Pathways of Progression From Intraductal Papillary Mucinous Neoplasm to Pancreatic Ductal Adenocarcinoma Based on Molecular Features.

BACKGROUND & AIMS: Intraductal papillary mucinous neoplasms (IPMNs) are regarded as precursors of pancreatic ductal adenocarcinomas (PDAs), but little is known about the mechanism of progression. This makes it challenging to assess cancer risk in patients with IPMNs. We investigated associations of IPMNs with concurrent PDAs by genetic and histologic analyses. METHODS: We obtained 30 pancreatic tissues with concurrent PDAs and IPMNs, and 168 lesions, including incipient foci, were mapped, microdissected, and analyzed for mutations in 18 pancreatic cancer-associated genes and expression of tumor suppressors. RESULTS: We determined the clonal relatedness of lesions, based on driver mutations shared by PDAs and concurrent IPMNs, and classified the lesions into 3 subtypes. Twelve PDAs contained driver mutations shared by all concurrent IPMNs, which we called the sequential subtype. This subset was characterized by less diversity in incipient foci with frequent GNAS mutations. Eleven PDAs contained some driver mutations that were shared with concurrent IPMNs, which we called the branch-off subtype. In this subtype, PDAs and IPMNs had identical KRAS mutations but different GNAS mutations, although the lesions were adjacent. Whole-exome sequencing and methylation analysis of these lesions indicated clonal origin with later divergence. Ten PDAs had driver mutations not found in concurrent IPMNs, called the de novo subtype. Expression profiles of TP53 and SMAD4 increased our ability to differentiate these subtypes compared with sequencing data alone. The branch-off and de novo subtypes had substantial heterogeneity among early clones, such as differences in KRAS mutations. Patients with PDAs of the branch-off subtype had a longer times of disease-free survival than patients with PDAs of the de novo or the sequential subtypes. CONCLUSIONS: Detailed histologic and genetic analysis of PDAs and concurrent IPMNs identified 3 different pathways by which IPMNs progress to PDAs-we call these the sequential, branch-off, and de novo subtypes. Subtypes might be associated with clinical and pathologic features and be used to select surveillance programs for patients with IPMNs.

Antimicrobial susceptibility of common pathogens isolated from postoperative intra-abdominal infections in Japan.

The principle of empirical therapy for patients with intra-abdominal infections (IAI) should include antibiotics with activity against Enterobacteriaceae and Bacteroides fragilis group species. Coverage of Pseudomonas aeruginosa, Enterobacter cloacae, and Enterococcus faecalis is also recommended for hospital-associated IAI. A nationwide survey was conducted to investigate the antimicrobial susceptibility of pathogens isolated from postoperative IAI. All 504 isolates were collected at 26 institutions and referred to a central laboratory for susceptibility testing. Lower susceptibility rates to ciprofloxacin and cefepime were demonstrated in Escherichia coli. Among E. coli, 24.1% of strains produced extended-spectrum ß-lactamase (ESBL). Carbapenems, piperacillin/tazobactam, cephamycins/oxacephem, aminoglycosides, and tigecycline had high activity against E. coli, including ESBL-producing isolates. Among E. cloacae, low susceptibility rates to ceftazidime were demonstrated, whereas cefepime retained its activity. P. aeruginosa revealed high susceptibility rates to all antimicrobials tested except for imipenem. Among B. fragilis group species, low levels of susceptibility were observed for cefoxitin, moxifloxacin, and clindamycin, and high susceptibility rates were observed for piperacillin/tazobactam, meropenem, and metronidazole. Ampicillin, piperacillin, and glycopeptides had good activity against E. faecalis. Imipenem had the highest activity against E. faecalis among carbapenems. In conclusion, we suggested the empirical use of antimicrobials with the specific intent of covering the main organisms isolated from postoperative IAI. Piperacillin/tazobactam, meropenem, or doripenem, are appropriate in critically ill patients. Combination therapy of cefepime (aztreonam in patients with ß-lactam allergy) plus metronidazole plus glycopeptides, imipenem/cilastatin or cephamycins/oxacephem plus ciprofloxacin plus metronidazole are potential therapeutic options.

Antimicrobial susceptibility of pathogens isolated from surgical site infections in Japan: Comparison of data from nationwide surveillance studies conducted in 2010 and 2014-2015.

A nationwide survey was conducted in Japan from 2014 to 2015 to investigate the antimicrobial susceptibility of pathogens isolated from surgical site infections (SSI). The resulting data were compared with that obtained in an earlier survey, conducted in 2010. Seven main organisms were collected, and 883 isolates were studied. A significant reduction in methicillin resistance was observed among Staphylococcus aureus isolates, dropping from 72.5% in 2010 to 53.8% in 2014-2015 (p < 0.001). MRSA isolates with a vancomycin minimum inhibitory concentration (MIC) of 2 µg/mL accounted for 1.2% of all MRSA isolates, which was significantly lower than in 2010 (9.7%, p = 0.029). Of the Escherichia coli isolates, 23.0% produced an extended spectrum ß-lactamase (ESBL) in the 2014-2015 survey, which was a significant increase from 9.5% in 2010 (p = 0.011). The geometric mean MICs for ESBL-producing isolates were 0.07 µg/mL for meropenem, 9.51 µg/mL for tazobactam/piperacillin, 0.15 µg/mL for flomoxef, and 1.56 µg/mL for gentamycin. There was a significant increase in the isolation rate of non-fragilis Bacteroides among Bacteroides fragilis group species between the two study periods (35.2% vs. 53.1%, p = 0.007). More than 90% of isolates belonging to the B. fragilis group remained susceptible to tazobactam/piperacillin, meropenem, and metronidazole. In contrast, lower levels of susceptibility were observed for cefmetazole (49.6%), moxifloxacin (61.9%), and clindamycin (46.9%). Non-fragilis Bacteroides isolates had lower rates of antibiotic susceptibility compared with B. fragilis. Overall, the surveillance data clarified trends in antimicrobial susceptibility for organisms commonly associated with SSI.

A case-matched comparison of single-incision versus multiport laparoscopic right colectomy for colon cancer.

PURPOSE: To minimize the parietal trauma associated with multiple surgical access sites, single-incision laparoscopic surgery for colectomy has been emerging with the improvements in instrumentation and surgical techniques. The purpose of this study was to compare the clinicopathological outcomes between single-incision laparoscopic right colectomy (SILC) and multiport laparoscopic right colectomy (MLC) for right colon cancer. METHODS: Thirty-five consecutive patients undergoing SILC from a prospective single-institution database were case matched according to demographic data to an equivalent number of patients who underwent MLC. RESULTS: The SILC patients had decreased scores for maximal pain assessed by a visual analog scale on postoperative days 1 and 3, and used fewer postoperative systemic narcotics. The median length of the hospital stay for the SILC patients was significantly shorter compared with the MLC patients. The postoperative morbidity rates were similar between the groups. The oncological findings were not significantly different between the groups. CONCLUSION: SILC is a feasible and safe alternative to conventional MLC for patients with right colon cancer.

[A case of adenoendocrine cell carcinoma on the ampulla of Vater].

The occurrence of an adenoendocrine cell carcinoma on the ampulla of Vater is rare, especially when the component of adenocarcinoma is not located on the mucosa of the ampulla. A 76-year-old man was referred to our hospital for further investigation of a mass lesion on the ampulla. EGD revealed SMT like mass lesion on the ampulla. Endoscopic ultrasonography showed an ampullary hypoechoic mass. We performed pylorus-preserving pancreatoduodenectomy on the basis of the diagnosis of poorly differentiated adenocarcinoma of the ampulla of Vater. Postoperative pathological examinations revealed two different components of the tumor;malignant endocrine cells, and adenocarcinoma. The component of adenocarcinoma was located on the Ap lesion. We deducted that the adenocarcinoma appeared on the epithelium of Ap, then grew and spread into the direction of duodenum lumen, degenerating to endocrine cells.

Adolescent Acute Pancreatitis Complicated With Pseudoaneurysms and Venous Thrombosis.

Vascular complications, such as pseudoaneurysms and thrombosis, are uncommon in pediatric acute pancreatitis (AP); hence, treatment experience remains limited. Here, we report a case of adolescent AP complicated with pseudoaneurysms and venous thrombosis simultaneously. Even after multiple endovascular embolizations for pseudoaneurysms, the patient experienced hemorrhagic shock resulting from pseudoaneurysm rupture after taking anticoagulants for thrombus. Inevitably, a total pancreatectomy was performed to prevent bleeding and control local complications. In AP, even among the pediatric population, a therapeutic dilemma between bleeding prevention and anticoagulation for thrombosis may occur. Despite the lack of experience with AP and its complications, a total pancreatectomy may become an alternative therapy for refractory AP or its complications.

Right hepatectomy under cardiopulmonary bypass for hepatocellular carcinoma with inferior vena cava tumor thrombus: a case report.

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) with vascular invasion is extremely poor, especially in patients with tumor thrombus (TT) of the inferior vena cava (IVC), which is an oncological emergency with a high risk of sudden death due to TT extension or migration. Herein, we describe a case of HCC with TT of the IVC that rapidly extended into the right atrium (RA), in which right hepatectomy was performed under cardiopulmonary bypass. CASE PRESENTATION: A 64-year-old man was diagnosed with HCC with IVC TT, and right hepatic lobectomy was scheduled. While awaiting surgery, he complained of respiratory distress and rushed to the emergency room. The TT had reached the RA, and the patient was in a state of oncologic emergency. We requested the cooperation of the cardiovascular surgery department, and under artificial cardiopulmonary support, the right atrium was incised, and a part of the TT was removed. The IVC was clamped to prevent tumor dispersal, and right hepatic lobectomy was performed. The remaining thrombus was excised along with the right lobe of the liver by incising the IVC. There were no serious postoperative complications, and the patient is alive 1 year and 5 months postoperatively. CONCLUSION: Hepatic resection with cardiopulmonary bypass could be an option for HCC with TT reaching the RA.

The preoperative SOFA score and remnant small intestine length are postoperative risk factors for mortality in patients with non-occlusive mesenteric ischemia: a case-control study.

Aim: Non-occlusive mesenteric ischemia (NOMI) is a fatal condition with a low survival rate in most cases. The risk factors for perioperative mortality in NOMI cases are unclear. The purpose of this study was to define the risk factors for mortality in patients with NOMI undergoing surgery. Methods: Thirty-eight consecutive patients who underwent surgery for NOMI at Teine Keijinkai Hospital between 2012 and 2020 were included in the study. Patient information, including age, sex, physical findings, comorbidities, laboratory data, and computed tomography and surgical findings were retrospectively analyzed. Results: Of the 38 patients, 18 (47%) died before discharge. Significant univariate predictors of mortality were a high Sequential Organ Failure Assessment (SOFA) score, high lactate level, low blood pH, and short intestinal length after surgery. In the multivariate analysis, a high SOFA score (odds ratio 1.33, P = 0.036) and short intestine length after surgery (odds ratio 34.7, P = 0.003) were identified as independent risk factors for perioperative mortality. Conclusion: The preoperative SOFA score and postoperative residual intestinal length may be predictors of death in NOMI surgical patients, not age and the content of comorbidities.

Spontaneous retroperitoneal hematoma: a case report.

BACKGROUND: Spontaneous retroperitoneal hematoma is defined as bleeding in the retroperitoneal space without any triggers such as trauma, invasive procedures, and abdominal aortic aneurysm. CASE PRESENTATION: A 48-year-old Japanese man who experienced sudden abdominal pain, severe hypotension, and decreased hemoglobin was diagnosed with spontaneous retroperitoneal hematoma. Contrast-enhanced computed tomography revealed massive left retroperitoneal hematoma; however, neither extravasation nor causative aneurysm was noted. Through conservative management with close monitoring, he was treated and discharged on the tenth hospital day without any morbidity. CONCLUSIONS: Spontaneous retroperitoneal hematoma treatment comprises conservative management, transcatheter arterial embolization, and surgical intervention. The mortality rate of spontaneous retroperitoneal hematoma is so high that the optimal treatment timing needs to be carefully judged on the basis of detailed evaluation, and management algorithm with clear criteria.

Bilateral video-assisted thoracic surgery for esophageal cancer with left inferior pulmonary vein invasion following chemoradiation therapy.

BACKGROUND: The surgical strategy for thoracic esophageal cancer that invades the lungs is controversial. In particular, invasion of the pulmonary vein is often regarded unresectable. We successfully applied bilateral video-assisted thoracic surgery (VATS) in esophagectomy for esophageal cancer with left inferior pulmonary vein invasion following induction chemoradiotherapy (CRT), with a favorable response. CASE PRESENTATION: A 64-year-old woman was diagnosed with squamous cell carcinoma of the lower third of the esophagus. Computed tomography (CT) revealed that the tumor was suspected to be invading the main trunk of the left lower pulmonary vein and left lower lung. We initiated induction CRT comprising 5-fluorouracil, cisplatin, and concurrent radiotherapy at 50.4 Gy/28Fr. CT revealed shrinkage of the tumor, and the main trunk of the left inferior pulmonary vein was released from the tumor invasion. We considered the tumor to be completely resectable. VATS esophagectomy is usually performed using a right-sided approach. However, the right-sided approach is inappropriate for evaluating tumors around the left inferior pulmonary vein. We started with left-sided VATS to determine tumor resectability and dissected between the esophagus and the main trunk of the left inferior pulmonary vein. We only needed to perform partial resection of the left lower lobe. We then performed a right-sided VATS esophagectomy and lymphadenectomy with partial en bloc resection of the left lower lobe. Following this, we performed hand-assisted laparoscopic proximal gastrectomy and reconstruction using the gastric remnant. The postoperative course was uneventful. The patient was discharged on postoperative day 14. Histopathological examination of the surgical specimen revealed a complete pathological response without any remnant tumor or lymph node metastasis. There were no signs of recurrence or metastasis at the 1-year follow-up. CONCLUSIONS: Curative resection for thoracic esophageal cancer that invades the pulmonary vein could be possible via the bilateral VATS approach following induction CRT with a favorable response.

PYloroplasty versus No Intervention in GAstric REmnant REconstruction after Oesophagectomy: study protocol for the PYNI-GAREREO phase III randomized controlled trial.

BACKGROUND: After esophagectomy for esophageal and esophagogastric cancer, more than half of patients have lost > 10% of their body weight at 12 months. In most cases, the gastric remnant is used for reconstruction after esophagectomy. One of the most serious nutritional complications of this technique is delayed gastric emptying caused by gastric remnant mobilization and denervation of the vagus nerve. The aim of the PYloroplasty versus No Intervention in GAstric REmnant REconstruction after Oesophagectomy (PYNI-GAREREO) trial is to analyze the clinical outcome of modified Horsley pyloroplasty (mH-P) as a method of preventing delayed gastric emptying. METHODS: The PYNI-GAREREO trial is designed as an open randomized, single-center superiority trial. Patients will be randomly allocated to undergo gastric remnant reconstruction with mH-P (intervention group) or no intervention (control group) in parallel groups. All patients with esophageal cancer or esophagogastric cancer planning to undergo curative minimally invasive esophagectomy will be considered for inclusion. A total of 140 patients will be included in the study and randomized between the groups in a 1:1 ratio. The primary outcome is the body weight change at 6 months postoperatively, and the secondary outcomes are the nutritional status, postoperative complications, functional outcome, and quality of life until 1 year postoperatively. DISCUSSION: We hypothesize that mH-P after minimally invasive esophagectomy more effectively maintains patients' nutritional status than no pyloroplasty. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000045104. Registered on 25 August 2021. https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000051346 .

Evaluation of extra capsular lymph node involvement in patients with extra-hepatic bile duct cancer.

BACKGROUND: Lymph node metastasis is one of the most important prognostic factors for extra-hepatic bile duct carcinoma (ExHBDC). Extra capsular lymph node involvement (ExCLNI) is the extension of cancer cells through the nodal capsule into the perinodal fatty tissue. The prognostic impact of ExCLNI has been shown to be significant mainly in head and neck malignancies. Recently, the prognostic impacts of ExCLNI have evaluated in gastrointestinal malignancies. However no data is available regarding the incidence and prognostic significance of extra-capsular lymph node involvement (ExCLNI) in resectable ExHBDCs. The aim of the present study is first to evaluate the incidence of ExCLNI in surgically-treated ExHBDCs and second, to determine the prognostic impact of ExCLNI in patients with surgically-treated ExHBDCs. METHODS: A total of 228 patients (110 cases of hilar cholangiocarcinoma and 118 cases of distal cholangiocarcinoma) with surgically-treated ExHBDCs were included in this retrospective study. ExCLNI was defined as the extension of cancer cells through the nodal capsule into the perinodal fatty tissue. The existence of ExCLNI and its prognostic value were analyzed as a subgroup of lymph node metastasis. RESULTS: ExCLNI was detected in only 22% of patients with lymph node metastasis of surgically-treated ExHBDC. The presence of ExCLNI correlated with distal cholangiocarcinoma (p = 0.002). On univariate analysis for survival, perineural invasion, vascular invasion, histological grade, and lymph node metastasis were statistically significant factors. On multivariate analysis, only lymph node metastasis was identified as a significant independent prognostic factor in patients with resectable ExHBDC. Subgroups of lymph node metastasis including the presence of ExCLNI, location of lymph node metastasis, and the number of lymph node metastasis had no statistically significant impact on survival. CONCLUSION: ExCLNI was present in only 22% of the LNM (7% of overall patients) in patients with surgical treated ExHBDCs. And ExCLNI would have no impact on the survival of patients with surgically-treated ExHBDCs.

[Long-term survival of a patient with giant liver metastatic breast cancer treated with trastuzumab].

We report the long-term survival of a patient with metastatic breast cancer treated with trastuzumab and chemoendocrine therapy. The patient was a 60-year-old female. She underwent right mastectomy with axillary lymphadenectomy I c for advanced right breast cancer in 1999. In 2007, she consulted our hospital for treatment of recurrent giant liver metastasis. A giant liver metastasis up to 15 cm in diameter was detected by CT upon arrival. After 4 years of trastuzumab and chemoendocrine therapy, she was diagnosed as in progressive remission with good quality of life. Breast cancer with liver metastasis often can be life-threatening. Therefore, an optimal chemotherapy should be applied as soon as possible. Trastuzumab and chemoendocrine therapy showed efficacy for the treatment of a HER2-positive breast cancer with recurrent giant liver metastasis.

Adrenocortical carcinoma with multiple liver metastases controlled by bland transarterial embolization and surgery resulting in long-term survival.

Adrenocortical carcinoma (ACC) is a rare malignant tumor with a poor prognosis. Local recurrence or distant metastases occur in more than 50% of cases. Patients with metastases have limited treatment options, and <15% have a 5-year survival time. Herein, we describe a 44-year-old woman with ACC and who underwent retroperitoneal tumor resection. Multiple liver and lung metastases were found 1-year postresection. Mitotane therapy started as systemic treatment. Lung metastases were controlled but liver metastases were progressive. The liver metastases were treated by performing 2 resections and 6 bland transarterial embolization (bland TAE), and are presently controlled with only 2 liver metastases of <20 mm. The present case showed that bland TAE can achieve long-term prevention of the progression of liver metastases of ACC. The ultraselective bland TAE for selective embolization supported by the latest computed tomography analysis techniques during arteriography could minimize liver damage caused by embolization and allowed multiple treatments which prolonged survival. We conclude that bland TAE can be effective for controlling liver metastases of ACC.

Preoperative embolization strategy for the combined resection of replaced right hepatic artery in pancreaticoduodenectomy: a small case series.

BACKGROUND: Replaced right hepatic artery (rRHA) is a common vascular variation, and combined resection of this vessel is sometimes needed for the curative resection of pancreatic head malignancy. Safe surgical management has not been established, and there is a small number of reported cases. Here, we reported five cases, wherein preoperative embolization of rRHA was performed for combined resection. CASE PRESENTATION: All patients had pancreatic head malignancies that were in contact with rRHA. We performed a preoperative embolization of the rRHA before the scheduled pancreaticoduodenectomy for the combined resection. Arterial embolization was safely accomplished, and the communicating arcade from the left hepatic artery via the hilar plate was clearly revealed in all cases. Four patients underwent the operative procedure, except for one patient who had liver metastasis at laparotomy. No patient suffered from a severe abnormal liver function during the management; however, one patient had multiple liver infarctions during the postoperative course. CONCLUSIONS: Preoperative embolization for the combined resection of rRHA in pancreaticoduodenectomy can be a management option for the precise evaluation of hemodynamics after sacrificing rRHA. In our cases, arterial flow to the right liver lobe was supplied by the left hepatic artery via the bypass route, including the communicating arcade of the hilar plate.

Appropriate Lymph Node Dissection Sites for Cancer in the Body and Tail of the Pancreas: A Multicenter Retrospective Study.

Distal pancreatectomy (DP) with lymphadenectomy is the standard surgery for pancreatic body-tail cancer. However, the optimal lymph node (LN) dissection area for DP remains controversial. Thus, we evaluated the frequency and patterns of LN metastasis based on the tumor site. In this multicenter retrospective study, we examined 235 patients who underwent DP for pancreatic cancer. Tumor sites were classified as confined to the pancreatic body (Pb) or pancreatic tail (Pt). The efficacy index (EI) was calculated by multiplying the frequency of metastasis to each LN station by the five-year survival rate of patients with metastasis to that station. LN metastasis occurred in 132/235 (56.2%) of the patients. Patients with Pb tumors showed no metastasis to the splenic hilum LN. Distal splenic artery LNs and anterosuperior/posterior common hepatic artery LNs did not benefit from dissection for Pb and Pt tumors, respectively. In multivariate analysis, splenic artery LN metastasis was identified as an independent predictor of poor overall survival in patients with pancreatic body-tail cancer. In conclusion, differences in metastatic LN sites were evident in pancreatic body-tail cancers confined to the Pb or Pt. Spleen-preserving pancreatectomy might be feasible for Pb cancer.

Carbon dioxide embolism during transanal total mesorectal excision: A hint of prevention from a case report.

Transanal total mesorectal excision is a relatively new approach for treating lower rectal cancer. Carbon dioxide embolism is a critical complication of this procedure. We report the case of a 69-year-old man with lower rectal cancer who underwent transanal total mesorectal excision followed by laparoscopic low anterior resection. He had a sudden intraoperative carbon dioxide embolism during the transanal mesorectal excision. During the ventral dissection of the rectum, end-tidal carbon dioxide and blood oxygen saturation suddenly decreased. We stopped the insufflation of carbon dioxide and suspended the procedure. There was no circulatory collapse, and the vital signs gradually recovered; therefore, we resumed the surgery approximately 30 minutes later and completed it without additional complications. Upon reviewing the video, we found a small injured vein that would aspirate carbon dioxide. These findings suggested that careful hemostasis is essential to prevent carbon dioxide embolus during transanal total mesorectal excision.

Individual patient data meta-analysis of adjuvant gemcitabine-based chemotherapy for biliary tract cancer: combined analysis of the BCAT and PRODIGE-12 studies.

BACKGROUND: Although gemcitabine-based chemotherapy is the standard of care for advanced biliary tract cancers (BTCs), adjuvant phase III studies (BCAT in Japan, PRODIGE 12 in France) failed to show benefit, possibly owing to fewer patients (n = 225 and n = 194) compared with the adjuvant capecitabine BILCAP trial (n = 447). We performed a combined analysis of both gemcitabine-based chemotherapy adjuvant studies. METHODS: We performed individual patient data meta-analysis of all patients included in BCAT and PRODIGE 12. BCAT study randomised patients with extrahepatic cholangiocarcinoma to single-agent gemcitabine or observation. PRODIGE 12 randomised patients with all BTC subtypes to gemcitabine-oxaliplatin combination or observation. Combined analysis was performed using Kaplan-Meier curves and a Cox regression model stratified on the trial. RESULTS: Two hundred and twelve versus 207 patients were randomised in the gemcitabine-based chemotherapy versus observation arms. Baseline characteristics were balanced between arms. The median follow-up was 5.5 years. After 258 relapse-free survival (RFS) events, there was no difference in RFS (log-rank p = 0.45; hazard ratio [HR] = 0.91 [95% confidence interval [CI] 0.71-1.16]; p = 0.46). RFS rates at five years were 40.8% (95%CI: 33.9%-47.5%) for gemcitabine-based chemotherapy versus 36.6% (95%CI: 29.8%-43.4%) for observation. After 201 deaths, there was no difference in overall survival (OS) (log-rank p = 0.83; HR = 1.03 [95%CI: 0.78-1.35]; p = 0.85). OS rates at five years were 50.5% (95%CI: 43.1%-57.4%) for gemcitabine-based chemotherapy versus 49.3% (95%CI: 41.6%-56.5%) for observation. CONCLUSION: With 419 patients included, this analysis did not show significant improvement in RFS and no trend in improvement in OS. Gemcitabine-based chemotherapy should not be used as an adjuvant treatment for BTC.