Tranexamic acid and blood loss in pancreaticoduodenectomy: TAC-PD randomized clinical trial.

BACKGROUND: Tranexamic acid (TXA) may reduce intraoperative blood loss, but it has not been investigated in pancreaticoduodenectomy (PD). METHODS: A pragmatic, multicentre, randomized, blinded, placebo-controlled trial was conducted. Adult patients undergoing planned PD for biliary, duodenal, or pancreatic diseases were randomly assigned to TXA or placebo groups. Patients in the TXA group were administered 1 g TXA before incision, followed by a maintenance infusion of 125 mg/h TXA. Patients in the placebo group were administered the same volume of saline as those in the placebo group. The primary outcome was blood loss during PD. The secondary outcomes included perioperative blood transfusions, operating time, morbidity, and mortality. RESULTS: Between September 2019 and May 2021, 218 patients were randomly assigned and underwent surgery (108 in the TXA group and 110 in the placebo group). Mean intraoperative blood loss was 659 ml in the TXA group and 701 ml in the placebo group (mean difference -42 ml, 95 per cent c.i. -191 to 106). Of the 218 patients, 202 received the intervention and underwent PD, and the mean blood loss during PD was 667 ml in the TXA group and 744 ml in the placebo group (mean difference -77 ml, 95 per cent c.i. -226 to 72). The secondary outcomes were comparable between the two groups. CONCLUSION: Perioperative TXA use did not reduce blood loss during PD. REGISTRATION NUMBER: jRCTs041190062 (https://jrct.niph.go.jp).

Removing part of the pancreas is an operation with a risk of major blood loss. Tranexamic acid is a drug thought to reduce blood loss. This study asked the question, 'Does tranexamic acid reduce blood loss during surgery on the pancreas?' Half of patients received tranexamic acid during surgery. The other half received only standard care. This study showed that tranexamic acid did not decrease the blood loss during the surgery and may have little effect in patients having a pancreaticoduodenectomy.

Is constant negative pressure for external drainage of the main pancreatic duct useful in preventing pancreatic fistula following pancreatoduodenectomy?

BACKGROUND: This study sought to investigate the utility of constant negative pressure for external drainage of the main pancreatic duct in preventing postoperative pancreatic fistula (POPF) after pancreatoduodenectomy. METHODS: Only patients with soft pancreas were included. In the former period (July 2013 to May 2015), gravity dependent drainage was applied (gravity dependent drainage group), and in the latter period (June 2015 to November 2016), constant negative pressure drainage (negative pressure drainage group) was applied to the main pancreatic duct stent. RESULTS: There were 37 patients in the gravity dependent drainage group and 39 patients in the negative pressure drainage group. Clinically relevant POPF occurred in 21 patients (56.8%) in the gravity dependent drainage group and 13 patients (33.3%) in the negative pressure drainage group (p = 0.040). The incidence rate of major complications (Clavien-Dindo grade > III) was significantly lower in the negative pressure drainage group (13.2%) compared to the gravity dependent drainage group (48.7%) (p = 0.001). In-hospital stay was also significantly shorter in the negative pressure drainage group compared to the gravity dependent drainage group (median 25 vs. 33 days, p = 0.024). Multivariate analysis demonstrated that the gravity dependent drainage was one of the independent risk factors for the incidence of POPF (odds ratio, 3.33; p = 0.032). CONCLUSIONS: In patients with soft pancreas, the incidence rate of clinically relevant POPF may be reduced by applying constant negative pressure to the pancreatic duct stent. It also has a potential to reduce overall incidence of major complications and shorten in-hospital stay after pancreatoduodenectomy.

Duration of Antimicrobial Prophylaxis in Patients Undergoing Major Hepatectomy With Extrahepatic Bile Duct Resection: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the optimal duration of antimicrobial prophylaxis in patients undergoing "complicated"' major hepatectomy with extrahepatic bile duct resection. BACKGROUND: To date, 4 randomized controlled trials (RCTs) have assessed the duration of antimicrobial prophylaxis after hepatectomy. However, all of these previous studies involved only "simple" hepatectomy without extrahepatic bile duct resection. METHODS: Patients with suspected hilar obstruction scheduled to undergo complicated hepatectomy after biliary drainage were randomized to 2-day (antibiotic treatment on days 1 and 2) or 4-day (on days 1 to 4) groups. Antibiotics were selected based on preoperative bile culture. The primary endpoint was the incidence of postoperative infectious complications. RESULTS: In total, 86 patients were included (43 patients in each arm) without between-group differences in baseline characteristics. Bile culture positivity was similar between the 2 groups. No significant between-group differences were observed in surgical variables. The incidence of any infectious complications was similar between the 2 groups (30.2% in the 2-day group and 32.6% in the 4-day group). The positive rate of systemic inflammatory response syndrome and the incidence of additional antibiotic use were almost identical between the 2 groups. According to Clavien-Dindo classification, grade 3a or higher complications occurred in 23 patients (53.5%) in the 2-day group and 29 patients (67.4%) in the 4-day group (P = 0.186). Postoperative hospital stay was not different between the 2 groups. CONCLUSIONS: Two-day administration of antimicrobial prophylaxis is sufficient for patients undergoing hepatectomy with extrahepatic bile duct resection [Registration number: ID 000009800 (University Hospital Medical Information Network, http://www.umin.ac.jp)].

Single-Incision Laparoscopic Splenectomy for an Unruptured Aneurysm of the Splenic Artery.

OBJECTIVE: We describe our experience of single-incision laparoscopic splenectomy (SILS) for an unruptured aneurysm of the splenic artery. CLINICAL PRESENTATION AND INTERVENTION: A 73-year-old woman was diagnosed as having a splenic aneurysm which grew from 14 to 22 mm in diameter within 2 years. Due to a contrast agent allergy, transcatheter arterial embolization could not be performed; therefore, SILS was performed with a 4-cm Z-shaped incision. The operative time and intraoperative blood loss were 132 min and 27 mL, respectively. The patient was discharged 4 days after surgery. CONCLUSION: In selected cases, SILS is a suitable and safe procedure for an unruptured aneurysm of the splenic artery.

Application of fluorescent cholangiography during single-incision laparoscopic cholecystectomy for cholecystitis with a right-sided round ligament: Preliminary experience.

An 82-year-old woman was diagnosed with cholecystitis with a right-sided round ligament. We planned a single-incision laparoscopic cholecystectomy. Based on the findings of fluorescent cholangiography, the running course of the common bile duct was confirmed before dissection of Calot's triangle, and the confluence between the cystic duct and the common bile duct was exposed after the dissection of Calot's triangle. The planned surgery was successful. The operative time and intraoperative blood loss were 157 min and 2 mL, respectively. The patient was discharged from our hospital 3 days after surgery. Application of fluorescent cholangiography during a laparoscopic cholecystectomy for the patients with a right-sided round ligament should be widely accepted.

Residual Carcinoma In Situ at the Ductal Stump has a Negative Survival Effect: An Analysis of Early-stage Cholangiocarcinomas.

OBJECTIVE: The aim of the study was to evaluate whether carcinoma in situ (CIS) residue at the ductal stump affects the survival of patients undergoing resection for extrahepatic cholangiocarcinoma. BACKGROUND: Positive ductal margin with CIS has been treated as a tumor-free margin from a prognostic viewpoint because several studies have reported that residual CIS foci at the ductal stump do not affect survival after resection. METHODS: Patients who underwent resection for extrahepatic cholangiocarcinoma were retrospectively reviewed. The surgical margin status was histologically divided into negative (R0), positive with CIS (R1cis), and positive with invasive cancer (R1inv). The survival and incidence of local recurrence were compared among the groups. RESULTS: Of 684 consecutive resected patients, 172 patients with early-stage (pTis-2N0M0) cholangiocarcinoma (perihilar, n = 144; distal, n = 28) were analyzed. The cumulative incidence of local recurrence in R1cis patients was higher than R0 patients (32.8% vs 4.4% at 5 years, P < 0.001) and lower than R1inv patients (50.0% at 2 years, P = 0.012). The disease-specific survival for R1cis patients was worse than for R0 patients (35.1% vs 78.7% at 5 years, P = 0.005) and better than for R1inv patients (40.0% at 2 years, P = 0.002). The uni- and multivariate analyses identified the surgical margin status as an independent prognostic factor (R1cis vs R0, relative risk 2.39, P = 0.026; R1inv vs R0, RR 10.28, P < 0.001). CONCLUSION: R1cis increases the incidence of local recurrence and shortens postoperative survival in patients with early-stage cholangiocarcinoma, although this prognostic effect was less severe compared with R1inv. R1cis should be avoided as much as possible in surgery for early-stage cancer, although it may be allowed in advanced tumors.

Trefoil factor family 1 expression in the invasion front is a poor prognostic factor associated with lymph node metastasis in pancreatic cancer.

OBJECTIVES: Trefoil Factor Family protein 1 (TFF1) is secreted from mucus-producing cells. The relationship between TFF1 expression and clinical outcome in pancreatic ductal adenocarcinoma (PDAC) remains unknown. We aimed to evaluate the prognostic significance of TFF1 expression in PDAC. METHODS: TFF1 expression was examined on paraffin-embedded sections from 91 patients with resected PDAC using immunohistochemistry. The relationships between TFF1 expression and clinicopathological features were analyzed. RESULTS: Among 91 PDAC patients, 71 patients (79.7%) showed TFF1 expression in cancer cells. In a subgroup of 71 patients, TFF1 expression was predominantly observed in the central part of the tumor, whereas TFF1 expression in the invasion front was reduced in 33 patients (46.4%). A significant correlation between preserved TFF1 expression in the invasion front and lymph node metastasis was observed. Univariate survival analysis revealed that preserved TFF1 expression in the invasion front, positive lymphatic invasion, lymph node metastasis and R1 resection was a significant poor prognostic factor in TFF1-positive PDAC patients. CONCLUSIONS: TFF1 expression is frequently lost or decreased in the invasion front of human PDAC, and preserved TFF1 expression in the invasion front might predict poor survival in patients with PDAC.

Surgery-Related Muscle Loss and Its Association with Postoperative Complications After Major Hepatectomy with Extrahepatic Bile Duct Resection.

BACKGROUND: Several studies have reported that preoperative sarcopenia negatively impacts postoperative outcomes. Meanwhile, changes in skeletal muscle mass during the acute phase after surgery and their association with postoperative complications are unknown. OBJECTIVE: The objective of this study was to investigate the relation between changes in skeletal muscle mass and postoperative complications after major hepatectomy with extrahepatic bile duct resection. METHODS: This study included 254 patients who underwent major hepatectomies with extrahepatic bile duct resections. Total psoas muscle area (TPA) was measured using abdominal computed tomography images obtained before and 1 week after surgery. The percent change in TPA after surgery was calculated. Patients were stratified by sex-specific tertiles according to the extent of muscle mass change by percentage. Surgery-related muscle loss (SML) was defined as the lowest tertile of percent change in TPA. RESULTS: Male patients with a percent change of TPA lower than -5.0 % (n = 54) and female patients with that lower than -2.6 % (n = 31) were included in the lowest tertile and were categorized into a group with SML. The incidence rates of major complications, pancreatic fistula, infectious complications, and mortality were all significantly higher in the group with SML than in the group without SML. By multivariate analyses, SML was identified as an independent factor associated with major complications (odds ratio 3.21; 95 % confidential interval 1.82-5.76, p < 0.001). CONCLUSIONS: SML is significantly associated with postoperative morbidity and mortality in patients who underwent major hepatectomies with extrahepatic bile duct resections.

Pulmonary Metastasis After Resection of Cholangiocarcinoma: Incidence, Resectability, and Survival.

BACKGROUND: There are few reports on pulmonary metastasis from cholangiocarcinoma; therefore, its incidence, resectability, and survival are unclear. METHODS: Patients who underwent surgical resection for cholangiocarcinoma, including intrahepatic, perihilar, and distal cholangiocarcinoma were retrospectively reviewed, and this study focused on patients with pulmonary metastasis. RESULTS: Between January 2003 and December 2014, 681 patients underwent surgical resection for cholangiocarcinoma. Of these, 407 patients experienced disease recurrence, including 46 (11.3%) who developed pulmonary metastasis. Of these 46 patients, 9 underwent resection for pulmonary metastasis; no resection was performed in the remaining 37 patients. R0 resection was achieved in all patients, and no complications related to pulmonary metastasectomy were observed. The median time to recurrence was significantly longer in the 9 patients who underwent surgery than in the 37 patients without surgery (2.5 vs 1.0 years, p < 0.010). Survival after surgery for primary cancer and survival after recurrence were significantly better in the former group than in the latter group (after primary cancer: 66.7 vs 0% at 5 years, p < 0.001; after recurrence: 40.0 vs 8.7% at 3 years, p = 0.003). Multivariate analysis identified the time to recurrence and resection for pulmonary metastasis as independent prognostic factors for survival after recurrence. CONCLUSION: Resection for pulmonary metastasis originating from cholangiocarcinoma can be safely performed and confers survival benefits for select patients, especially those with a longer time to recurrence after initial surgery.

The Benefits of a Wound Protector in Preventing Incisional Surgical Site Infection in Elective Open Digestive Surgery: A Large-Scale Cohort Study.

BACKGROUND: The objective of this study was to evaluate the benefits of wound protectors (WPs) in preventing incisional surgical site infection (I-SSI) in open elective digestive surgery using data from a large-scale, multi-institutional cohort study. METHODS: Patients who had elective digestive surgery for malignant neoplasms between November 2009 and February 2011 were included. The protective value of WPs against I-SSI was evaluated. RESULTS: A total of 3201 patients were analyzed. A WP was used in 1022 patients (32%). The incident rate of I-SSI (not including organ/space SSI) was 9%. In the univariate and the multivariate analyses for perioperative risk factors for I-SSI, the use of WP was an independent favorable factor that reduced the incidence of I-SSI (odds ratio 0.73, 95% confidence interval 0.55-0.98. P = 0.038). The subgroup forest plot analyses revealed that WP reduced the risk of I-SSI only in patients aged 74 years or younger, males, non-obese patients (body mass index <25 kg/m2), patients with an American Society of Anesthesiologists score of 1/2, patients with a previous history of laparotomy, non-smokers, and patients who underwent colon and rectum operations. In patients who underwent colorectal surgery, the postoperative hospital stay was significantly shorter in patients with WP than those without WP (median 13 vs. 15 days, P = 0.040). In terms of the depth of SSI, WP only prevented superficial I-SSI and did not reduce the incidence of deep I-SSI. CONCLUSIONS: WP is a useful device for preventing superficial I-SSI in open elective digestive surgery. TRIAL REGISTRATION NUMBER: UMIN000004723.

Adjuvant gemcitabine monotherapy for resectable perihilar cholangiocarcinoma with lymph node involvement: a propensity score matching analysis.

PURPOSE: The aim of this study was to evaluate the efficacy of adjuvant gemcitabine monotherapy following resection for perihilar cholangiocarcinoma with lymph node involvement. METHODS: We performed a retrospective analysis of 180 patients undergoing resection for perihilar cholangiocarcinoma with lymph node involvement between 2001 and 2012. The patients were divided into two groups according to the presence (n = 67) or absence (n = 113) of adjuvant gemcitabine monotherapy. Univariate and multivariate analyses were performed followed by a propensity score matching analysis to adjust for the differences in the baseline characteristics of the groups. RESULTS: The overall survival rates after surgery and the median survival times in patients who were treated with adjuvant chemotherapy were significantly longer than those who were treated without adjuvant chemotherapy (32.9 vs. 15.0 % at 5 years, 37 vs. 20 months, P = 0.001). A multivariate analysis indicated that adjuvant chemotherapy, a residual microscopic tumor, and pathological T stage were independent prognostic factors for survival. After two new cohorts of 32 patients were generated following 1:1 propensity score matching, the overall survival rate in the adjuvant chemotherapy group was found to be significantly longer than that in the surgery alone group (43.2 vs. 15.6 % at 5 years, P = 0.001). CONCLUSION: Adjuvant gemcitabine monotherapy may improve survival in node-positive perihilar cholangiocarcinoma patients.

The development of an automatically produced cholangiography procedure using the reconstruction of portal-phase multidetector-row computed tomography images: preliminary experience.

PURPOSE: Fusion angiography using reconstructed multidetector-row computed tomography (MDCT) images, and cholangiography using reconstructed images from MDCT with a cholangiographic agent include an anatomical gap due to the different periods of MDCT scanning. To conquer such gaps, we attempted to develop a cholangiography procedure that automatically reconstructs a cholangiogram from portal-phase MDCT images. METHODS: The automatically produced cholangiography procedure utilized an original software program that was developed by the Graduate School of Information Science, Nagoya University. This program structured 5 candidate biliary tracts, and automatically selected one as the candidate for cholangiography. The clinical value of the automatically produced cholangiography procedure was estimated based on a comparison with manually produced cholangiography. RESULTS: Automatically produced cholangiograms were reconstructed for 20 patients who underwent MDCT scanning before biliary drainage for distal biliary obstruction. The procedure showed the ability to extract the 5 main biliary branches and the 21 subsegmental biliary branches in 55 and 25 % of the cases, respectively. The extent of aberrant connections and aberrant extractions outside the biliary tract was acceptable. Among all of the cholangiograms, 5 were clinically applied with no correction, 8 were applied with modest improvements, and 3 produced a correct cholangiography before automatic selection. CONCLUSIONS: Although our procedure requires further improvement based on the analysis of additional patient data, it may represent an alternative to direct cholangiography in the future.

Clinical influence of preoperative factor XIII activity in patients undergoing pancreatoduodenectomy.

BACKGROUND: The influence of decreased factor XIII (FXIII) activity on perioperative bleeding has been reported in some surgical procedures. The purposes of this study were to investigate the perioperative dynamics of FXIII in patients undergoing pancreatoduodenectomy and to clarify the effects of low preoperative FXIII activity on intraoperative bleeding and postoperative complications. METHODS: Total of 43 patients who underwent a pancreatoduodenectomy were enrolled. The perioperative FXIII activities were measured, and their associations with intraoperative bleeding and postoperative outcomes were analyzed. RESULTS: Fifteen patients (35%) had low FXIII activities (<70%, lower than the institutional normal range). The patients with preoperative FXIII activities <70% experienced significantly greater blood loss (median, 1309 mL) during surgery compared to those with FXIII levels of ≥70% (median, 710 mL) (p = 0.001). The postoperative morbidity rates, including pancreatic fistula, were comparable between the patients with FXIII activities <70% and those with FXIII activities ≥70%. The FXIII levels substantially decreased on postoperative day 1 and remained at low levels until postoperative day 7. CONCLUSION: Unexpectedly high proportions of patients undergoing pancreatoduodenectomy had low preoperative FXIII activities. Preoperative FXIII deficiency may increase intraoperative bleeding but had no influence on the postoperative outcomes.

Cholangiocarcinoma with intraductal tubular growth pattern versus intraductal papillary growth pattern.

Intraductal neoplasms of the bile duct are macroscopically characterized by exophytic or polypoid growth patterns and have a favorable prognosis. Although some tumors with a predominantly tubular microscopic pattern have been reported, they have not been well characterized clinicopathologically. The purpose of the present study was to compare the newly recognized cholangiocarcinoma with an intraductal tubular growth pattern and cholangiocarcinoma with an intraductal papillary growth pattern and to investigate the pathological and prognostic significance of the former. This study analyzed 161 patients with tumors with exophytic or polypoid growth patterns from a large series of 733 cholangiocarcinoma cases surgically resected from January 1998 to May 2013. The study patients were divided into two groups: those whose tumors showed a predominantly tubular growth pattern (n=52) and those whose tumors exhibited a predominantly papillary growth pattern (n=109). Tubular growth pattern was associated with combined vascular resection and the absence of macroscopic mucin. Several histological indexes were significantly higher for the tubular growth pattern than the papillary one, including tubular adenocarcinoma, depth of invasion, microscopic lymphatic invasion, venous invasion, perineural invasion, and necrosis. Although the survival curves overlapped (P=0.693), the rate of liver metastasis was significantly higher for the tubular growth pattern than for the papillary one (P=0.012). Genomic DNA analysis focusing on somatic mutations in codons 12 and 13 of KRAS and codon 600 of BRAF revealed only one (4%) KRAS and no BRAF mutation among the 25 tubular cases examined. In conclusion, the tubular growth pattern exhibited differences in some histologic indexes, in addition to a higher hepatic metastasis rate and a lower KRAS mutation frequency, compared with the papillary growth pattern, but no difference in prognosis was observed. The distinctiveness of this tubular neoplasm should be further examined in the future.

The Predictive Value of Indocyanine Green Clearance in Future Liver Remnant for Posthepatectomy Liver Failure Following Hepatectomy with Extrahepatic Bile Duct Resection.

BACKGROUND: Postoperative liver failure (PHLF) is one of the most common complications following major hepatectomy. The preoperative assessment of future liver remnant (FLR) function is critical to predict the incidence of PHLF. OBJECTIVE: To determine the efficacy of the plasma clearance rate of indocyanine green clearance of FLR (ICGK-F) in predicting PHLF in cases of highly invasive hepatectomy with extrahepatic bile duct resection. METHODS: Five hundred and eighty-five patients who underwent major hepatectomy with extrahepatic bile duct resection, from 2002 to 2014 in a single institution, were evaluated. Among them, 192 patients (33 %) had PHLF. The predictive value of ICGK-F for PHLF was determined and compared with other risk factors for PHLF. RESULTS: The incidence of PHLF was inversely proportional to the level of ICGK-F. With multivariate logistic regression analysis, ICGK-F, combined pancreatoduodenectomy, the operation time, and blood loss were identified as independent risk factors of PHLF. The risk of PHLF increased according to the decrement of ICGK-F (the odds ratio of ICGK-F for each decrement of 0.01 was 1.22; 95 % confidence interval 1.12-1.33; P < 0.001). Low ICGK-F was also identified as an independent risk factor predicting the postoperative mortality. CONCLUSIONS: ICGK-F is useful in predicting the PHLF and mortality in patients undergoing major hepatectomy with extrahepatic bile duct resection. This criterion may be useful for highly invasive hepatectomy, such as that with extrahepatic bile duct resection.

Proposal for a Pancreatic Configuration Index for Determining Patients at High Risk of Pancreatic Fistula Following Pancreatoduodenectomy.

BACKGROUND/AIMS: The pancreatic configuration is one of the most important factors that have an impact on the incidence of postoperative pancreatic fistula (POPF). This study sought to propose a new index, called the pancreatic configuration index (PCI), to categorize patients at a high risk for POPF. METHODS: Two hundred and thirty-one patients who underwent pancreatoduodenectomies were subjected to the analysis. The pancreatic parenchymal thickness and the main pancreatic duct (MPD) diameter at the pancreatic neck were measured using axial computed tomography scan images. The PCI was calculated by dividing the axial thickness by the MPD diameter. RESULTS: Sixty-two of the patients (26.8%) developed clinically significant POPF. Using a receiver operating characteristic curve analysis, the cut-off value of the PCI in predicting POPF was 5.3. The incidence of POFP increased depending on the PCI level. Using a multivariate analysis that included the various risk factors of POPF, a high PIC (≥5) was identified as an independent risk factor of POPF, with the highest OR at 6.50. CONCLUSION: The PCI is useful for stratifying patients at a high risk for POPFs. This index may be used to classify the patient population when evaluating other risk factors for POPF.

Clinical value and pitfalls of fluorescent cholangiography during single-incision laparoscopic cholecystectomy.

PURPOSE: To clarify the clinical value and pitfalls of fluorescent cholangiography (FC) during single-incision laparoscopic cholecystectomy (SILC). METHODS: Our SILC procedure utilized the SILS-Port with additional 5-mm forceps through an umbilical incision. A laparoscopic fluorescent imaging system developed by Karl Storz Endoskope was utilized for fluorescent cholangiography. RESULTS: We performed fluorescent cholangiography during SILC in 21 patients. All procedures were completed successfully without biliary injury. The detectability of the running course of the cystic duct, the confluence between the cystic duct and the common hepatic duct, and the common hepatic duct before the dissection in Calot's triangle was 47.6, 71.4, and 81.0 %, respectively. The detectability of biliary structures was worse in 9 obese patients (body mass index ≥ 25.0 kg/m2) than in 12 non-obese patients. The mean operative time for the patients in whom fluorescent cholangiography could identify the running course of the cystic duct before dissection in Calot's triangle (68 ± 16 min) was shorter than that for the other patients (91 ± 35 min; p = 0.037). CONCLUSIONS: Fluorescent cholangiography can prevent biliary injury during SILC and facilitate SILC. Obesity is the most important factor that can prevent identification of biliary structures under fluorescent cholangiography.

Surgery for Recurrent Biliary Tract Cancer: A Single-center Experience With 74 Consecutive Resections.

OBJECTIVE: To review our experiences with surgery for recurrent biliary tract cancer (BTC). BACKGROUND: Few studies have reported on surgical procedures for recurrent BTC; therefore, it is unclear whether this surgery has survival benefit. METHODS: Between 1991 and 2010, 606 patients had recurrences after resection of BTC (gallbladder cancer, n = 135; cholangiocarcinoma, n = 471); 74 patients underwent resection for recurrence, whereas the remaining 532 did not. The medical records were retrospectively reviewed. RESULTS: Compared with the 532 patients without surgery for recurrence, the 74 patients with surgery had less advanced cancer, and their time to recurrence was significantly longer (1.4 vs 0.8 years; P < 0.001). A total of 89 surgical procedures for recurrence were performed in the 74 patients (1 time in 63 and ≥2 times in 11). Survival after recurrence was significantly better in the 74 patients with surgery than in the 532 without (32% vs 3% at 3 years; P < 0.001). Survival after surgery for recurrence was (1) similar between gallbladder cancer and cholangiocarcinoma; (2) significantly better in patients with initial disease-free interval of 2 or more years; (3) significantly worse in patients with chest or abdominal wall recurrences; and (4) significantly better in patients with pN0 disease in their primary cancer. Nodal status of the primary tumor and the site of initial recurrence were identified as independent prognostic factors after surgery for recurrence. CONCLUSIONS: Surgical resection for recurrent BTC can be performed safely and offers a better chance of long-term survival in selected patients.

Prognostic Value of Hepatocyte Growth Factor Receptor Expression in Patients with Perihilar Cholangiocarcinoma.

BACKGROUND: Although an aggressive surgical approach to perihilar cholangiocarcinoma (PHC) has improved survival, a prognosis of advanced PHC remains unsatisfactory. The overexpression of mesenchymal-epithelial transition factor (MET) and recepteur d'origine nantais (RON) has been shown to be associated with poor prognosis in some types of cancer. METHODS: One hundred sixty-nine patients who underwent histologically curative resection for PHC were subjected to immunohistochemical analysis for MET and RON. The association between a positive expression of MET or RON and clinicopathologic features as well as the patients' prognosis were analyzed. RESULTS: There were 27 patients (16 %) who had a positive expression for both MET and RON. Although clinicopathologic features in the either MET- or RON-negative group were not significantly different compared to the both MET- and RON-positive group, the prognosis tended to be worse in the patients with both MET and RON positivity. When the analysis was limited to patients with advanced-stage disease (stage III and IVa), a multivariate analysis revealed that both MET and RON positivity and lymph node metastasis were identified as independent poor prognostic factors. CONCLUSIONS: The overall survival rate for patients with both MET and RON positivity was worse than that with either MET or RON negativity in patients with advanced PHC. The poor prognosis in these patients was not associated with unfavorable clinicopathologic features. The examination of MET and RON expression in PHC may enable a tailored method for patient classification that could not otherwise be achieved using the conventional pathologic classification system.

Combined extrahepatic bile duct resection for locally advanced gallbladder carcinoma: does it work?

BACKGROUND: Prophylactic combined extrahepatic bile duct resection remains controversial for locally advanced gallbladder carcinoma without extrahepatic bile duct invasion. The aim of this study is to resolve this issue and establish an appropriate surgery for locally advanced gallbladder carcinoma. METHODS: A total of 52 patients underwent surgical resection combined with extrahepatic bile duct resection for locally advanced gallbladder carcinoma without extrahepatic bile duct invasion, and their medical records were retrospectively reviewed for microvessel invasion (MVI), including lymphatic, venous, and/or perineural invasions, around the extrahepatic bile duct. RESULTS: Of the 52 patients, 8 (15 %) had MVI around the extrahepatic bile duct. All of the 8 patients had Stage IV disease. According to a survival analysis of the 50 patients who tolerated surgery, MVIs around the extrahepatic bile duct and distant metastasis were identified as independent prognostic factors. Survival for patients with MVI around the extrahepatic bile duct was dismal, with a lack of 2-year survivors. CONCLUSIONS: MVI around the extrahepatic bile duct is a sign of extremely locally advanced gallbladder carcinoma; therefore, prophylactic combined bile duct resection has no survival impact for patients without extrahepatic bile duct invasion.