Clinical efficacy of pancreaticoduodenectomy for periampullary diseases: a report of 2 019 cases / 中华消化外科杂志

Objective:To investigate the clinical efficacy of pancreaticoduodenectomy (PD) for periampullary diseases.Methods:The retrospective cohort study was conducted. The clinico-pathological data of 2 019 patients with periampullary diseases who underwent PD in the First Affiliated Hospital of Nanjing Medical University from January 2016 to December 2020 were collected. There were 1 193 males and 826 females, aged 63(15) years. Observation indicators: (1) surgical situations; (2) postoperative conditions; (3) postoperative pathological examinations; (4) prognosis of patients with periampullary carcinoma. Regular follow-up was conducted by telephone interview and outpatient examination once every 3 months within the postoperative first year and once every 6 months thereafter to detect the survival of patients with periampullary carcinoma. The follow-up was up to December 2021. Measurement data with skewed distribution were represented as M(IQR) or M(range), and comparison between groups was analyzed using the rank sum test. Count data were described as absolute numbers and (or) percentages, and comparison between groups was analyzed by the chi-square test or Fisher exact probability. Kaplan-Meier method was used to draw survival curves and calculate survival rates, and Log-Rank test was used to conduct survival analysis. Results:(1) Surgical situations: of 2 019 patients, 1 116 cases were admitted from 2016-2018 and 903 cases were admitted from 2019-2020. There were 1 866 cases undergoing open PD and 153 cases undergoing laparoscopic or robot-assisted PD. There were 1 049 cases under-going standard PD and 970 cases undergoing pylorus-preserved PD. There were 215 cases combined with portal mesenteric vein resection, 3 cases combined with arterial resection. The operation time of 2 019 patients was 255(104)minutes and the volume of intraoperative blood loss was 250(200)mL. The intraoperative blood transfusion rate was 31.401%(623/1 984), with the blood transfusion data of 35 cases missing. The proportions of pylorus-preservation, combination with portal mesenteric vein resection, intraoperative blood transfusion were 585 cases(52.419%), 97cases(8.692%), 384 cases(34.941%) for patients admitted in 2016-2018, versus 385 cases(42.636%), 118 cases(13.068%), 239 cases(27.006%) for patients admitted in 2019-2020, showing significant differences between them ( χ2=19.14,10.05,14.33, P<0.05). (2) Postoperative conditions: the duration of postoperative hospital stay of 2 019 patients was 13 (10) days. One of 2 019 patients lacked the data of postopera-tive complications. The overall postoperative complication rate was 45.292%(914/2 018), of which the incidence rate of grade B or C pancreatic fistula was 23.439%(473/2 018), the rate of grade B or C hemorrhage was 8.127%(164/2 018), the rate of grade B or C delayed gastric emptying was 15.312%(309/2 018), the rate of biliary fistula was 2.428%(49/2 018) and the rate of abdominal infection was 12.884%(260/2 018). The reoperation rate of 2 019 patients was 1.932%(39/2 019), the in-hospital mortality was 0.644%(13/2 019), the postoperative 30-day mortality was 1.238%(25/2 019), and the postoperative 90-day mortality was 2.675%(54/2 019). There were 541 cases(48.477%) with overall postoperative complications, 109 cases(9.767%) with grade B or C hemorr-hage, 208 cases(18.638%) with grade B or C delayed gastric emptying , 172 cases(15.412%) with abdominal infection, 39 cases(3.495%) with postoperative 90-day mortality of 1 116 patients admitted in 2016-2018. The above indicators were 373 cases(41.353%), 55 cases(6.098%), 101 cases(11.197%), 88 cases(9.756%), 15 cases(1.661%) of 902 patients admitted in 2019-2020, respectively. There were significant differences in the above indicators between them( χ2=10.22, 9.00, 21.30, 14.22, 6.45 , P<0.05). The in-hospital mortality occurred to 11 patients(0.986%) of 1 116 patients admitted in 2016-2018 and to 2 cases(0.221%) of 903 patients admitted in 2019-2020, showing a significant difference between them ( P<0.05). (3) Postoperative pathological examinations. Disease area of 2 019 patients reported in postoperative pathological examinations: there were 1 346 cases(66.667%) with lesions in pancreas, including 1 023 cases of carcinoma (76.003%) and 323 cases(23.997%) of benign diseases or low potential malignancy. There were 250 cases(12.382%) with lesions in duodenal papilla, including 225 cases of carcinoma (90.000%) and 25 cases(10.000%) of benign diseases or low potential malignancy. There were 174 cases(8.618%) with lesions in bile duct, including 156 cases of carcinoma (89.655%) and 18 cases(10.345%) of benign diseases or low potential malignancy. There were 140 cases(6.934%) with lesions in ampulla, including 134 cases of carcinoma (95.714%) and 6 cases(4.286%) of benign diseases or low potential malignancy. There were 91 cases(4.507%) with lesions in duodenum, including 52 cases of carcinoma (57.143%) and 39 cases(42.857%) of benign diseases or low potential malignancy. There were 18 cases(0.892%) with carcinoma in other sites. Postoperative pathological examination showed carcinoma in 1 608 cases(79.643%), benign diseases or low potential malignancy in 411 cases(20.357%). The histological types of 1 608 patients with carcinoma included adenocarcinoma in 1 447 cases (89.988%), intra-ductal papillary mucinous carcinoma in 37 cases(2.301%), adenosquamous carcinoma in 35 cases(2.177%), adenocarcinoma with other cancerous components in 29 cases(1.803%), neuroendocrine carcinoma in 18 cases(1.119%), squamous carcinoma in 1 case (0.062%), and other histological malignancies in 41 cases(2.550%). The histological types of 411 patients with benign or low poten-tial malignancy included intraductal papillary mucinous neoplasm in 107 cases (26.034%), chronic or autoimmune inflammatory disease in 62 cases(15.085%), neuroendocrine tumor in 58 cases(14.112%), pancreatic serous cystadenoma in 52 cases(12.652%), pancreatic solid pseudopapillary tumor in 36 cases(8.759%), gastrointestinal stromal tumor in 29 cases(7.056%), villous ductal adenoma in 20 cases(4.866%), pancreatic mucinous cystadenoma in 2 cases(0.487%), pancreatic or duodenal trauma in 2 cases(0.487%) and other histological types in 43 cases(10.462%). (4) Prognosis of patients with periampullary carcinoma. Results of survival analysis of 1 590 patients with main locations of periampullary carcinoma showed that of 1 023 patients with pancreatic cancer, 969 cases were followed up for 3.0-69.6 months, with a median follow-up time of 30.9 months. The median overall survival time, 1-year, 3-year and 5-year survival rates of pancreatic cancer patients were 19.5 months [95% confidence interval ( CI) as 18.0-21.2 months], 74.28%, 29.22% and 17.92%. Of 225 patients with duodenal papillary cancer, 185 cases were followed up for 3.0-68.9 months, with a median follow-up time of 36.7 months. The median overall survival time, 1-year, 3-year and 5-year survival rates were unreached, 94.92%, 78.87% and 66.94%. Of 156 patients with distal bile duct cancer, 110 cases were followed up for 3.0-69.5 months, with a median follow-up time of 25.9 months. The median overall survival time, 1-year, 3-year and 5-year survival rates were 50.6 months (95% CI as 31.4 to not reached), 90.37%, 56.11% and 48.84%. Of 134 patients with ampullary cancer, 100 cases were followed up for 3.0-67.8 months, with a median follow-up time of 28.1 months. The median overall survival time, 1-year, 3-year and 5-year survival rates were 62.4 months (95% CI as 37.8 months to not reached), 90.57%, 64.98% and 62.22%. Of 52 patients with duodenal cancer, 38 cases were followed up for 3.0-69.5 months, with a median follow-up time of 26.2 months. The median overall survival time, 1-year, 3-year and 5-year survival rates were 52.0 months (95% CI as 30.6 months to not reached), 93.75%, 62.24% and 40.01%.There was a significant difference in overall survival after PD between patients with different locations of periampullary malignancies ( χ2=163.76, P<0.05). Conclusions:PD is safe and feasible in a high-volume pancreas center, but the incidence of overall postoperative complications remains high. With the increase of PD volume, the incidence of overall postoperative complications has significantly decreased. There is a significant difference in overall survival time after PD among patients with different locations of periampullary malignancies. The 5-year survival rate after PD for duodenal papillary cancer, ampullary cancer, duodenal cancer and distal bile duct cancer is relatively high, whereas for pancreatic cancer is low.

Cytotoxic effects of Thai noni juice product ethanolic extracts against cholangiocarcinoma cell lines

Objective: To investigate the cytotoxic activity and molecular mechanism(s) of two Thai noni juice (TNJ) products ethanolic extracts against cholangiocarcinoma (CCA) cell lines and non-cancerous cells, and to explore phenolic acid compositions of TNJ products. Methods: Phenolic acid profiles of TNJ Chiangrai (TNJ-Cr) and TNJ Buasri (TNJ-Bs) ethanolic extracts were determined by HPLC. The cytotoxicity of TNJ ethanolic extracts on cancer and non-cancerous cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and trypan blue assays. Mechanism(s) underlying the anti-CCA activity of TNJ ethanolic extracts were determined by cell cycle, apoptosis, and reactive oxygen species (ROS) generation assays. The expression levels of proteins involved in apoptosis and ERK signaling were evaluated by Western blot analysis. Results: Phenolic acid profiles of both TNJ ethanolic extracts showed that the p-hydroxybenzoic, vanillic, and protocatechuic acids were the major phenolic acids in TNJ products. Cytotoxicity assays revealed that the TNJ-Cr and TNJ-Bs ethanolic extracts reduced viability of CCA cell lines through induction of apoptosis by up-regulation of p53 and Bax proapoptotic proteins. Both TNJ ethanolic extracts promoted ROS generation by activating the ERK1/2 signaling in well-differentiated CCA cells KKU-213B. Meanwhile, TNJ ethanolic extracts did not induce ROS production in poorly differentiated CCA cells KKU-100. Both TNJ ethanolic extracts showed no toxicity to human peripheral blood mononuclear cells. Conclusions: TNJ ethanolic extracts could inhibit CCA cell proliferation by inducing ROS generation and apoptosis and may be applicable for combination therapies in CCA treatment.

Significance of serum IgG4 and CA19-9 in diagnosis and antidiastole of IgG4 related cholangitis / 中国免疫学杂志

Objective:To investigate the value of autoantibodies and serum levels of IgG4 and CA19-9 in the diagnosis of IgG4 associated cholangitis (IgG4-SC).Methods:Detect the serum IgG4 and CA19-9 of 41 clinical cases of IgG4-SC patients,162 clinical cases of non IgG4-SC patients and 40 healthy human serum samples by immunoassay and direct chemiluminescence methods, also detect the antinuclear antibodies (ANA),anti neutrophil antibody (ANCA),anti smooth muscle antibody (SMA) and anti mitochondrial antibody (AMA) of the above serum samples by indirect immunofluorescence and analyze the detection results.Results:①The positive rates of ANA,ANCA,SMA and AMA in patients with IgG4-SC were 41.46%,7.32%,0 and 2.44%.Among them,the positive rate of ANA was significantly different from that of the normal control group(P<0.01),and the positive rate of SMA and AMA was significantly different from that of non IgG4-SC group(P<0.01),and so as the positive rate of ANCA do with that of PSC group.②The number of serum IgG4 and CA19-9 increased samples were significantly compared with the normal control group (P<0.01);the area under the ROC curve (AUC) was 0.979 and 0.646,respectively,and P<0.05.Conclusion:The high level of serum IgG4 and CA19-9 and autoantibody detection are of great accuracy and important clinical value in the differential diagnosis of IgG4-SC.

Inverse Prognostic Relationships of ¹⁸F-FDG PET/CT Metabolic Parameters in Patients with Distal Bile Duct Cancer Undergoing Curative Surgery / 대한핵의학회잡지

PURPOSE: As there were few previous studies with a small number of subjects, the purpose of this was to evaluate the prognostic significance of ¹⁸F-FDG PET/CT in patients with distal bile duct cancer undergoing curative surgery.METHODS: The study included 40 patients (M/F = 24:16; age 68.0 ± 8.0 years) who underwent preoperative ¹⁸F-FDG PET/CT followed by curative surgical resection. The participant's age, sex, Eastern Cooperative Oncology Group performance-status score, baseline serum CA 19-9 level, stage, pathologic T and N stages, tumor size, tumor grade, tumor growth pattern, R0 resection, and adjuvant therapy were included as clinicopathological variables for predicting overall survival. The PET variables were maximum standardized uptake value (SUV(max)), average SUV (SUV(avg)), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the tumor. The Kaplan-Meyer method and Cox proportional hazards model were used for the survival analysis.RESULTS: A total of 15 of 40 patients (37.5%) died during the follow-up period. In univariate analysis, low SUVmax (≤ 2.7, p = 0.0005) and low SUV(avg) (≤ 2.6, p = 0.0034) were significant predictors of poor overall survival. In multivariate analyses, only low SUV(max) (HR = 6.7016, 95% CI 1.9961–22.4993, p = 0.0047) was an independent prognostic factor associated with poor overall survival.CONCLUSION: The SUVmax of the primary tumor measured by ¹⁸F-FDG PET/CT was an independent significant prognostic factor for overall survival in patients with distal bile duct cancer. However, different results from a previous study warrant further large sample-sized study.

Clinical Application of the Expression of LOXL2 mRNA and Tenascin-C mRNA in Tissues of the Bile Duct Cancer / 现代检验医学杂志

Objective To explore the clinical application of the expression of LOXL2 mRNA and Tenascin-C mRNA in tissues for the disease with the bile duct cancer.Methods The serum and clinical data in 35 cases of patients with the bile duct cancer (cancer group) and 28 cases of patients with normal bile duct tissue (control group) were collected,used the real-time fluorescent quantitative PCR (real-time-PCR,RT-PCR) technology to detect the expression of LOXL2 mRNA and TenascinC mRNA in tissues toobserve the relationship between the changes and the bile duct cancer for the two markers.Results The expression of LOXL2 mRNA and Tenascin-C mRNA in tissues in the cancer group were 1.27±0.18 and 1.39±0.19,which of ones in the control group were 0.20±0.06 and 0.23±0.06.In the cancer group,the expression of LOXL2 mRNA and Tenascin-C mRNA in tissues respectively with comparision to those in the control group were significantly higher,the differences had statistical significance(t=52.18,56.87,P＜0.01),which of ones in the cancer group was positively related (r=0.687,P＜0.01).Conclution The expression of LOXL2 mRNA and Tenascin-C mRNA in tissues may be a molecular targets for the disease with the bile duct cancer in the early diagnosis and judgment of progression in the courses of this disease.

Study on molecular mechanism of double hydrogen artemisinin inducing apoptosis of bile duct cancer cells / 国际检验医学杂志

Objective To study and discuss the effect of double hydrogen artesunate on Mcl-1 expression and its inducing effect on cancer cell apoptosis in the patients with cholangiocarcinoma.Methods Bile duct cancer cell lines QBC939 preserved in our hospital from June 2010 to December 2014 were randomly selected and divided into the control group and observation group for conducting experiments.The cells were cultured by using the conventional cultivation and double hydrogen artemisinin culture.Then the Mcl-1 expression and apoptosis of cancer cells were performed the statistical analysis and comparison.Results Statistical comparison showed that the expressions of MCL1-001 and-MCL1 201 at 12,24,48 h in the observation group were significantly higher than those in the control group,the comparison between groups were statistically significant (P0.05),but which at 48 h in the observation was significantly higher than that in the control group,the difference was statistically significant(P<0.05).And the mortality rate at 6,12,24,48,72 h in the observation group was significantly higher than that in the control group,the difference was statistically significant (P<0.05).Conclusion Double hydrogen artemisinin has obvious up-regulation effect on Mcl-1,moreover can effectively induces bile duct cancer cell apoptosis.

Dosimetry of 125Ⅰ seeds in different curvatures of bile ducts / 中华放射医学与防护杂志

Objective To study the dosimetry distribution of 125Ⅰ seed chains with different radians in different curvatures of bile ducts. Methods The outlines were drawn on the papers, which are the seed chain models with different radians. Radians formula (radian length=2πr × angle/360) was used to calculate the corresponding 0°, 30°, 60°, 90°, 120°, 150° and 180° models with a radian length at 45 mm, for the total length of seed chain model was 45 mm, and the seeds, had no interval or linear arrangements. The image was transmitted to the Brachytherapy planning system for seeds implantation( TPS) to simulate the seed chains with different radians. Using TPS to delineate the tumor target area, of which the activity was set as 1. 85 × 107 Bq, and the prescription dose was 60 Gy. It was prescribed to simulate the bile duct ( diameter at 8 mm) . TPS were used to calculate the D90 and V100 of the simulated bile duct with the diameter at 8 mm, and explore dosimetry of the points at the centripetal and centrifugal sides with 5 mm vertical distance which from two endpoints and center of seed chains with different radians. Results When the radian of seed chain was 30°, the D90and the V100 were the highest (the D90 was 132 Gy; the V100 was 100%). While the radian was 60°, the D90 and the V100 were the lowest (the D90 was 45 Gy, the V100 was 68%). As the radian was 30°, the highest dose was in the center ( dose in the centripetal side was 165 Gy, and centrifugal side dose was 142 Gy) . The center has the lowest dose as the radian up to 180°(dose in the centripetal side was 90 Gy, and centrifugal side dose was 50 Gy) . Among all radians, dose in the centripetal side was always higher than centrifugal side in the center. Between two endpoints, dose in the centrifugal side was higher than centripetal. Conclusions Distribution of seed chain dosage also changed along with the change of radian. When the radian of seed chain was 30°, the D90 and the V100 were the highest. The centripetal dose was higher than that of the centrifugal side.

Dosimetry of 125Ⅰ seeds in different curvatures of bile ducts / 中华放射医学与防护杂志

Objective To study the dosimetry distribution of 125Ⅰ seed chains with different radians in different curvatures of bile ducts. Methods The outlines were drawn on the papers, which are the seed chain models with different radians. Radians formula (radian length=2πr × angle/360) was used to calculate the corresponding 0°, 30°, 60°, 90°, 120°, 150° and 180° models with a radian length at 45 mm, for the total length of seed chain model was 45 mm, and the seeds, had no interval or linear arrangements. The image was transmitted to the Brachytherapy planning system for seeds implantation( TPS) to simulate the seed chains with different radians. Using TPS to delineate the tumor target area, of which the activity was set as 1. 85 × 107 Bq, and the prescription dose was 60 Gy. It was prescribed to simulate the bile duct ( diameter at 8 mm) . TPS were used to calculate the D90 and V100 of the simulated bile duct with the diameter at 8 mm, and explore dosimetry of the points at the centripetal and centrifugal sides with 5 mm vertical distance which from two endpoints and center of seed chains with different radians. Results When the radian of seed chain was 30°, the D90and the V100 were the highest (the D90 was 132 Gy; the V100 was 100%). While the radian was 60°, the D90 and the V100 were the lowest (the D90 was 45 Gy, the V100 was 68%). As the radian was 30°, the highest dose was in the center ( dose in the centripetal side was 165 Gy, and centrifugal side dose was 142 Gy) . The center has the lowest dose as the radian up to 180°(dose in the centripetal side was 90 Gy, and centrifugal side dose was 50 Gy) . Among all radians, dose in the centripetal side was always higher than centrifugal side in the center. Between two endpoints, dose in the centrifugal side was higher than centripetal. Conclusions Distribution of seed chain dosage also changed along with the change of radian. When the radian of seed chain was 30°, the D90 and the V100 were the highest. The centripetal dose was higher than that of the centrifugal side.

Pathologic Complete Remission in a Patient with Locally Advanced Unresectable Intrahepatic Cholangiocarcinoma Treated with Chemotherapy / 대한췌담도학회지

A 54-year-old female with postprandial dyspepsia and abdominal pain was diagnosed as locally advanced unresectable intrahepatic cholangiocarcinoma by radiologic imaging studies resulting in invasion to bilateral main bile duct and right portal vein. The patient underwent extended right hepatectomy and portal vein resection after gemcitabine and cisplatin combined chemotherapy for a total of 40 cycles after the diagnosis. Final pathology showed, followed by pathological complete remission, without any residual cancer cell. The patient has survived for over 6 years without any evidence of recurrence. This case suggests that locally advanced intrahepatic cholangiocarcinoma, which can't be resected, was also proved to be capable of pathological complete remission with active chemotherapy, and long-term survival could be achieved. Therefore, active multidisciplinary approach and patient-oriented treatments using various methods should be considered for locally advanced unresectable intrahepatic cholangiocarcinoma.

Postoperative radiotherapy appeared to improve the disease free survival rate of patients with extrahepatic bile duct cancer at high risk of loco-regional recurrence

PURPOSE: To investigate the outcomes of postoperative radiotherapy (RT), in patients with extrahepatic bile duct (EHBD) cancer by comparing the survival rate between patients undergoing surgery alone or surgery plus postoperative RT, and to identify the prognostic factors affecting survival. MATERIALS AND METHODS: Between 2000 and 2013, 52 patients with EHBD cancer underwent surgical resection. Of these, 33 patients did not receive postoperative RT (group I), and 19 patients did (group II). R1 resection was significantly more frequent in group II. The median radiation dose was 5,040 cGy. RESULTS: The 3-year overall survival (OS) rate for group I and group II was 38% and 56%, respectively (p = 0.274). The 3-year disease free survival (DFS) rate for group I and group II was 20% and 31%, respectively (p = 0.049), and the 3-year loco-regional recurrence free survival (LRFS) rates were 19% and 58%, respectively (p = 0.002). Multivariate analyses showed that postoperative RT and lymphovascular invasion were independent prognostic factors for DFS and LRFS. Overall, 42 patients (80%) experienced treatment failure. Distant metastasis was the predominant pattern of failure in group II. CONCLUSION: Postoperative RT after surgical resection appeared to improve the loco-regional control and DFS rate. More effort is needed to reduce distant metastasis, the major pattern of failure, in patients who receive postoperative RT.

Surgery Alone Versus Surgery Followed by Chemotherapy and Radiotherapy in Resected Extrahepatic Bile Duct Cancer: Treatment Outcome Analysis of 336 Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study analyzed the outcomes of patients with resected extrahepatic bile duct cancer (EHBDC) in order to clarify the role of adjuvant treatments in these patients. MATERIALS AND METHODS: A total of 336 patients with EHBDC who underwent curative resection between 2001 and 2010 were analyzed retrospectively. The treatment types were as follows: surgery alone (n=168), surgery with chemotherapy (CTx, n=90), surgery with radiotherapy (RT) alone (n=29), and surgery with chemoradiotherapy (CRT, n=49). RESULTS: The median follow-up period was 63 months. The 5-year rates of locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) for all patients were 56.5%, 59.7%, 36.6%, and 42.0%, respectively. In multivariate analysis, surgery with RT and CRT was a significant prognostic factor for LRFFS, and surgery with CTx was a significant prognostic factor for DMFS, and surgery with CTx, RT, and CRT was a significant prognostic factor for PFS (p < 0.05). Surgery with CTx and CRT showed association with superior OS (p < 0.05), and surgery with RT had marginal significance (p=0.078). In multivariate analysis of the R1 resection patients, surgery with CRT showed significant association with OS (p < 0.05). CONCLUSION: Adjuvant RT and CTx may be helpful in improving clinical outcomes of patients with resected EHBDC who have a high risk of disease recurrence, particularly R1 resection patients. Conduct of additional prospective, larger-scale studies will be required in order to confirm the benefit of adjuvant RT and CTx in these patients.

Gallstone ileus inducing obstructive jaundice at the afferent loop of Roux-en-Y hepaticojejunostomy after bile duct cancer surgery: a case report

The diagnosis of gallstone ileus is occasionally challenging due to the variability of its presentation. We herein present a very rare case of gallstone ileus inducing obstructive jaundice at the afferent loop of Roux-en-Y hepaticojejunostomy after 10 years of bile duct cancer surgery. We describe the case of a 74-year-old Korean woman with obstructive jaundice, treated conservatively. She showed severely impaired liver function test and obstructive jaundice. The computed tomography (CT) scan led to a diagnosis of very rare type of gallstones ileus at the afferent jejunal loop. Since the clinical manifestation was improved, we decided to observe her closely. On the next follow-up CT scan, the gallstone disappeared with mild distension of the afferent bowel loop, implicating spontaneous passage of the gallstone. She recovered and returned to normal life after 10 days of initiation of clinical manifestations. We presume that the gallstone may enter the afferent jejunal loop through the hepaticojejunostomy and later increase in size. The presence of narrow tract of intestine may facilitate the incidence of gallstone ileus. It appears to be the first report on this rare type of gallstone ileus inducing obstructive jaundice.

A Case of Fasciola hepatica Infection Mimicking Cholangiocarcinoma and ITS-1 Sequencing of the Worm

Fascioliasis is a zoonotic infection caused by Fasciola hepatica or Fasciola gigantica. We report an 87-year-old Korean male patient with postprandial abdominal pain and discomfort due to F. hepatica infection who was diagnosed and managed by endoscopic retrograde cholangiopancreatography (ERCP) with extraction of 2 worms. At his first visit to the hospital, a gallbladder stone was suspected. CT and magnetic retrograde cholangiopancreatography (MRCP) showed an intraductal mass in the common bile duct (CBD) without proximal duct dilatation. Based on radiological findings, the presumed diagnosis was intraductal cholangiocarcinoma. However, in ERCP which was performed for biliary decompression and tissue diagnosis, movable materials were detected in the CBD. Using a basket, 2 living leaf-like parasites were removed. The worms were morphologically compatible with F. hepatica. To rule out the possibility of the worms to be another morphologically close species, in particular F. gigantica, 1 specimen was processed for genetic analysis of its ITS-1 region. The results showed that the present worms were genetically identical (100%) with F. hepatica but different from F. gigantica.

Technical knacks and outcomes of extended extrahepatic bile duct resection in patients with mid bile duct cancer

BACKGROUNDS/AIMS: Mid bile duct cancers often involve the proximal intrapancreatic bile duct, and resection of the extrahepatic bile duct (EHBD) can result in a tumor-positive distal resection margin (RM). We attempted a customized surgical procedure to obtain a tumor-free distal RM during EHBD resection, so that R0 resection can be achieved without performing pancreaticoduodenectomy through extended EHBD resection. METHODS: We previously reported the surgical procedures of extended EHBD resection, in which the intrapancreatic duct excavation resembles a > or =2 cm-long funnel. This unique procedure was performed in 11 cases of mid bile duct cancer occurring in elderly patients between the ages of 70 and 83 years. RESULTS: The tumor involved the intrapancreatic duct in all cases. Deep pancreatic excavation per se required about 30-60 minutes. Cancer-free hepatic duct RM was obtained in 10 patients. Prolonged leakage of pancreatic juice occurred in 2 patients, but all were controlled with supportive care. Adjuvant therapies were primarily applied to RM-positive or lymph node-positive patients. Their 1-year and 3-year survival rates were 90.9% and 60.6%, respectively. CONCLUSIONS: We suggest that extended EHBD resection can be performed as a beneficial option to achieve R0 resection in cases in which pancreaticoduodenectomy should be avoided due to various causes including old age and expectation of a poor outcome.

Prognostic factors following surgical resection of distal bile duct cancer / 대한외과학회지

PURPOSE: Prognostic factors for distal bile duct cancer are contentious. This study was conducted to analyze the prognostic factors of distal bile duct cancer after surgery with the aim of identifying those associated with diminished survival. METHODS: Two hundred forty-one patients who underwent pylorus-preserving pancreaticoduodenectomy (PPPD) or Whipple procedure in our tertiary hospital from February 1995 to June 2011 were retrospectively analyzed. All patients were pathologically proven to have distal bile duct adenocarcinoma. Postoperative complications, survival, and well-known prognostic factors after resection for distal bile duct cancer were investigated. RESULTS: Preoperative elevated carbohydrate antigen 19-9 (CA 19-9) level (P = 0.006), positive resection margin (P < 0.001), advanced T stage (P = 0.043), and lymph node metastasis (P = 0.002) were significantly independent worse prognostic indicators by multivariate analysis of resectable distal bile duct cancer. CONCLUSION: R0 resection is the most important so that frozen sections should be utilized aggressively during each operation. For the distal bile duct cancer with elevated preoperative CA 19-9 level or advanced stage, further study on postoperative adjuvant treatment may be warranted.

Molecular biomarkers in extrahepatic bile duct cancer patients undergoing chemoradiotherapy for gross residual disease after surgery

PURPOSE: To analyze the outcomes of chemoradiotherapy for extrahepatic bile duct (EHBD) cancer patients who underwent R2 resection or bypass surgery and to identify prognostic factors affecting clinical outcomes, especially in terms of molecular biomarkers. MATERIALS AND METHODS: Medical records of 21 patients with EHBD cancer who underwent R2 resection or bypass surgery followed by chemoradiotherapy from May 2001 to June 2010 were retrospectively reviewed. All surgical specimens were re-evaluated by immunohistochemical staining using phosphorylated protein kinase B (pAKT), CD24, matrix metalloproteinase 9 (MMP9), survivin, and beta-catenin antibodies. The relationship between clinical outcomes and immunohistochemical results was investigated. RESULTS: At a median follow-up of 20 months, the actuarial 2-year locoregional progression-free, distant metastasis-free and overall survival were 37%, 56%, and 54%, respectively. On univariate analysis using clinicopathologic factors, there was no significant prognostic factor. In the immunohistochemical staining, cytoplasmic staining, and nuclear staining of pAKT was positive in 10 and 6 patients, respectively. There were positive CD24 in 7 patients, MMP9 in 16 patients, survivin in 8 patients, and beta-catenin in 3 patients. On univariate analysis, there was no significant value of immunohistochemical results for clinical outcomes. CONCLUSION: There was no significant association between clinical outcomes of patients with EHBD cancer who received chemoradiotherapy after R2 resection or bypass surgery and pAKT, CD24, MMP9, survivin, and beta-catenin. Future research is needed on a larger data set or with other molecular biomarkers.

Comparison of Survival Outcomes following Segmental Bile Duct Resection versus Pancreatoduodenectomy for Mid Bile Duct Cancer

PURPOSE: This study was designed to analyze the prognosis following segmental bile duct resection (BDR) versus pancreatoduodenectomy (PD) for mid bile duct (mBD) cancer. METHODS: During the 4 years between 2003 and 2006, 55 patients underwent surgical resection for mBD cancer in our institution. Medical records were reviewed retrospectively. They were divided into two groups, a BDR group (n=24) and a PD group (n=31) according to the extent of resection. RESULTS: Median follow-up was 43 months. Overall 3- and 5-year survival rates were 56.0% and 33.8%, respectively. The BDR group had lower tumor stages than the PD group (p=0.011). R0 resection was achieved in 17 (70.8%) of the BDR group and 30 (96.8%) of the PD group. Median survival periods were 43 and 34 months after R0 and R1 resections, respectively (p=0.715). Recurrence occurred in 41 patients after a mean period of 18 months. Three- and 5-year survival rates were 62.5% and 27.2% after BDR, respectively, and 51.5% and 34% after PD, respectively (p=0.715). No significant risk factors for shorter patient survival times was identified. Aggressive treatment of recurrence did not appear to prolong patient survival. CONCLUSION: The extent of resection for mBD cancer did not affect the survival outcome when R0 resection was achieved. Considering the operative risk in patients with older ages or co-morbidities, PD should be considered only after obtainment of simultaneous tumor-free radial and proximal longitudinal resection margins.

Early Bile Duct Cancer Detected by Direct Peroral Cholangioscopy with Narrow-Band Imaging after Bile Duct Stone Removal

Cholangioscopy not only enables the direct visualization of the biliary tree, but also allows for forceps biopsy to diagnosis early cholangiocarcinoma. Recently, some reports have suggested the clinical usefulness of direct peroral cholangioscopy (POC) using an ultra-slim endoscope with a standard endoscopic unit by a single operator. Enhanced endoscopy, such as narrow band imaging (NBI), can be helpful for detecting early neoplasia in the gastrointestinal tract and is easily applicable during direct POC. A 63-year-old woman with acute cholangitis had persistent bile duct dilation on the left hepatic duct after common bile duct stone removal and clinical improvement. We performed direct POC with NBI using an ultra-slim upper endoscope to examine the strictured segment. NBI examination showed an irregular surface and polypoid structure with tumor vessels. Target biopsy under direct endoscopic visualization was performed, and adenocarcinoma was documented. The patient underwent an extended left hepatectomy, and the resected specimen showed early bile duct cancer confined to the ductal mucosa.

Mrp14 is a potential biomarker for biliary tract neoplasms / 中华肝胆外科杂志

ObjectiveTo provide clues to find a biomarker for early diagnosis, prognosis and therapy, as well as to understand the molecular mechanisms governing cancer progression. Methods Surgical specimens were obtained from 87 patients with histopathologically proven malignant or benign lesions. The differential protein profiles of these malignant and benign specimens were detected using two-dimensional electrophoresis (2-DE) combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS). Western blotting and immuno-histochemistry were used to validate the results. RT-PCR was used to detect the gene expression in the tissues. ResultsMrp14 was found to be overexpressed in the tumor tissues of gallbladder cancer and extra-hepatic bile duct cancer, and in the bile of patients with malignant biliary tract tumours. The result was further verified using Western blot and immuno-histochemistry. RT-PCR confirmed the overexpression of Mrpl4 at the gene level. Mrp14 is a potential biomarker for biliary tract neoplasms. ConclusionsThis is the first report which described the overexpression of Mrp14 in biliary tract neoplasms and further studies are needed to confirm our findings. Mrp14 may be a potential hiomarker for biliary tract neoplasms. It may provide important clues on the molecular mechanisms governing cancer progression.

Research of interference Livin gene inhibits growth of QBC939 cell / 中华肝胆外科杂志

Objective To study the effect of transfection of livin antisense oligodeoxynucleotide (Livin ASODN) on Livin mRNA and Livin protein expression and proliferation of QBC939 cells.Methods Livin ASODN was transfected into cell line QBC939 by LipofectamineTM 2000. Fluorescence microscopy was used to observe the ASODN transfected cells and to calculate the rate of transfection.to measure Livin mRNA and Livin protein expression by RT-PCR and immunohistochemistry and con-focal laser scanning microscopy after the transfection. Changes in cell proliferation were detected by MTT. Results The highest efficiency was at 24 hours after 500 nmol/L Livin ASODN transfection.The results of MTT showed that the inhibition of cell proliferation of QBC939 cells was most obvious at 60 hours after Livin ASODN transfection (P<0. 05). The level of Livin mRNA and Livin protein expression in the ASODN group was obviously lower than that in the control group (P<0. 05).Conclusion The transfection of Livin ASODN inhibited Livin gene and Livin protein expression, and obviously inhibited the proliferation and depressed the vitality of QBC939 cells.