Proliferative activity of carcinoma of the papilla of vater - an immunohistochemical study demonstrating proliferating cell nuclear antigen (pcna).

The expression of proliferative cell nuclear antigen (PCNA) in carcinomas of the papilla of Vater were studied. The PCNA LI of the specimens ranged from 13.0 to 72.8% (mean +/- standard deviation=43.1 +/- 16.4%). The tumors with lymph node involvement had a higher PCNA LI than those without lymph node involvement. The PCNA LI of tumors extending to duodenum or pancreas was significantly higher than that of tumors restricted to the muscle of the sphincter of Oddi. These results indicate that PCNA LI is one of the important factors indicating spread of tumor, i.e., lymph node involvement and depth of invasion.

Surgical-management of carcinoma of the middle and distal bile-duct.

Forty patients underwent surgical resection for cancer of the middle and distal bile duct. Nineteen patients underwent a curative resection with 3- and 5-year survival rates of 63% and 48%, respectively. None of the patients who underwent a palliative resection survived two years. The factor most strongly associated with recurrence was the presence of tumor in the surgical margin. Recurrence was frequent in patients with disease in the middle portion of the bile duct who underwent extrahepatic biliary resection with choledochojejunostomy, while lower bile duct cancer was associated with peri-aortic or retroperitoneal recurrence. Pancreatoduodenectomy, with combined resection of the portal vein in middle bile duct cancer, regional lymphadenectomy, including peri-aortic lymph nodes and nerve plexus is required for curative resection of middle and distal biliary carcinoma beyond the early noninvasive stage.

Differential expression of vacuolar-type H+-ATPase between normal human pancreatic islet B-cells and insulinoma cells.

Recent studies have shown that bafilomycin A(1)-sensitive vacuolar type H+-ATPase (V-ATPase) is responsible for the acidification of intracellular compartments in eukaryotic cells. B-cells of pancreatic islets also are known to include acidifying secretory vesicles which are the major cellular site of proinsulin to insulin conversion. This study was designed to examine immunohistochemically the level of V-ATPase protein expression in normal pancreas (five cases) and benign insulinoma (six cases), using mouse monoclonal antibody raised against the 116 kDa subunit of human V-ATPase. Light microscopic immunohistochemistry revealed that moderate to marked V-ATPase expression was observed in normal islet B-cells, while insulinoma cells in each case expressed V-ATPase faintly or not at all. By immunoelectron microscopy, the majority of secretory vesicles in insulinoma cells did not express V-ATPase protein at their endomembranes, although mild to marked V-ATPase expression was noted at the endomembrane of secretory vesicles in normal islet B-cells. Thus, differential expression of V-ATPase protein at the endomembrane of secretory vesicles was observed between normal islet B-cells and insulinoma cells. These findings suggest that the reduced activity of V-ATPase per insulin secretory vesicle in insulinoma cells have a profound effect on the efficiency of proteolytic cleavage of proinsulin.

Inhibitory effect of a serine protease inhibitor, FOY-305 on the invasion and metastasis of human pancreatic cancers.

We examined the inhibitory effect of a serine protease inhibitor, FOY-305, on the invasion and metastasis of human pancreatic cancers. The in vitro matrigel invasion assay showed that the invasiveness of Capan-1 human pancreatic cancer cells was inhibited by FOY-305 treatment in a dose-dependent manner at concentrations greater than 100 nM. Intrasplenic injection of Capan-1 cells in nude mice resulted in frequent metastases to liver, however, its incidence was significantly decreased by FOY-305 treatment. These findings suggest that a serine protease inhibitor, FOY-305 can inhibit tumor invasion and metastasis by blocking the serine protease-mediated activation cascade.

Surgical strategy for carcinoma of the papilla of Vater on the basis of lymphatic spread and mode of recurrence.

BACKGROUND: Nodal status is one of the most important prognostic factors for carcinoma of the papilla of Vater. The pattern of lymphatic spread and mode of recurrence were analyzed by determining the frequency of nodal involvement and antemortem and postmortem examination of patients with recurrent disease. METHODS: From 1974 to 1994, 36 patients with carcinoma of papilla of Vater underwent pancreatectomy at the Kanazawa University Hospital. A precise evaluation of the nodal involvement was determined by means of careful pathologic review of the extended lymphadenectomy specimen. The mode of recurrence was determined by use of autopsy and radiographic examinations. RESULTS: Fifteen (42%) of 36 patients had nodal involvement. The lymph nodes with the highest metastatic rates were the inferior pancreaticoduodenal lymph nodes (number 13b) and the superior mesenteric lymph nodes (number 14) (13b, 31%; 14, 17%). There were no metastases in the perigastric lymph nodes. A significant relationship existed between the gross appearance of the primary tumor and nodal involvement (protruding, 22%; mixed type, 42%; ulcerative, 100%). The 5-year survival rates were 74% in the absence of nodal metastasis versus 31% with nodal metastasis. The 5-year survival rates for patients with protruding, mixed type, and ulcerative tumors were 75%, 49%, and 17%, respectively. Survival and recurrence were significantly correlated to gross appearance and nodal involvement. Retroperitoneal recurrence and liver metastasis were main modes of recurrence. CONCLUSIONS: Lymph node 13b is important in lymphatic metastasis to the superior mesenteric lymph nodes for carcinoma of papilla of Vater. Nodal dissection around the superior mesenteric artery is needed to improve the prognosis of carcinoma of papilla of Vater except in the nonexposed protruding tumor. Pylorus-preserving pancreatoduodenectomy may be indicated in patients with carcinoma of the papilla of Vater.

Hepatic resection guided by needles inserted under ultrasonographic guidance.

BACKGROUND: Operative ultrasonography for orienting the direction of transection of the liver is often useful in obtaining an adequate disease-free surgical margin. We have devised a new technique for hepatectomy guided by needles inserted under ultrasonographic guidance. METHODS: One hundred two hepatectomies were performed between January 1987 and September 1991, and the hepatectomy with this technique was begun in January 1989. RESULTS: In 10 of 29 limited hepatectomies performed in the first phase of the period in which this technique was not available, disease-free surgical margin of less than 1 cm was left because of inadequately directed division. Disease-free surgical margin of more than 1 cm was left in 18 of 23 limited hepatectomies in the second phase of the period in which this technique was available. In the other five operations where disease-free surgical margin of less than 1 cm was left, carcinomas were located too close to the major hepatic vessels. The average blood loss during the limited hepatectomies was reduced by this technique. Two-year and 3-year survival of patients undergoing hepatectomy for hepatocellular carcinoma were more favorable in the second phase than in the first phase. CONCLUSIONS: Although the difference between the two groups was not significant, this technique is useful in performing adequate transection of the liver.

Surgical strategy for carcinoma of the pancreas head area based on clinicopathologic analysis of nodal involvement and plexus invasion.

BACKGROUND: The pattern of tumor spread, vis-à-vis nodal involvement and invasion of the extrapancreatic plexus (Plx), has not been thoroughly described for carcinoma of the pancreatic head area. METHODS: From 1973 to 1991, 110 patients (49 with carcinoma of the pancreatic head [Ph], 29 with distal bile duct cancer [Bi], and 32 with carcinoma of the papilla of Vater [Pv]) underwent pancreatectomy at Kanazawa University Hospital. Nodal involvement and Plx invasion were precisely evaluated by histopathologic examination. RESULTS: Thirty-seven (76%) of the 49 patients with Ph, 20 (69%) of the 29 with Bi, and 14 (44%) of the 32 with Pv had nodal involvement. The lymph nodes most commonly involved for Ph were the posterior pancreaticoduodenal lymph nodes (numbers 13a [superior] and 13b [inferior]), the superior mesenteric lymph nodes (number 14), the paraaortic lymph nodes (number 16), and the anterior pancreaticoduodenal lymph nodes (number 17) (13a, 51%; 13b, 47%; 14, 36.7%; 16, 18.4%; 17a, 33%; 17b, 22%). In patients with Bi, lymph nodes around the hepatoduodenal ligament (number 12) and lymph nodes numbers 13a and 14 were most commonly involved (12, 27.6%; 13a, 51.7%; 14, 34.5%). In patients with Pv, lymph node numbers 13b and 14 were most frequently involved (13b, 34.4%; 14, 15.6%). No significant correlation was noted between the tumor size and nodal involvement in these three lesions. Nodal involvement was an important prognostic factor for carcinoma of the pancreatic head area. Plx invasion in these three carcinomas was observed in 61% of patients with Ph, 29% of patients with Bi, and 3% of patients with Pv. CONCLUSIONS: Nodal involvement and Plx invasion differed significantly among carcinomas of the pancreatic head area. We believe that nodal dissection of at least group number 14 is needed for Ph, Bi, and Pv cancers. In addition, dissection of lymph nodes of number 16 and the Plx around the superior mesenteric artery and celiac axis are needed in Ph cancer. Plx dissection of the first portion of plexus pancreaticus capitalis is needed in Bi cancer.

Presence of pancreatic alpha-amylase, trypsinogen, and lipase immunoreactivity in normal human pancreatic ducts.

Presence of pancreatic alpha-amylase, trypsinogen, and lipase in normal pancreatic ducts was evaluated immunohistochemically in 10 surgically resected normal pancreatic specimens, using monoclonal antibodies against human pancreatic alpha-amylase, trypsinogen, and lipase. Immunoreactivity to all enzymes occurred patchily in some epithelial cells not only of the common bile duct and its periductal glands but also of the main and interlobular pancreatic ducts and periductal glands in the main pancreatic duct, as well as in pancreatic acinar cells. Ductal staining was fine-granular, and generally present in the supranuclear cytoplasm. Immunoreactivity was abolished by preabsorption. Centroacinar cells and intercalated and intralobular pancreatic ducts did not stain for any enzyme. These findings suggest that some epithelial cells of the large-sized pancreatic duct and its periductal glands express pancreatic alpha-amylase-, trypsinogen-, and lipase-like peptides, as do some epithelial cells of common bile duct and its periductal glands.

Congenital arteriovenous malformation of the pancreas: its diagnostic features on images.

To analyze diagnostic features on images of congenital arteriovenous malformation (AVM) of the pancreas, we analyzed the diagnostic findings in six patients with the disease, using gray-scale ultrasonography (US), color Doppler US, computed tomography, and angiography and analyzed previously reported cases. AVM characteristic findings on images were multiple, small hypoechoic nodules on US, mosaic appearance of the lesion and pulsatile wave form in the portal vein on color Doppler US, conglomerated small nodular enhancement of the lesion and early appearance of the portal vein on CT, and a racemose network and early appearance of the portal vein on angiography. Five of the six patients underwent surgery, and all resected specimens were histologically found to be AVMs of the pancreas; however, one with developed portal hypertension at surgery died of repeated bleeding from esophageal varices. From analysis of total of 35 cases including our six cases, a mosaic appearance of the lesion was found in 100% and a pulsatile wave form in the portal vein in 77.8% on color Doppler US. Color Doppler US is noninvasive and useful for detecting congenital AVM of the pancreas at an early stage, preventing the portal hypertension causing esophageal varices and their rupture.

Differential expression of pancreatic trypsinogen and cathepsin-B in human scirrhous-type and intestinal-type gastric carcinomas.

Pancreatic trypsinogen and cathepsin B expression was evaluated in 44 surgically resected gastric carcinomas by immunohistochemical analysis. Carcinomatous tissues were subjected to immunohistochemical staining with a monoclonal antibody against human pancreatic trypsinogen and a polyclonal antibody against human cathepsin B. As a result, twenty-two of 24 scirrhous-type gastric carcinomas (92%) expressed pancreatic trypsinogen intensely and diffusely in a fine granular pattern over the entire cytoplasm of carcinoma cells. In contrast, only 5 of 20 intestinal-type gastric carcinomas (25%) reacted with the trypsinogen specific antibody and then only focally, in a fine granular pattern in the supra-nuclear cytoplasm of carcinoma cells. Cathepsin B expression was detected in 20 of 24 scirrhous-type gastric carcinomas (84%) in a fine, diffuse, granular pattern in the cytoplasm of carcinoma cells, while only 2 of 20 intestinal-type gastric carcinomas (10%) had detectable cathepsin B. From these results, we find that scirrhous-type gastric carcinomas express abundant quantities of pancreatic trypsinogen and cathepsin B immunoreactive peptides.

Histopathologic prognostic factors for ductal carcinoma of the head of the pancreas.

To establish useful prognostic factors for carcinoma of the head of the pancreas a retrospective analysis of histopathologic factors was performed for 44 patients treated with resection. Overall survival rates after 1, 2, 3 and 5 years were 63.6%, 34.5%, 26.9% and 23.9%, respectively. Eight patients lived for 5 years. The significant factors affecting survival were nodal involvement (n), retroperitoneal invasion (rp), and the degree of cancer cell invasion to the exposed cut surface (ew). Tumor size (t), serosal invasion (s) and histologic type did not influence survival by univariate analysis. According to the Cox multiregression analysis, nodal involvement is the only useful prognostic factor. Lymph node metastasis is the most important prognostic factor. To improve the prognosis of pancreatic cancer it is necessary to perform extended lymph node dissection.

Expression of pancreatic trypsinogen in human extrapancreatic gastrointestinal carcinomas.

Pancreatic trypsinogen expression in 149 surgically resected extrapancreatic gastrointestinal neoplasms was evaluated immunohistochemically. Immunohistochemistry was performed using a monoclonal antibody against human pancreatic trypsinogen. Pancreatic trypsinogen expression was detected in 28 of 55 gastric carcinomas (50.9%), 22 of 44 colorectal cancers (50%), 12 of 20 gallbladder cancers (60%), nine of 10 extrahepatic bile duct cancers (90%), and none of 20 hepatocellular carcinomas. The intensity of immunoreactivity in the tumor area varied from specimen to specimen, and from area to area within the same specimen. In most cases, however, immunoreactivity was more pronounced at the infiltrative margin of the tumor. Additionally, the highly differentiated carcinoma cells tended to display a focal, fine granular immunoreactive pattern, usually present in the supranuclear cytoplasm, while the poorly differentiated carcinoma cells displayed a fine granular pattern, usually present over the entire cytoplasm. These findings suggest that some extrapancreatic gastrointestinal neoplasms express pancreatic trypsinogen immunoreactive peptides, raising the possibility that secreted pancreatic trypsinogen plays a role in carcinoma invasion and metastasis, as has been shown for other classes of proteases.

Cationic trypsinogen produced by human pancreatic ductal cancer has the characteristics of spontaneous activation and gelatinolytic activity in the presence of proton.

We examined whether human pancreatic ductal cancer cells express and secrete pancreatic cationic trypsinogen in vitro which can be spontaneously converted into active trypsin at acidic pH (pH 4.5-5. 5), in contrast to anionic trypsinogen. Cationic trypsinogen expression at the mRNA level was observed in differentiated Capan-1 and BxPC-3 cell lines. However, expression was not detected in either poorly-differentiated Panc-1 or undifferentiated MIAPaCa-2 cell line. The gelatinolytic activity of the activated form of trypsinogen in each conditioned medium in the presence of enterokinase (1.0 microg/ml) (a band with a molecular weight of approximately 23 kDa) corresponded well to the level of cationic trypsinogen mRNA. The spontaneous activation of trypsinogen also was observed by gelatin zymography of the acid-loaded conditioned medium (pH 5.5). These findings suggest that trypsinogen produced by human pancreatic ductal cancer has the characteristics of spontaneous activation and gelatinolytic activity in the presence of proton.

Total resection of the head of the pancreas preserving the duodenum, bile duct, and papilla with end-to-end anastomosis of the pancreatic duct.

Many surgeons have recently attempted operative procedures for limited resection of the head of the pancreas. This site-specific approach has emerged as a result of precise diagnostic radiologic studies that have become available. The author performed a new operative procedure in 2 patients with mucin-producing pancreatic cysts that included total resection of the head of the pancreas with careful regard to its vasculature. The procedure provided a way of resecting the head of the pancreas while preserving the duodenum, bile duct, and papilla. The pancreatic duct was cut 5 mm before the point of confluence with the bile duct, and an end-to-end anastomosis was performed on the pancreatic duct. Both patients were discharged within 1 to 1.5 months after surgery, without complication. The operative procedure requires no processing of the jejunum, only a simple anastomosis of the pancreatic duct.

A new model of integrating Occidental and Oriental approaches.

In the Western countries, dynamically oriented psychoanalysis, behaviour modification based on learning principles and existential, humanistic psychology have been widely used as treatment modalities for neuroses and psychosomatic disorders. Autogenic therapy for relaxation and self-control has been utilized. In the Orient, Yoga, Zen, Acupuncture and Fasting Therapy have been applied to various neuroses and psychosomatic conditions. These unique Oriental approaches, in general, induce an altered state of consciousness in the subjects, and the characterized by the heightening of self-normalization and the restoration of homeostasis. Morita therapy aims at accepting reality as it is and at promoting constructive ego function, and is effective for suitable cases. The above-mentioned Western approaches, which are rather psychosomatic, and the Oriental approaches, which are rather somatopsychic, are considered to be complementary within the framework of a holistic and integrative therapeutic model.

Four cases of selenium deficiency in postoperative long-term enteral nutrition.

Because selenium is seldom added to formulations for enteral nutrition (EN), postoperative patients who are supported with EN are at risk for selenium deficiency. This report describes four cases of suspected selenium deficiency in long-term EN. Two patients underwent pancreaticoduodenectomy, one underwent total gastro-pancreatectomy, and one underwent esophageal resection and reconstruction with jejunal autotransplantation. They all developed malabsorption syndrome within 2 yr after operation. Enteral nutritional support with an elemental diet was provided continuously for 7-11 yr. Over the past 1-2 yr they experienced increasing bilateral muscular pain and weakness in the legs, gait disturbance, palpitation, and shortness of breath. Investigation for possible trace element deficiency revealed very low levels of selenium in the blood. After 10-20 d of supplementation with daily intravenous administration of selenious acid 0.16 mg/d (100 micrograms/d of selenium), their blood levels of selenium rose and their symptoms resolved. They were then continued on a maintenance regimen of oral sodium selenite 0.13 mg/d (60 micrograms/d of selenium).

Pancreas: imaging diagnosis with color/power Doppler ultrasonography, endoscopic ultrasonography, and intraductal ultrasonography.

Recent advances of ultrasound imaging have made possible to depict various diseases and conditions of the pancreas. Color/power Doppler ultrasonography, endoscopic ultrasonography, and intraductal ultrasonography are feasible to show vascular abnormalities, differentiate the solid and cystic tumors, decide tumor extent, and help to perform interventional treatments of the pancreatic diseases. Those techniques will contribute to the more precise and easier diagnosis and to prompt decision of the treatments of the pancreatic disorders. Radiologists should recognize the diagnostic feasibility and limitations of those techniques in order to avoid unnecessary examinations on the patients, and obtain precise diagnostic images.

Pancreatojejunostomy.

Pancreatoduodenectomy is a complex procedure associated with considerable mortality and morbidity. Pancreatojejunostomy is probably the main cause of morbidity, and controversy concerning the best type of reconstruction still exists. In this report the technique of pancreatojejunostomy is demonstrated. An end-to-side pancreatojejunostomy is performed on all patients. For patients with a pancreatic duct of less than 4 mm in diameter, the top of the pancreatic duct is inserted into a stab-wound of jejunum. It is secured with a purse-string suture. Furthermore, two layers of reinforcement are done. By using this technique, an end-to-side anastomosis was done on patients with soft glands and small ducts. In patients with a pancreatic duct greater than 4 mm, a three-layer anastomosis is done between pancreas and jejunum. This is a technique that allows the performance of an end-to-side anastomosis regardless of the pancreas consistency or pancreatic duct diameter.

Pancreatitis and anomalous union of the pancreaticobiliary ductal system in childhood.

From January 1978 to December 1989, 48 patients were diagnosed as having anomalous union of the pancreaticobiliary ductal system (AUPBD) at the Second Department of Surgery, Kanazawa University Hospital and its affiliated hospitals. Among these 48 patients, 13 (28.1%) were children under 13 years of age. Four of these patients had acute pancreatitis. The clinical, radiological, and surgical features of these patients are presented. The chief presenting complaint was epigastric pain in all cases; three patients had recurrent episodes of epigastric pain and had been diagnosed as having autotoxicosis. AUPBD was clearly demonstrated in all patients, three by endoscopic retrograde cholangiopancreatography (ERCP) and one by operative cholangiography. At operation, macroscopic evidence of pancreatitis was recognized in all cases. In one case, roentogenolucent pancreaticolithiases were seen on ERCP. We consider AUPBD as an important cause of pancreatitis in children and advocate ERCP in children who are suspected having biliary tract or pancreatic disease. The diagnosis of AUPBD should be considered when children with abdominal pain and elevated serum or urinary amylase levels are evaluated.

Modified pancreatic invagination into the jejunum with a double intestinal segment--a new technique.

A new technique for pancreaticojejunostomy after pancreaticoduodenectomy, Nagakawa's modified pancreatic invagination with a double intestinal segment, is described: in this method a double intestinal segment is prepared by an automatic instrument and the stump of the pancreas is invaginated into it. Suture of the stump of the pancreas and the jejunum is performed using a technique previously developed by the author. It is hoped that this technique will be widely applicable in pancreatic surgery.