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Feline calicivirus (FCV) is frequently used as a surrogate of human norovirus. We investigated eligibility of FCV for anti-viral assay by investigating the stability of infectivity and pH sensitivity in comparison with other viruses. We found that infectivities of FCV and murine norovirus (MNV) are relatively unstable in infected cells compared with those of coxsackievirus (CoV) and poliovirus (PoV) , suggesting that FCV and MNV have vulnerability. Western blotting indicated that inactivation of FCV was not due to viral protein degradation. We also demonstrated sensitivity of FCV to low pH, the 50% inhibitory pH value being ca. 3.9. Since human norovirus is thought to persist longer, in infectivity and to be a resistant virus, CoV, which is robust and not restrained in use as PoV, may be more appropriate as a test virus for disinfectants, rather than FCV and MNV.

Treatment-related quality of life (QOL) is an important aspect of diabetes management. However, no studies have compared the influence of dipeptidyl peptidase-4 inhibitors versus alpha-glucosidase inhibitors on treatment-related QOL. This prespecified sub-analysis of the Linagliptin Study of Effects on Postprandial blood glucose (L-STEP) compared the effects of linagliptin (5 mg once daily) and voglibose (0.2 mg/meal thrice daily) on treatment-related QOL in Japanese patients with type 2 diabetes (T2DM) inadequately controlled with diet and exercise therapy. Among 366 subjects in the original study, 182 in the linagliptin group and 173 in the voglibose group were included in this analysis. The outcome of this study was change in QOL as assessed by the Diabetes Therapy-Related Quality of Life 17 (DTR-QOL17) questionnaire from baseline to week 12. Compared with baseline data, total DTR-QOL17 scores were significantly higher after 12 weeks of linagliptin and voglibose treatment. The change in the total DTR-QOL17 score and the score of one domain, burden on social activities and daily activities, was significantly greater in the linagliptin group than in the voglibose group. In addition, only linagliptin treatment was identified as a factor associated with an increased total DTR-QOL17 score. Linagliptin is superior to voglibose in terms of improving treatment-related QOL in Japanese patients with T2DM.

Background This study assesses the safety and effectiveness of endoscopic biliary sphincterotomy (ES) in the treatment of papillary stenosis (PS) with and without biliary stones. Methods The records of all patients who had endoscopic retrograde cholangiopancreatography (2,689 patients) from January 1, 1991, to August 1, 2010, were reviewed. There were 117 patients with PS who had ES. Results All patients had biliary pain, a dilated common bile duct (CBD) with a maximum diameter of 10 to 25 mm, and elevated liver function tests. There were 46 patients who had prior cholecystectomy of whom 20 patients had CBD stones. The remaining 71 patients had no prior biliary surgery; there were no biliary stones in 14 patients. All patients were symptom free after ES with or without CBD stone retrieval. Conclusions ES is the optimal treatment for PS in patients with or without biliary stones. ES eliminates pain, corrects CBD dilation, and restores LFTs to normal.

T4 esophageal cancer is defined as the tumor invading adjacent structures, using tumor–node–metastasis (TNM) staging. For clinically T4 thoracic esophageal carcinoma, multimodality therapy, that is, neoadjuvant chemoradiotherapy (CRT) followed by surgery or definitive CRT, has generally been performed. However, the prognosis of patients with these tumors remains poor. Another strategy is needed to achieve curative treatment. In the present article, the treatment strategies employed to date are reviewed. Furthermore, the strategies for these malignancies are reassessed, based on our experiences. R1/2 and R0 resections are regarded as those with residual and no tumor after surgery. The present data show that patients who underwent R1/2 resection after neoadjuvant CRT experienced little survival benefit, while complete response (CR) cases after definitive CRT had comparatively better results. Therefore, curative surgery should not be attempted without down-staging, and definitive CRT should be the initial treatment. Then surgery is indicated for the eradication of residual cancer cells. Close surveillance is essential for early detection of relapse even after CR, because the operation will gradually become increasingly difficult due to post-CRT fibrosis. In conclusion, multimodality therapy consists of definitive CRT followed by R0 resection, which can be the treatment of choice for T4 esophageal carcinoma. These challenging treatments have the potential to constitute the most effective therapeutic strategy. (Cancer Sci 2007; 98: 937–942)

We report a case of abdominal wall abscess caused by diverticulitis of the jejunum penetrating through the abdominal wall. A 53-year-old Japanese woman visited a local hospital complaining of abdominal pain and a mass in the left lower abdomen. An abdominal computed tomography scan showed a tumor with isodensity in the left lower abdominal wall. Magnetic resonance imaging showed a mass in the abdominal wall with isointensity in the T1-intensified image and high intensity in the T2-intensified images. The mass was heterogeneous inside and protruded partially toward the intraperitoneal cavity. Ultrasound examination showed a heteroechoic mass extending into the intraperitoneal cavity. Laparotomy revealed a tumor in the abdominal wall with a fistulous tract extending to the jejunum. We resected the abdominal wall tumor with partial resection of the small intestine. The resected specimen contained a tumor with a fistulous tract passing through the abdominal wall. Histological examination revealed remarkable infiltration of neutrophils and a bacterial mass in the abdominal wall tumor, with a fistulous tract connected to the area adjacent to the mesenteric border of the jejunum. These findings suggested that diverticulitis of the jejunum had penetrated through the abdominal wall, leading to the formation of an abscess. We report this case to highlight the need for complete gastrointestinal evaluation with gastrointestinal barium studies and imaging analysis to examine extension of intra-abdominal lesions in patients with an unexplained abdominal wall abscess.

Recent observations suggest that an immune response is involved in the development of chronic pancreatitis. We report a case of autoimmune pancreatitis in a patient who showed complete obstruction of the lower common bile duct. A 63-year-old man was admitted to a local hospital, complaining of appetite loss and back pain. The patient had obstructive jaundice, and percutaneous transhepatic gallbladder drainage was performed. Fluorography through the biliary drainage catheter showed complete obstruction of the lower common bile duct. The patient had no history of alcohol consumption and no family history of pancreatic disease. Physical examination revealed an elastic hard mass palpable in the upper abdomen. Abdominal ultrasound and abdominal computed tomography (CT) scans showed enlargement of the pancreas head. While autoimmune pancreatitis was highly likely, due to the patient's high serum immunoglobulin level, the possibility of carcinoma of the pancreas and/or lower common bile duct could not be ruled out. Laparotomy was performed, and wedge biopsy samples from the pancreas head and body revealed severe chronic pancreatitis with infiltration of reactive lymphocytes, a finding which was compatible with autoimmune pancreatitis. Cholecystectomy and biliary reconstruction, using choledochojejunostomy, were performed, because the complete bile duct obstruction was considered to be irreversible, due to severe fibrosis. After the operation, prednisolone (30 mg/day) was given orally for 1 month, and the entire pancreas regressed to a normal size. Complete obstruction of the common bile duct caused by autoimmune pancreatitis has not been reported previously; this phenomenon provides an insight into autoimmune pancreatitis and provokes a controversy regarding whether biliary reconstruction is needed for the treatment of complete biliary obstruction caused by autoimmune pancreatitis.

We report a patient with rectal stenosis caused by peritoneal recurrence 8 years after a curative resection of advanced stage gastric carcinoma; the recurrence was effectively treated with the weekly administration of paclitaxel. The patient was a 66-year-old Japanese woman who was admitted to our hospital complaining of abdominal pain and frequent bowel movements. She had undergone total gastrectomy, due to advanced-stage gastric carcinoma with extensive lymph node metastasis, 8 years before, and had taken an oral anticancer agent, fluoropyrimidine, for 4 years after the operation. Colonofiberscopy performed on admission revealed circumferential rectal stenosis located 10 cm from the anal verge. Barium enema study demonstrated extensive poor expansion of the upper and lower rectum and irregularity of the descending colon. Abdominal computed tomography (CT) scanning revealed wall thickening in the rectum and descending colon. These findings were compatible with rectal stenosis caused by the peritoneal recurrence of gastric carcinoma. Weekly administration of paclitaxel was started. The abdominal symptoms soon disappeared when the second cycle of paclitaxel was completed, and they have not appeared since then. The rectal stenosis was attenuated, as confirmed by imaging analyses. Weekly paclitaxel has been effective for more than 13 months, suggesting that the patient is in a state of tumor dormancy of recurrent gastric carcinoma.

To test the clinical usefulness of hepatic asialogycoprotein receptor analysis in liver surgery, we have conducted univariate and multivariate analysis for the detection of cirrhotic patients and prediction of morbidity after hepatic resection. Liver scintigraphy using technetium 99m-labeled asialoglycoprotein analog (TcGSA), ICG test, and CT hepatic volumetry were undertaken in 158 surgical patients including 111 who underwent hepatic resection. Hepatic functional parameters including Child-Pugh score, indocyanine green retention at 15 minutes (ICG-R15), clearance index (HH15), receptor index (LHL15), receptor concentration ([R]0), total hepatic receptor amount (R0) and hepatic parenchymal volume (HPV) were compared among patients with normal, cirrhotic, and non-cirrhotic damaged liver. Preoperative hepatic functional parameters, resected parenchymal fraction (RPf), operative blood loss, and total receptor amount of the remnant liver (R0-remnant) were compared between patients with and without signs of postoperative liver failure. All parameters but HPV were significantly different among patients with normal, cirrhotic, and noncirrhotic damaged liver. The multivariate analysis selected two significant (p0.05) parameters, [R]0 and Child-Pugh score for the detection of liver cirrhosis. Of the 111 patients who underwent resection, 14 developed transient signs of postoperative liver failure. Of the parameters tested, presence of liver cirrhosis, LHL15, R0, intraoperative blood loss, and R0-remnant were significantly different between patients with and without signs of postoperative liver failure (p0.05). The multivariate logistic regression analysis selected only R0-remnant as a significant (p = 0.022) parameter for the prediction of liver failure. The morbidity rate in patients with R0-remnant under 0.05 mmoles was 100%, and the rate decreased in inverse proportion to R0-remnant. In conclusion, combining the ASGP-R concentration ([R]0) and the Child-Pugh score best detected liver cirrhosis in surgical candidates. Cirrhotic patients and patients with a low R0-remnant are at higher risk for postoperative liver failure. The present study confirms the usefulness of hepatic asialogycoprotein receptor analysis in liver surgery.

Background/Purpose: We investigated the molecular mechanisms of carcinogenesis in the biliary epithelium in patients with pancreaticobiliary maljunction. Methods: Point mutations of the K-ras gene and the p53 gene, and the overexpression of p53 gene products were examined in the cancerous and noncancerous biliary epithelium of 37 patients with pancreaticobiliary maljunction, with or without biliary dilatation. Results: In the gallbladder epithelium of 5 patients with pancreaticobiliary maljunction associated with biliary carcinoma, K-ras gene mutations were detected in 3 (60%), p53 gene mutations in 3 (60%), and the overexpression of p53 gene products in 4 (80%), while in the bile duct epithelium of these patients, these features were found in 2 of 3 (66.7%), in all of 3 (100%), and none of 3 (0%) specimens, respectively. In the gallbladder epithelium of patients with pancreaticobiliary maljunction without biliary carcinoma, K-ras gene mutations were detected in 8 of 24 (33.3%) specimens, p53 gene mutations were detected in 16 of 27 specimens (59.3%), and the overexpression of p53 protein was detected in 5 of 27 (18.5%) specimens, while in the bile duct epithelium of these patients, these features were found in 10 of 25 (40%) specimens, 14 of 25 (56%) specimens, and 6 of 24 (25%) specimens, respectively. Conclusions: These results suggest that noncancerous lesions of the biliary epithelium in patients with pancreaticobiliary maljunction have mutations of the K-ras gene and/or the p53 gene, which provides genetic evidence that biliary epithelium has high carcinogenic potential.

Although retroperitoneal or psoas abscess is an unusual clinical problem, the insidious and occult characteristics of this abscess sometimes cause diagnostic delays, resulting in considerably high morbidity and mortality. In particular, psoas abscess caused by perforated colon carcinoma is uncommon. We report a case of psoas abscess caused by a carcinoma of the cecum. A 72-year-old Japanese woman was admitted to our hospital, with pain in the right groin and buttock. The pain had appeared 6 months before admission, and the symptoms had then been relieved by oral antibiotics. On March 25, 1999, inflammatory signs in the right buttock indicated localized cellulitis, and incision and drainage was performed at a local hospital. The patient was referred to our hospital on the same day. On admission to our hospital, computed tomography (CT) scan revealed a thick right-sided colonic wall and enlargement of the right ileopsoas muscle. Barium enema and colonofiberscopy revealed an ulcerated tumor occupying the entire circumference of the cecum. A retroperitoneal abscess and fistula had been formed by the retroperitoneal perforation of cecum carcinoma: surgical resection was performed after remission of the local inflammatory signs. Operative findings indicated that the cancerous lesion and its surrounding tissues were firmly attached to the right iliopsoas and major psoas muscle, and en-bloc resection, including adjacent muscular tissue, was performed. The fact that carcinoma of the colon could be a cause of psoas abscess and cellulitis in the gluteal region should be considered when an unexplained psoas abscess is diagnosed.

Although hemihepatic portal vein embolization (PVE) has been used preoperatively to extend indications for hepatectomy in patients with colorectal metastases, the effects of this procedure on tumor growth and outcome remain controversial. To address this issue, we assessed the proliferative activity of intrahepatic metastases after PVE and the long-term outcome of this procedure. Eighteen patients with colorectal metastases underwent preoperative PVE between 1996 and 2000 (PVE group). Twenty-nine patients who underwent major hepatic resection without PVE served as control (non-PVE group). The hepatic parenchymal fraction of the left lobe had significantly increased from 38.1 +/- 3.2% to 45.9 +/- 2.9% 3 weeks after PVE (+20.5%, P

With carcinoma of the thoracic esophagus, clinical evidence of invasion of adjacent organs (T4) indicates a highly advanced stage, and most surgeons avoid esophagectomy. Although the therapeutic strategy for such disease is generally selected based on preoperative evaluation and intraoperative inspection, their accuracy and the relation to survival outcomes after esophagectomy have seldom been analyzed on the basis of exact histopathologic evidence. We performed esophagectomy, with perioperative adjuvant therapy when possible, on patients with clinical-T4 tumors unless absolutely unresectable conditions were detected. Among the 500 patients who underwent esophagectomy, the 78 patients whose tumors were confirmed to be T4 pathologically were compared with patients whose tumors were assessed as T4 preoperatively or intraoperatively to evaluate the role of esophagectomy for clinical-T4 carcinoma. Esophagectomy was possible for 99% of the pathologic-T4 tumors preoperatively assessed as resectable, but the resection was grossly incomplete in 35%. The true-positive rates in tumors preoperatively and intraoperatively assessed as T4 were 51% and 84%, respectively. The hospital mortality rate in patients with pathologic-T4 tumors was 4%. The overall 5-year survival rate for patients with pathologic-T4 tumors was 14%, compared with 60% for those with tumors assessed as T4 intraoperatively but not pathologically. Esophagectomy with perioperative adjuvant therapy yielded occasional cure with an acceptable mortality rate for patients with pathologic-T4 tumors assessed as technically resectable. Preoperative assessment and intraoperative macroscopic inspection had limitations for predicting pathologic-T4 disease and incomplete resection. Only patients with definitive evidence of unresectability should be excluded from esophagectomy.

While gallbladder carcinoma is occasionally associated with pancreaticobiliary maljunction, spontaneous necrosis of carcinoma is extremely rare. We herein present a case of spontaneous necrosis of gallbladder carcinoma associated with direct invasion of viable cancer cell nests to the muscularis propria and subserosal layer located beneath the primary nodules. A 65-year-old Japanese man was admitted to a local hospital, complaining of repeated discomfort in the right hypochondrium. Ultrasonography and computed tomography scanning revealed cholecystitis associated with gallstones. Cholecystectomy was performed, and operative cholangiography demonstrated pancreaticobiliary maljunction. The resected gallbladder showed multiple mixed stones filled with necrotic debris and bile sludge. Scrutiny of the mucosal surface revealed multiple small necrotic nodules in the fundus, which were histologically confirmed to be necrotic remnants of a cancerous glandular structure. Small nests of papillary adenocarcinoma were found beneath the nodules in the muscularis propria and in the venous structure located in the connective tissues next to the divided margin of the gallbladder bed. Resection of S4a and S5 of the liver and resection of the extrahepatic bile duct was then performed to remove the remaining cancerous tissues and/or micrometastasis in the liver and bile duct. The biliary tree was reconstructed with a hepaticoduodenostomy. No cancer nests or any precancerous lesions were found in the additionally resected specimens. This case indicates a unique morphological feature of gallbladder carcinoma associated with pancreaticobiliary maljunction, which provides some insight into the pathogenesis of spontaneous necrosis of gallbladder carcinoma.

We report a case of hyperplastic polyp of the gallbladder in a 6-year-old girl, successfully treated by laparoscopic cholecyctectomy after a 2-year follow-up from the original diagnosis. On her first admission, serum amylase level was very high, so that congenital pancreaticobiliary maljunction (PBM) was suspected. Although it became clear afterwards that the high serum amylase level was derived from a mumps infection, the diagnosis of PBM was not excluded until intraoperative cholangiography was conducted. The tumor in the gallbladder had doubled in size in 2 years. It was not possible to obtain biopsy specimens for histological diagnosis, so the risk of the tumor being malignant could not be completely excluded until surgical resection had been carried out. In spite of the rapid tumor growth, no neoplastic features were seen in the tumor by histopathological examination of the resected specimen; thus, a diagnosis of a hyperplastic polyp of the gallbladder was made.

Despite the relatively common incidence of sacrococcygeal dermoids, rectal cysts are uncommon. We report the case of a submucosal dermoid cyst occurring in the rectum. A 30-year-old woman visited the Gynecology Department because of pregnancy. A pelvic tumor was accidentally found during the checkup after miscarriage. A barium enema showed an anterior shift of the rectum by the presence of the tumor. Computed tomography and magnetic resonance imaging revealed a tumor located posterior to the rectum occupying almost the entire pelvic cavity, and the tumor was resected. The tumor was located in the submucosal layer of the posterior rectal wall and was well circumscribed. The resected tumor was a cyst entirely covered with a fibrous and firm capsule, which was filled with an amorphous white creamy substance. The histological findings showed the cyst consisting of a keratinizing stratified squamous epithelium with sebaceous gland and hair follicles, which was compatible with benign cystic teratoma. Primary rectal teratoma is very rare and only 36 cases have been reported in the literature worldwide. Furthermore, while the majority of cases were polypoid-shaped dermoid cysts protruding into the rectal lumen, only 3 cases were submucosal dermoid cysts. Therefore, such cases are considered to be extremely rare.

Background and Objectives: In carcinoma of the thoracic esophagus, most surgeons consider that esophagectomy is contraindicated in patients with clinical evidence of major extraesophageal involvement in the lower neck or peritracheal regions. However, metastases to these regions are commonly found even in early phases of carcinoma invasion. With recent progress in preoperative assessment, operative technique and adjuvant therapy, esophagectomy could possibly benefit appropriately selected patients. Methods: We retrospectively analyzed results in 42 patients who had major involvement in the neck or upper mediastinum and who underwent esophagectomy with systematic lymph node dissection. We operated upon patients unless lesions were assessed as definitely unresectable. Preoperatively, 32 had enlarged peritracheal nodes greater than 15 mm in diameter on computed tomography, 18 had hard unmobile tumors in the lower neck, 9 had recurrent laryngeal nerve palsy, and 10 had findings suggestive of tracheal invasion. Preoperative radiotherapy and/or chemotherapy was given to 32 low-risk patients. Results: The hospital mortality rate was 4%. Bowel reconstruction was completed in all cases. No macroscopically recognizable lesion remained after operation in 35 patients. Eight patients were alive 5 years after esophagectomy, including 2 who had had tracheal invasion and I with recurrent nerve palsy. The cumulative 5-year survival was 38%. Conclusions: Evidence of major involvement of the neck and/or upper mediastinum does not always contraindicate resection. Aggressive esophagectomy combined with perioperative adjuvant therapy yielded acceptable palliation and occasional cure in cases with technically resectable lesions.

Purpose: To reevaluate postoperative radiotherapy for thoracic esophageal carcinoma. Methods and Materials: Reviewed were the outcome of 89 patients who underwent esophagectomy with systematic dissection of regional lymph nodes between 1988 and 1993. Of the 89 patients, 19 underwent no adjuvant treatment, 22 underwent adjuvant chemotherapy alone, and 48 underwent postoperative radiotherapy. Twelve of the 48 also underwent adjuvant chemotherapy. Results: All patients who experienced local-regional recurrence had lymph node metastases at the time of surgery. The acturial local-regional control rate at 2-year of follow-up was 94% for patients with lymph node metastatses at the time of surgery who underwent postoperative radiotherapy alone or plus chemotherapy, and 74% for those who underwent adjuvant chemotherapy alone. The local-regional control rate was significantly better for those who had undergone postoperative radiotherapy (p < 0.01). Conclusions: Postoperative radiotherapy still plays an important role as adjuvant treatment.

To evaluate the effects of aggressive operation for esophageal cancer invading the trachea and main bronchi, we investigated retrospectively 62 patients with proven tracheobronchial involvement who underwent thoracotomy for esophagectomy between 1973 and 1993. We operated unless the tumor was assessed to be definitely unresectable. Esophagectomy was possible in 55 patients, and the resectability rate was 95% after preoperative computed tomography and bronchoscopy became routine. After esophagectomy, no residual cancer lesion was recognizable macroscopically in 53% of patients. The hospital mortality rate in esophagectomy cases was 7% in the past 8 years. The outcome in patients who underwent curative resection was significantly favorable (p0.0001), and the 2-year survival was 51%. The patients with nonresectable cancer all died within 6 months compared with a 23% 1-year survival rate for palliative esophagectomy cases (p0.006). Among patients with tracheobronchial involvement assessed as resectable on computed tomography and bronchoscopy, a considerable proportion benefited from aggressive therapy with esophagectomy. The possibility of complete cure was high, especially when the cancer responded well to preoperative therapy and no lymph nodes were involved.

The most effective treatment would be neoadjuvant chemoradiotherapy (NACRT) plus surgery with three-field lymphadenectomy, if tolerability and complications are acceptable. The aim of this prospective study was to evaluate the tolerability of NACRT+ systematic three-field lymphadenectomy.A total of 127 cases of advanced esophageal carcinoma were objected, among which 32 had NACRT, being the cases suspected to cT3-T4 or,cT3 with multiple lymph node metastasis. ≥ T2 of 95 cases were treated by surgery alone (NACRT [-] case). The effect of NACRT was evaluated by histological examination and corrected with the clinicopathologic factors, including postoperative prognosis. After reports JCOG9907, we treated eight cases with neoadjuvant chemotherapy at stages II and III. We examined Musashi-1 staining for these eight cases.Histological good response to NACRT group showed good prognosis. Lymph node metastasis is a predictive factor for prognosis. In this additional study, Musashi-1 was positive after neoadjuvant chemotherapy in three cases. The histological response was grade 1 in all of them and recurrence was observed within a short period of time. Two cases of grade 3 were negative staining to Musashi-1 and showed no recurrence.This study shows that NACRT plus surgery with three-field lymphadenectomy is a feasible therapeutic approach for the cases with multiple lymph node metastases. Prognosis was significantly better in cases with marked histological improvement. It is important to find the predictive factors of histological improvement. Musashi-1 might be a candidate maker for histological response and prognosis, and further studies are needed to prove it.

To investigate genetic features of esophageal cancer, we have examined 93 squamous cell carcinomas of the esophagus for loss of heterozygosity (LOH), using 41 restriction fragment length polymorphism (RFLP) markers representing all autosomal chromosomes. Allelic losses at frequencies of at least 30% were observed at loci on chromosomal arms 3p (35%), 3q (30%), 5q (36%), 9p (57%), 9q (60%), 10p (33%), 13q (43%), 17p (62%), 17q (46%), 18q (38%), 19q (32%), and 21q (37%). These results suggest that several putative tumor suppressor genes, in addition to the cyclin D and TP53 genes that are sometimes mutated in esophageal carcinomas, may be associated with development and/or progression of esophageal cancer. By a comparison of LOH on each chromosomal arm with clinicopathological parameters, we have found a significant correlation between LOH on 19q and regional lymph node metastases. Interestingly, the frequency of LOH on 17q was significantly higher in tumors in female patients (12 of 14 cases) than in those in male patients (20 of 56 cases) (P = 0.0009 by Fisher's exact test). Furthermore, we examined for mutations of the APC gene on chromosome arm 5q. Screening of nearly one third of the APC coding region, including the MCR (mutation cluster region), revealed no alterations. Therefore, although allelic loss at the APC locus is frequent in squamous cell carcinomas of the esophagus, it is likely that a gene on 5q other than APC is involved in esophageal tumorigenesis. Genes Chromosom Cancer 10:177–182 (1994). © 1994 Wiley-Liss, Inc.

Pancreaticobiliary maljunction is frequently associated with biliary carcinoma, whether or not there is choledochal dilatation. In this anomalous condition, pancreatic juice regurgitates and the mixture of bile and pancreatic juice stagnates in the biliary tree. In cystic choledochal dilatation, cancers arise, mainly in the dilated bile ducts, while in patients not having cystic dilatation, tumors arise in the gallbladder. Gallbladder bile and/or bile duct bile from fifteen cases of pancreaticobiliary maljunction, including five cancer patients, was analysed biochemically and compared with control bile from 6 patients with a normal pancreaticobiliary junction. Bile levels of pancreatic enzymes were extremely high in the anomalous junction group. In the bile duct bile from patients with cystic choledochal dilatation with pancreaticobiliary maljunction, the concentrations of deoxycholic acid (DCA), lithocholic acid (LCA) and unconjugated bile acid fractions were increased regardless of the presence of cancer. Increases of these bile acid fractions, which are known to have a cancer-promoting effect, were also seen in gallbladder bile from the cancer patients without cystic dilatation.

It is widely accepted that congenital choledochal cyst is associated with pancreaticobiliary maljunction (PBM). But, PBM is an independent disease entity from choledochal cyst. PBM is synonymous with “abnormal junction of the pancreaticobiliary ductal system”, “anomalous arrangement of pancreaticobiliary ducts”, “anomalous union of bilio-pancreatic ducts”, etc. Cases with PBM not associated with biliary duct dilatation are often found, and these cases are frequently complicated gallbladder cancer. The Japanese Study Group of Pancreaticobiliary Maljunction was started in 1983, and defined diagnostic criteria and nationwide registration system of PBM cases was started. PBM is defined as a union of the pancreatic and biliary ducts which is located outside the duodenal wall. Bile and pancreatic juice reflux and regurgitate mutually. The most bothersome problem is biliary carcinogenesis. Gallbladder cancers arise in 14.8% and bile duct cancers arise in 4.9%. The incidence of the gallbladder carcinoma of PBM without bile duct dilatation is 36.1%. Many investigators have tried to clarify the carcinogenic process, from various aspects. The biliary epithelia are injured by harmful substances, and in the course of repair, multiple alterations of oncogenes and tumor suppressor genes are followed, and they lead to carcinoma through multistage interaction. In the biliary epithelia of PBM, incidence and degree of hyperplasia are characteristic. K-ras gene mutations are observed in the cancerous as well as noncancerous lesions of biliary tract of PBM patients. Mutations of p53 gene and overexpression of p53 protein are also found in the cancerous and noncancerous lesions. These changes are called “hyperplasia–carcinoma sequence”. Total excision of the extrahepatic bile duct with gallbladder followed by hepaticojejunostomy, Roux-en-Y, or end-to-side hepaticoduodenostomy are treatment of choice, even for cases with not dilated bile duct, because the incidence of cancer in the nondilated bile duct is not negligible, and genetic changes are seen in a nondilated bile duct.

A case of intraductal papillary mucinous tumor of the pancreas with complete absence of the ventral pancreatic duct of Wirsung is presented. A 74-year-old Japanese man was admitted to our hospital because of elevated serum amylase concentration. Abdominal computed tomography (CT) scanning revealed diffuse dilatation of the main pancreatic duct and a diffuse and uncircumscribed area with heterogeneous density in the pancreas head. Endoscopic retrograde cholangiopancreatography revealed that the main pancreatic duct was connected with an accessory papilla and was diffusely dilated, without any irregularity of the duct wall being observed in the entire length of the duct. The common bile duct was detected only by cannulation through Vater's papilla, and no pancreatic duct or its communicating branch was found. Some branches, directed to the dorsal portion of the pancreas head, were found arising from the accessory pancreatic duct. Intraductal ultrasound examination performed through the accessory papilla and the common bile duct revealed a small tumor with a heterogeneous echo level in the pancreas head. From these findings, intraductal papillary-mucinous tumor (IPMT) occurring in the pancreas head was diagnosed, and pylorus-preserving pancreaticoduodenectomy was performed. The resected specimen revealed IPMT in the pancreas head. A roentgenographic study of the resected specimen revealed a defect caused by the tumor located in the pancreatic duct connected with the accessory papilla and showed that there was complete absence of the pancreatic duct connected with Vater's papilla. Surgical resection enabled us to completely analyze the duct system of pancreas divisum. Although it is not known whether there is a relationship between the pathogenesis of IPMT and embryological anomaly of the pancreatic duct system, this case may provide an insight into the pathogenesis of IPMT.

A 92-year-old man was admitted to the hospital for rehabilitation. Upper gastrointestinal endoscopy was performed 2 weeks after admission because of vomiting which was found to be due to a Barrett's esophageal carcinoma at the lower esophagus. We chose chemotherapy with TS-1 at the dose of 50 mg/day in consideration of his age and performance status. His difficulty in swallowing disappeared rapidly. After 7 days of treatment, grade 3 anorexia appeared, so the dosage of TS-1 was reduced to 25 mg/day. After the reduction of TS-1, anorexia soon disappeared. The regimen consisted of TS-1 every 6 weeks as 1 cycle. After 7 cycles of treatment, upper gastrointestinal endoscopy and upper gastrointestinal series revealed that the tumor had a completely disappeared. The effects of chemotherapy were judged as CR. This case suggests that administration of TS-1 is an effective choice of chemotherapy not only for gastric carcinoma but also Barrett's esophageal carcinoma.

Purpose: To assess the risk of subsequent malignancies after esophagectomy for squamous cell carcinoma of the thoracic esophagus for the establishment of an adequate follow-up program. Patients and Methods: We statistically analyzed clinical factors in 114 cases of second malignancy after esophagectomy that developed in 94 of 679 patients who underwent curative resection. The cancer incidence rates in the general population estimated by the Research Group for Population-Based Cancer Registration in Japan were used as standards for comparison. Results: The 10-year cumulative risk of second malignancy was 34.5%, and the overall relative risk (RR) was 2.98 (95% CI, 2.41 to 3.65). The risk of head and neck cancer was markedly elevated (RR, 34.9; 95% CI, 24.3 to 48.6), followed by the risks of lung cancer (RR, 3.24; 95% CI, 1.89 to 5.19) and stomach cancer (RR, 2.00; 95% CI, 1.17 to 3.21). Multifactor analysis demonstrated that independent factors affecting the risk of subsequent malignancies were presence of other malignancies detected before esophagectomy and any of the following factors: masculine sex, alcohol consumption, and smoking. The 5-year survival rate after detection of subsequent malignancy was 45%. The outcome in patients with subsequent head and neck cancer was significantly less favorable as a result of difficulty in early detection. Conclusion: Patients had a remarkably high risk of subsequent cancer of the upper aerodigestive tract after esophagectomy, in particular, head and neck cancer. Minute postoperative surveillance is strongly recommended, especially in patients with a history of malignancies before esophagectomy. Early detection of second malignancies allowed less invasive treatment with favorable outcome.

Although duodenal diverticulum is not uncommon, precise preoperative diagnosis is occasionally difficult. We report a patient with perforated duodenal diverticulum successfully diagnosed preoperatively by an upper gastrointestinal series followed by abdominal computed tomography (CT) scanning. An 81-year-old Japanese woman visited a local hospital because of right-sided abdominal pain. Physical examination revealed diffuse muscle guarding localized in the entire right-side of the abdomen indicative of peritonitis. While plain abdominal X-ray film revealed no free air, abdominal ultrasound and abdominal CT scanning revealed fluid collection and gas in the anterior perirenal space. An emergency upper gastrointestinal series, using water-soluble contrast media, demonstrated multiple diverticula in the descending portion and the horizontal portion of the duodenum. Leakage of the contrast material was found by the upper gastrointestinal series followed by the abdominal CT scanning, suggesting that the peritonitis was caused by the perforated duodenal diverticulum, and an emergency laparotomy was performed. The diverticulum in the descending portion of the duodenum was mobilized from the retroperitoneum and complete resection and peritoneal drainage were performed. The resected specimen showed that the diverticulum was 42 × 23 mm in size, and two separate sites of perforation were identified. The present case suggests that upper gastrointestinal series followed by CT scan is useful for the preoperative diagnosis of perforated duodenal diverticulum.

A 71-year-old man with nausea and epigastralgia was referred to our hospital and was diagnosed with type 3 gastric cancer. Palliative resection was performed since radical surgery was impossible due to massive tumorous invasion to the retroperitoneum. Chemotherapy with TS-1 100 mg p.o. was started for the residual cancer lesions, with CDDP i.v. 50 mg added from the 3rd course. We did not find any remarkable side effects except for grade 1 loss of appetite. This chemotherapy was ended after the eighth course. The residual tumor did not disappear but did not grow, and a no change status was maintained for twelve months after the gastrectomy.

A 60-year-old female had undergone laparoscopic oophorectomy for right ovarian tumor. At the time of surgery, peritoneal dissemination and ascites was observed. Histological examination revealed that the resected ovary, peritoneal nodes and floating cells in the ascites were metastatic adenocarcinomas. Later, the primary malignant lesion was found to be a type 4 gastric carcinoma. The carcinoma was judged to be unresectable and treated by combination chemotherapy with TS-1 and CDDP every 6 weeks. After 3 courses of treatments, upper gastrointestinal series and endoscopic examinations were conducted and revealed a marked reduction of the tumor size. No carcinoma cells were detected by endoscopic biopsy. CT-scan showed complete disappearance of metastatic lesions. Staging laparoscopy was performed for evaluation of the effects of chemotherapy, and no adenocarcinoma cells at peritoneal nodes or ascites were found histologically. We performed total-gasterectomy with D1 + alpha lymph node dissection. Histopathologically, resected specimens showed severe fibrosis in most parts of the stomach. Following chemotherapy, the carcinoma was judged to be Grade 2 by histopathological examination.

We report a patient with a minute gastric carcinoid tumor with lymph node metastasis, and a small gastric cancer. A 50-year-old man having a diagnosis of an elevated lesion on the anterior wall of the gastric body, detected by a series of upper gastrointestinal examinations, was referred to the Cancer Institute Hospital. Careful upper fluoroscopy disclosed a small superficial depressed lesion with converging folds and a superficial elevated lesion covered with nonspecific gastric mucosa. With a final preoperative diagnosis of depressed early cancer and minute carcinoid tumor of the stomach, made by upper gastrointestinal examinations including biopsy, the patient underwent segmental gastrectomy and perigastric lymph node dissection. Histological examination of the resected specimen revealed a lymph node metastasis from a gastric carcinoid tumor of 5-mm diameter, in addition to an early gastric cancer of poorly differentiated adenocarcinoma. Small gastric carcinoid tumors have been regarded as being benign neoplasms biologically. However, the case we present suggests that attention should be paid to the possibility of metastasis at the time of treatment for a minute sporadic gastric carcinoid tumor. We therefore discuss the malignant potential of these tumors, mainly from the viewpoint of histopathological classification, to gain understanding so that the patients can be treated adequately.

A 57-year-old man, who had undergone subtotal esophagectomy and bowel reconstruction with a stomach roll located in the retrosternal space 4 years before, developed pneumopericardium (Fig. 1) due to ulcer perforation (Fig. 2). He is alive and well 8 years after partial gastrectomy and pericardial drainage followed by pericardiectomy for secondary constrictive pericarditis. European Journal of Cardio-thoracic Surgery 22 (2002) 1007

Although allergic granulomatous angiitis (AGA) is occasionally associated with gastrointestinal lesions, multiple perforated ulcers of the gastrointestinal tract are uncommon. We report herein a case of AGA associated with multiple perforated ulcers that erupted in the small intestine during corticosteroid therapy. A 31-year-old Japanese man was admitted to our hospital with epigastralgia, edema of the bilateral lower extremities, and general malaise. He had a persistent high fever, abdominal pain, and watery diarrhea. Laboratory data showed remarkable eosinophilia. The abdominal pain became exacerbated after the administration of oral prednisolone. Physical examination indicated positive signs of peritoneal irritation in the entire abdomen, and abdominal computed tomography scanning showed intra-abdominal free air, suggesting generalized peritonitis due to intestinal perforation. Laparotomy revealed multiple perforated ulcers in the jejunum and ileum. Histological examination indicated remarkable eosinophilic infiltration in the surrounding area of the small arteries and arterioles located in the submucosal layer, which was compatible with AGA. Although the association of intestinal perforation with AGA is relatively infrequent, intensive perioperative management is essential to ensure a favorable clinical outcome, particularly during the period on corticosteroid therapy.

While the liver and lung are primary targets for distant metastasis from colorectal carcinoma, metastasis in other distant sites is rarely found. We report herein an unusual case of metastasis to the skeletal muscle of the right forearm from an adenocarcinoma of the transverse colon. A 60-year-old man was originally admitted to our hospital for surgical treatment of an intestinal obstruction caused by a transverse colon carcinoma. Transverse colon resection along with lymph node dissection was performed and no evidence of distant metastatic foci was found. Angiography-enhanced computed tomography scanning done 14 months after the first operation revealed multiple hepatic metastases which were resected. A metastasis was subsequently detected in the right extensor carpi ulnaris muscle 2 years after the primary resection, and a major part of the right extensor carpi ulnaris and the extensor digiti minimi muscle were resected, warranting a sufficient margin of 5 cm of normal tissue from the tumor. Reattachment of the residual muscles into the ulna was performed. Metastases to bone and/or soft tissues from colorectal carcinomas are extremely rare and to our knowledge, only eight other cases have been reported in the world literature. This low incidence may be related to the anatomical characteristics and/or the biochemical environment of the skeletal muscle, but it is also possible that the true incidence is underestimated. Recent improvements in interventional radiological procedures may facilitate a diagnosis of skeletal muscle metastasis being made more frequently.

BACKGROUND Most surgeons consider esophageal carcinoma with lymph node involvement a systemic disease. However, it is possible that the disease may be localized in the earlier phases of lymphatic metastasis. The distribution of involved lesions in the initial phase of lymph node metastasis has not been thoroughly investigated yet. METHODS Among 329 patients that underwent curative (R0 International Union Against Cancer [UICC]) esophagectomy with systematic mesoesophageal dissection, 51 cases of patients with only 1 involved lymph node (solitary involvement) were retrospectively investigated and compared with patients with multiple involved lymph nodes. The regional lymph nodes were divided into the thoracocervical junction group (lower deep cervical and recurrent nerve lymph nodes), perigastric group, and intrathoracic group. RESULTS Lymph node involvement was limited to a solitary lymph node in 46% of lymph node positive patients with esophageal carcinoma confined to the wall (T1 and T2, UICC) and in 17% of lymph node positive patients with cancer that invaded the extramural layer (T3 and T4, UICC). Of patients with solitary involvement, 82% had a positive thoracocervical junction or perigastric lymph node. The 5-year survival rate in solitary involvement cases was 61%, and 65% when solitary involvement was not intrathoracic. Most of the 5-year survivors had involvement of a thoracocervical junction or perigastric lymph node and had not received systemic chemotherapy. CONCLUSIONS Solitary involvement was not rare and not directly associated with a disseminated disease. Solitary involvement was commonly located in the thoracocervical junction or abdomen that are accessible without thoracotomy. Systematic dissection of the regional lymph nodes including thoracocervical junction and perigastric groups is recommended for resectable esophageal carcinoma at this time. However, less extensive dissection may be performed in selected cases if the sentinel lymph node concept proves valid. Cancer 2000;89:1869–73. © 2000 American Cancer Society.

Ultrasonically activated coagulating shears (CS) can coagulate and divide blood vessels of up to medium size by a tissue-welding technique. We present an application of CS in hepatic parenchymal transection during liver surgery. Intrahepatic vessels are uncovered by the so-called forceps fracture method, and they are coagulated and divided by CS. Larger vessels are tied only on the preserving side before the application of CS. Although further refinement of the CS tip is needed, this method has the potential to significantly simplify and improve surgical procedures for hepatic parenchymal transection.

Angiomyomatous hamartoma is a rare disease with a predisposition for the inguinal lymph nodes. A 51-year-old male patient visited a local hospital because of a right inguinal mass, measuring 3 x 4 cm in size, which was resected. The resected specimen showed irregularly distributed thick-walled vessels in the hilum, extending into the medulla and focally into the cortex of the node, eventually becoming more dispersed and associated with smooth muscle cells splaying into sclerotic stroma. These findings are compatible with an angiomyomatous hamartoma. Another tumor-like mass appeared shortly after the resection at the same location, but was not an angiomyomatous hamartoma, rather it was composed of edematous stromal tissue with proliferating smooth muscle cells. The stromal component included thick-walled blood vessels and lymphatics. Although it could not be determined whether these associated changes in the surrounding stroma are a cause or an effect of angiomyomatous hamartoma, they indicate the clinical difficulty in determining an appropriate area of resection and may provide clues to the pathogenesis of angiomyomatous hamartoma.

PURPOSE: Lymph node metastasis in the hepatoduodenal ligament is known as one of the most significant prognostic factors after liver resection for colorectal metastasis. However, there have been very few articles on the clinical features of node-positive patients and on detailed distribution of positive nodes. Further, there has been no established strategy on how to handle hepatic lymph nodes during liver resection. To address these subjects, a retrospective study was conducted. METHODS: During the period of 1980 through April 1998, 182 hepatic resections were performed for metastatic colorectal carcinoma. Of these, 78 cases had hepatic lymph node sampling during the operation. Distribution of positive nodes, location of liver metastasis, stage of the primary lesion, and outcome after liver resection were analyzed. RESULTS: Nine cases (12 percent) had secondary lymph node metastases in the hepatoduodenal ligament. The incidence was slightly higher (13.5 percent) in the most recent 44 consecutive cases. There was a tendency for liver metastases in the right lobe to metastasize to No. 12b (or node of the foramen of Winslow, lymph nodes along the common bile duct) and liver metastases in the left lobe to metastasize to No. 8a (anterosuperior group of the lymph nodes along the common hepatic artery). Outcome of node-positive patients (n=9) was extremely poor (P

To investigate the molecular mechanisms of the high incidence of carcinogenesis in the biliary epithelium of patients with pancreaticobiliary maljunction, we examined p53 gene mutations, loss of heterozygosity of p53, and overexpression of p53 gene product in the cancerous and noncancerous biliary epithelium of 27 patients with pancreaticobiliary maljunction. Mutations of the p53 gene were examined by polymerase chain reaction-single strand conformation polymorphism and a direct sequencing method. Loss of heterozygosity of the p53 gene was determined using a double-targeted fluorescence in situ hybridization method. Expression of p53 gene product was examined using immunohistochemical staining. Mutations of the p53 gene were found in 4 of 5 biliary carcinomas (80%) and in 10 of 26 noncancerous biliary lesions (38.5%). Point mutations of the p53 gene were detected at codons 207, 212, and 217 on exons 5 through 8. The incidence of p53 gene mutations on exons 5, 6, 7, and 8 was 12. 9%, 36.4%, 0.0%, and 13.8%, respectively. Loss of heterozygosity of p53 was shown in 72% of the cells obtained from the cancerous lesion, and in an average of 14% obtained from the noncancerous lesions. Overexpression of p53 protein was found in 57.1% of carcinoma, and in 31.3% of the noncancerous lesions. These results suggest that p53 gene mutations are involved in the carcinogenesis of biliary epithelium in patients with pancreaticobiliary maljunction.

An aortogastric fistula is a rare but fatal complication after an esophagectomy and intrathoracic esophagogastric anastomosis. A 54-year-old man underwent an esophageal resection due to carcinoma in his lower esophagus. The alimentary tract continuity was restored by intrathoracic esophagogastric anastomosis. Forty-six days later, he suffered a massive hematemesis due to an aortogastric fistula which had formed at the esophagogastric suture line. The fistula was surgically obliterated twice, but each operation was followed by pseudoaneurysm formation. The patient was finally successfully treated with an endovascular stent graft placement. This is the first report of a patient surviving after developing this complication.

Although the survival benefit of hepatic resection for colorectal metastasis has been established, some controversy remains regarding the significance of adjuvant chemotherapy after hepatic resection.One hundred thirty-two consecutive patients who had liver resection for colorectal metastasis at our hospital between 1980 and 1997 were studied. After curative hepatic resection, 37 patients underwent systemic chemotherapy, administered orally or intravenously, and 38 patients underwent regional chemotherapy, given intra-arterially or intraportally. Forty patients had no adjuvant chemotherapy. The chemotherapeutic agents used for oral administration were uracil and Tegafur or Tegafur alone. Mitomycin C (MMC) or 5-FU was used for IV chemotherapy. Combinations of 5-FU/leucovorin or MMC/5-FU (doxorubicin) were used for regional chemotherapy. Univariate and multivariate analyses were applied to test the significance of adjuvant chemotherapy for patient survival or disease-free survival.Overall 5-year survival was 42.2% (95% CL: 31.2%, 53.2%). Among the possible prognostic factors studied, univariate analysis showed a significant difference in survival based on the number of tumors and lymph node metastases in the hepatic hilum. There was a significant difference in disease-free survival based on adjuvant chemotherapy and lymph node metastasis. The multivariate analysis for patient survival selected four prognostic factors (P.05), including adjuvant chemotherapy, lymph node metastasis, disease-free interval, and tumor size. The multivariate analysis for disease-free survival selected adjuvant chemotherapy, lymph node metastasis, and disease-free interval as significant factors. The most common recurrence site was remnant liver, regardless of adjuvant chemotherapy.Adjuvant chemotherapy significantly improved survival and disease-free survival after hepatic resection for colorectal metastases. It did not decrease recurrence rate in the remnant liver.

Background: The clinical significance of lymph node involvement along the recurrent laryngeal nerves in cancer of the thoracic esophagus is still controversial. Although these lymph nodes are anatomically located in a well-defined compartment (proximal mesoesophagus), appropriate procedures for dissecting them are not well established. Study Design: We retrospectively investigated clinical results over the past 10 years in 276 patients who underwent systematic dissection of cervical, mediastinal, and upper abdominal lymph nodes. We routinely performed the cervical procedure before thoracotomy for total dissection of the proximal mesoesophagus and to minimize the operative risk. Results: All macroscopically recognizable lesions were resected in 94% of the patients. The hospital mortality rate was 2.5%. Recurrent nerve palsy developed in 59 patients, but it was successfully managed without prolonged hoarseness in 50 of them. The recurrent nerve node group was most frequently involved (frequency of 25% in superficial cancer, 57% in non-superficial cancer). Supradiaphragmatic lymph node involvement was limited to the recurrent nerve nodes in 25% of the patients with positive supradiaphragmatic node. The 5-year survival rate in patients with positive recurrent nerve nodes was 34%. Conclusions: Dissection of the recurrent nerve lymph nodes is essential for curative esophagectomy even in the early phase of cancer invasion. Our cervicothoracic approach for total dissection of the proximal mesoesophagus yielded acceptable outcomes.

It is well known that the frequency of an associated gallbladder cancer in patients with pancreaticobiliary maljunction (PBM) without congenital choledochal dilation (CCD) is very high, while that of bile duct cancer with CCD is remarkably high, and that of bile duct malignancy without CCD is low. However, recent statistical evaluations have demonstrated that the coincidence rates of gallbladder and bile duct cancer with CCD are 11.5% and 4.6%, respectively, whereas without CCD the rates are 57.1% and 4.1%, respectively. Rates of bile duct cancer with CCD are comparable to those without CCD. We have performed biliary reconstruction after resection of extrahepatic bile ducts along with the gallbladder for PBM patients who had neither CCD nor cancer. Our surgical strategy for these patients without CCD with PBM was assessed from K-ras point mutations and overexpression of p53 protein in the epithelia of the cancerous portions and non-neoplastic portions of the gallbladder and bile duct affected by PBM regardless of choledochal dilatation. The mutation rate in the non-neoplastic gallbladder epithelium without CCD was 80%, that of the bile duct without CCD 57%, not significantly different from the 50% and 40%, respectively, with CCD. The frequency of p53 overexpression in the non-neoplastic bile duct epithelium without CCD was 14%, comparable to the 11% in gallbladder epithelium with CCD. Judging from the statistical data and the molecular biological data, resection of an extrahepatic bile duct with the gallbladder should be the treatment of choice for carcinogenesis prevention.

A 65-year-old woman was admitted to our hospital with the diagnosis of gallbladder tumor. Right extended hepatic lobectomy plus lymph node dissection of the hepatoduodenal ligament and left hepaticojejunostomy with Roux-en-Y reconstruction was performed in July, 1993. The gallbladder tumor was histologically proven to be squamous cell carcinoma. Seventeen months later, the patient experienced dyspnea and pitting edema of the lower legs and was admitted, in December 1994, with a diagnosis of heart failure. Despite intensive cardiac support, she died 12 days after the second admission. Autopsy revealed multiple cardiac tumors in the left and right ventricles, left atrium, left coronary artery, and left diaphragm. Histologically, these tumors were shown to be squamous cell carcinoma, considered to have metastasized from the primary gallbladder carcinoma. As neither local recurrence of the gallbladder carcinoma. As neither local recurrence of the gallbladder carcinoma nor any lymph node metastasis was found, the cardiac metastasis of the gallbladder carcinoma may have occurred via the hematogenous route. Although rare, this route of cardiac metastasis of gallbladder carcinoma may be an important aspect of distant metastasis, which should be monitored for during follow-up after resection of the primary tumor.

Background: Pulmonary complications have been a major cause of mortality after operations for cancer of the thoracic esophagus. Although the risk involved in esophagectomy associated with a major pulmonary operation is expected to be high, it has seldom been evaluated on the basis of clinical experience. Study Design: Of 408 patients who underwent esophagectomy, 8 had previously undergone major pulmonary operation (7 for tuberculosis and 1 for pulmonary cancer) and 10 underwent concurrent major pulmonary resection (7 for pulmonary invasion of esophageal cancer, 2 for synchronous pulmonary cancer, 1 for extensive bronchiectasia). All patients underwent systematic lymph node dissection for esophageal cancer, except one patient with mucosal cancer. To prevent postoperative complications, the operative approach and dissection procedures for esophageal cancer were modified according to the associated pulmonary operation and the extent of cancer invasion. All thoracotomies for esophagectomy were performed on the same side as the major pulmonary operation. Additional median sternotomy was performed when necessary. In the most recent 8 patients who underwent major pulmonary resection concurrent with esophagectomy, the bronchial stump was covered with a pedicle flap. Results: Of the 18 patients who underwent pulmonary operation, postoperative complications developed in 13 of the 18 object patients, but none was fatal. The 3-year survival rate was 45%. All deaths were caused by esophageal cancer or another cancer. Conclusions: Aggressive esophagectomy associated with major pulmonary operation is not contraindicated in patients with fair risk conditions. The operative procedures for esophagectomy should be appropriately modified to minimize the effect of the associated pulmonary operation. Special care should be taken with respect to the approach for mediastinal dissection and closure of the bronchial stump.

Background. Primary esophageal cancer developing after hypopharyngeal or laryngeal cancer is increasing in frequency, but operative treatment of such cases is not well established. The proximity of both cancers could produce interactive influence on surgical procedures and risk factors. There have been few reports focusing on surgical strategy for such cases. Methods. We retrospectively investigated the most recent series of 18 patients who had previously undergone pharyngolaryngectomy for cancer and subsequently underwent esophagectomy for second primary cancer of the esophagus. At esophagectomy special care was taken to preserve the tracheal vascularity and to select adequate procedures for lymph node dissection and bowel reconstruction. Results. Curative resection as confirmed macroscopically was achieved in all cases except one. Lymph node involvement was found in half of the patients. No major postoperative complication was observed except for partial necrosis of the trachea in two cases that were conservatively treated. No patient died during hospitalization. The 3-year survival rate was 64% overall and 55% in cases with lymph node involvement. Conclusions. Although increased operative risk was expected in esophagectomy after pharyngolaryngectomy, our operative results were acceptable. Most risk factors were controllable by selecting appropriate operation procedures. In patients with technically resectable cancer, esophagectomy with systematic lymph node dissection is recommended as in ordinary esophageal cancer.

BACKGROUND. Pancreaticobiliary maljunction (PBM), an anomalous union of the pancreatic duct with the common bile duct, has frequently been shown to be associated with biliary carcinoma. However, the mechanism of carcinogenesis is unknown. METHODS. Mutations of the K-ras oncogene were examined in cancerous and noncancerous biliary tract epithelium of 20 patients with PBM by an extraction of DNA from surgically resected histologic specimens. DNA was analyzed by a polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) method and direct sequencing. RESULTS. An abnormally mobilized DNA band was detected not only in cancerous epitlielium but also in hyperplastic, metaplastic, and inflammatory epithelium of the gallbladder and/or common bile duct in patients with PBM. Among the biliary epithelium of patients with PBM, point mutation of K-ras oncogenes were detected in 4 of 5 (80%) cancerous epithelium, 7 of 12 (58%) hyperplastic and metaplastic epithelium, and 8 of 18 (44%) inflammatory epithelium, whereas no point mutation of the K-ras oncogene was detected in the gallbladder epithelium in 3 control patients without PBM. Direct sequence analysis of the K-ras oncogene revealed the mutation at codon 12 substituting the wild-type glycine (GGT) for aspartic acid (GAT) in all cancerous lesions of patients with PBM. Simultaneous two-point mutations from the wild-type glycine (GGC) to arginine (CGC) at codon 13 associated with the mutation at codon 12 were also found in one case of gallbladder carcinoma and one case of bile duct carcinoma. CONCLUSIONS. K-ras gene mutation is involved in the carcinogenesis of biliary tract epithelium in patients with PBM, and appears to be a high risk factor for carcinogenesis of the biliary tract.