Biomedical subjects
Publications and source records attributed to T A Broughan.
In a 57-year-old woman, Crohn's disease involving the gallbladder and duodenum caused biliary tract obstruction and necessitated surgery. The patient's symptoms did not improve postoperatively until corticosteroids provided rapid resolution. Inflammatory bowel disease often involves the hepatobiliary tree, yet the gallbladder is rarely involved directly. This patient highlights a rare complication of Crohn's disease.
Concanavalin A (Con A)-binding glycoproteins accelerate the rate of cholesterol crystal formation as a prelude to gallstone formation. Immunoglobulins (IgM, IgA, and IgG), aminopeptidase N (APN), phospholipase C (pcPLC), and alpha 1-acid glycoprotein from this Con A fraction have all been proposed as candidate promoters. We immunopurified each of the six putative promoters and examined their comparative effects by adding equal amounts to a cholesterol crystal growth assay. The effects of immunoabsorptive removal of each of the specific candidate promoters from native bile were also compared. In additional studies, the potency of these proteins was in the following order: IgM > IgA = AAG > IgG. APN and pcPLC showed no effect on cholesterol crystal growth at their apparent physiological concentrations. In subtractive experiments, only a minor loss (< 10%) of net promoting activity from that of the whole Con A-bound fraction was observed after immunoabsorptive removal of pcPLC, APN, or immunoglobulins. Total removal of AAG, however, showed a far greater loss (/33%) of the net promoting activity. These data indicate that AAG accounts for the greatest portion of net biliary Con A-bound promoting activity derived from currently defined and well-identified glycoproteins. However, more than 60% of total Con A-binding promoting activity remains unaccounted for, indicating the presence of other important and still unidentified promoters in human bile.
The treatment of potentially curable carcinoma of the breast has changed from one operation, radical mastectomy, to a flexible approach. At the Cleveland Clinic, we use four types of treatment for primary potentially curable carcinoma of the breast (Stages 0, I and II)--modified radical mastectomy, simple mastectomy, partial mastectomy with postoperative adjuvant radiation therapy and partial mastectomy without radiation therapy. The latter treatment (partial mastectomy without adjuvant radiation) is controversial. We recommend this procedure for patients with T(is) and T1 carcinomas that appear to be localized, without lymph node metastases, Stages 0 and I disease. The overall and disease-free survival rates are similar to those of patients having modified radical or partial mastectomy with radiation. Local recurrence is slightly higher at five years (11.0 percent) as compared with the other procedures, but at ten years, is only 16.1 percent, a figure comparable with patients having partial mastectomy with radiation (14.4 percent). For patients with Stages 0 and I carcinoma of the breast, the addition of postoperative radiation therapy after partial mastectomy seems to be unnecessary.
Neurological complications occurred in 4 (19%) of 21 consecutive patients (Group II) undergoing orthotopic liver transplantation, compared with a 47% (9/19) incidence in our initial series (Group I). In Group II, the neurological problems included new recurrent headaches and delayed intracerebral hemorrhage (1 patient), partial third nerve palsy and brachial plexopathy (1 patient), and ataxic dysarthria with encephalopathy (2 patients). Seizures, noted in 8 of 9 neurologically affected Group I patients, were not encountered in Group II. Of the 4 patients in the entire series with the cerebrocerebellar syndrome, 2 had partial recovery after stopping treatment with cyclosporine, 1 stabilized when cyclosporine was discontinued but later worsened when rechallenged, and 1 had full recovery but died following a second transplantation. Brain magnetic resonance images appeared normal in 3 of the 4 patients. Complications affecting vision included cortical blindness in 2 patients and occipital lobe hemorrhage in 1. All completely recovered. Survival was comparable for patients with and those without neurological complications (69% and 63%, respectively). Immediate withdrawal of cyclosporine at the onset of a change in mental status or dysarthria and improvement in intra- and postoperative management may have contributed to the decreased incidence of neurological complications.
Cancer of the proximal bile ducts continues to pose a formidable problem to even the most experienced biliary surgeon. From 1977 through 1985, 51 patients with histologically confirmed proximal bile duct cancers underwent surgical treatment. The lesion was confined to the hilar region in 30 patients; there was extensive hepatic infiltration or distant metastatic disease in 21 patients. One patient underwent resection. Biopsy only was performed in six patients. In the remaining 44 patients, transtumoral dilation and intubation were performed. These 44 patients were further analyzed with regard to how survival was affected by the presence of metastatic disease and by the adjunctive use of radiation therapy. Mean survival in those patients with metastatic disease (n = 16) was 6.1 months, and survival was not improved by the use of postoperative radiation. In the absence of metastatic or advanced local disease, however, the addition of external beam radiation did significantly extend the mean survival from 4.5 to 12.2 months and the median survival from 2.2 to 12.2 months. The operative mortality for the series was 14% and postoperative complications occurred in 18 patients. These findings suggest that the addition of external beam radiation improves survival in patients undergoing palliative treatment of hilar tumors. Further confirmation of the value of radiation awaits prospective investigation.
Controversies in palliation of pancreatic carcinoma include the best biliary bypass, the best gastric by-pass, and how routinely gastric bypass should be used. We reviewed the records of 142 patients who underwent palliative operations for pancreatic carcinoma at the Cleveland Clinic over a 5-year period. Direct choledochal-enteric anastomosis proved superior to cholecystojejunostomy because of the high incidence of postoperative biliary sepsis and obstruction with the latter. The lowest incidence of these complications was achieved with choledochoduodenostomy. Loop gastrojejunostomy and Roux-Y gastrojejunostomy resulted in similar complication rates and postoperative stays, but, because loop reconstruction was simpler, it was deemed superior. Blood loss, operative time, and hospital stay were similar in patients with loop gastrojejunostomy and patients with no gastric bypass. This finding, coupled with a 10% incidence of subsequent gastric outlet obstruction in those without gastric bypass, indicates that gastric bypass should be liberally applied in the palliation of pancreatic carcinoma.
Nineteen adult patients underwent 21 orthotopic liver transplants at the Cleveland Clinic between November 1984, and August 1986. Eight of 19 (42%) patients developed seizures. One patient suffered a single seizure, and seven patients had multiple, generalized seizures. Two of these seven patients became comatose after several days of seizure activity. Over several weeks, both of these patients regained consciousness--however, they exhibited a cerebellar-type syndrome, manifested as severe ataxia, weakness, and dysarthria. Both patients have improved, but remain neurologically impaired. Laboratory evaluation included serum electrolytes, magnesium, osmolality, and cyclosporine levels. Neurologic testing consisted of cerebrospinal fluid (CSF) analysis, computed tomographic (CT) scanning, and electroencephalography (EEG). Although the CSF protein was mildly elevated in two patients, all cultures remained sterile. None of the CT scans demonstrated any abnormalities. In five patients, the EEG showed generalized slowing consistent with diffuse encephalopathy. Other factors associated with seizures in transplant patients were analyzed, including fluid retention, hypertension, high-dose steroids, hypomagnesemia, graft dysfunction, and demyelinization. Many of our patients had the first three of these factors, since all but one developed their seizures within the first ten postoperative days. Only one patient had mild hypomagnesemia. Trough cyclosporine levels (whole blood, HPLC) were not in the toxic range (greater than 500 ng/mL). The serum osmolality was elevated in all four patients in whom it was measured, ranging from 309 to 341 mOsm/kg. Only three patients exhibited graft dysfunction--two moderate and one severe. The cause of neurologic toxicity following transplantation is unclear. Although many factors have been implicated, no common denominator has emerged. Several reports have linked cyclosporine with seizures and other neurologic problems, such as the cerebellar-type syndrome exhibited in two of our patients. Future studies should include magnetic resonance (MR) imaging of the head and measuring osmolality and cyclosporine levels in the blood and CSF.
The records of 100 patients operated on for primary hyperparathyroidism, from Jan 21, 1982 to June 11, 1984, were reviewed. In each patient, hypercalcemia had been documented on at least two separate occasions. A history, physical examination, chest roentgenogram, complete blood cell count with differential, 18-factor automated blood chemistry analysis, and urinalysis were used to screen for other causes of hypercalcemia. Of the 100 patients who had surgery, 88 had a preoperative parathyroid hormone level determination. Preoperative parathyroid hormone levels were normal in 41% of patients with parathyroid disease demonstrated at surgery. Parathyroid hormone assays produce variable results even from the best laboratories. A serum calcium determination remains the best test for diagnosing primary hyperparathyroidism.
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.
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.
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.
Fine-needle aspiration and large-needle biopsy allow 87% of patients with nodular thyroid disease to avoid operation. We have been concerned that fine-needle aspiration used alone will miss a significant number of follicular neoplasms. Between January 1980 and April 1985, 46 patients had fine-needle aspiration, large-needle biopsy, and thyroidectomy, and the preoperative biopsy specimens suggested or the postoperative pathologic findings confirmed a follicular neoplasm. Seventeen patients had a thyroid carcinoma. All 17 patients also had hypercellular large-needle biopsies, but only nine of these patients had a fine-needle aspiration suspicious of malignancy (p = 0.0078). The inability of fine-needle aspiration to detect a significant number of thyroid cancers emphasizes the need to concomitantly perform large-needle biopsies in all acceptable cases.
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.
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The widespread use of laparoscopic cholecystectomy 2 years after its introduction suggests that the procedure is a viable therapeutic option for uncomplicated gallstone disease. Early results seem to support a shorter convalescence for this procedure compared to open cholecystectomy. However, the actual complication rate is unknown. The outcome appears to be highly dependent on the skill and experience of the surgeon. How this operation is ranked against the classical cholecystectomy remains to be assessed.
Gram-negative and fungal infections are the most important cause of morbidity and mortality after liver transplantation, especially in the first postoperative month. From February 1989 to February 1990, all liver transplant recipients at The Cleveland Clinic Foundation, Cleveland, Ohio, were placed on a selective bowel decontamination regimen employing oral quinolones and nystatin beginning at the time they were put on the active waiting list for transplantation and continuing until the fourth postoperative week. The incidence of gram-negative and fungal infections for these patients was compared against a historical control group. Selective bowel decontamination was well tolerated and highly effective in reducing early serious gram-negative and fungal infections. This regimen may also reduce mortality.