Shin-E Wang

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.

Comparison of Resected and Non-resected Intraductal Papillary Mucinous Neoplasms of the Pancreas

By comparing the clinicopathological features and survivals between the resected and non-resected intraductal papillary mucinous neoplasms (IPMNs) of the pancreas, this study tried to clarify the natural history of IPMNs, to provide a strategy for treatment, and to determine the justification of not performing resection for some patients. A total of 57 patients with IPMN, including 39 resected and 18 non-resected IPMNs, were recruited for study. Data on demographics, clinical presentations, diagnostic work-up, treatment modality, clinical course, and outcomes were evaluated and compared between the resected and non-resected IPMNs. The most common clinical presentation was abdominal pain (57% in total IPMNs, 67% in resected, 33% in non-resected), followed by body weight loss (32% in total IPMNs, 33% in resected, 28% in non-resected). The sensitivity in the diagnosis of IPMN was highest by magnetic resonance cholangiopancreatography (MRCP) (88%), followed by endoscopic retrograde cholangiopancreatography (ERCP) (68%), and computed tomography scan (CT scan) (42%) and sonography (10%). The median survival was 21.5 months for patients with resected IPMNs, ranging from 2 to 124 months, and 14 months in non-resected IPMN patients, ranging from 5.5 to 70 months. There is no significant survival difference between the resected and non-resected groups, with a 5-year survival of 69.8% in resected IPMNs and 59.8% in non-resected IPMNs, P = 0.347. The survival outcome of the unresectable non-resected IPMNs was much inferior to the resected IPMNs, P = 0.002 and resectable non-resected IPMNs, P = 0.001. Thus, the prime prognostic factor in predicting the survival outcome of IPMNs is resectability, instead of resection itself. Long-term survival could also be expected in resectable IPMNs without resection. No resection for the IPMN may be justified for patients with high surgical risks, especially for those who are asymptomatic and very aged.

Longterm survival after pancreaticoduodenectomy for periampullary adenocarcinomas

OBJECTIVES The aim of this study was to identify predictors for longterm survival following pancreaticoduodenectomy (PD) for pancreatic and other periampullary adenocarcinomas. METHODS Clinicopathological factors were compared between short-term (<5 years) and longterm (≥ 5 years) survival groups. Rates of actual 5-year and actuarial 10-year survival were determined. RESULTS There were 109 (21.8%) longterm survivors among a sample of 501 patients. Patients with ampullary adenocarcinoma represented 76.1% of the longterm survivors. Favourable factors for longterm survival included female gender, lack of jaundice, lower blood loss, classical PD, absence of postoperative bleeding or intra-abdominal abscess, non-pancreatic primary cancer, earlier tumour stage, smaller tumour size (≤ 2 cm), curative resection, negative lymph node involvement, well-differentiated tumours, and absence of perineural invasion. Independent factors associated with longterm survival were diagnosis of primary tumour, jaundice, intra-abdominal abscess, tumour stage, tumour size, radicality, lymph node status and cell differentiation. The prognosis was best for ampullary adenocarcinoma, for which the rate of actual 5-year survival was 32.8%, and poorest for pancreatic head adenocarcinoma, for which actual 5-year survival was only 6.5%. CONCLUSIONS The majority of longterm survivors after PD for periampullary adenocarcinomas are patients with ampullary adenocarcinoma. The longterm prognosis in pancreatic head adenocarcinoma remains dismal.

Risk factors for post-pancreaticoduodenectomy bleeding and finding an innovative approach to treatment.

Background: This study is to determine the risk factors and outcome for post-pancreaticoduodenectomy bleeding, and to assess the roles of surgery and intravascular intervention in its management. Methods: Post-pancreaticoduodenectomy data of 628 patients were analyzed with regards to post-pancreaticoduodenectomy bleeding. Results: Post-pancreaticoduodenectomy bleeding occurred in 58 patients (9.2%) and led to death in 23 patients. Pancreatic leakage and intra-abdominal abscess were independent risk factors for both extraluminal and intraluminal post-pancreaticoduodenectomy bleeding. The most common source of bleeding was the gastroduodenal artery (n = 9, 24.3%), and 8 of these patients (88.9%) experienced gastroduodenal artery bleeding in late post-pancreaticoduodenectomy bleeding. Hemostasis for post-pancreaticoduodenectomy bleeding was achieved by surgery in 22 patients (78.6%) and intravascular intervention in 7 patients (58.3%). Transarterial embolization for gastroduodenal artery bleeding did not deteriorate liver function in most patients except for 1 who died of hepatic failure. Conclusions: The placement of metallic clips on the gastroduodenal artery stump during a pancreaticoduodenectomy is helpful in identifying overlooked intermittent sentinel bleeding during angiography. Transarterial embolization for gastroduodenal artery bleeding could not guarantee against hepatic failure. The intravascular placement of a covered stent is the preferred procedure to avoid the complete interruption of arterial blood supply to the liver.

Comparison of functional and nonfunctional neuroendocrine tumors in the pancreas and peripancreatic region.

Objective: To present our experience of 93 neuroendocrine tumors (NETs) in the pancreas and peripancreatic region, with emphasis on how resectability affects long-term survival and the impact of functional status on the survival outcome. Methods: Ninety-three patients with NETs in the pancreas and peripancreatic region were included to compare the clinical features between functional and nonfunctional NETs. Prognostic factors were determined by univariate and multivariate analyses. Results: There were 39 functional (41.9%) and 54 nonfunctional NETs (58.1%). According to World Health Organization (WHO) tumor categories, there were 57 well-differentiated tumors (61.3%), 26 well-differentiated carcinomas (28%), and 10 poorly differentiated carcinomas (10.8%). Univariate analysis showed that functional status of the tumor, tumor stage, lymph node status, and pathological classification were prognostic factors for both disease-free survival and disease-specific survival. Resectability did not influence the survival outcome, with the resectable and unresectable groups demonstrating a 5-year disease-specific survival of 86.4% and 65.6%, respectively (P = 0.210). Only the WHO pathological classification was an independent prognostic factor after multivariate analysis. Conclusions: Irresectability does not necessarily preclude long-term survival for both functional and nonfunctional NETs. It is the WHO pathological classification, instead of hormonal functional status, that is an independent prognostic factor and has impact on the survival outcome.

Retroperitoneal Bronchogenic Cyst Mimicking Pancreatic Cystic Lesion

Retroperitoneal bronchogenic cyst is detected extremely rarely and often masquerades as other diseases. Here, we report 2 cases of retroperitoneal bronchogenic cyst mimicking pancreatic mucinous tumor. Histologically, both cysts were composed of ciliated respiratory-like epithelium with abundant mucin content, smooth muscle bundles and mature cartilage, compatible with the diagnosis of retroperitoneal bronchogenic cyst. In addition to these 2 cases, another 42 retroperitoneal bronchogenic cysts reported in the English literature were collected for review and analysis. Twelve (28%) were located over the peripancreatic area. Just over half (51%) of them were asymptomatic. No accurate preoperative diagnosis could be made for any of the lesions. About a third (33.3%) of the peripancreatic retroperitoneal bronchogenic cysts masqueraded as pancreatic cystic lesions.

Resection for secondary malignancy of the pancreas.

Objectives This study tried to clarify the role of pancreatic resection in the treatment of secondary malignancy with metastasis or local invasion to the pancreas in terms of surgical risk and survival benefit. Methods Data of secondary malignancy of the pancreas from our 19 patients and cases reported in the English literature were pooled together for analysis. Results There were 329 cases of resected secondary malignancy of the pancreas, including 241 cases of metastasis and 88 cases of local invasion. The most common primary tumor metastatic to the pancreas and amenable to resection was renal cell carcinoma (RCC) (73.9%). More than half (52.3%) of the primary cancers with local invasion to the pancreas were colon cancer, and nearly half (40.9%) were stomach cancer. The median metastatic interval was 84 months (7 years) for overall primary tumors and 108 months (9 years) for RCC. The 5-year survival for secondary malignancy of the pancreas after resection was 61.1% for metastasis and 58.9% for local invasion, with 72.8% for RCC metastasis, 69.0% for colon cancer, and 43.8% for stomach cancer with local invasion to the pancreas. Conclusions Pancreatic resection should not be precluded for secondary malignancy of the pancreas because long-term survival could be achieved with acceptable surgical risk in selected patients.

Hepatoid carcinoma of the pancreas

BackgroundHepatoid carcinoma of the pancreas is extremely rare. This article tries to summarize the clinical features and outcomes of pancreatic hepatoid carcinoma.MethodsThe data pool for analysis includes the case we encountered with hepatoid carcinoma of the pancreas and the reported cases in the literature.ResultsTwenty-three cases of hepatoid carcinoma of the pancreas were analyzed. This tumor occurred more frequently in male than in female patients (69.6 vs. 30.4 %). Tumor sizes range from 0.5 to 11.0 cm with median of 6.0 cm. The most common symptom was epigastric pain (36.4 %). When the tumor locates at pancreatic head, nausea/vomiting (62.5 %) is more common, followed by jaundice and epigastric pain (50.0 %). For those at pancreatic body-tail, 42.9 % of the patients presented no symptom. Alpha-fetoprotein (AFP) was abnormally elevated in 60 % of the cases. Hepatoid carcinoma in the pancreas could be either pure form or mixed form with other malignancy (40.9 %), with the most common coexisted pathology of malignant neuroendocrine tumor (22.7 %). Metastasis occurred in 36.4 % of the cases at the diagnosis of this tumor, including liver metastasis in 31.8 % and lymph node metastasis in 21.1 %. The overall 1-year survival rate was 71.1 % and 5-year 40.4 %, with a median of 13.0 months. Unresectability, hepatic, and lymph node metastases are associated with negative impact on survival outcome.ConclusionsElevation of serum AFP may be a clue leading to the diagnosis of pancreatic hepatoid carcinoma. This tumor could be mixed form with other malignancy. Surgical resection should be the treatment of choice whenever possible.

Alleviation of hyperglycemia in diabetic rats by intraportal injection of insulin-producing cells generated from surgically resected human pancreatic tissue

Although islet transplantation holds promise for the treatment of diabetes, the scarcity of donor tissue remains a major drawback. The aim of this study is to generate insulin-producing cells from adult human pancreatic cells isolated from surgically resected pancreatic tissue. To isolate pancreatic endocrine precursor cells from 57 surgically resected pancreases, the cells were cultured and propagated in conditioned medium after which they were differentiated in Matrigel. The resultant cells were characterized using morphology, immunofluorescent studies, expression of differentiated pancreatic islet-specific genes using quantitative reverse transcription-PCR, and glucose-induced insulin secretion through analysis of C-peptide secretion. The relationships between propagation of insulin-producing cells and clinical variables of the donor were also analyzed. Finally, insulin-producing cell function was examined in streptozotocin-induced diabetic rats. Pancreatic endocrine precursor cells were successfully cultured; insulin-producing cells cultured from soft pancreas parenchyma had a significantly higher success rate. Morphological examination revealed islet-like cluster formation upon transfer to Matrigel. The presence of the neural stem cell marker nestin, duct cell marker cytokeratin 19, and endocrine cell markers C-peptide and pancreatic and duodenal homeobox 1, was also observed. In addition, glucose-stimulated C-peptide release was significantly increased in the insulin-producing cells. Furthermore, in diabetic rats, transplantation of insulin-producing cells reduced hyperglycemia. Isolated pancreatic endocrine precursor cells from surgically resected pancreatic tissue differentiated into insulin-producing cells and showed characteristics of functional endocrine cells. Thus, surgically resected pancreatic tissue may represent an alternative source of functional insulin-producing cells.

Elevation of β-galactoside α2,6-sialyltransferase 1 in a fructoseresponsive manner promotes pancreatic cancer metastasis

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive type of pancreatic cancer with clinical characteristics of local invasion and early metastasis. Recent cohort studies indicate high fructose intake is associated with an increase in pancreatic cancer risk. However, the mechanisms by which fructose promotes pancreatic tumorigenesis remain unclear. Herein, Kras+/LSLG12D mice were crossed with Elas-CreER transgenic mice to determine whether fructose intake directly contributes to tumor formation. Orthotopic tumor-xenograft experiments were performed to determine whether fructose substitution enhances the metastatic potential of PDAC cells. The mechanisms underlying the effects of fructose were explored by RNAseq analysis in combination with high-performance anion exchange chromatography. Dietary fructose was initially found to promote the development of aggressive pancreatic cancer in mice conditionally expressing KrasG12D in the adult pancreas. We further revealed that fructose substitution enhanced the metastatic potential of human PDAC cell via selective outgrowth of aggressive ABCG2-positive subpopulations and elevating N-acetylmannosamine levels that upregulated β-galactoside α2,6-sialyltransferase 1 (ST6Gal1), thereby promoting distant metastasis. Finally, we observed that PDAC patients expressing higher levels of ST6Gal1 and GLUT5 presented poorer prognosis compared to other groups. In conclusion, our findings have elucidated a crucial role of ST6Gal1 in regulating the invasiveness of PDACs in a fructose-responsive manner.