Francesco M. Polignano

Photodynamic therapy is associated with an improvement in survival in patients with irresectable hilar cholangiocarcinoma

BACKGROUND The majority of patients with hilar cholangiocarcinoma have irresectable disease and require palliation with biliary stenting to alleviate symptoms and prevent biliary sepsis. Chemotherapy and radiotherapy have proved ineffective, but recent studies suggest photodynamic therapy (PDT) may improve the outlook for these patients. This prospective clinical cohort study has evaluated the efficacy of radical curative surgery, standard palliative therapy (stent +/- chemotherapy) and a novel palliative therapy (stent +/- Photofrin-PDT) in 50 consecutive patients treated for hilar cholangiocarcinoma over a 5-year period. METHODS Between January 2002 and December 2006, 50 patients with hilar cholangiocarcinoma were evaluated for treatment. Ten patients were considered suitable for curative resection (Cohort 1). Forty patients with irresectable disease were stratified into Cohort 2 - Stent +/- chemotherapy (n= 17); and Cohort 3 - Stent +/- PDT (n= 23). Prospective follow-up in all patients and data collected for morbidity, mortality and overall patient survival. RESULTS The median age was 68 years [range 44-83]. Positive cytology/histology was obtained in 28/50 (56%). One death in Cohort 1 occurred at 145 days after surgical resection. No treatment related-deaths occurred in Cohort 2 or 3, chemotherapy-induced morbidity in three patients in cohort 2, PDT-induced morbidity in 11 patients in cohort 3. Actual 1-year survival was 80%, 12% and 75% in Cohorts 1, 2 and 3, respectively. Mean survival after resection was 1278 days (median survival not reached). Mean and median survival was 173 and 169 days, respectively, in Cohort 2; and 512 and 425 days in Cohort 3. Patient survival was significantly longer in cohorts 1 and 3 (P < 0.0001; Log rank test). CONCLUSION This prospective clinical cohort study has demonstrated that radical surgery and palliative Photofrin-PDT are associated with an increased survival in patients with hilar cholangiocarcinoma.

Optimal surgical technique, use of intra-operative cholangiography (IOC), and management of acute gallbladder disease: the results of a nation-wide survey in the UK and Ireland

INTRODUCTION There is debate on optimal techniques that reduce bile duct injury during laparoscopic cholecystectomy (LC). A national survey of Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS) members was carried out to determine current surgical practice for gallstones, including the use of intra-operative cholangiography (IOC) or critical view of safety to reduce the risk of bile duct injury. SUBJECTS AND METHODS An anonymous postal survey was sent to all 417 AUGIS members. Data on grade of surgeon, place of work (district general hospital, teaching), subspecialty, number LC per year, use of IOC, critical view of safety, and management of stones detected during surgery were collated. RESULTS There was a 36% (152/417) response - 134 (88%) from consultant surgeons (36, HPB; 106,OG; 64, DGH; 88, teaching hospital). Of these, 38% performed > 100 LC per year, 36% 50-100 LC per year, and 22% 25-50 LC per year. IOC was routine for 24%; and selective for 72%. Critical view of Calots triangle was advocated by 82%. Overall, 55% first clip and divide the cystic artery, whereas 41% first clip and divide the cystic duct. Some 39% recommend IOC and 23% pre-operative MRCP if dilated common bile duct (CBD) is noted on pre-operative ultrasound. When bile duct stones are identified on IOC, 61% perform laparoscopic CBD exploration (LCBDE), 25% advise postoperative ERCP, and 13% perform either LCBDE or ERCP. Overall, 88% (n = 134) recommend index cholecystectomy for acute pathology, and this is more likely in a teaching hospital setting (P = 0.003). Laparoscopic CBD exploration was more likely to be performed in university hospitals (P < 0.05). CONCLUSIONS A wide dissection of Calots triangle to provide a critical view of safety is the technique most commonly recommended by AUGIS surgeons (83%) to minimise risk of bile duct injury, in contrast to 24% that recommend routine IOC. The majority (88%) of AUGIS surgeons advise index admission cholecystectomy for acute gallbladder disease.

Preoperative Serum C-Reactive Protein Levels and Post-Operative Lymph Node Ratio Are Important Predictors of Survival After Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma

CONTEXT There is paucity of data on the prognostic value of pre-operative inflammatory response and post-operative lymph node ratio on patient survival after pancreatic-head resection for pancreatic ductal adenocarcinoma. OBJECTIVES To evaluate the role of the preoperative inflammatory response and postoperative pathology criteria to identify predictive and/or prognostic variables for pancreatic ductal adenocarcinoma. DESIGN All patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma between 2002 and 2008 were reviewed retrospectively. The following impacts on patient survival were assessed: i) preoperative serum CRP levels, white cell count, neutrophil count, neutrophil/lymphocyte ratio, lymphocyte count, platelet/lymphocyte ratio; and ii) post-operative pathology criteria including lymph node status and lymph node ratio. RESULTS Fifty-one patients underwent potentially curative resection for pancreatic ductal adenocarcinoma during the study period. An elevated preoperative CRP level (greater than 3 mg/L) was found to be a significant adverse prognostic factor (P=0.015) predicting a poor survival, whereas white cell count (P=0.278), neutrophil count (P=0.850), neutrophil/lymphocyte ratio (P=0.272), platelet/lymphocyte ratio (P=0.532) and lymphocyte count (P=0.721) were not significant prognosticators at univariate analysis. Presence of metastatic lymph nodes did not adversely affect survival (P=0.050), however a raised lymph node ratio predicted poor survival at univariate analysis (P<0.001). The preoperative serum CRP level retained significance at multivariate analysis (P=0.011), together with lymph node ratio (P<0.001) and tumour size (greater than 2 cm; P=0.008). CONCLUSION A pre-operative elevated serum CRP level and raised post-operative lymph node ratio represent significant independent prognostic factors that predict poor prognosis in patients undergoing curative resection for pancreatic ductal adenocarcinoma. There is potential for future neo-adjuvant and adjuvant treatment strategies in pancreatic cancer to be tailored based on preoperative and postoperative factors that predict a poor survival.

Laparoscopic colectomy for cancer and adequate lymphadenectomy

We read with great interest the article titled ‘‘Laparoscopic resection for colon adenocarcinoma’’ by Jacob and Salky [3] from the prestigious Mount Sinai School of Medicine of New York and congratulate the authors on their experience and wish to contribute to the discussion with our own observations on survival and technique. We note that in their experience the mean number of lymph nodes in the resected specimens was consistently lower than 12 for any TNM stage (mean, 10.1). We consider 12 to be the minimum number for an appropriate lymphadenectomy, and this is used for entry into adjuvant therapy trials, as recommended by the National Cancer Institute (NCI) and the American Joint Committee on Cancer [5]. Although long a controversial issue, the recommended minimum number of lymph nodes to be retrieved and examined was eventually set at 12 by the NCI in 2000 and, in all likelihood, it will be raised to at least 18. Strong evidence in support of this is available following the recent publication of two large-scale, European RCT secondary analyses showing that removal of more than 18 lymph nodes correlates with improved survival [4, 7]. Secondary analysis of the INTACC multicenter trials showed that Duke s B patients with fewer than seven lymph nodes in the specimen had significant shorter overall and relapse-free survival compared to those in whom 8–12, 13–17, and >18 lymph nodes had been retrieved (p trend = 0.0009 and 0.0000, respectively) [7]. This finding is reinforced by another similar secondary survey (INT-0089 RCT) confirming, by stepwise multivariate regression analysis, that the number of lymph nodes retrieved by the surgeon and analyzed by the pathologist is a prognostic variable for survival [4]. In N0 patients, a strong correlation was indeed observed because overall and causespecific survival improved as more nodes were recovered (p = 0.0005 and p = 0.0071, respectively). In Dukes C patients, survival also improved as more nodes were removed, in both N1 and the N2 group, reaching 90% 5-year survival in N1 patients when >40 nodes were removed (vs 74% when only 11–40 nodes were removed, p < 0.0001) and 71% in N2 group for >35 lymph nodes (vs 51% for <35, p = 0.002). This linear correlation between survival and nodes recovered indicates a therapeutic effect of lymphadenectomy rather than merely better staging. We also note the striking difference in survival rates between those achieved in Europe by means of a complete radical lymphadenectomy and extensive pathologic exam and those reported by Jacob and Salky [3] (66% for Duke s B and 60% for Dukes C). This may identify a potential area for improvement in both surgical and pathological practice (particularly for Duke s B), which is likely to translate directly into a dramatic improvement in survival. Lymphadenectomy technique can be improved by routinely performing high division of the primary feeding vessel, which allows radical lymphadenectomy. This is often neglected during right hemicolectomy because it requires fine dissection along the superior mesenteric vein and good technical skills. Our personal experience [6] confirms that the number of lymph nodes retrieved during a laparoscopic right hemicolectomy can be easily increased by routinely uncovering and clearing the superior mesenteric vein to reach the origin of the ileocolic and right colic arteries (mean, 27.2 ± 16.1 SD vs 18.7 ± 7.4 SD, p < 0.05). Pathological technique and modality of pathological examination are also an important area for potential improvement because fat clearance techniques have been clearly shown to improve identification of lymph nodes in the resected specimen and should be used more extensively if not routinely [1, 8]. In our experience in right hemicolectomy, when alcohol clearance techniques are routinely used to clear adipose tissue before lymph node harvesting, the mean number of nodes increases to 39.9 (±19.2 SD; median, 38; p< 0.02), and less than 12 lymph nodes could be obtained in just 3.5% of the specimens [6]. In conclusion, the evidence supports our belief that in colorectal cancer the more nodes retrieved, the better. We believe that the suggestion of Goldstein et al. [2], that as many lymph nodes as possible should be picked up and analyzed during curative resections for cancer, is to be favored. Both the surgeon and the pathologist can have a dramatic impact on the survival of colorectal cancer Surg Endosc (2006) 20: 996–997 DOI: 10.1007/s00464-005-0555-1

Index laparoscopic cholecystectomy for acute admissions with cholelithiasis provides excellent training opportunities in emergency general surgery

BACKGROUND There is minimal data on the outcome of early laparoscopic cholecystectomy (LC) for acute gallbladder disease when performed by trainees. This study assesses the outcomes of a policy of same admission LC incorporated into a surgical training programme in a major teaching hospital. METHODS 447 index LCs performed over a 3-year period were reviewed retrospectively. The indications, operating surgeon, operating time, use of IOC, conversion rates, reasons for conversion and post-operative stay were analysed. Multivariate analysis of reasons for conversion was performed. RESULTS 150 LCs were performed by consultants and 297 by registrars; 67 were performed by year 1-3 specialist registrars (SpR) and 230 by year 4-6 SpRs. The indications were biliary colic (n=7), acute cholecystitis (n=180), chronic cholecystitis (n=260), carcinoma (n=1). No difference was found in demographics, operating time (105 min Vs 115 min), use of IOC (34% Vs 29%; P=0.2) and post-operative stay (2 days Vs 1 day) between consultants and registrars. The conversion rates were higher for consultants compared to registrars (29 (19%) Vs 28 (9%), P=0.004). The overall conversion rate was 11%. There were no bile duct injuries. Predictors for conversion were CRP>50 at admission and acute cholecystitis. CONCLUSION In a teaching hospital setting most acute admission LCs (66%) were performed by trainees. A step wise training programme with active consultant supervision of all index LCs results in low morbidity, low conversion rates, and a short post-operative stay for acute gallbladder disease. This model of same admission cholecystectomy provides a good training opportunity in emergency general surgery.

Impact of methicillin-resistant Staphylococcus Aureus (MRSA) infection on patient outcome after pancreatoduodenectomy (PD)--a cause for concern?

Objectives: This study evaluated the impact of methicillin-resistant Staphylococcus aureus (MRSA) hospital-acquired infection on postoperative complications and patient outcome after pancreatoduodenectomy (PD). Methods: Seventy-nine patients who underwent PD were monitored for hospital-acquired MRSA. The patients were grouped as (1) no MRSA infection, (2) skin colonization with MRSA, and (3) systemic MRSA infection. Results: Forty (51%) of the 79 patients were MRSA positive during hospital admission. Fourteen of the 40 patients swabbed for MRSA were found positive (skin colonization), and 26 patients (33%) developed systemic MRSA infection after PD. The sites of MRSA infection included (1) abdominal drain fluid (16/26; 42%), (2) sputum (4/26; 15%), (3) blood cultures (2/26; 8%), and (4) combination of sites (9/26; 35%). The patients with systemic MRSA infection had a longer postoperative stay (31 vs 22 days; P = 0.005) and increased incidence of chest infections compared with MRSA-negative patients (14 vs 4; P = 0.02). Four of the 16 patients with MRSA-positive drain fluid had a postpancreatectomy hemorrhage compared with 3 of the 63 patients with no MRSA infection in drain fluid (P = 0.02). Conclusion: Of the 79 patients admitted for PD, 51% became colonized with MRSA infection. Systemic hospital-acquired MRSA infection in 33% was associated with prolonged postoperative stay, increased wound and chest infections, and increased risk of postoperative hemorrhage.