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.

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.

[Indication for and problems of hepatopancreatoduodenectomy for carcinoma of the biliary tract based on the statistical registry in Japan].

Hepatopancreatoduodenectomy (HPD) as radical surgery for advanced carcinoma of the biliary tract was previously eschewed due to the high rate of postoperative complications. However, recently many institutes have performed it due to the improvement of operative procedures, such as hepatectomy and pancreatoenterostomy, and of pre-intra-postoperative management. Four hundred and sixty-five patients undergoing HPD were registered in Japan during the past 10 years, of whom 355 had carcinoma of the gallbladder and 110 carcinoma of the bile duct. The 30-day operative mortality rate was 9.2% (43 patients). The 5-year survival rates according to the Kaplan-Meier method was 18.1% (32 patients). Survival rates of those with ss and se or si gallbladder cancer were 36% and more than 10%, respectively, but that of those with se or si bile duct cancer was less than 6%. Only 3 patients with 16 lymph node metastases survived for more than 5 years. Fewer patients with biliary infiltration survived for more than 5 years compared with those with hepatic infiltration in carcinoma of the gallbladder. For such patients, extended surgery combining so-called total resection of the hepatoduodenal ligament is thought necessary.

Dihydropyrimidine dehydrogenase activity in human pancreatic tumor tissues.

Dihydropyrimidine dehydrogenase (DPD) activity was investigated using pancreatic tumors and normal pancreatic tissues surrounding the tumors obtained from 12 patients with pancreatic cancer. The mean DPD activity (+/- SD) was 2.69 +/- 1.88 nmol/mg protein/hr in normal pancreatic tissue and was 6.59 +/- 5.36 nmol/mg protein/hr in pancreatic tumor tissues. The DPD activity in tumor tissue was two- to threefold higher (p < 0.01) than that in normal tissue, but no marked difference was observed in DPD activity among cancer stages. The DPD activity of pancreatic tumors may be a useful clinical marker of the responsibility of fluorinated pyrimidine dosing in pancreatic cancer.

[Spreading patterns of hilar bile duct cancer].

Spreading patterns of hilar bile duct cancer were investigated based on cases resected in our institution and reported cases in Japan. Forty-seven patients underwent resection in our institution during the past 20 years. Three patients(12%) survived for more than 5 years. The depth of tumor invasion was m or fm in 4 and se or si in 26 patients. Positive cancer invasion in the cut end was classified as hm2 or dm2 in 8 patients and em2 in 13. Twenty-four (60%) of 40 patients investigated histologically had positive lymph node metastases. Invasion of the ss layer or deeper perineural invasion occurred in 92.5%. In terms of direct invasion of the liver, hinf1 occurred in 20(42.6%). Fourteen(29.8%) han invasion of the portal vein(more than vs1). Patients with invasion of the hepatic artery were not resected. The 5-year survival rate by cancer stage was 38% in stage I, 20% in stage II, 16% in stage III, and 0% in stage IV. Surgery was assessed as Cur A in 19 patients (46.3%), Cur B in 7 (17.1%), and Cur C in 15 (36.6%). In Cur A patients the 5-year survival rate was 18%, while that for our Cur B and Cur C patients was 0%. Our patient series was more advanced in terms of cancer stage than the statistical Japanese series and both included a significant number of noncurative cases. Hepatic resection of the right or left lobe, medial segment, and S4a and S5, combined resection of the caudal lobe, and combined portal vein resection are important as radical surgery in the treatment of this cancer.

Early and late complications of pylorus-preserving pancreatoduodenectomy in Japan 1998.

Early (within 1 month after operation) and late (more than 1 month after surgery) complications after pylorus-preserving pancreatoduodenectomy (PpPD) were analyzed in 1066 Japanese patients collected from 74 authentic institutions in Japan. As early postoperative complications after PpPD, delayed gastric emptying was evident in 46% of patients, pancreatoenterostomy leakage in 16%, intra-abdominal infection in 14%, cholangitis in 8.9%, hepaticojejunostomy leakage in 4.7%, intra-abdominal hemorrhage in 3. 5%, upper gastrointestinal hemorrhage in 3.2%, and duodenojejunostomy leakage in 2.0%. Delayed gastric emptying resolved 1-24 months after PpPD (mean, 3.1 months). The direct operative mortality (death within 1 month after the operation) was 2. 4%. Univariate and multivariate analysis of pancreatoenterostomy leakage showed that male sex (P = 0.0151) and soft consistency of the pancreas (P < 0.0001) were independent significant factors. Univariate analysis of delayed gastric emptying showed that establishment of gastrostomy (P < 0.0001), length of the preserved duodenum (P = 0.0406), gastric juice output (P = 0.0001), length of gastric tube placement (P < 0.0001), and administration of cisapride (P = 0.0059) were significant variants. As late complications, stomal ulcer was evident in 3.6% of patients, cholangitis in 6.7%, and liver abscess in 1.2%. Glucose intolerance appeared in 61 patients, resolved in 15, showed no change in 170, was absent in 695, and was ameliorated in 17. As a result, the dosage of hypoglycemic agents or insulin showed no change in 187 patients, decreased in 16, and increased in 52. Diabetes appeared 0-42 months after PpPD (mean, 102 months). When present, diabetes deteriorated 0-36 months postoperatively (mean, 6.3 months). Univariate analysis of the appearance or deterioration of diabetes showed that diabetes occurred more frequently in the following patients; those with Billroth I reconstruction compared with those with Billroth II (P = 0.0041), those with pancreatogastrostomy vs those with pancreatojejunostomy (P = 0.0229), those with pancreatogastrostomy vs those with end-to-side pancreatojejunostomy (P = 0.0165), and those with total tube drainage vs those with pancreatico-whole thickness anastomosis (P = 0.0392); a high American Society of Anesthesiologist (ASA) score (P = 0.0211) and pancreatoenterostomy leakage (P = 0.0361) were also significant factors. Postoperative body weight loss (>3 kg) was evident in 62% of patients. Body weight loss reached a maximum 4.2 +/- 5.8 months after PpPD (mean, 6.0 kg) and returned to the preoperative level 4.8 months thereafter. These results suggest that PpPD has been performed safely in Japan, the operative mortality being 2.4%. However, delayed gastric emptying was evident in 46% of the patients and pancreatoenterostomy leakage in 16%. Impairment of glucose tolerance occurred in about 10% of patients more than 1 month after PpPD. Therefore, during the early postoperative period, patients should be closely monitored for pancreatoenterostomy leakage and delayed gastric emptying and in the late postoperative period, glucose tolerance should be carefully followed-up.

Analysis of paraaortic lymph node involvement in pancreatic carcinoma: a significant indication for surgery?

BACKGROUND: Lymph node status is a key prognostic factor for pancreatic carcinoma. The paraaortic lymph nodes are the highest level of lymph nodes that can be resected safely in the abdomen for pancreatic and other gastrointestinal tumors. The pattern of paraaortic lymph node involvement and its relation with other lymph node groups were analyzed and the significance of this information relative to surgical therapy examined. METHODS: Between 1974-1996, 99 patients with invasive ductal carcinoma of the pancreas underwent pancreatectomy at the study institution. The pattern of lymph node involvement, particularly paraaortic, was evaluated by careful pathologic review of extended lymphadenectomy specimens. RESULTS. Fifty-eight of 76 patients (76%) with carcinoma in the pancreatic head (Ph) and 19 of 23 patients (83%) with carcinoma of the pancreatic body and tail (Pbt) had lymph node involvement. Fourteen patients with Ph disease (18%) and 4 with Pbt disease (17%) had paraaortic lymph node involvement. Tumor size did not correlate with paraaortic lymph node involvement. A correlation was found between Group 13 (posterior pancreaticoduodenal lymph nodes), Group 14 (lymph nodes surrounding the superior mesenteric artery), and the paraaortic lymph nodes for Ph disease. All paraaortic lymph node metastases were located in the 16M region (the region between the celiac trunk and the inferior mesenteric artery). For patients with Pbt disease, the distribution of paraaortic lymph node metastases was the same as for those with Ph disease. Only 33% of cases of paraaortic lymph node metastases were suspected preoperatively or perioperatively. The longest survival for a patient with paraaortic lymph node metastases was 36 months and 17 months, respectively, for patients with Ph and Pbt disease. CONCLUSIONS: The paraaortic lymph nodes are frequent sites of metastasis from pancreatic carcinoma, and are difficult to evaluate preoperatively or perioperatively. This situation mandates paraaortic lymph node dissection, at least in the 16M region.

Role of nodal involvement and the periductal soft-tissue margin in middle and distal bile duct cancer.

OBJECTIVE: To determine the pattern of middle (Bm) and distal (Bi) bile duct cancers in an attempt to optimize surgical treatment. SUMMARY BACKGROUND DATA: Lymph node involvement and neural plexus invasion are the prognostic factors most amenable to surgery in Bm and Bi disease. However, a detailed analysis of these factors has not been conducted. METHODS: Fifty patients with Bm and Bi disease (Bm 14 patients, Bi 36 patients) were examined histopathologically. A precise determination was made of lymph node involvement and neural plexus invasion. Important prognostic factors were examined by clinicopathologic study to apply these findings to surgical management. RESULTS: Frequencies of nodal involvement for Bm and Bi disease were 57% and 71%, respectively. The inferior periductal and superior pancreaticoduodenal lymph nodes were most commonly involved. Neural plexus invasion occurred in 20% of patients, particularly involving the plexus in the hepatoduodenal ligament and pancreatic head. Tumor was present at the surgical margin in 50% and 14% of patients with Bm and Bi disease, respectively. Five-year survival rates were 65% in the absence of nodal metastasis and 21% with nodal metastasis. A significant correlation existed between absence of tumor at the surgical margin and survival. A Cox proportional hazard model projected absence of tumor at the surgical margin, followed by nodal involvement, as the strongest prognostic variables. CONCLUSIONS: Absence of tumor at the surgical margin and nodal involvement are important independent prognostic factors in Bm and Bi disease. Skeletonization of the hepatoduodenal ligament, including portal vein resection, is necessary for patients with Bm disease, and a wide nodal dissection is essential in all patients.

Expression of nerve growth factor in hepatolithiasis.

AIMS/BACKGROUND: Nerve growth factor (NGF) has recently been shown to influence the survival and function of non-neuronal inflammatory cells, possibly through its activity as a colony-stimulating factor. It may also play an important role in acute inflammation and tissue repair. However, no prior report has focused on NGF in chronic inflammatory diseases of the gastrointestinal and biliary tracts. The aim of this study was to examine the expression of NGF in hepatolithiasis. METHODS: Twenty-six liver specimens resected from 22 patients with intrahepatic calcium bilirubinate stones and from 4 patients with intrahepatic cholesterol stones were examined immunohistochemically. RESULTS: The 22 patients with calcium bilirubinate stones demonstrated NGF immunoreactivity associated with surrounding inflammatory cells that was localized to the epithelia of proliferative peribiliary glands in the ductal wall. However, neither the surface lining of the bile duct nor hepatocytes expressed detectable NGF immunoreactivity. In the cholesterol stones cases in contrast, peribiliary glandular elements and inflammatory cell infiltration were less extensive than those observed in cases of calcium bilirubinate stones, and NGF immunoreactivity was not noted. CONCLUSIONS: These observations suggest that proliferative peribiliary glands express NGF protein in chronic proliferative cholangitis. This is characteristic of intrahepatic calcium bilirubinate stones.

Clinicopathological evaluation of long-term survivors treated for cancer of the head of pancreas.

BACKGROUND/AIMS: This is a study of 43 patients with cancer of the pancreatic head treated by resection in the past 13 years; 8 patients survived for 3 years or more and were compared with 17 who died of cancer within 3 years, in terms of histopathological spread. METHODOLOGY: Eight patients with cancer of the pancreatic head who survived for 3 years or more after resection were evaluated clinically. They were compared histologically with 17 patients who died of cancer within 3 years. RESULTS: The long-term survivors had s0 lesion (no frontal invasion of the pancreatic capsule). Lymph node metastasis was absent, or if present, limited to the n1 group. Histological examination showed rpe (positive retroperitoneal invasion) in four of the eight patients (50%). E-ew (-) (no evidence of invasion to the exposed cut surface) was obtained in all patients. They had stage (histological cancer Stage) II or III except for one patient with stage IV. CONCLUSIONS: Based on the results of the evaluation of our patients, the preconditions at present for prolonged survival for patients with cancer of the pancreatic head would appear to be as follows: --no frontal invasion of the pancreatic capsule; --no retropancreatic invasion or no evidence of invasion to the exposed cut surface even if the retroperitoneal tissues are invaded; --no lymph node metastasis or metastasis limited to the first lymph node group.

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.

Bafilomycin A1 induces apoptosis in the human pancreatic cancer cell line Capan-1.

Bafilomycin A1, a specific inhibitor of vacuolar type H(+)-ATPase, can inhibit the growth of a variety of cultured cells in a dose-dependent manner, but its mechanism is unclear. The aim of this study was to examine whether bafilomycin A1 inhibits the growth of Capan-1 human pancreatic cancer cells through apoptosis. The effect of bafilomycin A1 on tumour growth in vitro and in vivo was examined using an MTT assay and an in vivo tumour model. The presence or absence of apoptosis was determined by morphology and DNA analysis of tumour cells. The concentration of bafilomycin A1 for 50 per cent inhibition of cell viability during 72 h by the MTT assay was 5 nm. In DNA analysis, a ladder of fragmented DNA was detected in Capan-1 cells treated with bafilomycin A1 at concentrations greater than 10 nm for 24 h. Nude mice bearing a xenografted Capan-1 cell line tumour received 4 weeks of bafilomycin A1 (1.0 mg/kg per day). This treatment significantly inhibited tumour growth compared with controls after 21 days (P < 0.05). Histopathological examination of tumour cells in the treated group demonstrated signs of apoptosis with chromatin condensation and cell shrinkage. These observations suggest that bafilomycin A1 inhibits the growth of Capan-1 human pancreatic cancer cells through apoptosis.

[The evaluation of the pre-operative interviews using information sheets].

This investigation deals with patients of more than 15 years of age and family members of children younger than 12 years of age to evaluate the pre-operative interviews using information sheets. The information sheets describe the anesthetic management and complications in a simple style. Sixty% of the patients and 75% of the children's family felt anxiety about the anesthesia and/or the operation (P < 0.05). More than a half of the patients did not want to receive informations about the anesthetic management and the risk of anesthesia. On the other hand, 9% of children's family did not want to know informations about the risk (P < 0.05). More than 80% of patients read the information sheets after the pre-operative interviews and about a half of patients answered that their anxiety before the surgery decreased. In this investigation, the children's family wanted to have information about the anesthesia or the operation more than patients themselves. The pre-anesthetic interviews using information sheets is useful to give information about anesthesia and to relieve anxiety of the patients and the children's family.

Distal pancreatectomy--does it have a role for pancreatic body and tail cancer.

BACKGROUND/AIMS: Pancreatic resection is the only hope for clinical improvement for patients with carcinoma of the body and tail of the pancreas. However, it is unclear whether palliative pancreatic resection is effective or not for patients with carcinoma of the body and tail of the pancreas. METHODOLOGY: To determine the appropriate treatment for patients with pancreatic body and tail cancer, we analyzed the records of 74 patients with ductal carcinoma of the body or tail of the pancreas who were treated at Kanazawa University Hospital between 1970 and 1995. RESULTS: Using a multivariate Cox proportional-hazard model (factors: age, sex, chemotherapy, radiotherapy, hepatic metastasis, peritoneal dissemination, operative procedure), the presence of hepatic metastasis, peritoneal dissemination, and the type of operative procedures (resection or not) were found to be significant prognostic factors. Surgical resection was the most important prognostic factor. The patients with surgical resection had a significantly higher survival rate than those without resection (p < 0.0001). The survival rate of the patients with palliative resections was also significantly higher than that of the patients without resection, except for the patients with advanced liver metastasis (H3). The survival rate of the patients with palliative resections was also higher than that of the patients without resection, even in patients with peritoneal dissemination. CONCLUSIONS: Surgical resection prolongs the average survival for patients with carcinoma of the body and tail of the pancreas, except for the patients with multiple liver metastasis. These data support the role of palliative pancreatectomy in patients with carcinoma of the body and tail pancreas.

Extended radical pancreatectomy for carcinoma of the head of the pancreas.

BACKGROUND/AIMS: Pancreatic cancer has a poor prognosis, which is, in part due, to the unfortunately advanced stage, in which the tumor is diagnosed. Since 1973, we have utilized a unique method of extended radical pancreatectomy, using the translateral retroperitoneal approach (TRA) to facilitate combined portal resection. The advantages of this operation are described herein, for patients with carcinoma of the head of the pancreas. In addition, the problems associated with this operation are discussed. METHODOLOGY: Survival was calculated based on type of resection, degree of invasion of the retroperitoneal tissues, degree of lymph node involvement, and cancer stage. Extensive surgery has been performed for pancreatic carcinoma 216 patients. Of these, 14 patients had carcinoma of the head of the pancreas. There were 58 patients who underwent macroscopically curative resections. RESULTS: Only 39 patients were microscopically curative. Ten of the patients who underwent microscopically curative resections, survived for 5 years (34.0%). There were no statistically significant differences in survival based on tumor size. However, there was a significant difference in survival based on extent of invasion of the anterior capsule of the pancreas, extent of invasion of the retroperitoneal tissue, extent of lymph node involvement, cancer stage, and extent of invasion at the surgical margin of resection. CONCLUSION: The results suggest that extended radical pancreatectomy may be indicated for the treatment of cancer of the head of the pancreas.

[Clinical assessment of contrast-enhanced ultrasonography for the diagnosis of gall bladder diseases].

We evaluated the efficacy of contrast-enhanced ultrasonography (CEUS) with intra-arterial injection of CO2 microbubbles in 37 cases of gall bladder diseases. CEUS clearly visualized arterial flow and vascularity in every lesions without debris and gave us the precise information of vascular structure for the differential diagnosis of gall bladder tumors. For example, highly bifurcated tumor vessels and strong enhancement was observed in gall bladder cancer and we could detect relatively strong enhancement along the lumen with lack of enhancement of Rokitansky-Aschoff sinus in localized-type adenomyomatosis. Though CEUS is now an invasive modality, it will enable us to understand the non-invasive modality such as color doppler imaging with intra-venous administration of microbubbles in the future.

Obstructive jaundice caused by lymphangitis carcinomatosa of bile duct wall from gastric carcinoma.

We report a case of advanced gastric carcinoma presenting with obstructive jaundice. Computed tomography showed marked lymphadenopathy in the hepatoduodenal ligament and concentric bile duct wall thickening. Histologically, extrahepatic bile duct wall was thickened due to submucosal lymphangitic spread of gastric carcinoma (lymphangitis carcinomatosa). Lymphangitis carcinomatosa may be considered when extrahepatic bile duct wall thickening is seen in patients with obstructive jaundice.

Diagnosis of arteriovenous malformation of the pancreas by color Doppler ultrasonography.

Arteriovenous malformation (AVM) of the pancreas is a rare disease, and once this silent disease develops portal hypertension it is too difficult for the physician to successfully control the disease. AVM is usually diagnosed by invasive diagnostic modalities, and noninvasive modalities should be developed for its diagnosis. We have experienced two cases of AVM of the pancreas, which were located at the pancreatic head and diagnosed by color Doppler ultrasonography (Doppler US). The two AVM lesions were detected as a mosaic pattern, and the lesions were connected to the main portal vein on Doppler US; the pulsatile waves were also observed in the mosaic lesions by the analysis of the Doppler spectrum. We determined the two patients suffered from congenital AVM of the pancreas, since they had no abnormal findings on past and physical histories, laboratory data, and other images. One patient refused surgery, and another underwent pancreatoduodenectomy. Histology of the resected specimen demonstrated the lesion was AVM of the pancreas. These cases support that the present modality is useful for the diagnosis of the pancreatic AVM as a noninvasive procedure, and we discuss the usefulness of noninvasive Doppler US which shows not only static but also hemodynamic informations.