Biliary proteins. Unique inhibitors of cholesterol crystal nucleation in human gallbladder bile.

The onset time for cholesterol crystal nucleation of supersaturated normal human gallbladder biles is consistently prolonged when compared with biles from patients with cholesterol gallstone disease. Investigation of the factor(s) responsible for the suspended supersaturation (metastability) of normal human biles revealed that model bile solutions of cholesterol saturation index (CSI) and molar lipid composition identical to individual gallbladder bile specimens had much shorter crystal nucleation times, i.e., exhibited decreased metastability. Unsaturated normal biles, after supplementation with lecithin, cholesterol, and sodium taurocholate to a 'standard' supersaturated lipid composition, also demonstrated nucleation times three- to 15-fold longer than the comparable standard model bile. Total lipid extracts of normal biles, however, when similarly supplemented, did not differ in nucleation time from the control model solution. Gallbladder biles were fractionated by gel chromatography and the eluted fractions were pooled into two fractions. The fractions eluting in about the first 25% of the included volume when mixed with the supersaturated standard model bile induced a modest increase in nucleation time of approximately 1.5 times the control value. The fractions eluting in the second 25% of the included volume and which contained all of the bile lipids, were concentrated and supplemented with lipids to the standard composition. The nucleation times of these supplements were 3-10 times longer than the control nucleation times. Delipidated bile protein mixtures, purified by discontinuous sucrose gradient centrifugation, were recombined with purified lipids at the standard composition used previously. The nucleation times of these mixtures were significantly prolonged to the same extent as those associated with the second chromatographic fraction. These observations demonstrate that the delayed onset (inhibition) of cholesterol crystal nucleation observed in normal human gallbladder bile is produced by a factor(s) present in the biliary protein fraction.

Partial mastectomy: pathologic findings and prognosis.

In an attempt to identify patients best suited for limited surgery as well as those at risk for recurrence and increased mortality, the authors reviewed the clinical and pathologic features of 130 patients who had undergone partial mastectomy as primary treatment for breast cancer (adjuvant therapy was administered only after disease recurrence). Patients were followed up for 57 to 128 months (mean, 85 months). Univariate and multivariate analyses were performed for the entire group and repeated for the large subgroup of patients with infiltrating ductal cancer, not otherwise specified. Three features were independently significant in correlating with poor survival and/or tumor recurrence: lymph node metastasis, mitotic rate, and nuclear atypia. Combinations of these factors further separated survivors from non-survivors. These prognostically significant pathologic features may be helpful in both selecting patients for partial mastectomy and identifying those who may require adjuvant therapy.

Ligation procedures in the management of portal hypertension.

In the 10 year period from 1964 through 1973, 25 patients bleeding from esophageal varices underwent ligation procedures coupled with splenectomy rather than a shunt. These procedures included the transesophageal and transgastric approaches and extragastric ligations. For patients with normal liver function, the risk of this urgent or emergency surgery is comparatively low (two of 12 patients died). The chance of recurrent hemorrhage is high (nine of nine surviving patients), as is the need for subsequent surgery (eight of nine patients). Nevertheless, despite these drawbacks, nine of these 12 patients (75 percent) are alive, and seven have survived 5 or more years. In patients with cirrhosis, the initial operative mortality rate (three of 12 patients) and the subsequent mortality rate (five additional patients) reflect the greater risk because of liver disease. Only five of 13 patients (38 percent) survive, three of whom are alive 5 or more years. In patients with cirrhosis, the initial operative mortality rate (three of 12 patients) and the subsequent mortality rate (five additional patients) reflect the greater risk because of liver disease. Only five of 13 patients (38 percent) survive, three of whom are alive 5 or more years after their initial surgery. These results indicate that there are situations when ligation procedures are valuable, especially in the noncirrhotic patient.

The role of hepatic veins in liver operations.

In this report we review the role of the hepatic veins in resective operations of the liver. Emphasis is placed on the distribution of the hepatic veins, their relationship to hepatic arterial and portal venous inflow tracts, and the drainage patterns of hepatic lobules. An extensive review of the older literature has emphasized the necessity to preserve hepatic venous drainage for the various hepatic segments to prevent postoperative liver congestion and injury. Recent experimental and clinical reports have identified the mechanisms through which hepatic vein obstruction can be well tolerated. These mechanisms include interlobar and interlobular collateral development, reversal of blood flow in the portal vein with conversion of the portal vein to an outflow tract, development of extrahepatic collaterals, drainage through the caudate lobe, and increased lymphatic draining to relieve hepatic congestion.

The management of retained and recurrent bile duct stones.

The records of 156 consecutive patients treated for retained and recurrent bile duct stones between 1965 and 1980 were reviewed to compare current management techniques. One hundred sixty-eight procedures were performed in the 156 patients: 36 endoscopic sphincterotomies, 89 common bile duct explorations, and 43 common bile duct explorations with drainage procedure. Mean follow-up was 7.2 years. The overall success rates were 81% for endoscopic sphincterotomy, 80% for common bile duct exploration, and 86% for common bile duct exploration with drainage procedure. Five variables were evaluated in regard to the success of these procedures: (1) the time interval between cholecystectomy and the next procedure on the biliary system, (2) the number of previous biliary procedures or operations performed, (3) the diameter of the common bile duct, (4) the number of stones in the duct and their size, and (5) morbidity and mortality. The time interval and number of previous biliary procedures did not affect the success of any procedure group. Endoscopic sphincterotomy has become our procedure of choice. When common bile duct exploration with drainage procedure is performed and a dilated bile duct or more than five bile duct stones are found, the addition of a drainage procedure provides better long-term results.

The natural history of splenic infarction.

Our experience at the Cleveland Clinic and that in the literature with splenic infarction were reviewed to describe the natural history of splenic infarction and provide guidelines for management. Data for this review included 75 patients identified by clinical studies or at autopsy during a 10-year period and a review of 77 cases reported in the literature. The cause of the infarct varied with age; patients under 40 years old most often had an associated hematologic disorder, while those older than 41 years old most often had an embolic event. Other etiologic factors included splenic vascular disease, anatomic abnormalities, collagen vascular disease, pancreatic disease, and nonhematologic malignancy. Left upper quadrant pain was the predominant symptom. Changes in the blood count included anemia (53%), leukocytosis (49%), and thrombocytosis (7%). Liver-spleen scans were diagnostic in 90% of patients and computerized tomography identified the infarct in 75%. Initial management consisted of hydration, analgesics, and frequent monitoring, with resolution of symptoms in 7 to 14 days. Splenectomy was performed for persistent symptoms or a complication of the infarct (splenic pseudocyst, abscess, or hemorrhage). An uncomplicated splenic infarction can be managed safely with medical treatment, but early surgical intervention (splenectomy) is necessary to lower the mortality rate of a complication of the infarct.

Hepatic resection in 128 patients: a 24-year experience.

The records of 128 patients who underwent hepatic resection at the Cleveland Clinic Foundation between 1960 and 1984 were reviewed. Sixty patients (47%) had major resections and 68 patients (53%) had wedge or segmental resections. One hundred five patients had malignant tumors; 29 were primary liver tumors and 78 were metastatic (61 from a colorectal primary). Twenty-three patients had benign hepatic tumors. The overall operative mortality rate was 7% (7.6% for malignant tumors and 4.3% for benign lesions). Survival rate after resection of a hepatocellular carcinoma (22 patients) at 3, 5, and 10 years was 50%, 33%, and 12%. Survival rate after resection of colorectal metastases at 3, 5, and 10 years was 44%, 28%, and 21%. Overall survival was better for patients who were less than 56 years of age (p = 0.003) and for patients with no tumor at the line of resection (p less than 0.001). In patients with colorectal metastases, survival after wedge or segmental resection was better than after a major anatomic resection (p = 0.004). In these patients, the number or size of the metastases, the time interval between resection of the primary tumor and of the hepatic metastases, and/or the presence of mesenteric lymph node metastases were not significant. Most patients with primary malignant tumors require major hepatic resection. Patients with benign tumors and metastatic colorectal carcinomas require resection only to the extent that the tumor is sufficiently encompassed.

Pancreatic islet cell tumors.

Tumors arising from the pancreatic islet cells represent a heterogeneous group of lesions. Some tumors present with well-characterized syndromes, while others appear to be nonfunctioning. Eighty-four patients with pancreatic islet cell tumors operated on at the Cleveland Clinic during a 35-year period were reviewed. The tumor types include 21 nonfunctioning tumors, 41 insulinomas, 16 gastrinomas, two vasoactive intestinal polypeptide (VIP)-omas, two carcinoids, and two probable cases of pancreatic parathyrinoma. Eleven patients had multiple endocrine neoplasia type I syndrome. Preoperative localization was possible in 63% of patients in whom it was attempted. Complete mobilization of the head and distal pancreas with bimanual palpation of the entire gland is critical for intraoperative tumor localization. Distal pancreatectomy is favored for tumors in the body and tail. In the head of the pancreas, small, benign lesions require enucleation, and large or malignant lesions necessitate a Whipple procedure. The operative morbidity rate was 24%, and the mortality rate was 3.6%. The 10-year survival rate was 54.7% for nonfunctioning lesions, 68.4% for gastrinomas, and 92.4% for insulinomas. At this time surgery represents the only way to cure these lesions.

Benign biliary strictures: an analytic review (1970 to 1984).

This report concerns 105 patients with benign biliary stricture operated on at the Cleveland Clinic from 1970 through 1984; in 102 patients the stricture was iatrogenic. The mean follow-up was 5 years (3 months to 13 years). Fifty-eight patients (55%) had undergone one or more attempts at correction of the stricture before referral to us; in 47 patients (45%) we performed the first corrective repair. Percutaneous transhepatic cholangiography was the optimal preoperative diagnostic procedure to define the site of stricture. Most patients had undergone a biliary-intestinal anastomosis, either choledochoduodenostomy, choledochojejunostomy, or hepatojejunostomy. Morbidity and mortality rates were 13% and 4%, respectively. The results of operative repair were correlated with the number of previous operations, site of stricture, type of operation, presence of a fistula, presence of cirrhosis, and length of T or Y tube stenting. The overall recurrence rate after a first operation was 18% and after a second operation was 26%. With continued attempts at repair, eventual success was achieved in 93% of patients.

Results of surgical treatment of periampullary tumors: a thirty-five-year experience.

Data on 126 consecutive patients with periampullary tumors resected at the Cleveland Clinic between January 1950 and December 1984 were reviewed. One hundred five patients underwent pancreatoduodenal resection, 10 patients total pancreatectomy, and 11 patients local resection of the tumor. The site of tumor was ampulla of Vater (59), head of the pancreas (30), duodenum (20), and distal common bile duct (11). Six patients had benign disease. The operative mortality rate for radical resection for the entire period was 7.8%; it has declined to 5.4% since 1974. The operative mortality rate for local resection was 9.1% (one patient). The overall 5-year survival rate for all malignant tumors of the periampullary area was 28% and 25.5% for invasive adenocarcinoma. Survival was affected primarily by location and histologic findings. The 5-year survival rate for adenocarcinoma of the ampulla of Vater was 37.2%, 27.5% for the duodenum, 16.7% for the distal common bile, and 4.3% for the pancreas (p = 0.0001). Papillary adenocarcinoma had a 5-year survival rate of 49.2% in contrast to 18.4% for nonpapillary ductal adenocarcinoma (p = 0.002). Patients with ampullary adenocarcinoma treated by local resection had a 5-year survival rate of 40.9%. These data justify continued use of a selective radical approach in the resection of most periampullary tumors with local resection for small tumors in high-risk patients.

Failure of LeVeen shunting in refractory ascites--a view from the other side.

We have reviewed our experience with 11 patients treated with LeVeen peritoneovenous shunts during a 22-month period from March, 1976, through December, 1977, to assess long-term results and shunt patency. Nine patients had follow-up studies to assess shunt patency at a mean of 26 months. After insertion of the shunt, the mean weight loss was 7.9 kg at hospital discharge. At 26-month follow-up evaluation, six patients had minimal ascites (responders), whereas five had massive ascites (nonresponders). Of the six responders, three patients with nonfunctioning shunts lost an average of 15.8 kg of ascites, three whereas with patent shunts lost an average of 15.0 kg. Eight of 11 patients (73%) required revision or replacement of the shunt because of malfunction; clotting was the most common cause of failure. We conclude that the role and effectiveness of LeVeen peritoneovenous shunts remain questionable. They may cause diuresis, maintain it, or not be responsible for it all. Clinical reports that cite their effectiveness should document patency of these shunts.

Antiestrogen-cytotoxic chemotherapy and bacillus Calmette-Guerin vaccination in stage II breast cancer: seventy-two-month follow-up.

A prospective, randomized clinical trial of adjuvant treatment of 312 stage II breast cancer patients with use of chemotherapy, antiestrogen therapy, and immunotherapy is reported after 72 months of follow-up. The stratification of patients was based on nodal involvement and estrogen receptor (ER) assay of the primary tumors. Findings at 72 months indicate that antiestrogen therapy (tamoxifen, Nolvadex) added to chemotherapy with cyclophosphamide (Cytoxan), methotrexate, and fluorouracil (5-Fluorouracil) (CMF) resulted in significant delayed recurrence in ER-positive postmenopausal patients, ER-positive patients with four or more positive nodes, and ER-positive patients with tumors greater than 3 cm in diameter. The addition of nonspecific immunotherapy with bacillus Calmette-Guerin had no effect on disease-free survival. ER and progesterone receptor measurements in patients with primary breast cancer provide valuable prognostic information on subsequent recurrence and overall survival and should be documented in future clinical trials.

Antiestrogen, cytotoxic chemotherapy, and bacillus Calmette-Guerin vaccination in stage II breast cancer: a preliminary report.

A prospective, randomized clinical trial of three treatment regimens: (1) Cytoxan, methotrexate, and 5-fluorouracil (CMF), (2) CMF plus the antiestrogen drug, tamoxifen (CMFT), and (3) CMFT plus bacillus Calmette-Guerin (BCG) vaccinations in women with stage 22 breast cancer is reported. All patients underwent mastectomy and estrogen receptor (ER) analysis was performed. The results of this study show that patients with ER- tumors have recurrences more rapidly and have a higher mortality rate than patients with ER+ tumors (P less than 0.0001). In ER+ patients CMFT treatment is more effective in delaying recurrence than CMF alone at 33 months (P = 0.0176). This effect appears to be occurring in both premenopausal and postmenopausal women. In ER- patients the recurrence rate is high, and there is no significant difference among the three treatment groups. In premenopausal patients treated with CMF alone, however, ER- patients recur more rapidly than ER+ patients (P = 0.0313) and suggests that the effect of CMF may be related to the suppression of ovarian function. These findings have demonstrated a significant role for the use of antiestrogen therapy in patients with state II, ER+ breast cancer.

Hepatic vein ligation and preservation of liver segments in major resections.

To preserve as much normal liver tissue as possible in patients having segmental and major anatomical liver resections for primary and metastatic cancer, one of us (Q.-J.O.) performed segmental hepatic vein ligation with preservation of the involved liver segments in eight patients undergoing hepatic resections. No early complications were found related to necrosis of the involved segments. Needle biopsy of the segments in five patients revealed normal survival of the hepatic tissue. The results in these patients indicate that hepatic vein ligation is a safe procedure that permits preservation of segments of the liver in patients having hepatic resection and can be used as an alternative to routine hepatic lobectomy for the treatment of liver tumors in selected patients.

Control of arteriovenous fistula of splenic vessels by Fogarty catheter.

A large arteriovenous fistula of the splenic vessels was identified by angiography. A splenic-artery-to-splenic-vein fistula developed shortly after a staging procedure for Hodgkin disease. A second surgical procedure failed to adequately control the arteriovenous communication. Intra-arterial obliteration of the fistula was accomplished by use of a Fogarty catheter.

Pseudolymphoma of the stomach.

Pseudolymphoma of the stomach is an unusual condition that is frequently confused with true gastric lymphoma. This has resulted in favorable long-term results in several large series of gastric lymphoma. The distinction between lymphoma and pseudolymphoma may be difficult to make on the basis of frozen sections and, occasionally, on permanent histologic sections. When the diagnosis can be made intraoperatively, a conservative procedure is indicated. When the diagnosis is suspected but cannot be made microscopically, it is suggested that observation for definite evidence of malignancy on follow-up be undertaken before initiating adjuvant therapy. This condition is frequently associated with chronic peptic ulcer disease and is considered benign. It has be proposed that pseudolymphoma, if left untreated, may progress to true lymphoma.

Recertification in surgery, 1980.

The first recertification process of the American Board of Surgery was completed in 1980. The process consisted of a review of diplomates' credentials, peer review, a requirement for continuing education in surgery, submission of an operative experience list, and a multiple-choice examination. Of the 478 diplomates who completed the process, 471 were recertified. The mean score for participants in the examination was 82.8% correct. The passing score was 67.2% correct. An analysis of examination scores, correlated with biographic and demographic data, showed that the highest scores were achieved by the younger diplomates and those who indicated that their practice was full-time academic.

Papillary cystic epithelial neoplasms of the pancreas. A clinical study of four cases.

We treated four cases of papillary cystic epithelial neoplasm of the pancreas. This neoplasm typically presents in young female patients as a slowly growing mass that may attain large size. It is of low malignant potential, and surgical resection will be curative in almost all cases. One patient presented with a liver metastasis from the pancreatic tumor; both lesions were successfully resected. Papillary cystic epithelial neoplasm should be considered in the differential diagnosis of any cystic pancreatic neoplasm.

Results of conservative operations for breast cancer.

The results of conservative operations for breast cancer in 1,593 patients treated at the Cleveland Clinic between 1957 through 1975 are reported. During this period, we individualized our treatment of breast cancer depending on tumor size, location in the breast, and clinical stage of the disease. The following three principal operations were performed: modified radical mastectomy in 592 patients (37%), simple (total) mastectomy in 442 patients (28%), and partial (segmental) mastectomy in 291 patients (18%). Survival results at 5, 10, and 15 years are reported. Factors important in long-term survival included stage of the disease, number of lymph node metastases, delay in therapy, size of the tumor, histologic type, and estrogen receptor status; type of operation was not a significant factor. In this series, partial (segmental) mastectomy without radiation therapy provided five- to 15-year survival rates equal to modified radical mastectomy and simple (total) mastectomy.

Predicting the likelihood of residual disease in women treated for ductal carcinoma in situ.

BACKGROUND: To identify women at risk for residual disease after excision of ductal carcinoma in situ (DCIS), we assessed the relationship between characteristics of the initial biopsy and the presence of residual DCIS at a subsequent operation. STUDY DESIGN: We identified 134 consecutive "paired" operations from 112 women who had undergone 2 or more operations for DCIS between February 1995 and December 1996. Cancer status of the margins, patient age and leading presentation, tumor subtype and grade, and the presence of multifocal-extensive disease were assessed as potential predictors. RESULTS: Residual DCIS was found in 60 patients (45%): in 2 of 12 patients (17%) with negative margins, in 11 of 36 (31%) with close margins (< 2 mm), in 30 of 52 (58%) with positive margins, and in 17 of 34 patients (50%) with margins of unknown status. Patients with positive or unknown margins were 7.7 and 8.3 times, respectively, more likely to have residual disease than patients with negative margins (95% CI 1.1-59.1; 1.1-66.4). Patients with clinical presentations were 8.0 times more likely to have residual disease than patients who presented with abnormal mammograms (95% CI 2.3-27.6). Multifocal-extensive DCIS was associated with residual disease (adjusted odds ratio [OR] = 7.7, 95% CI 2.9-20.5), as was comedo subtype (OR = 2.7, 95% CI 1.1-6.7). CONCLUSIONS: Positive or unknown biopsy margins, a clinical presentation, multifocal-extensive cancer, and the comedo subtype are associated with higher risk of residual DCIS.