Disparate E-cadherin mutations in LCIS and associated invasive breast carcinomas.

AIMS: The relation between lobular carcinoma in situ (LCIS) and invasive breast cancer is unresolved. In an attempt to establish whether LCIS is a precursor of invasive cancer the mutational status and the expression of E-cadherin was analysed in LCIS and associated invasive breast carcinoma in 23 patients. METHODS: Foci of LCIS and associated invasive carcinoma were individually microdissected from tissue from 23 patients. Exons 4-16 of the E-cadherin gene were analysed using single strand conformation polymorphism (SSCP); protein expression and the localisation of E-cadherin and beta-catenin were assessed with the use of immunohistochemistry. RESULTS: Immunohistochemistry revealed a lack of expression of E-cadherin and beta-catenin in most LCIS samples and invasive foci. In all but four cases, the staining pattern was identical in the LCIS and associated invasive areas. When E-cadherin was absent, beta-catenin was also undetected, suggesting a lack of expression of alternative classic cadherin members in these lesions. Coincident E-cadherin mutations in LCIS and associated invasive carcinoma were not identified in this series of patients. However, mutational analysis of E-cadherin in multiple foci of carcinoma in situ surrounding an invasive lesion provided evidence to support ductal carcinoma in situ as a precursor of invasive ductal carcinoma. CONCLUSION: These data support the hypothesis that LCIS is not a precursor of invasive breast carcinoma but a marker of increased risk of developing invasive disease.

Expression of classic cadherins type I in urothelial neoplastic progression.

Loss or reduced expression of E-cadherin has been shown to be associated with poor survival in patients with bladder cancer. In numerous cases, loss of E-cadherin expression in bladder tumors has been accompanied by continued association of catenins with the membrane, suggestive of the expression of an alternative cadherin member. In this study we examined 75 bladder tumors using immunohistochemistry for the expression of E-, P-cadherin, and alpha-, beta-, and gamma-catenins. As reported previously, loss or reduced E-cadherin expression is a frequent event in late stage bladder cancer, accompanied by less frequent alterations associated with different catenin family members. Analysis of 51 tumors for expression of E-, P-, and N-cadherin showed P-cadherin localized to the basal cell layers of normal urothelium, with retention of expression in the majority of tumors. In low-grade tumors P-cadherin was found localized to an expanded basal cell compartment, contrasting with the more extensive staining observed in late stage tumors. Membranous P-cadherin staining was often found in the absence of E-cadherin staining. N-cadherin is not expressed in normal bladder mucosa, but detection of this cadherin member was recorded in 39% (20/51) of bladder tumors. Unlike P-cadherin, membranous N-cadherin was detected in focal regions within tumors, representing novel expression in urothelial neoplastic progression. Although focal N-cadherin staining was observed in 3 noninvasive lesions, the majority of tumors expressing N-cadherin were invasive (17/20). Coexpression of E-, P-, and N-cadherin was recorded in 5 grade 2 bladder tumors. Expression of P-cadherin is maintained throughout bladder tumorigenesis, accompanied by aberrant expression of N-cadherin. Clearly, neither P- nor N-cadherin act in an invasive-suppressor mode in bladder cancer, but whether they have a primary role to play in urothelial neoplastic progression has yet to be established.

Management of hilar cholangiocarcinoma: comparison of an American and a Japanese experience.

OBJECTIVE: To compare the experience and outcome in the management of hilar cholangiocarcinoma at one American and one Japanese medical center. SUMMARY BACKGROUND DATA: Controversies surround the issues of extent of resection for hilar cholangiocarcinoma and whether the histopathology of such cancers are similar between patients treated in America and in Japan. METHODS: Records were reviewed of 100 patients treated between 1980 and 1995 at the Lahey Clinic in the United States, and of 155 patients treated between 1977 and 1995 at Nagoya University Hospital in Japan. Selected pathologic slides of resected cancers were exchanged between the two institutions and reviewed for diagnostic concordance. RESULTS: In the Lahey cohort, there were 25 resections, 53 cases of surgical exploration with biliary bypass or intubation, and 22 cases of percutaneous transhepatic biliary drainage or endoscopic biliary drainage without surgery. In the Nagoya cohort, the respective figures were 122, 10, and 23. The overall 5-year survival rate of all patients treated (surgical and nonsurgical) during the study periods was 7% in the Lahey cohort and 16% in the Nagoya cohort. The overall 10-year survival rates were 0% and 12%, respectively. In patients who underwent resection with negative margins, the 5- and 10-year survival rates were 43% and 0% for the Lahey cohort and 25% and 18% for the Nagoya cohort. The surgical death rate for patients undergoing resection was 4% for Lahey patients and 8% for Nagoya patients. Of the patients who underwent resection, en bloc caudate lobectomy was performed in 8% of the Lahey patients and 89% of the Nagoya patients. Histopathologic examination of resected cancers showed that the Nagoya patients had a higher stage of disease than the Lahey patients. CONCLUSIONS: In both Lahey and Nagoya patients, survival was most favorable when resection of hilar cholangiocarcinoma was accomplished with margin-negative resections. Combined bile duct and liver resection with caudate lobectomy contributed to a higher margin-negative resection rate in the Nagoya cohort.

Historical perspectives of biliary tract injuries.

The development of repair of biliary tract operative injuries proceeded in tandem with the advancement of abdominal surgery in the late nineteenth and early twentieth centuries. The important auxiliary role of stents, imaging, and hilar dissection, and the recognition of the common duct arterial supply are related to technical advances. The place of percutaneous or endoscopic dilation is being established in the 1990s.

Surgery for sclerosing cholangitis.

The diagnosis of primary sclerosing cholangitis is made radiologically in patients with extrahepatic obstructive jaundice. This condition lacks a known cause and another method of diagnosis, and its treatment is palliative-mechanical, with bypasses, dilation, or orthotopic liver transplantation. Recent progress has been seen in stratifying patients with respect to prognosis. Stratification is important for conducting clinical trials and for predicting which patients should receive a transplant at an earlier, less risky stage in the course of the disease. Expandable metal stents are on trial in patients with benign or malignant strictures. These newer stents seem to be better than polyethylene stents, although their use has not been reported in sclerosing cholangitis. With survival data used as a measuring point, relief of jaundice does not appear to correlate with increased survival. Of concern has been the association of cholangiocarcinoma with sclerosing cholangitis. Cholangiocarcinoma is difficult to recognize clinically and has a negative impact on the results of transplantation.

Hepatoma registry of the Western world. Repeat Hepatic Resection Registry.

The western HCC registry comprised data from 322 patients who underwent hepatic resection for HCC over a 50-year period. The majority of patients had lesions > 4 cm and were symptomatic at presentation. Lesions were mostly unicentric. Cirrhosis was not a prevalent problem, unlike the East. In the most recent decade, 1980-1989, we noted a significant decrease in operative mortality from 19% to 10% overall, and 15% to 4% in the noncirrhotic group. We identified four variables that resulted in poorer postresectional outcome: cirrhosis, regional nodal disease, multicentric disease, and tumor-free resectional margin < 1 cm. Although these factors are associated with a poorer outcome after resection, whether they should serve as contraindications to surgery should be determined by individual surgeons, taking into account the patient's overall status, concomitant risk factors, and treatment objectives.

Laparoscopic bile duct injuries. Risk factors, recognition, and repair.

Records of 11 patients undergoing biliary reconstruction after laparoscopic cholecystectomy are reviewed. Ductal injuries resulted from failure to define the anatomy of Calot's triangle. Risk factors include scarring, acute cholecystitis, and obesity. Presenting findings included anorexia, ileus, failure to thrive, pain, ascites, and jaundice. All patients required hepaticojejunostomies, which were multiple and above the hepatic bifurcation in four patients. Given the extensive nature of these injuries and the frequent need for intrahepatic anastomosis and early stenosis of repairs by referring physicians, we recommend reconstruction be undertaken by an experienced hepatobiliary surgeon. To avoid injuries, a greater appreciation of risk factors and anatomic distortion and variance and strict adherence to principles of dissection and identification of anatomic structures are suggested. The use of cholangiography and a low threshold for conversion to the open procedure are advised.

Primary adenocarcinoma of third and fourth portions of duodenum. Favorable prognosis after resection.

Duodenal adenocarcinoma, a rare malignant lesion, is associated with a poor 5-year survival. Few series have addressed differences between resectable tumors of the proximal and distal duodenum. We reviewed records of 17 consecutive patients with adenocarcinoma of the duodenum who underwent resection: 10 had adenocarcinoma of the proximal duodenum, and seven had tumors of the distal duodenum. Most patients underwent pancreatoduodenectomy. Five patients with adenocarcinoma of the distal duodenum underwent segmental resection. No perioperative deaths occurred. Six of 10 patients with proximal tumors died of metastatic disease. Of the seven patients with tumors of the distal duodenum, five are alive without evidence of disease, and two died of unrelated causes. The survival of patients with adenocarcinoma of the distal duodenum is surprisingly good, and segmental resection is the procedure of choice.

Primary sclerosing cholangitis.

Primary sclerosing cholangitis is a condition of unknown cause. It is recognized by liver dysfunction and its characteristic radiologic appearance, which is related to portal tract inflammation, bile duct proliferation, and periductal fibroses involving small intrahepatic and large extrahepatic ducts. The disease lasts about 10 years from the time of diagnosis. Primary sclerosing cholangitis is recognized by abnormal results on routine liver function tests or by the development of clinical jaundice. An autoimmune cause has been suggested because of its strong association with inflammatory bowel disease, certain antigens, AIDS, and immunoregulatory abnormalities. Results of medical management of sclerosing cholangitis have been disappointing. Immunosuppressive drugs, copper chelating agents, and antibiotics have failed to alter progression of the disease. Colectomy in patients with inflammatory bowel disease also has no influence. The judicious use of dilations of strictures, bypass procedures, or resection can palliate jaundice in patients with primary sclerosing cholangitis, but liver transplantation is the definitive treatment. Because palliative operations increase the hazards of liver transplantation, percutaneous dilations and stentings are preferred initially. Cirrhosis and portal hypertension are indications for transplantation. In the future, transplantation may be indicated earlier in the course of the disease.

Common operative problems in hepatobiliary surgery.

The pace of change in hepatobiliary surgery requires a sound foundation in basic surgical principles. Further reductions in morbidity and mortality rates and appropriate use of alternative therapies require careful attention to preoperative risk assessment and patient selection. To operate safely and successfully on the liver and bile ducts, the surgeon must be well versed in normal and variant hepatobiliary anatomy, understand the underlying disease and therapeutic alternatives, and known techniques of reoperative biliary surgery. Surgeons who operate on the gallbladder must be prepared to confront a host of unexpected and difficult operative problems. Bile duct injuries must be repaired properly at the first attempt. Complex biliary operations require a great level of technical expertise and judgment to obtain successful results and should only be undertaken by experienced hepatobiliary surgeons. As proficiency with the more routine procedures improves, increasingly complex and extensive procedures become possible. We must constantly police ourselves to be certain that these more extensive procedures truly benefit our patients.

Common difficulties and complications in pancreatic surgery.

Pancreatic surgery requires dedicated surgeons to optimize results. Difficult operative situations faced during the course of pancreatic procedures and ways of dealing with them are suggested. The horizons of surgery on the pancreas will expand as the morbidity and mortality rates fall.

Analysis of morbidity and mortality rates in right hepatectomy with the preoperative APACHE II score.

Morbidity and mortality rates in 70 patients who underwent major liver resection for liver tumors (primary and metastatic) were determined and correlated with the preoperative APACHE II score. Patients were divided into three groups according to their preoperative APACHE II score: low (0 to 3), mid (4 to 7), and high (8 and above). A higher score was closely correlated with increased postoperative morbidity and operative mortality rates. The group with low scores had a postoperative morbidity rate of 34% and a mortality rate of 0%, the group with mid scores had a postoperative morbidity rate of 54% and a mortality rate of 3%, and the group with high scores had a postoperative morbidity rate of 80% and a mortality rate of 20%. Age did not correlate with morbidity. It was therefore postulated that morbidity and mortality rates were related to the combination of points for abnormal physiologic variables and points for chronic health, or APACHE II score minus points for age. As the combination of these points increases the postoperative morbidity and operative mortality rates increase significantly (from 24% in the 0-point group to 69% in the greater than or equal to 3-point group). Also the two deaths occurred in the group with 3 or more points. The preoperative APACHE II score may be used by clinicians to evaluate before surgery the risk of postoperative morbidity and death in elective major liver surgery.

Pancreaticobronchial fistula causing lung abscess: case report and brief discussion of the literature.

A case report of a patient with an abscess of the lung caused by a pancreaticobronchial fistula is presented. The patient was treated by pulmonary resection and distal pancreatectomy-splenectomy.

Novel approach to iatrogenic bile peritonitis.

Bile peritonitis after injury to the biliary tree is a serious complication that requires exploratory laparotomy. Our patient had an obstructing ampullary carcinoma, and generalized bile peritonitis developed from attempted percutaneous transhepatic cholangiography. The patient's condition was managed by peritoneal lavage and endoscopic transampullary stenting, with immediate relief of pain and toxicity. Exploratory laparotomy was avoided, and an eventual pylorus-sparing Whipple resection was the definitive treatment. We believe this to be the first report of successful nonoperative treatment of a patient with bile peritonitis with obstructive jaundice.

Surgical management of nonparasitic cystic liver disease.

We report clinical features, surgical management, recurrences, and follow-up study of 12 patients with simple hepatic cyst, 11 patients with polycystic liver disease, and 19 patients with cystadenoma who were surgically treated over a 25-year period. The median age of patients was 48 years, and 37 women and 5 men were in the series. The most common presenting symptom and physical finding were chronic abdominal pain and tenderness in the right upper quadrant. The most commonly associated disease was polycystic kidney disease, which was an associated finding in 5 of the 11 patients with polycystic liver disease (45%). The most valuable diagnostic studies in all groups were computed tomography and ultrasonography. The location of the disease was bilobar in patients with polycystic liver disease, with a right lobe predominance in 18% of patients. The right lobe was also predominant in 83% of patients with simple hepatic cyst and 58% of patients with cystadenoma. Of all solitary cystic lesions in the left lobe, 75% of them were cystadenomas. Of the 66 surgical procedures performed, aspiration was associated with a failure rate of 100%; partial excision, a failure rate of 61%; and total excision and liver resection, a failure rate of 0%. Orthotopic liver transplantation was performed in three patients and was associated with two early deaths. Partial excision relieved symptoms in three patients (43%) with polycystic liver disease. Total excision, enucleation, or liver resection with cyst(s) is the treatment of choice for non-parasitic cystic lesions of the liver.