Gen Sugawara

Perioperative Synbiotic Treatment to Prevent Postoperative Infectious Complications in Biliary Cancer Surgery A Randomized Controlled Trial

Summary Background Data:Use of synbiotics has been reported to benefit human health, but clinical value in surgical patients remains unclear. Objective:To investigate the effect of perioperative oral administration of synbiotics upon intestinal barrier function, immune responses, systemic inflammatory responses, microflora, and surgical outcome in patients undergoing high-risk hepatobiliary resection. Methods:Patients with biliary cancer involving the hepatic hilus (n = 101) were randomized before hepatectomy, into a group receiving postoperative enteral feeding with synbiotics (group A); or another receiving preoperative plus postoperative synbiotics (group B). Lactulose-mannitol (L/M) ratio, serum diamine oxidase (DAO) activity, natural killer (NK) cell activity, interleukin-6 (IL-6), fecal microflora, and fecal organic acid concentrations were determined before and after hepatectomy. Postoperative infectious complications were recorded. Results:Of 101 patients, 81 completed the trial. Preoperative and postoperative changes in L/M ratio and DAO activity were similar between groups. Preoperatively in group B, NK activity, and lymphocyte counts increased, while IL-6 decreased significantly (P < 0.05). Postoperative serum IL-6, white blood cell counts, and C-reactive protein in group B were significantly lower than in group A (P < 0.05). During the preoperative period, numbers of Bifidobacterium colonies cultured from and total organic acid concentrations measured in feces increased significantly in group B (P < 0.05). Postoperative concentrations of total organic acids and acetic acid in feces were significantly higher in group B than in group A (P < 0.05). Incidence of postoperative infectious complications was 30.0% (12 of 40) in group A and 12.1% (5 of 41) in group B (P < 0.05). Conclusions:Preoperative oral administration of synbiotics can enhance immune responses, attenuate systemic postoperative inflammatory responses, and improve intestinal microbial environment. These beneficial effects likely reduce postoperative infectious complications after hepatobiliary resection for biliary tract cancer.

Evolution of surgical treatment for perihilar cholangiocarcinoma: a single-center 34-year review of 574 consecutive resections.

Objective:To review our 34-year experience with 574 consecutive resections for perihilar cholangiocarcinoma and to evaluate the progress made in surgical treatment of this disease. Background:Few studies have reported improved surgical outcomes for perihilar cholangiocarcinoma; therefore, it is still unclear whether surgical treatment of this intractable disease has progressed. Methods:Between April 1977 and December 2010, a total of 754 consecutive patients with perihilar cholangiocarcinoma were treated, of whom 574 (76.1%) underwent resection. The medical records of these resected patients were retrospectively reviewed. Results:The incidence of major hepatectomies has increased, and limited resections, including central hepatectomies and bile duct resections, were rarely performed. Combined vascular resection was being used more often. Operative time has become shorter, and intraoperative blood loss has also decreased significantly. Because of refinements in surgical techniques and perioperative management, morbidity decreased significantly but was still high, with a rate of 43.1% in the last 5 years. Mortality rate has also decreased significantly (P < 0.001) from 11.1% (8/72) before 1990 to 1.4% (3/218) in the last 5 years. The ratio of advanced disease defined as pStage IVA and IVB has increased significantly from 49.4% before 2000 to 61.4% after 2001. The disease-specific survival for the 574 study patients (including all deaths) was 44.3% at year 3, 32.5% at year 5, and 19.9% at year 10. The survival was significantly better in the later period of 2001 to 2010 than in the earlier period of 1977 to 2000 (38.1% vs 23.1% at year 5, P < 0.001). For pM0, R0, and pN0 patients (n = 243), the survival in the later period was good with 67.1% at year 5, which was significantly better than that of the earlier period (P < 0.001). For pM0, R0, and pN1 patients (n = 142), however, the survival in the later period was similar to that of the earlier period (22.1% vs 14.6% at year 5, P = 0.647). Multivariate analysis revealed that lymph node metastasis was the strongest prognostic indicator. Conclusions:Surgical treatment of perihilar cholangiocarcinoma has been evolving steadily, with expanded surgical indication, decreased mortality, and increased survival. Survival for R0 and pN0 patients was satisfactory, whereas survival for pN1 patients was still poor, suggesting that establishment of effective adjuvant chemotherapy is needed.

Hepatopancreatoduodenectomy for cholangiocarcinoma: a single-center review of 85 consecutive patients.

Objective:To outline our experience with hepatopancreatoduodenectomy (HPD) as a treatment for cholangiocarcinoma and to appraise the clinical significance of this challenging procedure. Background:Cholangiocarcinomas often exhibit an extensive ductal spread invading from the hepatic hilus to the lower bile duct, and such tumors can be completely resected only by HPD. Early experiences with HPD were associated with high mortality and morbidity, leading to an underestimation of the survival benefit of HPD. Methods:We retrospectively reviewed the medical records of 85 patients with cholangiocarcinoma who underwent HPD from 1992 to 2011. Major hepatectomy was performed in 79 patients (92.9%), and combined vascular resection was performed in 26 patients (30.6%). Results:The operating time was 762 ± 141 minutes, and blood loss was 2696 ± 1970 mL. Liver failure was the most common abdominal complication (n = 64), followed by pancreatic fistula (n = 60), wound sepsis (n = 33), intra-abdominal abscess (n = 22), refractory ascites (n = 17), bacteremia (n = 16), bile leakage (n = 13), and delayed gastric emptying (n = 12). Re-laparotomy was necessary in 9 cases (11.1%). Overall, 19 patients (22.4%) exhibited Clavien grade 0 to II complications, 58 (68.2%) exhibited grade III, 6 (7.1%) exhibited grade IV, and 2 (2.4%) exhibited grade V (mortality). The overall survival rate for the 85 patients was 79.7% after 1 year, 48.5% after 3 years, 37.4% after 5 years, and 32.1% after 10 years; 9 (10.5%) patients survived for more than 5 years. The rate of survival for the 53 patients with pM0 disease who underwent R0 resection was the most favorable, with 5- and 10-year survival rates of 54.3% and 46.6%, respectively. Conclusions:HPD is technically demanding and is associated with high morbidity. However, this surgery can be performed with low mortality and offers a better probability of long-term survival in selected patients. As hepatobiliary surgeons, we should consider HPD to be a standard procedure for laterally advanced cholangiocarcinomas that are otherwise unresectable.

Value of indocyanine green clearance of the future liver remnant in predicting outcome after resection for biliary cancer

It is difficult to predict hepatic functional reserve accurately before major hepatectomy. The aim of this study was to analyse the usefulness of the future liver remnant plasma clearance rate of indocyanine green (ICGK‐F, calculated as plasma clearance rate of indocyanine green (ICGK) × proportion of the future liver remnant) in predicting death after major hepatectomy.

Incidence of and risk factors for incisional hernia after abdominal surgery

Few larger studies have estimated the incidence of incisional hernia (IH) after abdominal surgery.

Assessment of Nodal Status for Perihilar Cholangiocarcinoma: Location, Number, or Ratio of Involved Nodes.

Objective:To analyze lymph node status in resected perihilar cholangiocarcinoma, to clarify which index (ie, location, number, or ratio of involved nodes) is better for staging, and to determine the minimum requirements for node examination. Background:In the TNM classification for perihilar cholangiocarcinoma, the number or ratio of involved nodes is not considered for nodal staging. The minimum requirement for histologic examination of lymph nodes is arbitrary. Methods:This study involved 320 patients with perihilar cholangiocarcinoma who underwent resection from January 2000 to December 2009 at Nagoya University Hospital. The relationship between lymph node status and patient survival was retrospectively analyzed. Results:Total lymph node counts (TLNCs), ie, the number of lymph nodes examined histologically, averaged 12.9 ± 8.3 (range: 1–59). Lymph node metastasis was found in 146 (45.6%) patients and was an independent, powerful prognostic factor. The survival rates were not significantly different between patients with regional node metastasis alone and those with distant node metastasis (19.2% vs 11.5% at 5 years, P = 0.058). The survival for patients with multiple node metastases was significantly worse than that for patients with single metastasis (12.1% vs 27.6% at 5 years, P = 0.002), regardless of the presence or absence of distant lymph node metastasis. The survival for patients with lymph node ratios (LNRs) of 0.2 or less was significantly better than that for patients with LNRs greater than 0.2 (21.4% vs 13.5% at 5 years, P = 0.032). Upon multivariate analysis of the 146 patients with lymph node metastasis, the number of involved nodes (single vs multiple) was identified as an independent prognostic factor (RR of 1.61, P = 0.045), whereas the locations (regional alone vs distant) and ratios (LNR ⩽ 0.2 vs LNR > 0.2) of involved nodes were not. When the 148 pN0-R0 patients were divided into 3 groups (ie, those with TLNC ≥ 8, with TLNC = 5, 6, or 7, and with TLNC ⩽ 4), survivals were identical between the first and second groups, whereas they were largely different between the former two and the third. Conclusions:Lymph node metastasis is a powerful, independent prognostic factor in perihilar cholangiocarcinoma and is better classified based not on location but on the number of involved nodes. To adequately assess nodal status, histologic examination of 5 or more nodes is recommended.

Portal Vein Embolization before Extended Hepatectomy for Biliary Cancer: Current Technique and Review of 494 Consecutive Embolizations

Backgrounds: Portal vein embolization (PVE) has been widely applied before extended hepatectomy; however, its clinical utility for patients with biliary cancer has not been fully addressed. Methods: Between 1991 and 2010, 494 patients with cholangiocarcinoma (n = 353) or gallbladder cancer (n = 141) underwent PVE before extended hepatectomy. PVE was performed by a transhepatic ipsilateral approach using fibrin glue or absolute ethanol with steel coils. Surgical outcomes of this cohort were retrospectively reviewed. Results: PVE-related complications requiring interventions were found in 3 (0.6%) of the 494 patients; no patient died of these complications. Among the 494 patients, 122 (24.7%) did not undergo subsequent hepatectomy. The unresectability rate was significantly higher in patients with gallbladder cancer than in those with cholangiocarcinoma [43.2% (61/141) and 17.3% (61/353), respectively, p < 0.001]. The remaining 372 patients underwent hepatectomy, and 24 (6.5%) died of postoperative complications [13 of 80 (16.3%) with gallbladder cancer vs. 11 of 292 (3.8%) with cholangiocarcinoma, p < 0.05]. The overall survival for patients with cholangiocarcinoma was significantly better than that for patients with gallbladder cancer, where the 5-year survival rate was 39 and 23%, respectively (p < 0.001). Thirty-six patients with cholangiocarcinoma and 10 patients with gallbladder cancer survived more than 5 years after extended surgery. Conclusion: PVE can be performed safely in patients with cholestatic liver, and it has a potential benefit for patients with advanced biliary cancer who are to undergo extended, difficult hepatectomy.

Clinical Significance of Left Trisectionectomy for Perihilar Cholangiocarcinoma: An Appraisal and Comparison With Left Hepatectomy

Objective:To review our experiences with left-sided hepatectomy for perihilar cholangiocarcinoma, to compare left hepatectomy with left trisectionectomy, and to evaluate the clinical significance of left trisectionectomy from the viewpoint of surgical oncology. Background:Only 4 large case series have been reported on left trisectionectomy, with only a few patients diagnosed with perihilar cholangiocarcinoma. Therefore, the oncologic advantage of left trisectionectomy compared with left hepatectomy for perihilar cholangiocarcinoma is still unclear. Methods:This study involved 201 patients who underwent left-sided hepatectomy for perihilar cholangiocarcinoma (86 trisectionectomies and 115 hepatectomies). Surgical outcome and survival were compared between the 2 types of hepatectomy. The length of the resected right posterior bile duct was also measured. Results:Patients who underwent trisectionectomy had more advanced tumors, thus requiring combined vascular and/or other organ resection. Operative time and blood loss were significantly greater in trisectionectomy than in hepatectomy; therefore, overall morbidity was significantly higher in the former (59.3% vs 33.0%, P < 0.001). Mortality was similar (1.2% vs 0.9%) in both techniques. The length of the resected supraportal right posterior bile duct was significantly longer in trisectionectomy than in hepatectomy (20.7 ± 6.4 vs 13.6 ± 5.2 mm, P < 0.001). However, there was no difference in length of the infraportal type right posterior bile duct. The percentage of negative radial and distal common bile duct margins was similar, but the percentage of negative right posterior bile duct margins was significantly higher in trisectionectomy than in hepatectomy (97.7% vs 89.6%, P = 0.027). Overall, R0 resection was achieved in 84.9% of patients with trisectionectomy and in 70.4% of patients with hepatectomy (P = 0.019). Survival rates were similar between patients with trisectionectomy and those with hepatectomy (36.8% vs 34.0% at 5-year), despite the fact that the former had more advanced disease. Conclusions:Left trisectionectomy for perihilar cholangiocarcinoma, although technically demanding, can be performed with similar mortality rates as left hepatectomy. From an oncologic viewpoint, this operation can increase the number of negative proximal ductal margins, leading to a high proportion of R0 resection, and, in turn, to improved survival rates of patients with advanced left-sided perihilar cholangiocarcinoma.

Gallbladder cancer involving the extrahepatic bile duct is worthy of resection.

Objective: To clarify the value of resection of gallbladder cancer involving the extrahepatic bile duct. Background: Several recent studies have proven that jaundice and extrahepatic biliary involvement are independent predictors of a poor outcome. Only a few authors recommend resection of such advanced disease. Methods: One hundred patients with pT3/4, pN0/1, M0 disease were the subjects of this study. Mortality and long-term outcome were analyzed using a prospectively collected database. Results: The only factor associated with mortality in univariate and multivariate analyses was intraoperative blood loss. The 5-year survival rate and median survival time were 23% and 1.5 years for patients with pathologic extrahepatic biliary invasion (pEBI), and 54% and 15.4 years for patients without pEBI. Twelve patients with pEBI survived beyond 5 years. Multivariate analysis revealed that R1/2 resection and combined resection of adjacent organs other than the liver and extrahepatic bile duct (CRAO) were independent predictors of poor outcome. Five-year survival rate and median survival time after R0 resection without CRAO were 36% and 3.8 years even in patients with pEBI. In contrast, after R0 resection with CRAO 5-year survival and median survival time were 16% and 0.8 years, respectively. Conclusions: Patients with advanced gallbladder cancer with pEBI are candidates for resection when distant metastases are absent and R0 resection is achievable. When CRAO is unnecessary, surgical resection should be aggressively planned.

The effect of preoperative biliary drainage on infectious complications after hepatobiliary resection with cholangiojejunostomy

BACKGROUND Arguments against biliary drainage before pancreatoduodenectomy have been gaining momentum recently. The benefits of biliary drainage before hepatobiliary resection, ie, combined liver and extrahepatic bile duct resection, however, are still debatable. OBJECTIVE To review the outcomes of patients who underwent hepatobiliary resection, with special attention to preoperative biliary drainage, to investigate whether biliary drainage increases the risk of postoperative infectious complications. METHODS This study involved 587 patients who underwent hepatobiliary resection with cholangiojejunostomy, including 475 patients who underwent preoperative biliary drainage and 112 patients who did not. Before each operation, surveillance bile cultures were performed at least once a week. Postoperatively, the bile and drainage fluid were cultured on days 1, 4, and 7. The hospital records of consecutive patients who underwent hepatobiliary resection were reviewed retrospectively. RESULTS Of the 475 patients with biliary drainage, 356 (74.9%) had a positive bile culture during the preoperative period. The incidence of postoperative infectious complications, including surgical-site infection and bacteremia, was similar between patients with biliary drainage and those without (28.2% vs 28.6%, P = .939). A positive bile culture during the perioperative period was highly associated with infectious complications and was one of the independent predictive factors related to infectious complications in a multivariate analysis. CONCLUSION Preoperative biliary drainage is unlikely to increase the incidence of infectious complications after hepatobiliary resection. Perioperative surveillance bile culture is useful for the perioperative selection of appropriate antibiotics because of the high likelihood that micro-organisms isolated from infected sites are identical to those isolated from bile.