Yi-Ming Shyr

Factors Influencing Postoperative Morbidity, Mortality, and Survival After Resection for Hilar Cholangiocarcinoma

UNLABELLED OBJECTIVE; Morbidity and mortality involved in the resection of hilar cholangiocarcinoma were reviewed retrospectively. The clinicopathologic and laboratory parameters that might influence the patients survival also were re-evaluated. SUMMARY BACKGROUND DATA Although much progress has been made in the diagnosis and management of hilar cholangiocarcinoma, long-term outlook for most patients remains poor. Surgical resection is usually prohibited because of its local invasiveness, and most patients can only be managed by palliative drainage. Recently, many surgeons have adopted a more aggressive resection with varying degrees of success. Several prognostic factors in bile duct carcinoma have been proposed; however, no reports have specifically focused on resected hilar cholangiocarcinoma and its prognostic survival factors using multivariate analysis. METHODS The clinical records and pathologic slides of 49 cases with resected hilar cholangiocarcinoma were reviewed retrospectively. Twenty clinical and laboratory parameters were evaluated for their correlation with postoperative morbidity and mortality, whereas 31 variables were evaluated for their significance with postoperative survival. Variables showing statistical significance in the first univariate analysis were included in the following multivariate analysis using stepwise logistic regression test for factors affecting morbidity and mortality and Cox stepwise proportional hazard model for factors influencing survival. RESULTS There were 5 in-hospital deaths, and the cumulative 5-year survival rate in 44 patients who survived was 14.9%, with a median survival of 14.0 months. Multivariate analysis disclosed that co-existent hepatolithiasis and lower serum asparate aminotransferase levels (<90 U/L) had a significant low incidence of postoperative morbidity, whereas a serum albumin of less than 3 g/dL was the only significant factor affecting mortality. Regarding survival, univariate analysis identified eight significant factors: 1) total bilirubin > or = 10 mg/dL, 2) curative resection, 3) histologic type, 4) perineural invasion, 5) liver invasion, 6) depth of cancer invasion, 7) positive proximal resected margin, and 8) positive surgical margin. However, multivariate analysis disclosed total bilirubin > or = 10 mg/dL, curative resection, and histologic type as the three most significant independent variables. CONCLUSIONS Surgical resection provides the best survival for hilar cholangiocarcinoma. An adequate nutritional support to increase serum albumin over 3 g/dL is the most important factor to decrease postoperative mortality. Moreover, preoperative biliary drainage to decrease jaundice and a curative resection with adequate surgical margin are recommended if longer survival is anticipated. Patients with well-differentiated adenocarcinoma seem to survive longer compared to those with moderately or poorly differentiated tumors.

Mucin-producing neoplasms of the pancreas. Intraductal papillary and mucinous cystic neoplasms.

OBJECTIVE The authors compared the clinicopathologic features of the intraductal papillary and mucinous cystic neoplasms of the pancreas and clarified the similarities as well as the differences between these two tumors. In addition, they reviewed 104 cases of the intraductal papillary neoplasm in the English literature to provide a global view of the condition. SUMMARY BACKGROUND DATA Controversy about the term and clinicopathologic entity still exist regarding intraductal papillary neoplasm of the pancreas. Currently, with only a few cases of this rare tumor in each report, there continues to be inadequate knowledge available regarding the tumor and methods by which to distinguish it from the mucinous cystic neoplasm. METHODS Multiple demographic and clinicopathologic parameters were compared between intraductal papillary and mucinous cystic neoplasms identified from 1985 to 1994 in the Medical Center, Veterans General Hospital--Taipei. RESULTS There were four intraductal papillary adenocarcinomas and 10 mucinous cystic neoplasms (8 cystadenocarcinoma and 2 cystadenoma). The sex, age, size, tumor location, and pathologic findings were quite different between these two groups. Clinical presentation of intraductal papillary adenocarcinomas were similar to those of periampullary tumors. The most common presentations of mucinous cystic neoplasm were epigastric pain and abdominal mass. All four intraductal papillary adenocarcinoma showed mucin secretion from a patulous orifice of the ampulla of Vater and filling defects in the dilated main pancreatic duct by endoscopic retrograde cholangiopancreatography (ERCP). Accurate preoperative diagnosis was not easy regarding either group. Serum carbohydrate antigen 19-9 (CA 19-9) was more useful for diagnosis in both groups. CONCLUSIONS The intraductal papillary neoplasm is a unique clinical entity but not a variant of mucinous cystic neoplasm in terms of sex, age, size, tumor location, or pathologic picture. The pathognomonic findings of ERCP should lead to diagnosis. Very aggressive surgical procedures should be attempted for these two mucin-producing neoplasms with low-grade malignancy.

Biochemical predictors for absence of common bile duct stones in patients undergoing laparoscopic cholecystectomy

BackgroundTo provide optimal selection of patients for preoperative endoscopic retrograde cholangiopancreatography or intraoperative cholangiography, we evaluated simple, noninvasive biochemical parameters as screening tests to predict the absence of common bile duct stones prior to laparoscopic cholecystectomy.MethodsA total of 1002 patients underwent laparoscopic cholecystectomy. Five biochemical parameters were measured preoperatively: gamma glutamyl transferase (GGT), alkaline phosphatase, total bilirubin, alanine aminotransferase, and aspartate aminotransferase. Conventional diagnostic tests, including ultrasound imaging, computed tomography, magnetic resonance imaging, common bile duct diameter, endoscopic retrograde cholangiopancreatography, and serum amylase were performed. Along with the five biochemical tests above, these diagnostic tests were scrutinized and compared as potential predictors for common bile duct stones.ResultsEighty-eight (8.8%) patients with gallstone disease who underwent laparoscopic cholecystectomy had concurrent common bile duct stones. Among all diagnostic tests, endoscopic retrograde cholangiopancreatography had the highest sensitivity (96.0%), specificity (99.1%), probability ratio (107.3), accuracy (98.0%), and positive predictive value (98.8%) in detecting common bile duct stones. At least one abnormal elevation among the five biochemical parameters had the highest sensitivity (87.5%). Total bilirubin had the highest specificity (87.5%), highest probability ratio (3.9), highest accuracy (84.1%), and highest positive predictive value (27.4%). All five biochemical predictors had high negative predictive values; gamma glutamyl transferase was highest (97.9%), while the lowest was total bilirubin (94.7%). Multivariate analysis showed only gamma glutamyl transferase, alkaline phosphatase, and total bilirubin to be independent predictors; gamma glutamyl transferase appeared to be the most powerful predictor (odds ratio 3.20).ConclusionBiochemical tests, especially gamma glutamyl transferase with 97.9% negative predictive value, are ideal noninvasive predictors for the absence of common bile duct stones in patients undergoing laparoscopic cholecystectomy. We suggest that unnecessary, costly, or risky procedures such as endoscopic retrograde cholangiopancreatography can be omitted prior to laparoscopic cholecystectomy in patients without abnormal elevation of these biochemical values.

A novel in vitro retinal differentiation model by co-culturing adult human bone marrow stem cells with retinal pigmented epithelium cells

Human retinal pigment epithelium (HRPE) cells are important in maintaining the normal physiology within the neurosensory retina and photoreceptors. Recently, transplantation of HRPE has become a possible therapeutic approach for retinal degeneration. By negative immunoselection (CD45 and glycophorin A), in this study, we have isolated and cultivated adult human bone marrow stem cells (BMSCs) with multilineage differentiation potential. After a 2- to 4-week culture under chondrogenic, osteogenic, adipogenic, and hepatogenic induction medium, these BMSCs were found to differentiate into cartilage, bone, adipocyte, and hepatocyte-like cells, respectively. We also showed that these BMSCs could differentiate into neural precursor cells (nestin-positive) and mature neurons (MAP-2 and Tuj1-positive) following treatment of neural selection and induction medium for 1 month. Furthermore, the plasticity of BMSCs was confirmed by initiating their differentiation into retinal cells and photoreceptor lineages by co-culturing with HRPE cells. The latter system provides an ex vivo expansion model of culturing photoreceptors for the treatment of retinal degeneration diseases.

Does Drainage Fluid Amylase Reflect Pancreatic Leakage after Pancreaticoduodenectomy

This study tried to determine if drainage fluid amylase reflects pancreatic leakage after pancreaticoduodenectomy and to determine the factors affecting the drainage amylase level. Patients undergoing pancreaticoduodenectomy were recruited. The drainage amylase was measured from postoperative day (POD) 1 to POD 7. Direct evidence of pancreatic leakage was provided by upper gastrointestinal studies using a water-soluble contrast medium and methylene blue dye in the pancreaticogastrostomy group or by pancreaticography with injected contrast medium via an exteriorized pancreatic stent in the pancreaticojejunostomy group on POD 7. A total of 37 patients were recruited. The drainage amylase level was higher than the normal serum amylase (≥ 190 U/L) in more than half of the cases on the initial POD 2 specimen, with a median of 745 U/L on POD 1 and 663 U/L on POD 2. The drainage amylase level was more than three times the normal serum amylase level (≥ 190 × 3 U/L) in 56.8% on POD 1, in 51.4% on POD 2, and in nearly one-third on POD 7 (29.7%). However, no pancreatic leakage occurred in any of the patients with a drainage amylase of ≥ 190 U/L. Only one case of pancreatic leakage with a small amount of drainage fluid (10 ml) and low amylase level (74 U/L), was noted. Soft pancreatic parenchyma and a nondilated pancreatic duct were significantly associated with higher drainage amylase levels. In conclusion, biochemical leakage defined by amylase-rich drainage fluid might have no clinical significance and was not necessarily clinical pancreatic leakage following pancreaticoduodenectomy.

Functional and morphological changes in pancreatic remnant after pancreaticoduodenectomy.

Objectives: Pancreatic exocrine insufficiency has been reported to be more common in pancreaticogastrostomy (PG) than in pancreaticojejunostomy (PJ) after pancreaticoduodenectomy (PD). This study aimed to evaluate the long-term outcome after PD between these 2 groups. Methods: We evaluated the long-term functional status of 42 surviving patients diagnosed with periampullary lesions who underwent PJ or PG after PD and followed up for more than 1 year. Among these, 23 patients underwent PJ and 19 patients underwent PG. To compare the 2 groups, we analyzed the (1) pancreatic exocrine insufficiency by questioning the presence or absence of steatorrhea, (2) pancreatic endocrine function by measuring glycohemoglobin A1c, fasting blood glucose, and history of new-onset diabetes, (3) nutritional status by measuring serum total protein, albumin, cholesterol, and triglyceride, (4) gastric emptying time, (5) panendoscopic findings, (6) changes of pancreatic duct diameter by computed tomography, and (7) relaparotomy rate. Results: The mean follow-up time for PG and PJ were 37 ± 23 and 103 ± 52 months, respectively (P < 0.05). A total of 52.4% patients developed pancreatic exocrine insufficiency, and 11.9% had new-onset diabetes. There was no significant difference between PJ and PG groups. A significantly improved postoperative nutritional state regarding serum total protein and albumin were noticed in both groups. There was no significant difference in terms of gastric emptying time, positive panendoscopic findings, and changes in pancreatic duct diameter. The pancreatic remnant-related relaparotomy rate was higher in the PJ group as compared with the PG group (17.4% vs 0%; P = 0.056). Conclusions: There is no significant difference in pancreatic exocrine or endocrine insufficiency, gastric emptying time, and positive panendoscopic findings between PJ and PG. Pancreaticojejunostomy was associated with a higher pancreatic remnant-related relaparotomy rate; however, because of a shorter follow-up in the PG group, a continuous long-term follow-up is still needed.

Diagnostic and prognostic values of CA 19-9 and CEA in periampullary cancers

BACKGROUND The roles of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) in periampullary cancers have not been clearly established. Diagnostic and prognostic values of these two tumor markers were clarified in this study. STUDY DESIGN Preoperative serum levels of CEA and CA 19-9, and clinicopathologic features were retrospectively reviewed in 143 surgical patients with periampullary cancer from 1989 to 1997. RESULTS There were 86 resectable and 57 unresectable periampullary cancers. CA 19-9 demonstrated significantly higher sensitivity in detecting these cancers than CEA. The cancer with unresectable lesion, total bilirubin >7.3 mg/dL, or tumor size >2 cm tended to associate with higher CA 19-9 level. CEA level was significantly higher in the tumor >2 cm, not in the tumor < or =2 cm. CA 19-9 was a significant prognostic factor in both resectable and unresectable periampullary cancers, but CEA was significant only in the resectable group. Multivariate analysis revealed that independent prognostic factors included CA 19-9, resectability, primary tumor, and stage, and CA 19-9 was the most important one. CONCLUSION CA 19-9 provided more important diagnostic and prognostic values than CEA in periampullary cancers and was the most important independent prognostic factor for periampullary cancers. This study recommends serum CA 19-9 as an adjunct in detecting periampullary cancers, in evaluating resectability, and in predicting prognosis.

Management of pancreatic lesions in von Hippel-Lindau disease.

Abstract. Twelve patients with von Hippel-Lindau disease were collected in our institute from 1981 to 1995. All had a family history of the disease. Eleven patients underwent abdominal computed tomography, sonography, or angiographic studies. Ten had pancreatic involvement that included cystic lesions in nine and a solid lesion in one. Seven patients were asymptomatic. Another three presented with obstructive jaundice or upper gastrointestinal (UGI) bleeding. Except for case 8, who died of a central nervous system complication soon after diagnosis of the pancreatic lesion, the other patients had been found to have pancreatic involvement for a variable period of time, ranging from 1 to 13 years (median 5 years). Serous cystadenoma was proved pathologically in two with cystic lesions, and pancreatic endocrine tumor was diagnosed in one with a solid mass. One patient (case 1) underwent biliary bypass due to obstructive jaundice and died of cholangitis and pneumonia 6 years later. One patient (case 3) had total pancreatectomy and lived well with good diabetic control for more than 5 years. The patient with a solid lesion was explored because of repeated UGI bleeding. Surgical resection was impossible owing to advanced tumor with vascular involvement, and a pancreatic endocrine tumor was diagnosed pathologically. He was followed for 1 year. The other seven patients remained asymptomatic during the successive follow-up period. From a literature review and our own experience, we suggest that conservative measures are adequate for the cystic lesions; however, aggressive resection is mandatory for a solid pancreatic lesion in von Hippel-Lindau disease.

Transplantation of insulin-producing cells from umbilical cord mesenchymal stem cells for the treatment of streptozotocin-induced diabetic rats

BackgroundAlthough diabetes mellitus (DM) can be treated with islet transplantation, a scarcity of donors limits the utility of this technique. This study investigated whether human mesenchymal stem cells (MSCs) from umbilical cord could be induced efficiently to differentiate into insulin-producing cells. Secondly, we evaluated the effect of portal vein transplantation of these differentiated cells in the treatment of streptozotocin-induced diabetes in rats.MethodsMSCs from human umbilical cord were induced in three stages to differentiate into insulin-producing cells and evaluated by immunocytochemistry, reverse transcriptase, and real-time PCR, and ELISA. Differentiated cells were transplanted into the liver of diabetic rats using a Port-A catheter via the portal vein. Blood glucose levels were monitored weekly.ResultsHuman nuclei and C-peptide were detected in the rat liver by immunohistochemistry. Pancreatic β-cell development-related genes were expressed in the differentiated cells. C-peptide release was increased after glucose challenge in vitro. Furthermore, after transplantation of differentiated cells into the diabetic rats, blood sugar level decreased. Insulin-producing cells containing human C-peptide and human nuclei were located in the liver.ConclusionThus, a Port-A catheter can be used to transplant differentiated insulin-producing cells from human MSCs into the portal vein to alleviate hyperglycemia among diabetic rats.

Secretome-Based Identification of ULBP2 as a Novel Serum Marker for Pancreatic Cancer Detection

Background To discover novel markers for improving the efficacy of pancreatic cancer (PC) diagnosis, the secretome of two PC cell lines (BxPC-3 and MIA PaCa-2) was profiled. UL16 binding protein 2 (ULBP2), one of the proteins identified in the PC cell secretome, was selected for evaluation as a biomarker for PC detection because its mRNA level was also found to be significantly elevated in PC tissues. Methods ULBP2 expression in PC tissues from 67 patients was studied by immunohistochemistry. ULBP2 serum levels in 154 PC patients and 142 healthy controls were measured by bead-based immunoassay, and the efficacy of serum ULBP2 for PC detection was compared with the widely used serological PC marker carbohydrate antigen 19-9 (CA 19-9). Results Immunohistochemical analyses revealed an elevated expression of ULPB2 in PC tissues compared with adjacent non-cancerous tissues. Meanwhile, the serum levels of ULBP2 among all PC patients (n = 154) and in early-stage cancer patients were significantly higher than those in healthy controls (p<0.0001). The combination of ULBP2 and CA 19-9 outperformed each marker alone in distinguishing PC patients from healthy individuals. Importantly, an analysis of the area under receiver operating characteristic curves showed that ULBP2 was superior to CA 19-9 in discriminating patients with early-stage PC from healthy controls. Conclusions Collectively, our results indicate that ULBP2 may represent a novel and useful serum biomarker for pancreatic cancer primary screening.