at the surgical margin (22% versus 3%, P = 0.01). DISCUSSION R1 resections were associated with a higher risk of intra-hepatic and surgical margin recurrence but did not negatively impact survival suggesting that in the era of efficient chemotherapy, the risk of an R1 resection should not be considered as a contraindication to surgery.