Gallbladder carcinoma associated with pancreaticobiliary maljunction presenting as severe acute pancreatitis.
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Abnormalities, Multiple↗
Biomedical subjects
Atsutake Okamoto
Publications and source records attributed to Atsutake Okamoto.
Clinicopathological features of autoimmune pancreatitis in relation to elevation of serum IgG4.
OBJECTIVES: To examine the clinicopathological differences between patients with autoimmune pancreatitis in relation to presence or absence of elevated serum IgG4 concentrations. METHODS: We divided 21 patients with autoimmune pancreatitis into 2 groups on the basis of serum IgG4 concentration: elevated (>135 mg/dL) and low. The number of IgG4-immunoreactive plasma cells in the pancreas, bile duct, gallbladder, gastric mucosa, and abdominal lymph nodes was examined. RESULTS: Serum IgG4 concentrations were elevated in 14 patients (150-1890 mg/dL). No significant differences in age and sex, frequencies of pancreatic swelling, biliary stenosis, presence of autoantibodies, and salivary glands enlargement were identified between the 2 groups. Abdominal lymphadenopathy was detected at laparotomy more frequently in patients with high serum IgG4 (P < 0.05). Although no difference in number of IgG4-positive plasma cells infiltrating the pancreas was observed between the 2 groups, patients with elevated IgG4 tended to exhibit more of these cells infiltrating the wall of the bile duct and abdominal lymph nodes, significantly more of these cells infiltrating the gastric mucosa (P < 0.01). CONCLUSION: IgG4-related phenomena occurred in various organs of patients with autoimmune pancreatitis associated with elevated IgG4, whereas these phenomena tended to be rather confined to the pancreas in patients with low serum IgG4.
Adult↗
Pancreatic tumor associated with pancreas divisum.
BACKGROUND: Although there has been considerable controversy regarding pancreas divisum and pancreatitis, little discussion of this has taken place. The purpose of the present paper was to investigate the relationship between these two conditions. METHODS: A retrospective investigation was undertaken of pancreatic tumors associated with pancreas divisum, in 650 cases of pancreatic carcinoma, 80 cases of intraductal papillary mucinous tumor of the pancreas and 32 cases of pancreas divisum. RESULTS: Of these 32 cases, four (12.5%) were associated with pancreatic tumor: pancreatic carcinoma (n = 3) and intraductal papillary mucinous tumor (n = 1). All tumors developed from the dorsal pancreas of pancreas divisum. Periductal and interlobular fibrosis detected in the non-carcinomatous pancreas of the margin of distal pancreatectomy implied that chronic dorsal pancreatitis associated with pancreas divisum preceded carcinoma. CONCLUSIONS: Pancreatic tumors were detected in 12.5% of cases of pancreas divisum. In pancreas divisum, longstanding pancreatic duct obstruction caused by relative stenosis of the minor duodenal papilla might be a factor promoting oncogenesis.
Adenocarcinoma↗
Enhancement of the caspase-independent apoptotic sensitivity of pancreatic cancer cells by DHMEQ, an NF-kappaB inhibitor.
The effects of the nuclear factor (NF)-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), combined with tumor necrosis factor (TNF)-alpha were evaluated in PK-8 pancreatic cancer cells. NF-kappaB was activated by TNF-alpha; however, the administration of DHMEQ abrogated its transcriptional activity. The addition of DHMEQ to TNF-alpha markedly induced apoptosis in PK-8 cells with down-regulation of anti-apoptotic c-FLIP and survivin. Combined treatment significantly suppressed cell viability in vitro, and the anti-tumor effect of DHMEQ was also significant in vivo. We investigated the apoptosis signaling pathway involved in these cell killing effects. Truncated Bid was produced by activated caspase-8, and the subsequent depolarization of the mitochondrial membrane potential (Delta Psi m) peaked at 6 h. Then, the activity of caspase-3 was up-regulated 8-fold. Z-VAD-fmk (a pan-caspase inhibitor) perfectly inhibited the up-regulation of caspase-3 but failed to reverse the cell viability. The above findings indicated that the growth inhibitory effect of combined treatment largely depended on mitochondria-associated caspase-independent apoptosis. The intracellular behavior of apoptosis-inducing factor (AIF) following depolarization of Delta Psi m suggested that AIF executed such a caspase-independent apoptosis. Interestingly, caspase-dependent apoptosis appeared within 6 h, whereas the caspase-independent apoptosis lagged. Thus, the addition of DHMEQ to TNF-alpha was capable of inducing caspase-independent apoptosis in pancreatic cancer cells. Once caspase-independent apoptosis was induced, the apoptosis demonstrated powerful cytotoxicity. Therefore, DHMEQ in combination with TNF-alpha may be a promising treatment for pancreatic cancer.
Apoptosis↗
[Gemcitabine concurrent with radiation for locally advanced pancreatic cancer].
Gemcitabine (GEM) concurrent with radiation is clinically not well defined. We herein report four cases of chemo-radiotherapy against locally advanced pancreatic cancer using low-dose GEM concurrent with extra-beam radiation. A total of eight cases entered the study. Three were resected and five were non-resected cases. Intraoperative radiation was carried out in every case using an 8 or 10 centimeter cone with a radiation dose of 25 Gy. Postoperative radiation was 2 Gy per day on weekdays for 5 weeks. Four cases were concurrent with low-dose GEM (40 mg/m2) twice a week, whereas the other four were radiation only. With the use of GEM concurrent with radiation, tumor markers decreased more than 80 percent regardless of the tumor resection. CT scan confirmed a necrotic change and the decrease of the tumor size. In conclusion, low dose GEM concurrent with radiation therapy may be a promising therapeutic choice for the local control of advanced pancreatic cancers.
Aged↗
Clinical and radiological findings in dominance of Santorini's duct.
BACKGROUND/AIMS: Few studies on Santorini's duct dominance, in which the ventral pancreatic duct is narrower than and anastomoses with Santorini's duct have been performed. We examined clinical and radiological findings in cases characterized by dominance of Santorini's duct. METHODS: We reviewed 3,800 cases of endoscopic retrograde cholangiopancreatography. Clinical and pancreatographic findings including caliber, course, terminal shape, and patency of Santorini's duct were examined in cases of Santorini's duct dominance. RESULTS: Twenty-nine cases were diagnosed as Santorini's duct dominant. Chronic pancreatitis, acute relapsing pancreatitis, pancreatic-type pain, and hyperamylasemia not associated with obvious pancreatitis were observed in 3, 1, 5, and 6 cases, respectively. Cholangiopancreatographic findings indicated congenital choledochal cyst (n = 2), branch fusion between the ventral and dorsal pancreatic ducts (n = 23), and normal pancreatic duct system characterized by a straight course through the body and tail to join the ventral pancreatic duct in the neck portion of the pancreas (n = 4). Regarding terminal shapes of Santorini's duct, cudgel type (n = 9) and spindle type (n = 8), which showed frequent patency, were observed significantly more frequently than in controls. Patency of Santorini's duct was observed in 90% (17/19). CONCLUSIONS: Many Santorini's duct-dominant cases exhibited branch fusion between the ventral and dorsal pancreatic ducts. Although Santorini's duct functions well in most cases in which it is dominant, pancreatitis or pancreatic-type pain occurs in half of such cases due to relative impairment of function of the minor duodenal papilla.
Cholangiopancreatography, Endoscopic Retrograde↗
Chronic pancreatitis in the elderly in Japan.
BACKGROUND/AIM: Although the elderly comprise an increasingly large segment of the population, little has been written about chronic pancreatitis in this age group in Japan. In this study, we analyzed the clinical features of elderly Japanese patients with chronic pancreatitis and compared them with those of late-onset chronic pancreatitis patients in Western countries. METHODS: Subjects were 182 patients (162 males and 20 females) with chronic pancreatitis. They were divided into two groups: early-onset group (onset <65 years of age, n = 119) and late-onset group (onset > or =65 years of age, n = 63). Clinical findings and follow-up data were examined for each group. RESULTS: Alcohol abuse was the most common etiological factor in early-onset pancreatitis patients. In the late-onset group, the frequencies of idiopathic and autoimmune pancreatitis increased. Furthermore, the age at onset of autoimmune pancreatitis was >60 years in 94% of the cases. The late-onset group was more likely to have painless disease, and calcification of the pancreas and steatorrhea were rare in this group. Major causes of death were malignancy and malnutrition in each group. CONCLUSIONS: Early- and late-onset chronic pancreatitis showed different clinical features. Clinicians should consider autoimmune pancreatitis in the differential diagnosis in elderly patients with obstructive jaundice.
Age Factors↗
A comparative clinical study of gallbladder tubular adenocarcinoma according to the grade of differentiation.
BACKGROUND: We sought to elucidate differences in the clinical characteristics of gallbladder carcinoma according to the histological degree of glandular formation. METHODS: The subjects consisted of 66 autopsy cases out of 331 patients admitted for gallbladder carcinoma between 1975 and 2000. After identifying 49 tubular adenocarcinoma cases, we arbitrarily divided them into two categories: a well-differentiated type (group W; n=41; well or moderately differentiated tubular adenocarcinoma), and a poorly differentiated type (group P, n=8). The clinical features of the groups were compared. RESULTS: No significant differences were found with regard to sex, age, or serum carcinoembryonic antigen (CEA) levels between the two groups. Moreover, no intergroup difference was found in either the time interval from the initial symptoms to admission, or the grade of tumor progression on admission. Although the frequency of liver metastases on admission was similar in both groups, the frequency at autopsy was significantly higher in group W than in group P (73% vs 25%; P <0.05). When survival was determined based on the duration after primary treatment, the longest and median periods were 48.7 months and 3.7 months, respectively, in group W, whereas none of the subjects in group P survived for over 2 months. This difference was statistically significant ( P <0.001). CONCLUSIONS: Hematogenous metastasis was more prominent in group W. Poorly differentiated tubular adenocarcinoma can be closely associated with a poor prognosis.
Adenocarcinoma↗
Pathologic changes in the non-carcinomatous epithelium of the gallbladder in patients with a relatively long common channel.
BACKGROUND: Except for pancreaticobiliary maljunction, the relationship between a relatively long common channel and gallbladder carcinoma is unknown. METHODS: For purposes of this study, a high confluence of pancreaticobiliary ducts was defined as a common channel that is 6 mm or greater in length, together with occlusion of the communication between the pancreatic and bile ducts during sphincter contraction. Pancreaticobiliary maljunction and high confluence of the pancreaticobiliary ducts were detected in 69 (2.1%) and 54 (1.6%), respectively, of 3300 consecutive patients who underwent ERCP. Proliferation activity and genetic alteration were examined in the non-carcinomatous epithelium of the gallbladder in patients with these two radiographic findings at ERCP. RESULTS: The Ki-67 labeling index in the epithelium in cases of a high confluence of the pancreaticobiliary ducts and pancreaticobiliary maljunction without biliary dilatation was significantly greater than that in cases of gallbladder carcinoma without these anomalies (p < 0.01). Overexpression of p53 and K-ras mutations were detected in, respectively, 22.2% and 27.8% of cases of a high confluence of pancreaticobiliary ducts. CONCLUSIONS: A relatively long common channel may be an important risk factor for the development of gallbladder carcinoma. Vigilance for the development of gallbladder carcinoma is indicated in patients with a relatively long common channel, in addition to those with pancreaticobiliary maljunction.
Bile Ducts↗
Intraoperative radiation therapy for pancreatic adenocarcinoma: the Komagome hospital experience.
We analyzed 144 patients with pancreatic adenocarcinoma who had received intraoperative radiation therapy (IORT) in combination with external beam radiation therapy (EBRT) within the past 20 years. The patients were divided into 2 groups: group 1 contained 65 patients with locally unresectable tumors who underwent bypass operations and group 2 contained 68 patients with resectable tumors who underwent pancreatic resection. As a pilot study, we performed additional arterial infusion chemotherapy after changing peripancreatic hemodynamics during EBRT in the remaining 11 patients. The 30 patients who received R0 resection had the best survival rates (3-year survival rate of 35.4%), while 3 patients with stage III disease survived more than 5 years. The survival of group 1 patients nearly equaled that of group 2 patients who underwent R1 or R2 resection (median survival, 10.9 vs. 11.1 months, respectively; P = 0.43). The 1-year survival rate for the 11 patients receiving arterial infusion chemotherapy was 45.4%, and 5 patients survived over 1 year without developing hepatic metastasis or regrowth of primary tumors. The survival benefits obtained using this form of radiotherapy are apparently limited. On the other hand, additional arterial infusion chemotherapy employing a new drug delivery system using hemodynamic change does appear promising.
Adenocarcinoma↗
DFU, a selective COX-2 inhibitor, suppresses MCF-7 xenograft tumor growth in mice.
Cyclooxygenase-2 (COX-2) inhibitors are regarded as potentially important in strategies for cancer treatment. however, the precise mechanisms of these anti-inflammatory drugs as anti-cancer therapy are still unknown. In this study, we examined the effect of DFU both in vitro on MCF-7 cell growth, as well as in vivo on tumor growth produced by MCF-7 cell injection in mice. DFU has growth inhibitory effects on tumor growth in mice compared to the control group. We examined the tumor tissues for apoptosis and angiogenesis by immunostaining. Apoptosis was detected only in the treatment group. DFU treatment also resulted in the inhibition of angiogenesis, as well as decreased COX-2 expression. Results of this study suggest that inhibitory effects of DFU might be COX-2 dependent.
Animals↗
[Successful hepatic arterial infusion therapy of CDDP/5-FU/IFN-beta3 for recurrent hepatocellular carcinoma].
A 52-year-old male patient was admitted to our hospital for a further examination of liver tumor. He was positive for hepatitis C virus antibody. CT scanning revealed two hyper vascular tumors at the lateral segment of the liver and another one located at segment 8, an indication of hepatocellular carcinoma (HCC). Ascites were not detected and major serological findings were T-Bil 1.1 mg/dl, Alb 3.5 g/dl, ICG R15 12% and PT 88%. Lateral segmentectomy and a partial resection of the segment 8 were performed at the same time. An insertion of catheter in hepatic artery via gastroduodenal artery was carried out. Dehydropyrimidine dehydrogenase (DPD) activity of the tumor was 157 pmol/min/mg proteins. Recurrence was detected one year after the operation at segments 4 and 8. Arterial infusion chemotherapy using CDDP (10 mg), 5-FU (1,000 mg) and IFN-beta 3MU (continuous infusion for 5 days) was started two months later, and a complete response was achieved. The chemotherapy continued as long as severe adverse effects were not observed. However, two months after the tumor disappearance, the treatment discontinued due to occlusion of the infusion system. Recurrence occurred in two months at the same location where the previous tumor was. In conclusion, these results suggest that arterial chemotherapy using CDDP/5-FU/IFN-beta against HCC may be beneficial.
Antineoplastic Combined Chemotherapy Protocols↗
Resection versus palliation: treatment of stage III and IVA carcinomas of the pancreas employing intraoperative radiation.
Whether advanced pancreatic carcinomas should be surgically removed has been a basic issue because performing an extended resection is futile if it has only a minimum impact on survival. The purpose of this study was to compare the results of pancreatic resection with those of a bypass operation for patients with stage III or IVA pancreatic carcinomas while applying intraoperative radiation therapy (IORT). The therapeutic outcomes of 132 patients who had received IORT for stage III or IVA carcinoma were analyzed retrospectively. The patients were divided into two groups: Group 1 included 68 patients with locally unresectable tumors who underwent a bypass operation; group 2 included 64 patients with resectable tumors who underwent pancreatic resection. Postoperative external beam radiation therapy (EBRT) was also delivered to 90 patients. Multivariate analysis indicated that strong independent predictors of increased survival were EBRT for group 1 ( p < 0.0001) and R0 resection for group 2 ( p = 0.017). Twenty patients who had been subjected to R0 resection showed the best survival, with a 3-year survival rate of 45%. The survival of group 1 patients receiving EBRT ( n = 47) nearly equaled that of group 2 patients undergoing R1 or R2 resection ( n = 44) ( p = 0.72); but group 1 patients with tumors 3 cm ( n = 28) ( p = 0.03). We concluded that postoperative EBRT is essential for improving the survival outcome, even after administering IORT. Patients with stage III lesions undergoing an R0 resection and receiving IORT demonstrated an excellent 3-year survival. A bypass operation plus IORT in combination with EBRT is preferred over IORT used as an adjuvant to R1 or R2 resection.
Adenocarcinoma↗
A new clinicopathological entity of IgG4-related autoimmune disease.
BACKGROUND: Autoimmune pancreatitis (AIP) is occasionally associated with other autoimmune diseases. METHODS: To investigate the pathophysiology of AIP, we immunohistochemically examined the pancreas and other organs in eight patients with AIP, and in controls, using anti-CD4-T and CD8-T cell subsets, as well as IgG4 antibodies. RESULTS: In AIP patients, severe or moderate infiltration of IgG4-positive plasma cells associated with CD4- or CD8-positive T lymphocytes was detected in the peripancreatic tissue (6/6), bile duct (8/8), gallbladder (8/8), portal area of the liver (3/3), gastric mucosa (5/7), colonic mucosa (2/2), salivary glands (1/2), lymph nodes (6/6), and bone marrow (2/2), as well as in the pancreas (8/8). There were few IgG4-positive plasma cells at the same sites in controls. CONCLUSIONS: These results suggest that AIP is not simply pancreatitis but that it is a pancreatic lesion involved in IgG4-related systemic disease with extensive organ involvement. We propose a new clinicopathological entity, of a systemic IgG4-related autoimmune disease in which AIP and its associated diseases might be involved. Autoimmune pancreatitis (AIP) is occasionally associated with other autoimmune diseases.
Aged↗
Papillary carcinoma of the extrahepatic bile duct: characteristic features and implications in surgical treatment.
BACKGROUND: Papillary carcinoma of the extrahepatic bile duct presents clinically and histologically distinct features relevant to surgical decision-making. STUDY DESIGN: Serial sections of 15 specimens of resected papillary carcinoma of the bile duct were histologically examined to determine mode of spread, possibility of multicentric tumor origins, and coincidence with other neoplastic lesions. The presence of anomalous pancreaticobiliary ductal union was also investigated. These characteristics were considered with regard to surgical treatment. RESULTS: Three patients displaying pancreaticobiliary maljunction and one of three patients with a long common channel (> or = 8 mm) exhibited multicentric tumors. Eight patients (53%) demonstrated superficial spread along a mean length of 37.8 mm (range, 5 to 67 mm) of bile duct mucosa. Multicentric tumors developed synchronously in 4 patients, while metachronous tumors were identified in three patients displaying tumor histology similar to the primary lesions. Two of these three underwent successful repeated resection. Concomitant neoplastic lesions in the biliary tract were identified as mucosal dysplasia in four patients and cholangiocellular carcinoma of the liver in two. All tumors but one were removed via hepatic lobectomy or pancreatoduodenectomy, or both, resulting in a 5-year survival rate of 60%. CONCLUSIONS: Aggressive resection offers clear survival benefits for patients presenting with tumors displaying extensive superficial spread or multicentric origins. Closer attention should be paid to long common channels in relation to carcinogenesis of the bile duct, in addition to pancreaticobiliary maljunction. The risk of secondary tumor development remains, particularly in patients with pancreaticobiliary maljunction even after excision of the tumor-bearing extrahepatic bile duct.
Adult↗
Pancreatic endocrine and exocrine function and salivary gland function in autoimmune pancreatitis before and after steroid therapy.
INTRODUCTION: Autoimmune pancreatitis (AIP) is a distinct clinical entity in which an autoimmune mechanism may be involved in pathogenesis. AIM: To investigate salivary gland function in addition to pancreatic endocrine and exocrine function in patients with AIP, and to determine changes occurring after steroid therapy. METHODOLOGY: Fasting serum glucose levels, oral glucose tolerance tests or glycosylated hemoglobin values were examined in 19 patients with AIP. N-benzoyl-L-tyrosyl-p-aminobenzoic acid excretion test, sialochemistry and parotid gland scintigraphy were performed in 8 patients. RESULTS: Eight patients had evidence of DM. Steroid therapy subsequently improved insulin secretion and glycemic control in 3 of 5 patients treated. Pancreatic exocrine function was reduced in 88% of patients. Impaired pancreatic exocrine function improved after steroid therapy in 3 of 6 patients treated. The 3 patients also showed treatment-related improvement in endocrine function. Concentration of beta2-microglobulin in saliva was significantly raised in patients with AIP compared with controls (P < 0.05). Ratio of cumulative peak count to injected radionuclide and washout ratio in parotid scintigraphy in patients with AIP was significantly lower than those of controls (P < 0.01). Salivary gland dysfunction improved after steroid therapy in all 5 patients treated. CONCLUSIONS: Pancreatic endocrine and exocrine and salivary gland function were frequently impaired in patients with AIP, and steroid therapy was occasionally effective for these dysfunctions.
Adult↗
Clinical difficulties in the differentiation of autoimmune pancreatitis and pancreatic carcinoma.
OBJECTIVES: Autoimmune pancreatitis (AIP) is a newly described entity with characteristic clinical, histologic, and morphologic changes, in which autoimmune mechanisms are involved in pathogenesis. However, difficulties can arise in the differentiation of AIP from pancreatic carcinoma. The aims of this study were to clarify clinical and radiologic features of AIP to elucidate areas of diagnostic confusion. METHODS: Clinical, serologic, and radiologic findings were evaluated in 17 patients with AIP. RESULTS: All 17 patients were initially suspected to have pancreatic carcinoma. The patients were predominantly elderly men who frequently presented with jaundice but without features of acute pancreatitis. Elevation of serum gamma-globulin and IgG along with the presence of autoantibodies were usually evident, whereas serum tumor markers were elevated in 54% of cases. Stenosis of the bile duct was detected in 94% of cases. Diffuse enlargement of the pancreas and irregular narrowing of the main pancreatic duct were radiologically characteristic; however, segmental swelling and narrowing were detected in seven and two patients, respectively. In segmental cases, neither atrophy of the distal pancreas nor marked upstream dilation of the distal main pancreatic duct was observed. Angiographic abnormalities occurred in 54% of cases. Serologic and radiologic abnormalities showed considerable improvement with steroid therapy. CONCLUSIONS: Frequent stenosis of the bile duct, elevation of serum tumor markers, segmental pancreatic enlargement or narrowing of the main pancreatic duct, and angiographic abnormalities can cause confusion in the differential diagnosis of AIP and pancreatic carcinoma.
Adult↗