Search

A 63-year-old man was followed-up for diabetes mellitus. During follow-up, computed tomography(CT)showed dilatation of the main pancreatic duct in the tail of the pancreas. Abdominal enhanced CT revealed a 25 mm tumor in the body of the pancreas. Endoscopic ultrasound-fine needle aspiration(EUS-FNA)was performed, and the pathological diagnosis was adenocarcinoma. Therefore, based on the diagnosis of pancreatic body carcinoma, distal pancreatectomy with splenectomy was performed. The postoperative course was uneventful. Histological and immunohistochemical examination revealed that the tumor consisted of a ductal carcinoma and a neuroendocrine component. Therefore, combined pancreatic tumor (fT3N1M0, StageⅡB)was diagnosed. The patient subsequently received postoperative adjuvant chemotherapy(S-1 100mg/ day), and survived without recurrence 6 months after the operation. We report this case of combined pancreatic tumors with a review of the literature.

A 64-year-old man presented with a chief complaint of abdominal pain. An abdominal computed tomography (CT) scan showed a mass 30-mm in diameter at the splenic flexure, and we diagnosed a retroperitoneal abscess. Conservative therapy was successful, and the patient was discharged. However, 1 month later, he again experienced abdominal pain. To reassess the abscess, contrast-enhanced abdominal CT was performed. In addition to the retroperitoneal abscess, the CT scan showed an approximate 30-mm mass in the head of the pancreas with no contrast uptake. The abscess was also detected by endoscopic retrograde pancreatography. We suspected but could not confirm pancreatic cancer. Two months later, the patient developed obstructive jaundice. At this time, we diagnosed pancreatic cancer, and subtotal stomach-preserving pancreaticoduodenectomy was performed. The histopathologic diagnosis was pancreatic cancer, T4, N0, M0, Stage IVa. The postoperative course was favorable, and the patient received postoperative adjuvant chemotherapy. He remains alive without recurrence 15 months after surgery.

A 66-year-old woman was diagnosed with pancreatic tail cancer, and she was referred to our hospital. Abdominal computed tomography(CT)revealed a tumor(2.5 cm in diameter)in the pancreatic tail, with invasion to the spleen and splenic vein. In February 2013, we performed distal pancreatectomy with splenectomy, left adrenal gland resection, and D2 lymph node dissection. Diagnostic peritoneal lavage cytology during surgery was positive; however, we performed curative resection because there were no signs of peritoneal dissemination and distant metastasis. The patient was discharged from the hospital 23 days after the operation, with good postoperative course. Histological diagnosis was pancreatic tail cancer, pT4N0H0P0M(-) fStage IVa. Subsequently, the patient received postoperative adjuvant chemotherapy(TS-1: 100mg/day, 4 courses)combined with Wilms'tumor 1(WT1)peptide-pulsed dendritic cell therapy. No serious adverse events occurred during the postoperative adjuvant therapy. The patient remains alive without recurrence 16 months after the operation.

A 70-year-old female suffered from jaundice was admitted to our hospital for a tumor in the pancreas head. CA19-9 and DUPAN-2 levels were increased in laboratory test. Enhanced abdominal computed tomography (CT) scan revealed a low density area of pancreas head. Cytology of pancreatic juice was performed by ERCP, and malignant cells were detected. Pancreaticoduodenectomy was performed under a diagnosis of pancreatic cancer (T3N1M0, stage III). Despite of adjuvant chemotherapy (gemcitabine) after surgery, CT scan revealed a low density area in the cut end of remnant pancreas at 3 months, which was accompanied with elevation of and CA19-9 and DUPAN-2 levels. We diagnosed as a recurrent pancreatic cancer of remnant pancreas without any other side of recurrence and re-resection was performed. Because of chylous ascites and depression following a second surgery, postoperative adjuvant chemotherapy could not be started. Re-recurrence was detected at 3 months after the second surgery, and she died 6 months after the surgery. Remnant or repeated pancreatectomy for local recurrent pancreatic carcinomas is extremely rare with limited number of cases reported in the literature. We report our experience, and discuss the significance of re-resection for recurrence of remnant pancreas.

Intraductal papillary-mucinous carcinoma (IPMC) is a recently recognized pancreatic tumor and this is the first report to present two patients with IPMC complicating tumor thrombi in the portal vein. Two women, a 74- and a 55-year-old, each revealed a round, cystic and well-demarcated tumor of the pancreas in an abdominal computed tomography (CT). However, the inner lumen of the splenic and portal veins was insufficiently stained during iv-infusion of the contrast medium, suggesting the presence of tumor thrombi. Owing to this information, the presence of tumor thrombus was investigated and correctly identified during laparotomy, and it was completely removable together with the primary pancreatic tumor. The resected tumors showed expansive growth because mucin and tumor tissues rose up when they were cut. Microscopically, the tumor was diagnosed as adenocarcinoma without ovarian-like stroma, and the final diagnosis of branch type of IPMC was made for the two patients. However, within one postoperative year, both patients developed liver metastasis. Although IPMC is known as having a lower potential for metastasis or invasion, the tumor thrombi can form when it reveals an expansive growth suggesting a high inner pressure. In addition, a higher possibility for subsequent liver metastasis should be anticipated after the tumor forms a thrombus in the portal vein.

Background: Intraductal papillary mucinous neoplasm (IPMN) is a recently discovered pancreatic tumor that has continuous or discontinuous (skip) lesions. Recent reports suggest a higher frequency of cancer recurrence in the remnant pancreas after surgical resection of IPMN. It is therefore important to precisely detect intraductal cancer extension and skip lesions when resecting IPMN., Methods: Both intraoperative histologic examination of the surgical margin and cytologic examination of the pancreatic juice from each pancreatic segment (head, body, or tail) were performed on 43 IPMN patients. In addition to the preoperatively planned resection, 1 or 2 pancreatic segment(s) were additionally resected if the pancreatic juice tested positive in cytology. When a surgical margin was positive but the cytology in the remaining segment was negative, a subsegment (2-cm slice in width) was additionally resected until a negative margin was confirmed., Results: Twenty-five patients (58%) demonstrated negative results in both histology and cytology obtained from the segment(s) that were not initially intended to be removed. In contrast to the preoperative estimation, 5 patients were found to have a positive surgical margin and negative cytology, 5 patients demonstrated a negative surgical margin and positive cytology, and 8 patients demonstrated a positive surgical margin and positive cytology. Investigations of the resected specimens revealed that 8 patients (19%) had skip lesions in addition to the main lesion. Logistic regression analysis revealed that patients with a dilated main pancreatic duct, or those with cancerous lesions in the main tumors, were at high risk for positive histology and/or cytology., Conclusions: Using intraoperative frozen-section histology and pancreatic juice cytology, 18 out of 43 patients in the current study (42%) required additional resection of the pancreas. A necessary and sufficient range of resection should be determined by intraoperative examination., ((c) 2006 American Cancer Society.)

Due to a high incidence of local recurrence, the long-term outcome after resection of locally advanced pancreatic cancer is still pessimistic. Many previous reports showed that locoregional control was partly improved by intraoperative radiation or postoperative chemoradiation, while others suggested its insufficient effects for patients with R1- or R2-resections. Therefore some recent authors have recommended preoperative chemoradiation for more promising results in advanced pancreatic cancer. Since patient survival is influenced not only by local control but also by distant (the liver is the most common) metastases, we should develop other strategies that can prevent liver metastases, in addition to the combination of chemoradiation with sur-

Background: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas has been recognized recently and is being diagnosed with increasing frequency. Although IPMN has a more favorable prognosis than standard invasive ductal carcinoma (IDC) of the pancreas, recent reports suggest that IPMN patients are at higher risks of synchronous or metachronous primary cancers arising from various organs other than the pancreas (extrapancreatic cancers)., Methods: Records of 370 patients (69 of IPMN, 301 of IDC) who underwent surgery were used to assess risk factors for preoperative or postoperative extrapancreatic cancers. To calculate the rate of increase of extrapancreatic cancers in IPMN patients, compared with the normal population, the observed/expected ratio (O/E ratio) was calculated by using the Osaka Cancer Registry, one of the world largest cancer databases., Results: The incidence of preoperative extrapancreatic cancers was significantly higher in IPMN patients (28%, 19 patients) than that in IDC (9%, 27 patients). In the IPMN-group, the preoperative incidence of colorectal cancer was 12% followed by gastric cancer at 4%. Logistic regression analysis showed IPMN and age to be independent risk factors for preoperative colorectal cancer development. The O/E ratio of preoperative colorectal cancer was significantly high in IPMN patients (5.37; 95% confidence interval, 2.31-10.58) but not in IDC patients (1.24; 95% confidence interval, 0.46-2.70). The incidence of postoperative extrapancreatic cancers also was significantly higher in IPMN patients (15%, 10 patients) than that in IDC (4%, 12 patients). During the postoperative follow-up, 4% of IPMN (3 patients) and 0.7% of IDC (2 patients) died from extrapancreatic cancers., Conclusions: Our results indicate that IPMN patients are at significantly higher risks of extrapancreatic cancers including colorectal cancer. A careful systemic checkup is therefore required for preoperative screening and postoperative follow-up for IPMN patients.

Recently there has been an increase in the number of case reports detailing the recurrence of cancer in the pancreatic remnants following surgical resection of intraductal papillary mucinous carcinoma (IPMC) of the pancreas. A case is presented here to indicate the advantage of pancreaticogastrostomy (PG) in terms of postoperative follow-up after pancreaticoduodenectomy (PD) for IPMC. A 68-year-old man underwent PD for IPMC of the pancreatic head, and the cut margin of the pancreatic duct was diagnosed as having no cancer but moderately dysplastic epithelium by an intraoperative frozen section of histology. Thus, we decided to proceed with a PG rather than pancreaticojejunostomy (PJ) in order to facilitate easier postoperative examinations. Eight years and 6 months later, during a routine follow-up examination, duct dilation of the remnant pancreas was detected by magnetic resonance imaging (MRI). Upon examination by endoscopic gastroscopy, the anastomotic site was found to be covered with a large amount of mucin from which we easily obtained both cytologic and biopsied specimens, which subsequently proved positive for cancer. In line with our diagnosis of recurrent IPMC, the patient underwent a second surgery (resection of the remnant pancreas, total pancreatectomy) and postoperative histology confirmed that indeed the patient had experienced recurrent IPMC with no nodal involvement or invasion beyond the pancreatic confines. Based on this experience, we decided to recommend PG for all patients deemed to be at high risk for the recurrence of cancer in the pancreatic remnants following PD for IPMC of the pancreatic head., (Copyright 2006 Wiley-Liss, Inc.)

Background: The outcome after resection of advanced pancreatic cancers is extremely poor because of the high incidence of the postoperative development of liver metastasis and local recurrence. We performed a combination of chemoradiation and liver perfusion chemotherapy and extended pancreatectomy., Methods: Nineteen patients with T3 pancreatic head cancers were enrolled. A total of 24 Gy in 12 fractions of 10-MV x-rays with a concurrent intravenous infusion of 5-fluorouracil (5-FU; 3 g/12 days) was administered to the pancreatic head area. An extended pancreaticoduodenectomy was performed, and catheters were placed into the gastroduodenal artery and the superior mesenteric vein. During the first 28 postoperative days, 5-FU was continuously infused via the hepatic artery and portal vein (3.5 g/28 days x 2). Finally, 36 Gy in 18 fractions with 5-FU (3 g/6 days) was applied to the pancreatic bed., Results: After preoperative chemoradiation, four patients did not undergo surgical resection because of distant metastases. Fifteen patients underwent pancreaticoduodenectomy, liver perfusion chemotherapy, and postoperative chemoradiation. No patient developed grade 3 toxicity as a result of preoperative chemoradiation, but one patient (7%) developed grade 3 leukopenia during the postoperative treatments. The morbidity rate was 20% (3 of 15 patients), and the mortality rate was 0%. The overall 3-year survival rate was 53%. The 3-year disease-free survival rate was 66% in patients who pathologically responded well (>50%), versus 0% in patients with poor responses (P = .04)., Conclusions: A combination of preoperative and postoperative chemoradiation plus postoperative liver perfusion chemotherapy with an extended pancreatectomy is feasible, and the long-term outcomes are also promising.

Background: The objectives of the present study are to determine the long-term changes in glucose tolerance function after pancreaticoduodenectomy and to compare the effects of pancreaticojejunostomy (PJ) and pancreaticogastrostomy (PG). Patients and methods The present study consisted of 51 patients who received a pancreaticoduodenectomy for tumors of the pancreatic head area and survived more than 7 postoperative years without tumor recurrence. According to the type of pancreatic anastomosis, they were classified into 2 groups of 25 PJ patients and 26 PG patients. Changes in the patterns of a 75-g oral glucose tolerance test (OGGT) (normal, impaired glucose tolerance [IGT], and diabetic [DM] patterns) and the need for beginning diabetic treatment (oral hypoglycemic agents or insulin) were compared between groups., Results: Within 3 months after surgery, 14 (56%) patients in the PJ group had normal OGTT patterns, 8 (32%), IGT patterns, and 3 (25%), DM patterns. In the PG group, the patterns of OGTT were similar with 16 (62%) normal patterns, 6 (23%) IGT patterns, and 4 (15%) DM patterns. During the first 7 postoperative years, the 2 groups showed similar results: (1) none of the patients with normal patterns developed functional decline in glucose tolerance; (2) a high percentage of patients with initial IGT or DM patterns developed worsening glucose intolerance (7 [64%] of 11 PJ patients vs 7 [70%] of 10 PG patients); (3) the onset of functional decline in glucose tolerance occurred predominantly within the first 3 postoperative years; and (4) no specific causative event prior to the subsequent functional decline was detected., Conclusion: The decline of glucose tolerance after pancreaticoduodenectomy seems to be associated with a low reserve of endocrine function rather than anastomotic procedures or their related complications. Regardless of the types of pancreatic anastomosis, a close follow-up of glucose tolerance function is recommended during the first 3 postoperative years, especially among IGT or DM patients.

The pancreatic endocrine tumors are uncommon neoplasms and are classified into non-functional and functional tumors. According to whether the secreted hormones are originated from pancreatic islet cells or not, the tumors are also classified into normotopic and ectopic tumors. Except for insulinoma, more than 60% of them reveal malignant behavior. The presence of endocrine tumor is diagnosed when patients develop a hormone-specific symptom, and the location of tumors are usually diagnosed by a combination of ultrasonography, computed tomography, magnetic resonance imaging and selective angiography. A somatostatin receptor scintigraphy is promising. Nevertheless, these examinations occasionally failed to precisely locate the tumors especially when they are very small and/or multiple. For such cases, both portal venous sampling and arterial provocation test are helpful.

Background: For locally advanced and nonresectable cancer of the pancreas, we performed intra-arterial infusion chemotherapy with angiotensin-II (AT-II). In our preliminary report, this treatment resulted in a median of 14 months of survival without objective adverse effects. This study was designed to clarify the prognostic factor in this chemotherapy by using a larger number of cases., Methods: For 32 patients, intra-arterial chemotherapy was performed: 1 or 2 catheters were intraoperatively placed into the pancreas-supplying arteries. The tissue blood flow and its change by AT-II infusion were determined. For intra-arterial chemotherapy, a mixture of methotrexate (50 or 100 mg/m(2)) and AT-II (.4 microg/kg/hour) was repeatedly infused from the catheter, mainly at our outpatient clinic., Results: With our intra-arterial chemotherapy, the median survival period was 13 months. The median survival period was 19 months in patients without coexisting pancreatitis but was only 9 months in those with it (P =.0003). The presence or absence of coexisting fibrosis in the neighboring uninvolved pancreas offered the only prognostic indicator. The blood flow in cancerous tissue was increased during AT-II infusion, and this was characteristic in the patients whose neighboring uninvolved pancreas had normal parenchyma (nonatrophic) or higher blood flow before AT-II infusion., Conclusions: Because the AT-II infusion played a role in shifting the blood flow from the surrounding uninvolved pancreas to the cancer tissues, we can speculate that cancer tissues might have thereby received a higher dose of anticancer drugs if the surrounding uninvolved pancreas had been nonfibrotic and more rich in tissue blood flow.

Objective: To evaluate the postoperative cytology of drained fluid from the pancreatic bed as a predictive indicator of local recurrence after curative (R0) resection of pancreatic cancer., Summary Background Data: The pancreatic bed offers a common site of cancer recurrence (local recurrence), even after curative (R0) resection is performed for pancreatic cancer. If local recurrence is thereby predicted precisely, soon after surgery, we have a chance to treat it by adding radiation or some other locoregional therapy before it can grow or spread beyond the pancreatic bed. However, there have been no previous reports of cytology performed on the drained fluid after pancreatectomy., Methods: This study includes 94 patients who had shown negative results in the peritoneal washing cytology before resection and subsequently received pancreatectomies for pancreatic tumors. They consisted of 12 benign tumors, 17 noninvasive or minimally invasive carcinomas and 65 invasive ductal carcinomas (R0 = 58; R1/2 = 7). Postoperatively, the drained fluid from the pancreatic bed was collected for 24 hours and used for cytologic examination. The cytologic results were examined in association with the histopathology of the resected tumor, patient's survival, and mode of cancer recurrence, including local recurrence., Results: Patients with benign tumors or noninvasive/minimally invasive carcinomas had negative result in cytology, and none of them have died of local recurrence (limited to the pancreatic bed) to date. However, patients with invasive ductal carcinoma revealed higher cytology-positive rates: 28% (16/58) in curative (R0) resection; and 71% (5/7) in noncurative (R1/2) resection. Among 58 patients with R0 resection, the 3-year survival rate was 14% in 16 cytology-positive patients and 55% in 42 cytology-negative patients (P < 0.05). The 3-year cumulative rate of local recurrence was 85% and 23%, respectively (P < 0.05). Compared with other histopathologic parameters obtained from the resected specimens, the drain cytology was more specific in predicting the subsequent development of local recurrence., Conclusions: Drain-cytology was a quick examination that enabled us to specifically indicate both minute residual cancer and subsequent development of local recurrence even after R0 resection of pancreatic cancer.

Ductal adenocarcinoma of the pancreas is still characterized by (1) poor prognosis after surgery and (2) extreme difficulty in early diagnosis, and we need a breakthrough. For the first problem, we have performed a wide range of lymphatic and connective tissue clearance (extended pancreatectomy) which has succeeded in improving the 5-year survival rate from 8% to 24% via decreasing the incidence of locoregional recurrence. When liver perfusion chemotherapy via the hepatic artery and the portal vein was added to the patients who had received extended pancreatectomy, the 5-year survival rate was further elevated to 40% via decreasing the incidence of hepatic metastasis. We conclude that pancreatic cancer should be treated by the better-balanced treatments between locoregional control and prevention of hepatic metastasis. For the second problem, we have more actively collected pancreatic juice to perform cytodiagnosis even though no obvious tumor was delineated by the conventional imaging diagnoses. When cancer cells were detected in the pancreatic juice, our method of intraoperative cytology was very useful in precisely locating the occult lesion indicating an appropriate range of pancreatectomy. The resected pancreas was proven to have included borderline malignancy and in situ or minimally-invasive carcinoma by the postoperative histology, and disease-free 5-year survival rate was 100%. In the future, we need to detect patients with a high risk of pancreatic cancer and develop a less-painful method to collect the pancreatic juice.

Recently, there have been a few case reports of invasive ductal adenocarcinoma (IDC) developed in the remnant pancreas after partial pancreatectomy for intraductal papillary-mucinous neoplasm (IPMN). It is necessary to clarify their histogenetic relationships among two sporadic tumors and their surrounding duct epithelium and it would be more reliable if genetic analysis is added to the conventional histology. We report a 76-year-old woman who received pancreaticoduodenectomy for IPMN with a focal in situ carcinoma (IPMC), which was transitional to the surrounding duct epithelium with papillary proliferation and a wide variety of dysplasia. Nine years after the operation, she died of IDC in the remnant pancreatic body and its surrounding duct epithelium consisted of hyperplastic mucous cells with slight-mild dysplasia. Analysis of K-ras mutation at codon 12 (wild-GGT) by direct sequencing after polymerase chain reaction indicated that their transitioning patterns differed from each other: CGT in IPMC; no mutation in the mildly dysplastic duct epithelium around IPMC; GAT in IDC of the remnant pancreas; and AGT in mucous cell hyperplasia with mild dysplasia close to the IDC. This is the first report in which the DNA sequence of K-ras mutation was determined for the two sporadic pancreatic cancers and surrounding duct changes. The following two suggestions are made: (1) the cell-origin might have differed between the two types of cancer (IDC and IPMC); and (2) no precursor lesion toward IDC or IPMC was identified in their surrounding duct epithelium.

Owing to the recent advances in surgical techniques and postoperative care, the operative indication for adenocarcinoma of the pancreas has been widened in Japan. In our institution, we have extended lymphatic and connective tissue clearance during surgical resection of this cancer. As a result, the 5-year survival rate has increased from 8% to 25% due to a significant decrease in the incidence of locoregional recurrence. The prognostic benefit gained by this procedure is seen mainly in those patients with stage III cancer or in whom no positive nodes were detected beyond the pancreatic head region. Thus, our extended surgery seems to have been useful due to eradicating the microinvasion in the peripancreatic connective tissues, rather than dissecting the positive lymph nodes. More advanced cancers should be treated by effectively combining chemo- and/or radiation-therapies with surgery. In order to cure the patients more easily with less-invasive surgery in the future, we should develop both an early diagnosis system and sensitive examinations of micrometastases or microinvasions.

Background: Adenocarcinoma of the pancreas is likely to spread into the nerve plexuses around the superior mesenteric artery (SMA) at a microscopic level. Since there has been no detailed report on how minute cancer invasion is distributed among the peri-SMA plexuses or which cases are more vulnerable to such an event, it has long been controversial how to treat this area when resecting the pancreatic head cancer., Hypothesis: The K-ras mutation assay is more sensitive than the conventional histologic diagnosis in detecting minute cancer invasion around the SMA., Design: Prospective consecutive series., Setting: Cancer center hospital., Patients and Methods: The entire circle of the peri-SMA tissues was obtained from 24 patients who had received an extended pancreatectomy for adenocarcinoma of the pancreatic head. They were divided into right and left hemicircular samples (48 samples), and each sample was used for both histologic and genetic diagnoses. Since all patients' primary tumors were positive for point mutation at codon 12 of the K-ras gene, the presence or absence of the mutation was determined for the peri-SMA plexuses using the mutant allele specific amplification method., Results: Compared with results of the histologic examination, the K-ras mutation assay was more sensitive in detecting positive findings in the peri-SMA plexuses (12 samples from 9 patients). According to the distribution of the K-ras mutation into the right- and left-half samples, 24 patients were classified into the following 4 patterns (right/left): negative/negative in 15 patients; positive/negative in 6 patients; positive/positive in 3 patients; and negative/positive in 0 patients. In 3 patients who showed a positive/positive pattern in the genetic diagnosis, their right-half samples included more cancer cells that were detectable by routine microscopy. There was no relation between K-ras mutation and lymphatic invasion, while K-ras mutation was particularly related with the invasion of portal vein (P =.04) and posterior peripancreatic tissues (P =.002). All 3 patients with K-ras mutation in bilateral plexuses were classified by the TNM staging system as T4 using Union Internationale Contre le Cancer classification., Conclusions: The K-ras mutation (at codon 12) assay indicated a simple and regular pattern of cancer extension into the nerve plexuses around the SMA from adenocarcinoma of the pancreatic head: (1) The left half of the plexus was unlikely to be involved by cancer in cases in which the right half was intact. (2) Cancer extension into the peri-SMA plexuses occurred after the posterior confine of the pancreas had been involved by direct invasion from the primary pancreatic tumor. (3) The left half was not involved in cancerous tumors classified as T1 to T3 but was occasionally involved in those classified as T4 tumors. These data seem to provide a useful indicator of some additional treatments (resection, irradiation, etc) for the peri-SMA region when a locally advanced pancreatic head cancer is treated with a curative intent.

Background: The precise intraoperative localization of insulinoma is essential for successful surgical treatment. In addition to various imaging modalities developed recently, arterial stimulation and venous sampling (ASVS) has also been used for tumor localization., Methods: Preoperative and intraoperative ASVS procedures were performed in 6 patients with insulinoma. Intraoperative ASVS was performed before and after tumor resection. Immunoreactive insulin (IRI) concentrations and the IRI ratio (IRI concentration at each time interval after calcium injection/baseline IRI concentration) were determined by the conventional or a quick IRI method., Results: The site of the tumor was identified preoperatively in all patients. The peak of the IRI ratio varied widely, but setting the cutoff value at 3.0 clearly differentiated peak IRA ratios in feeding arteries from those of nonfeeding arteries. Intraoperative ASVS showed a similar elevation of IRI levels, but the elevation disappeared after tumor resection in all but 1 patient. In 2 patients, resection of the tumor was confirmed during surgery by measuring IRI levels by the quick IRI method., Conclusions: A combination of ASVS and conventional imaging modalities is useful for precise localization of insulinoma. Resection of the tumor can be confirmed intraoperatively by comparing IRI levels associated with preoperative and postresective ASVS.

Background/aims: Abnormal glucose tolerance during oral glucose tolerance test (OGTT) is frequently observed in patients with pancreatic cancer. The abnormality shown in previous studies, however, was characterized mainly by analyses based on immunoreactive insulin or C-peptide response during OGTT, despite their cross-reactivity with proinsulin. The mechanisms responsible for glucose intolerance in patients with pancreatic cancer remain controversial., Methodology: Both proinsulin and C-peptide responses during 75 g of OGTT were determined without influence of immunologic cross-reactivity in 32 patients with pancreatic cancer and 32 control subjects of similar age, sex, fasting blood glucose levels, and OGTT pattern., Results: The pancreatic cancer patients had higher proinsulin and lower C-peptide levels than the control subjects both in the non-diabetic and diabetic groups. The ratio of the sum of five proinsulin values observed at 0, 30, 60, 120, and 180 min to that of the five C-peptide values (sigma proinsulin/sigma C-peptide ratio) was 6.1 +/- 3.2% in patients with pancreatic cancer and 2.5 +/- 1.0% in control subjects (p < 0.05), while it was not associated with the diabetic pattern in OGTT. The sigma proinsulin/sigma C-peptide ratio was not associated with tumor size, location or resectability but was associated with the number of islets left within or close to cancer stroma. The increased sigma proinsulin/sigma C-peptide ratio decreased after tumor removal., Conclusions: Patients with pancreatic cancer are characterized by increased proinsulin secretion and decreased C-peptide production during OGTT probably due to impaired proinsulin conversion. Although further studies are required in a large scale of patients, measurement of proinsulin and C-peptide levels during OGTT should serve as an early marker to identify high risk groups of the disease.

Background/aims: According to Tsuchiya's collective review on small pancreatic cancer measuring 2 cm or less in diameter (5), more than half of them had obstructive jaundice and the 5-year survival rate was as low as 30%. Thus, a more aggressive diagnostic approach is needed to detect a smaller and more curable cancer of the pancreas., Methodology: Thus, we collected 36 reported cases of "minute" pancreatic cancer measuring 1 cm or less in diameter, from Japanese medical literature, to analyze the relationships between the diagnostic processes and long-term results., Results: Excluding 3 patients with obstructive jaundice, the other 33 patients did not show any specific initial symptoms. However, 28 (78%) out of 36 patients showed an elevation in serum pancreatic enzyme levels and/or glucose intolerance. Among the 35 patients who had received ultrasonography (US) and/or computed tomography (CT), 20 (57%) patients showed duct dilation alone, whereas only 9 patients (26%) showed tumor mass. Among 35 patients who received an endoscopic retrograde pancreatography (ERP), all patients showed positive findings such as obstruction/stenosis, filling defect or duct dilation. All 36 patients underwent pancreatectomy and the 5-year survival rate was 57%. However, the 5-year survival rate was 34% in the 13 patients with jaundice and/or tumor mass depicted in US/CT, while it was 69% for the 22 patients without these two findings (p < 0.05)., Conclusions: These data lead us to conclude that an elevation of serum pancreatic enzyme levels, glucose intolerance, and duct dilation alone depicted by US/CT should not be overlooked. ERP should be more widely applied to such patients, instead of persisting in delineating the tumor mass by US/CT or follow-up by tumor marker.

In order to increase the long-term survival after resection of pancreatic adenocarcinoma, it is essential to eradicate both locoregional recurrence and hepatic metastasis. We have added a wide range of lymphatic and connective tissue clearance to conventional pancreatectomy (extended pancreatectomy) and succeeded in improving the 5-year survival rate from 8 to 25% via decreasing the incidence of local failure. Among many procedures which together compose an extended pancreatectomy, connective tissue clearance seems to have played a more important role on patients' prognosis rather than wide range lymphadenectomy. Concomitant resection of the portal vein is recommended for selected patients, and it is important not to overlook a minute invasion even though it appears macroscopically intact. With regard to adjuvant therapy in combination with our extended pancreatectomy, the addition of preoperative irradiation failed to further improve the long-term survival rate because the cause of cancer deaths shifted from local recurrence to hepatic metastasis. When liver perfusion chemotherapy was added to this operation (without radiation), the 5-year survival rate was improved to 39% by decreasing the incidence of hepatic metastasis. In the future, a combination of extended pancreatectomy with chemoradiation plus liver perfusion chemotherapy is one of the promising approaches for this cancer.

Unlabelled: Pancreatoduodenectomy has become the standard procedure in resection of the duodenal adenocarcinoma, and some adjuvant therapies can be added to obtain further improvement in postoperative outcome. However, for patient selection, it is necessary to have a predictive indicator showing, if possible before laparotomy, which instances are noncurable by surgery alone or need adjuvant therapies., Methods: A retrospective analysis was made for 24 consecutive patients whose duodenal adenocarcinoma were treated by pancreatoduodenectomy plus a wide range of lymphadenectomies without any adjuvant therapies at Osaka Medical Center for Cancer and Cardiovascular Diseases. Patient survival rates were related to macroscopic and microscopic findings and to findings obtained by preoperative imaging techniques., Results: The overall survival rate was 69% at 3 years and 57% at 5 years; locoregional recurrence was the primary cause of death. Although the 5-year survival rate was 44% in patients with nodal involvement and 76% in those without, this difference did not reach statistical significance (P = .079). Instead, invasion into the pancreatic parenchyma at a macroscopic level was the most significant prognostic factor; the 5-year survival rate was 78% in the 16 patients without and 16% in the 8 patients with pancreatic invasion (P = .0047). Invasion into the pancreas correlated well with the angiographic findings; the 5-year survival rate was 25% in patients whose angiograms delineated the pancreatic invasion and 83% in patients whose angiograms did not (P = .0084)., Conclusion: When duodenal adenocarcinoma was treated by pancreatoduodenectomy plus a wide range of lymphadenectomy, pancreatic invasion at a macroscopic level was most associated with patient survival. Pancreatic invasion was well delineated by the preoperative angiogram, which would be helpful in patient selection.

By means of the differential display method, we isolated a novel human gene that is expressed specifically in pancreas. The cDNA, designated "pancpin," contained an open reading frame of 1,215 nucleotides encoding a 405 amino acid protein, showing a high degree of similarity to serine protease inhibitors belonging to the serpin superfamily. To investigate its possible role in pancreatic carcinogenesis, we looked for genetic alterations of this gene in pancreatic cancer cell lines and primary pancreatic cancer tissues. Expression of pancpin was barely detectable in any of the four pancreatic cancer cell lines examined, and very weak also in 10 of 13 pancreatic cancer tissues. A somatic missense mutation at codon 221 was found in two of 16 primary pancreatic cancers. These findings indicate that down-regulation of pancpin expression may play a significant role in development or progression of pancreatic cancer.

For locally advanced non-resectable cancer of the pancreas, we have routinely performed intra-arterial chemotherapy: Each catheter is placed in the splenic artery and gastroduodenal artery during laparotomy, and a mixture of Methotrexate and Angiotensin-II is infused within 30 minutes. This treatment is repeated weekly at our outpatient clinic as long as possible. However, obstruction of the catheter or corresponding artery is the major cause of interruption of treatment. The present paper reports a case in which intra-arterial chemotherapy was possible by repeated catheterization for the catheter obstruction. A 54-year-old woman with non-resectable pancreatic cancer underwent catheter placement during laparotomy, but they became occluded one month later. Another catheter was placed into the common hepatic artery by the Seldinger method. After this catheter was occluded again, another catheter was placed into the inferior pancreaticoduodenal artery via the superior mesenteric artery by the Seldinger method. By repeating this catheter placement, we succeeded in continuing the intra-arterial chemotherapy, and the patient has remained alive (30 postoperative months) without losing her quality of life.

During pancreatoduodenectomy for adenocarcinoma of the pancreatic head, we frequently encountered cases in which the superior mesenteric-portal venous confluence (SMPVC) was involved with cancer. With regard to the indication of the concomitant SMPVC resection, as suggested by recent papers, a better long-term outcome would be expected if the cancer invasions were limited to the tunica adventitia or media of the SMPVC wall. Since this raised fears whether such a small SMPVC invasion was always detectable by macroscopic inspection alone, we have performed an intraoperative cytology on the touch smear of the exposed SMPVC wall for 23 patients with pancreatic head cancer. All of their SMPVCs were separated from the pancreatic head and appeared to be intact at a macroscopic level. As a result of the cytologic examination, however, 7 patients (30%) were newly diagnosed as having cancer cells on the SMPVC wall, and they received an additional resection of the SMPVC. Postoperative histology indicated that cancer invasion into the SMPVC wall was present in 6 of the 7 patients, and that the cancer invasions were limited in the tunica adventitia in 5 patients and to the tunica media in 1 patient. Thus, in order not to miss the chance of cure by SMPVC resection, our intraoperative cytology on the touch smear of the SMPVC is worth performing more actively on the macroscopically intact-looking SMPVC during resection of pancreatic cancer.

Background/aims: The poor prognosis after pancreatic cancer resection is attributed to a high incidence of locoregional recurrence and hepatic metastasis. The present study was carried out in order to determine whether adjuvant therapies improve patient survival., Methodology: Preoperative irradiation and postoperative liver perfusion chemotherapy have been added to the extended pancreatectomy procedure, and a retrospective analysis of 111 patients was performed., Results: Preoperative irradiation (n = 17) significantly decreased the incidence of locoregional recurrence but increased the incidence of hepatic metastasis, with no improvement in the 5-year survival rate (from 27% to 23%). In contrast, postoperative liver perfusion chemotherapy (n = 27) succeeded in improving the 5-year survival rate to 39% by significantly decreasing the incidence of hepatic metastasis., Conclusion: These data suggest that the patients' survival rate may be increased when these two types of adjuvant therapy are combined with extended pancreatectomy.

Although endothelial cell retraction is required before tumor cell invasion, its molecular mechanism still remains obscure. We previously demonstrated that conditioned medium (CM) derived from a human pancreatic cancer cell line, PSN-1, induced endothelial cell retraction and facilitated tumor cell invasion. To investigate the molecular change of events in the transduction of extracellular signals during endothelial cell retraction, we examined the effect of the CM derived from PSN-1 cells on the tyrosine phosphorylation in endothelial cells. Immunoblot analyses revealed that the PSN-1 CM decreased tyrosine phosphorylation of a 120-130 kD protein, and induced the concomitant down-regulation of focal adhesion kinase, pp125FAK, during endothelial cell retraction in time- and dose-dependent fashions. These changes preceded endothelial cell retraction and were reversible after removal of the CM. Further quantitative densitometric analyses demonstrated that the extent of decrease in tyrosine phosphorylated 120-130 kD protein during the endothelial cell retraction was likely to be proportional to that of the down-regulation of pp125FAK. A tyrosine phosphorylated 120-130 kD protein immunoprecipitated by anti-phosphotyrosine antibody immunoreacted with anti-pp125FAK antibody. These results suggested that decreased amount of a tyrosine phosphorylated 120-130 kD protein probably due to the down-regulation of pp125FAK might be associated with the signal transduction pathway in the endothelial cells during their retraction. Furthermore, these findings were also observed in the CM from another four human cancer cell lines, suggesting the down-regulation of pp125FAK in endothelial cells during tumor cell invasion.

Background/aims: Liver metastasis is one of the major causes of cancer death after resection of pancreatic cancer. To deal with this problem, we developed a liver perfusion chemotherapy via the hepatic artery and portal vein. The present paper is designed to introduce the technique of this method and report on the promising results., Methodology: Between 1987 and 1995, 98 consecutive patients with adenocarcinoma of the pancreas received an extended pancreatectomy, in which a wide range of lymphatic and connective tissue clearance was performed in addition to the conventional pancreatectomy, at Osaka Medical Center for Cancer and Cardiovascular Diseases. All patients were followed-up to determine whether and where cancer recurrence developed., Results: Excluding 4 patients who died of postoperative complications, our liver perfusion chemotherapy was performed on 27 patients. The other 67 patients did not receive this treatment. In the group that underwent liver perfusion chemotherapy, no patients experienced complications such as leucocytopenia (< 3000/mm3), thrombocytopenia (< 50,000/mm3), or liver disfunction. The cumulative survival rate differed remarkably between the two groups: 92% vs 62% at one year (p < 0.05); 51% vs 35% at three years (p < 0.05); and 41% vs 25% at five years (ns)., Conclusions: When this method was performed after an extended pancreatectomy for adenocarcinoma of the pancreas, our preliminary report (Am J Surg. 1994; 168:361-364) indicated that it was useful not only for preventing hepatic metastasis, but also for improving patients' survival rate. Since then, further positive and supportive results have been obtained in an additional investigation.

Intra-arterial infusion chemotherapy was given preoperatively to one patient with pancreatic head adenocarcinoma, in order to prevent local failure after surgery. Under an angiographic procedure, a catheter was placed in the gastroduodenal artery after embolizing the right gastric artery and gastroepiploic artery. Before surgery, 5-fluorouracil (250 mg/day) had been continuously infused for 2 weeks and bolus infusion of methotrexate (25 mg) with 5 micrograms of angiotensin-II had been performed every 3 days. As a results, the maximum diameter of the pancreatic tumor decreased from 3 cm to 2 cm on the CT-Scan. An extended pancreatoduodenectomy with portal vein reconstruction was performed. In histologic study, degenerative tumor cells were shown not only in the primary tumor but also in the extrapancreatic perineural invasion.

Reverse transcriptase-polymerase chain reaction (RT-PCR) targeted at keratin 19 mRNA was applied to detect circulating cancer cells in the peripheral and portal blood of pancreatic and gastric cancer patients. Keratin 19 mRNA expression was studied by RT-PCR in cancer tissues (12 pancreatic and 15 gastric cancers) and in peripheral and/or portal blood samples from patients with pancreatic cancer (stage I, n = 5; stage II, n = 1; stage III, n = 15; stage IV, n = 19), gastric cancer (stage la,b, n = 28; stage II, n = 9; stage IIIa,b, n = 5; stage IVa,b, n = 7) and benign pancreatic diseases (n = 7). Peripheral blood samples from 50 healthy volunteers served as controls. RT-PCR was conducted in duplicate in each sample, and only samples showing keratin 19 transcript in both determinations were considered as being positive. All the pancreatic and gastric cancers, but none of the control blood samples, were found to be positive. Dilution study using pancreatic cancer cells serially mixed against peripheral blood showed that detection sensitivity was more than one cancer cell in 10(6) peripheral blood mononuclear cells. In pancreatic cancer patients, RT-PCR analysis of the portal blood samples gave positive results in one stage III and one stage IV patient, and that of peripheral blood samples gave positive results in 2 stage IV patients. No positive results were obtained in any of the blood samples from gastric cancer patients. Our results indicate that incidence of circulating cancer cells is unexpectedly very low even in advanced pancreatic and gastric cancer patients.

The present article reviews previous reports on the systemic and regional chemotherapies for adenocarcinoma of the pancreas. When non-resectable pancreatic cancer was treated by the systemic chemotherapy, most reports showed that the mean or median survival periods were less than 6 months. Although the response rate to multi-drug chemotherapy was superior than that to single-drug chemotherapy, the survival period did net differ significantly between the two. In general, in terms of the patients, survival rates, the combination og chemo-therapy and radiation was slightly superior to either chemotherapy or radiation alone. On the other hand, regional chemotherapy seems to be more promising because our intra-arterial chemotherapy using angiontensin-II has succeeded in improving the mean survival period to 14 months for non-resectable pancreatic cancer. Likewise, liver perfusion chemotherapy via the hepatic artery and portal vein was effective in preventing the development of liver metastasis after pancreatectomy. Considering that the pancreatic cancer is a poorly vascularized tumor, it is essential to deliver a high dose of anti-cancer drug effectively into the cancer tissue. Secondarily, the selection of drug to which the pancreatic cancer cell is sensitive is also important.

Background: Tumor cells induce endothelial cell retraction before invasion. In pancreatic cancer cells, the factors affecting endothelial cell retraction are not well-understood., Methods: The activities of the endothelial cell retraction in conditioned media (CM) derived from three human pancreatic cancer cell lines, PSN-1, MiaPaca-2, and Capan-1, were measured for the amount of intercellular junctional transport of FITC dextran through an endothelial cell monolayer in a transwell cell culture system., Results: The CM derived from the three pancreatic cancer cells induced endothelial cell retraction. The endothelial cell retraction activity in the CM from PSN-1 cells was significantly higher than those from MiaPaca-2 and Capan-1 cells. The CM from PSN-1 cells enhanced both the adhesion and the invasion of MiaPaca-2 and Capan-1 cells. The factors with endothelial cell retraction activity in the CM from PSN-1 cells were characterized as heat-stable, trypsin-sensitive glycoproteins ranging from 10,000 to 50,000 in molecular weight, and were found both in heparin-bound and unbound fractions., Conclusions: PSN-1 cells produced and secreted at least two factors inducing the endothelial cell retraction. The factors could play an important role in the establishment of invasion and metastasis of PSN-1 cells.

Background: Until recently long-term survival has not been expected when at least one positive node was detected at any site in pancreatic head cancer treated by conventional pancreatectomy. However, even when nodal involvement is seen, there has been an increasing number of long-term survivors after extended pancreatectomy in which a wide range of lymphatic and connective tissues were cleared. Thus the purpose of the present study was to establish a practical rational grouping of positive lymph nodes in pancreatic head cancer treated by extended pancreatectomy., Methods: In 81 patients who tolerated extended pancreatectomy for cancer of the pancreatic head, a mean of 56 +/- 23 (range, 28 to 89) lymph nodes in each patient were examined under a microscope to determine the presence or absence of cancer. They were classified anatomically into 14 lymph node groups, and the incidence, distribution, and number of positive nodes were examined. A simplified grouping was made on the basis of the histologic findings and was checked against long-term survival rates., Results: Nodal involvement was detected in 59 (73%) of 81 patients, and positive nodes were more commonly observed in the posterior pancreaticoduodenal (PPD), superior mesenteric (SM), and anterior pancreaticoduodenal (APD) groups than in the 11 other groups (p < 0.05). The PPD, APD, and SM groups offered the sole sites of nodal involvement with incidence levels of 23%, 17%, and 6%, respectively, whereas none of the 11 other groups did. Thus patients were classified into four groups: (a), negative in all 14 lymph node groups (n = 22); (b), positive but limited to the PPD/APD groups (n = 14); (c), also positive in the SM group, but negative in the 11 other groups (n = 13); and (d), also positive in at least one of the 11 other groups (n = 32). This classification was associated well with the 5-year survival rate: 59% in group (a), 53% in group (b), 15% in group (c), and 0% in group (d) [p < 0.05; group (b) versus group (c)]. Also this grouping associated well with the total number of positive nodes (p < 0.05). The 5-year survival rate in patients with one to three positive nodes was 47% and was more than 6% in patients with four to seven positive nodes (p < 0.05)., Conclusions: In the clinicopathologic staging of the lymphatic spread from carcinoma of the pancreatic head, the PPD and APD groups were considered the first stations of lymphatic metastasis, whereas the 12 other groups-including the SM group-were categorized as second or more distant stations.

In the treatment of adenocarcinoma of the pancreas, surgical resection is the only curative strategy. However, the long-term survival rate after pancreatectomy remains poor, and most patients died of loco-regional and/or hepatic recurrence. Thus, we should perform effective adjuvant therapies in combination with surgery, in order to completely prevent these two types of cancer relapse. The present article is designed to introduce the recent reports on the adjuvant chemo-and/or radio-therapies for this cancer. As for loco-regional control, extended pancreatectomy plus chemoradiation seems to be most promising, and preoperative chemoradiation will be more popular in the near future. In order to decrease hepatic metastasis, our "2-channel chemotherapy", a continuous infusion of 5-FU via both hepatic artery and portal vein, is very promising. If postoperative survival is improved by combining these two types of regional therapy, the role of pancreatectomy will be enlarged and more widely understood in the near future.

This is a report of a 62-year-old woman whose non-resectable pancreatic cancer had been treated effectively by a new method of intra-arterial regional chemotherapy for more than 4 years. A catheter was placed into the celiac artery during laparotomy, and an intra -arterial chemotherapy (methotrexate (50 mg) and Angiotensin-II (AT-II, 5 micrograms)) has been repeated every other week (108 times) in addition to the external beam therapy (50 Gy). Both pain relief and "partial response" in the size of tumor have been obtained, with no hepatic metastasis or adverse effect. She died of brain metastasis at 51 postoperative months. Autopsy revealed that the pancreatic tumor was mostly replaced by fibrous connective tissues. Scintigraphic study indicated that the intra-arterial infusion of AT-II increased the blood flow in the tumor but decreased it in the surrounding non-cancerous tissues. This seemed to explain the effective loco-regional control in the present case.

Background/aims: In order to deliver the anti-cancer drugs more selectively into the cancer tissues, we have developed a new method of intra-arterial regional chemotherapy for locally unresectable cancer of the exocrine pancreas., Materials and Methods: This method involved placing the catheters selectively into the splenic artery and/or into the gastroduodenal artery during laparotomy. Postoperatively, via the catheter, we infused 50-100 mg of Methotrexate mixed with 10 micrograms of Angiotensin-II with an intent of increasing the blood flow in the tumor tissue but decreasing that to the non-tumor tissues. Simultaneously, a bolus iv-infusion of 5-fluorouracil (5-Fu, 500 mg) was performed. One day after each chemotherapy, citrovorum factor (Leucovorin, 30mg) was given per orally, For 15 patients with locally non-resectable pancreatic cancer, this treatment was repeated weekly or biweekly at our out-patient clinic., Results: As a result, the toxicity was so slight that all patients could tolerate this treatment as long as the catheter was patent (11 +/- 8 postoperative months). The survival period was 16 +/- 9 months (range: 5-36 months; median: 14 months), and one-, two- and three- year survival rates were 60%, 23% and 11%, respectively. Patients could take care of themselves within 12 +/- 9 months, and either complete (50%) or partial (50%) pain-relief was obtained among the 12 patients with severe pain. Only one patient experienced local tumor regression during the chemotherapy, and the incidence of liver metastasis was as low as 13%., Conclusions: Comparing with the previously reported data in the traditional chemo- and/or radio-therapies, we consider that our method of intra-arterial chemotherapy is quite useful not only for the prolongation of patient's survival but also for improving the quality of life. Thus, this new treatment seems worthy of entering into the prospective randomized study.

Our previous studies have suggested that the presence of intact islets is essential for the induction of pancreatic exocrine tumors in the Syrian hamster model. To validate this, we investigated the effect of the carcinogen, N-nitrosobis(2-oxo-propyl)amine (BOP) in hamsters, in which homologous isolated intact islets were transplanted into the submandibular gland (SMG). Freshly isolated pure islets from hamster donors were transplanted into the left SMG of 20 female host hamsters. Ten of these hamsters (group 1) received BOP (40 mg/kg) weekly for 3 weeks. Another 10 hamsters (group 2) were kept untreated. In groups 3 and 4 (10 hamsters each) the salt solution or isolated pancreatic ductal cells, respectively, was injected into the gland. In other groups (10 hamsters each) islets were transplanted into the peri-SMG connective tissue (group 5) or into the renal subcapsular space (group 6). Hamsters of group 1 (40 mg/kg, weekly for 3 weeks) as were group 7 hamsters, which served as BOP-treated controls. All BOP-treated hamsters developed pancreatic lesions. Similar hyperplastic and atypical ductal/ductular proliferation and in situ carcinoma were found in the SMG of many group 1 hamsters. No such lesions were found in the SMG, peri-SMG, or renal subcapsular space of the other groups. Islets appear to be involved in carcinogenicity of BOP. The mechanism is obscure.

To investigate the factors affecting endothelial-cell retraction, we have studied the interaction of tumor cells with endothelial cells in 2 human pancreatic cancer cell lines, PSN-1 and MiaPaca-2. The extent of endothelial-cell retraction measured by the amount of intercellular junctional transport of FITC-dextran through an endothelial monolayer was increased by the addition of a conditioned medium (CM) from both cell lines, while CM from PSN-1 cells was 2 to 3 times more potent than that from MiaPaca-2 cells. After the treatment of endothelial monolayer with CM of PSN-1 cells, the ability of both PSN-1 cells and MiaPaca cells to adhere to or invade the monolayer increased. The addition of CM from PSN-1 cells did not affect the growth rate of either the endothelial or the tumor cells. The activity in the CM was heat-stable and bound to heparin-Sepharose, but was inactivated when treated by 0.5% trypsin. Protease inhibitors did not influence the activity. Pre-treatment of PSN-1 cells by an inhibitor of protein synthesis, cycloheximide, or of protein processing, benzyl-N-acetyl-alpha-D-galactosaminide, reduced endothelial-cell-retraction activity in the CM. The active substance in the CM fractionated in the molecular-weight range of 10,000 to 50,000. These results suggest that PSN-1 cells produce and secrete (a) soluble factor(s) that can induce endothelial-cell retraction, thus facilitating tumor-cell invasion.

Background/aim: In recent years, we have succeeded in treating an occult cancer of the pancreas by making the most of cytodiagnosis for the pure pancreatic juice., Materials and Methods: Even for the patients in whom obvious tumor was not depicted by imaging techniques, the pure pancreatic juice was collected during endoscopic retrograde pancreatography and it was cytologically examined., Results: When cancer cell was detected, both the location of occult lesion and the range of pancreatectomy were determined by the intraoperative cytology for the pancreatic juice which was collected separately from the cranial and caudal segments (2-segmental cytology). More recently, using a balloon catheter, the pancreatic juice of the head, body and tail, (3-segmental cytology) was examined. The former method was effective to prevent the blind resection of the entire pancreas, and the latter provided us with the opportunities to preserve much more pancreatic function., Conclusions: This method was a useful aid in resecting potentially curable cancer of the pancreas. The present paper introduces the detailed techniques of this method.

Mutations of the p53 gene have been found in a variety of human cancers and are implicated in the biologic functions of cancer. To investigate the clinical implications of p53 mutations in pancreatic adenocarcinoma, we examined the association of mutations of the p53 gene with patients' prognosis. Single-strand conformational polymorphism analysis and direct DNA sequencing were used to detect p53 gene mutations in 37 pancreatic adenocarcinomas. p53 gene mutations were detected in 16 (43%) of the 37 pancreatic adenocarcinomas. Direct sequencing did not reveal preferential clustering at any specific codon. There was no significant association of the presence of p53 gene mutations with histologic types, extent of tumor invasion, the presence of lymph node metastasis, or tumor stage. Univariate analysis showed that survival of patients with p53-gene-mutated tumors was significantly poorer than that of patients with p53-gene-nonmutated tumors (P = 0.02). Cox's multivariate analysis of ten clinicopathologic features including p53 gene mutations revealed that presence of p53 gene mutations (P = 0.026) and curativity of operation (P = 0.014) were independent predictors of survival. Furthermore, the survival of patients with p53-gene-mutated tumor was significantly poorer than that of patients with p53-gene-nonmutated tumors, both in patients who underwent curative operation (P = 0.04) and in patients who underwent non-curative operation (P = 0.01). These results suggested that mutations of the p53 gene might play an important role in cancer aggressiveness and could be a clinically useful predictor of prognosis in patients with pancreatic adenocarcinoma.

A new method of intraoperative cytodiagnosis was performed for one patient with occult neoplasms of the pancreas in order to locate the original site of cancer cells, using a balloon catheter. Cancer cells were detected in the pancreatic juice obtained from the pancreatic body only. The pancreatic body was removed, and the tail of the pancreas was anastomosed to the stomach. The post operative course was good without diabetes, and it was confirmed histologically that minimally invasive adenocarcinoma existed in the pancreatic body. Thus this procedure is beneficial because it can preserve as much pancreatic function as possible without losing the chance of cure by surgery.

Objective: To determine whether or not both regional control and long-term survival rate were improved by preoperative irradiation prior to curative pancreatectomy for adenocarcinoma of the pancreatic head., Design: Retrospective study of recorded medical data from 1985 to 1989., Setting: The Center for Adult Diseases, Osaka, one of the major cancer centers in Japan., Patients and Intervention: Fifty-four consecutive patients in whom pancreatic head cancer had been judged to be resectable by preoperative diagnostic techniques. A total of 50 Gy per 10 MeV of x-ray was irradiated preoperatively to the wide field, including the pancreatic head area, in 23 patients (group A) but not in the 31 remaining patients (group B). The background factors before treatment did not differ between these two groups., Outcome Measures: Resectability, postoperative survival, and modes of cancer recurrence., Results: At laparotomy, curative pancreatectomy was possible in 17 patients (74%) in group A and 19 (61%) in group B (not significant). In patients undergoing resection, the 1-year survival rate was 75% in group A and 43% in group B (P < .05). However, 3- and 5-year survival rates were almost the same in both groups (28% vs 32% and 22% vs 26%, respectively). With regard to the cause of death after pancreatectomy, group A had a significantly lower incidence of deaths due to regional recurrence within 1.5 postoperative years compared with group B, whereas deaths due to hepatic metastasis were markedly higher after 1 postoperative year in group A compared with group B., Conclusions: Preoperative irradiation prior to pancreatectomy succeeded in reducing the incidence of early deaths due to regional recurrence. However, owing to the next barrier--death due to hepatic metastasis after 1 postoperative year--long-term (3- and 5-year) survival rate was not improved at all.

Since hepatic metastasis is a common cause of treatment failure after curative pancreatectomy for adenocarcinoma of the pancreas, we developed a new method of postoperative hepatic perfusion chemotherapy via both the hepatic artery and portal vein. The present study was conducted to determine if this method decreases the hepatic recurrence and improves the survival rate. Following extended pancreatectomy with wide lymphatic and connective tissue clearance for pancreatic cancer, one catheter was placed in the hepatic artery and one in the portal vein. Immediately after surgery, 5-fluorouracil (125 mg/d) was continuously infused via these two routes simultaneously for 28 to 35 days. There were no treatment-related complications in the 20 patients who survived surgery. The 3-year survival rate was 54%, and the cumulative rate of death from hepatic metastasis was 8%. These figures were significantly better than those of our historical control groups. We conclude that this method should be evaluated in a prospective, randomized controlled study.

Very early detection of pancreas cancer is most desirable, since it permits less invasive surgery which has a correspondingly greater chance of success. The present study investigated both surgical outcome and postsurgical quality of life in 8 patients whose occult neoplasms were successfully treated. In all 8 patients, cytology of the pancreatic secretion obtained during endoscopic retrograde pancreatography (ERP) was positive, although no pancreatic tumor was detected by ERP, other examinations or intraoperative inspection. In these 8 patients, our method of intraoperative cytodiagnosis to locate occult neoplasms of the pancreas (Surgery 1992; 111: 294-300) was used (1). Using this method of cytodiagnosis, we were able to avoid total pancreatectomy in 6 patients (75%; 3 pancreatoduodenectomies and 3 caudal pancreatectomies), but not in the other 2 patients. Histopathological study of the resected specimens indicated that the extent of pancreatic resection was quite appropriate in all 8 patients. There were 6 minimally invasive carcinomas, one carcinoma in situ and one borderline lesion. Neither nodal involvement nor severe invasion was found on microscopic inspection, and all have been disease-free for 23 +/- 13 months after surgery. In the 6 patients with partial pancreatectomies, both postoperative quality of life and general health were good, with no insulin-dependent diabetes developing. Thus, our cytology-guided surgical technique is very useful not only for locating occult and potentially curable neoplasms, but also for avoiding blind resection of the entire pancreas, permitting better preservation of pancreatic endocrine function.