Pascal Gervaz

Universal screening for methicillin-resistant Staphylococcus aureus at hospital admission and nosocomial infection in surgical patients.

CONTEXT Experts and policy makers have repeatedly called for universal screening at hospital admission to reduce nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection. OBJECTIVE To determine the effect of an early MRSA detection strategy on nosocomial MRSA infection rates in surgical patients. DESIGN, SETTING, AND PATIENTS Prospective, interventional cohort study conducted between July 2004 and May 2006 among 21 754 surgical patients at a Swiss teaching hospital using a crossover design to compare 2 MRSA control strategies (rapid screening on admission plus standard infection control measures vs standard infection control alone). Twelve surgical wards including different surgical specialties were enrolled according to a prespecified agenda, assigned to either the control or intervention group for a 9-month period, then switched over to the other group for a further 9 months. INTERVENTIONS During the rapid screening intervention periods, patients admitted to the intervention wards for more than 24 hours were screened before or on admission by rapid, multiplex polymerase chain reaction. For both intervention (n=10 844) and control (n=10 910) periods, standard infection control measures were used for patients with MRSA in all wards and consisted of contact isolation of MRSA carriers, use of dedicated material (eg, gown, gloves, mask if indicated), adjustment of perioperative antibiotic prophylaxis of MRSA carriers, computerized MRSA alert system, and topical decolonization (nasal mupirocin ointment and chlorhexidine body washing) for 5 days. MAIN OUTCOME MEASURES Incidence of nosocomial MRSA infection, MRSA surgical site infection, and rates of nosocomial acquisition of MRSA. RESULTS Overall, 10 193 of 10 844 patients (94%) were screened during the intervention periods. Screening identified 515 MRSA-positive patients (5.1%), including 337 previously unknown MRSA carriers. Median time from screening to notification of test results was 22.5 hours (interquartile range, 12.2-28.2 hours). In the intervention periods, 93 patients (1.11 per 1000 patient-days) developed nosocomial MRSA infection compared with 76 in the control periods (0.91 per 1000 patient-days; adjusted incidence rate ratio, 1.20; 95% confidence interval, 0.85-1.69; P = .29). The rate of MRSA surgical site infection and nosocomial MRSA acquisition did not change significantly. Fifty-three of 93 infected patients (57%) in the intervention wards were MRSA-free on admission and developed MRSA infection during hospitalization. CONCLUSION A universal, rapid MRSA admission screening strategy did not reduce nosocomial MRSA infection in a surgical department with endemic MRSA prevalence but relatively low rates of MRSA infection. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN06603006.

Human colon cancer epithelial cells harbour active HEDGEHOG-GLI signalling that is essential for tumour growth, recurrence, metastasis and stem cell survival and expansion

Human colon cancers often start as benign adenomas through loss of APC, leading to enhanced βCATENIN (βCAT)/TCF function. These early lesions are efficiently managed but often progress to invasive carcinomas and incurable metastases through additional changes, the nature of which is unclear. We find that epithelial cells of human colon carcinomas (CCs) and their stem cells of all stages harbour an active HH‐GLI pathway. Unexpectedly, they acquire a high HEDGEHOG‐GLI (HH‐GLI) signature coincident with the development of metastases. We show that the growth of CC xenografts, their recurrence and metastases require HH‐GLI function, which induces a robust epithelial‐to‐mesenchymal transition (EMT). Moreover, using a novel tumour cell competition assay we show that the self‐renewal of CC stem cells in vivo relies on HH‐GLI activity. Our results indicate a key and essential role of the HH‐GLI1 pathway in promoting CC growth, stem cell self‐renewal and metastatic behavior in advanced cancers. Targeting HH‐GLI1, directly or indirectly, is thus predicted to decrease tumour bulk and eradicate CC stem cells and metastases.

Randomized clinical trial of mechanical bowel preparation versus no preparation before elective left-sided colorectal surgery

Mechanical bowel preparation (MBP) is performed routinely before colorectal surgery to reduce the risk of postoperative infectious complications. The aim of this randomized clinical trial was to compare the outcome of patients who underwent elective left‐sided colorectal surgery with or without MBP.

Continuous preperitoneal infusion of ropivacaine provides effective analgesia and accelerates recovery after colorectal surgery: a randomized, double-blind, placebo-controlled study

Background:Blockade of parietal nociceptive afferents by the use of continuous wound infiltration with local anesthetics may be beneficial in a multimodal approach to postoperative pain management after major surgery. The role of continuous preperitoneal infusion of ropivacaine for pain relief and postoperative recovery after open colorectal resections was evaluated in a randomized, double-blinded, placebo-controlled trial. Methods:After obtaining written informed consents, a multiholed wound catheter was placed by the surgeon in the preperitoneal space at the end of surgery in patients scheduled to undergo elective open colorectal resection by midline incision. They were thereafter randomly assigned to receive through the catheter either 0.2% ropivacaine (10-ml bolus followed by an infusion of 10 ml/h during 48 h) or the same protocol with 0.9% NaCl. In addition, all patients received patient-controlled intravenous morphine analgesia. Results:Twenty-one patients were evaluated in each group. Compared with preperitoneal saline, ropivacaine infusion reduced morphine consumption during the first 72 h and improved pain relief at rest during 12 h and while coughing during 48 h. Sleep quality was also better during the first two postoperative nights. Time to recovery of bowel function (74 ± 19 vs. 105 ± 54 h; P = 0.02) and duration of hospital stay (115 ± 25 vs. 147 ± 53 h; P = 0.02) were significantly reduced in the ropivacaine group. Ropivacaine plasma concentrations remained below the level of toxicity. No side effects were observed. Conclusions:Continuous preperitoneal administration of 0.2% ropivacaine at 10 ml/h during 48 h after open colorectal resection reduced morphine consumption, improved pain relief, and accelerated postoperative recovery.

Risk factors for survival after lung metastasectomy in colorectal cancer patients: a systematic review and meta-analysis.

BackgroundResection of lung metastases (LM) from colorectal cancer (CRC) is increasingly performed with a curative intent. It is currently not possible to identify those CRC patients who may benefit the most from this surgical strategy. The aim of this study was to perform a systematic review of risk factors for survival after lung metastasectomy for CRC.MethodsWe performed a meta-analysis of series published between 2000 and 2011, which focused on surgical management of LM from CRC and included more than 40 patients each. Pooled hazard ratios (HR) were calculated by using random effects model for parameters considered as potential prognostic factors.ResultsTwenty-five studies including a total of 2925 patients were considered in this analysis. Four parameters were associated with poor survival: (1) a short disease-free interval between primary tumor resection and development of LM (HR 1.59, 95 % confidence interval [CI] 1.27–1.98); (2) multiple LM (HR 2.04, 95 % CI 1.72–2.41); (3) positive hilar and/or mediastinal lymph nodes (HR 1.65, 95 % CI 1.35–2.02); and (4) elevated prethoracotomy carcinoembryonic antigen (HR 1.91, 95 % CI 1.57–2.32). By comparison, a history of resected liver metastases (HR 1.22, 95 % CI 0.91–1.64) did not achieve statistical significance.ConclusionsClinical variables associated with prolonged survival after surgery for LM in CRC patients include prolonged disease-free interval between primary tumor and metastatic spread, normal prethoracotomy carcinoembryonic antigen, absence of thoracic node involvement, and a single pulmonary lesion.

Converted laparoscopic colorectal surgery.

BackgroundConversion rates following laparoscopic colorectal surgery vary widely between studies, and the outcome of converted patients remains controversial.MethodsA comprehensive search of the English-language literature was updated until May 1999.ResultsTwenty-eight studies on 3232 patients were considered for analysis. The overall conversion rate was 15.38%. Seventy nine percent of the studies did not include a definition for conversion; in these studies, the conversion rate was significantly lower than in the series where a specific definition was considered (13.7% vs 18.9%, chi-square test, p<0.001). Converted patients had a prolonged hospital stay (11.38 vs 7.41 days) and operative time (209 vs 189 min) in comparison with laparoscopically completed patients (95% confidence interval (CI), 1.70–4.00 and 35.90–37.10, respectively). The factors associated with an increased rate for conversion were left colectomy (Odds Ratio [OR]=1.061), anterior resection of the rectum (OR=1.088), diverticulitis (OR=1.302), and cancer (OR=2.944) (for each parameter, Wald chi-square value, p<0.001).ConclusionsIn nonrandomized studies, the rate of laparoscopically completed colorectal resections is close to 85%. Because converted patients have a distinct outcome, a clear definition of conversion is required to compare the results of randomized trials. Such trials should also consider a 20% rate of conversion when estimating the sample size for the desired power level. It is likely that converted patients will have a significant impact on the results of future clinical research in laparoscopic colorectal surgery.

percutaneous Ct Scan-guided Drainage vs. antibiotherapy Alone for Hinchey Ii Diverticulitis: A Case-control Study

PurposeCT-scan–guided percutaneous abscess drainage of Hinchey Stage II diverticulitis is considered the best initial approach to treat conservatively the abscess and to subsequently perform an elective sigmoidectomy. However, drainage is not always technically feasible, may expose the patient to additional morbidity, and has not been critically evaluated in this indication. This study was undertaken to compare the results of percutaneous drainage vs. antibiotic therapy alone in patients with Hinchey II diverticulitis.MethodsThis was a case-control study of all patients who presented in our institution with Hinchey Stage II diverticulitis between 1993 and 2005. Thirty-four patients underwent abscess drainage under CT-scan guidance (Group 1), and 32 patients were treated with antibiotic therapy alone (Group 2), in most cases because CT-scan-guided abscess drainage was considered technically unfeasible by the interventional radiology team. Initial conservative treatment was considered a failure when: 1) emergency surgery had to be performed, 2) signs of worsening sepsis developed, and 3) abscess recurred within four weeks of drainage.ResultsThe median size of abscess was 6 (range, 3–18) cm in Group 1 and 4 (range, 3–10) cm in Group 2 (P = 0.002). Median duration of drainage was 8 (range, 1–18) days. Conservative treatment failed in 11 patients (33 percent) of Group 1, and in 6 patients (19 percent) of Group 2 (P = 0.26). Ten patients (29 percent) in Group 1 and five patients (16 percent) in Group 2 underwent emergency surgery (P = 0.24); there were four postoperative deaths (26.6 percent) in this subgroup. Twelve patients (35 percent) in Group 1 and 16 patients (50 percent) in Group 2 subsequently underwent an elective sigmoid resection (P = 0.31). In this subgroup of patients, there was neither anastomotic leakage nor postoperative death.ConclusionsEmergency surgery for Hinchey Stage II diverticulitis carries a high mortality rate and should be avoided. To achieve this, antibiotic therapy alone seems to be a safe alternative, whenever percutaneous drainage is technically difficult or hazardous. Actually, our data did not demonstrate any benefit of CT scan-guided percutaneous abscess drainage, suggesting that the role of interventional radiology techniques in this indication deserves further critical evaluation.

‘Liver First’ Approach in the Treatment of Colorectal Cancer with Synchronous Liver Metastases

Background: In patients with synchronous colorectal liver metastases, an approach reversing the traditional therapeutic order – i.e. starting with chemotherapy first, doing the liver surgery second, and performing the colorectal surgery last – is theoretically appealing as it avoids the risk of metastatic progression during treatment of the primary tumor. The present series updates on a previously reported pilot experience. Patients and Methods: 35 patients with advanced synchronous colorectal metastases and nonobstructive colorectal tumors were treated with the reversed approach. Data were collected in a prospective database. Results: The median number of metastases was 6, the median size of the largest metastasis was 6 cm. Five patients could not complete the program (one death from sepsis during chemotherapy, 3 cases of progressive disease under treatment, and one case of vanishing liver metastases). The remaining 30 patients responded and underwent R0 liver resections with no major complications. One patient needed a Hartmann’s procedure for obstruction after a first-step hepatectomy, and 1 patient had a rectal anastomotic leak. Median survival was 44 months. Overall survival rates of the 30 patients who completed the program at 1, 2, 3, 4 and 5 years were 100, 89, 60, 44 and 31%. Conclusions: The reverse approach appeared feasible and safe, with operability and survival rates better than expected for patients with similar severity. Potential problems, in particular regrowth of vanishing metastases and primary tumors, chemotherapy-associated liver damage, and large bowel obstruction, can be minimized by careful multidisciplinary selection, planning and execution.

A Prospective, Randomized, Single-Blind Comparison of Laparoscopic Versus Open Sigmoid Colectomy for Diverticulitis

Objective:The aim of this study was to compare open and laparoscopic sigmoid resection for diverticulitis with the patient and the nursing staff blinded to the surgical approach. Methods:A total of 113 patients scheduled for an elective sigmoidectomy were randomized to receive either a conventional open (54 patients) or a laparoscopic (59 patients) approach. Postoperatively, an opaque wound dressing was applied and left in place for 4 days, and patients from both groups were managed similarly. The primary endpoints for analysis were (1) postoperative pain; (2) duration of postoperative ileus; and (3) duration of hospital stay (ClinicalTrials.gov, number NCT 00453830). Results:The median duration of procedure was 165 minutes (range, 90–285) in the laparoscopy group and 110 minutes (range, 70–210) in the open group (P < 0.0001). The median delay between surgery and first bowel movement was 76 (range, 31–163) hours in the laparoscopy group versus 105 (range, 53–175) hours in the open group (P < 0.0001). The median score for maximal pain (assessed by a visual analog scale) was 4 (range, 1–10) in the laparoscopy group and 5 (range, 1–10) in the open group (P = 0.05). Finally, the median duration of hospital stay was 5 days (range, 4–69) in the laparoscopy group versus 7 days (range, 5–17) in the open group (P < 0.0001). Conclusion:Laparoscopic sigmoid resection is associated with a 30% reduction in duration of postoperative ileus and hospital stay; by comparison, benefits in terms of postoperative pain appear less impressive, when the patient is blinded to the surgical technique.

Dukes B colorectal cancer: distinct genetic categories and clinical outcome based on proximal or distal tumor location.

PURPOSE: The aim of this study was to determine whether tumor location proximal or distal to the splenic flexure is associated with distinct molecular patterns and can predict clinical outcome in a homogeneous group of patients with Dukes B (T3–T4, N0, M0) colorectal cancer. It has been hypothesized that proximal and distal colorectal cancer may arise through different pathogenetic mechanisms. Althoughp53 and Ki-ras gene mutations occur frequently in distal tumors, another form of genomic instability associated with defective DNA mismatch repair has been predominantly identified in the proximal colon. To date, however, the clinical usefulness of these molecular characteristics remains unproven. METHODS: A total of 126 patients with a lymph node-negative sporadic colon or rectum adenocarcinoma were prospectively assessed with the endpoint of death by cancer. No patient received either radiotherapy or chemotherapy. p53 protein was studied by immunohistochemistry using DO-7 monoclonal antibody, andp53 and Ki-ras gene mutations were detected by single strand conformation polymorphism assay. RESULTS: During a mean follow-up of 67 months, the overall five-year survival was 70 percent. Nuclearp53 staining was found in 57 tumors (47 percent), and was more frequent in distal than in proximal tumors (55vs. 21 percent; chi-squared test,P<0.001). For the whole group, p53 protein expression correlated with poor survival in univariate and multivariate analysis (log-rank test,P=0.01; hazard ratio=2.16; 95 percent confidence interval=1.12−4.11,P=0.02). Distal colon tumors and rectal tumors exhibited similar molecular patterns and showed no difference in clinical outcome. In comparison with distal colorectal cancer, proximal tumors were found to be statistically significantly different on the following factors: mucinous content (P=0.008), degree of histologic differentiation (P=0.012), p53 protein expression, and gene mutation (P=0.001 and 0.01 respectively). Finally, patients with proximal tumors had a marginally better survival than those with distal colon or rectal cancers (log-rank test,P=0.045). CONCLUSION: In this series of Dukes B colorectal cancers, p53 protein expression was an independent factor for survival, which also correlated with tumor location. Eighty-six percent ofp53-positive tumors were located in the distal colon and rectum. Distal colon and rectum tumors had similar molecular and clinical characteristics. In contrast, proximal neoplasms seem to represent a distinct entity, with specific histopathologic characteristics, molecular patterns, and clinical outcome. Location of the neoplasm in reference to the splenic flexure should be considered before group stratification in future trials of adjuvant chemotherapy in patients with Dukes B tumors.