The evolution of a contemporary academic health care system.

The story I wish to tell today is of the emergence, over the last two centuries, of an integrated academic health care delivery system from the foundations of this country's fourth medical school, New Hampshire's first major hospital, and a multidisciplinary practice group, unique in its time. I will trace the covergence of each of these into a system that we offer as an answer to the contemporary puzzle of how to provide the best available care at value and still support the academic missions of education and research. We believe this to be the current delemma of American medicine, and while our answer may not be either successful or universally applicable, we are committed to the attempt. As background, let me provide some perhaps familiar details of the growth of these Hanover [NH] and Lebanon [NH] institutions.

Interstitial microwave-induced hyperthermia and iridium brachytherapy for the treatment of obstructing biliary carcinomas.

In a phase I clinical study, 10 patients with obstructive biliary carcinomas were treated with single-antenna interstitial microwave hyperthermia and iridium-192 brachytherapy. For each patient a standard biliary drainage catheter was implanted percutaneously through the obstructed common bile duct. This catheter accommodated a single microwave antenna which operated at 915 MHz, and one or two fibreoptic thermometry probes for temperature measurement. Under fluoroscopic guidance the microwave antenna and temperature probes were positioned in the CT-determined tumour mass. The 60-min heat treatment achieved a central tumour temperature of 45-55 degrees C while keeping temperatures at the proximal and distal margins at 43 degrees C. Immediately following the hyperthermia treatment the microwave antenna and temperature probes were removed, and a single strand of iridium-192 double-strength seeds was inserted to irradiate the tumour length. A dose of 5500-7900 cGy calculated at 0.5 cm radially from the catheter was administered over 5-7 days. Upon removal of the iridium a second hyperthermia treatment was performed. A total of 18 hyperthermia treatments were administered to the 10 patients. In two cases the second hyperthermia treatment after brachytherapy was not possible due to a kink in the catheter, or bile precipitation in the catheter. All patients tolerated the procedure well, and there were no acute complications. To evaluate the volumetric heating potential of this hyperthermia method, specific absorption rate (SAR) values were measured at 182 planar points in muscle phantom. Insulated and non-insulated antenna performance was tested at 915 MHz in a biliary catheter filled with air, saline, or bile to mimic clinical treatments. The insulated antenna exhibited the best performance. Differences between antenna performance in saline and bile were also noted. In summary, this technique may have potential for tumours which obstruct biliary drainage and are accessible to percutaneous decompression using standard diagnostic radiological procedures.

Male breast cancer.

Male breast cancer is uncommon but important. The diagnosis is easily made by breast biopsy, and patients are presenting earlier in the course of the disease than in the past. Despite this, patients are often first seen with tumors that have metastasized to the axillary nodes, which markedly decreases the survival rate. Therapy of localized disease includes simple excision, modified radical mastectomy, and radical mastectomy, but there is no consensus for which operation is appropriate. Radiation therapy should be strongly considered in patients with metastases to the axillary nodes, but the role of adjuvant hormonal therapy or chemotherapy is unclear. For treatment of disseminated disease, tamoxifen seems to be replacing orchiectomy. The favorable response rate, especially in patients with estrogen-receptor-positive tumors, the lack of side effects, and the high level of patient acceptability make it an attractive therapeutic choice.

Intraoperative radiation therapy and hyperthermia. Morbidity and mortality from this combined treatment modality for unresectable intra-abdominal carcinomas.

This is a report of a phase I trial of intraoperative radiation therapy in combination with intraoperative hyperthermia for the treatment of locally advanced, unresectable intra-abdominal carcinomas. Using an ultrasound transducer system specifically designed for intraoperative applications, 19 patients have been successfully treated, demonstrating the feasibility of this combination modality. The morbidity (58%) and mortality (11%) rates reported in this series are comparable to rates reported in series of similar patients receiving intraoperative radiation therapy alone. There is still a great need for considerable technological development to enable the use of intraoperative hyperthermia to treat large, complexly shaped intra-abdominal tumors, and phase II and III trials of this combination treatment modality should be performed.

Carcinoma of the male breast and Klinefelter's syndrome: is there an association?

There appear to be no substantial data to confirm the assumption that breast cancer in men with Klinefelter's syndrome is as common as breast cancer in the normal female population. The number of reported cases of breast cancer in Klinefelter's males is only 27, a number too small for any meaningful statistical analysis. There is evidence, however, to suggest that Klinefelter's males have an increased risk of breast cancer that approaches three percent. Physicians should therefore be aware of potential breast pathology in XXY males and incorporate a careful breast examination and specific education into the routine health maintenance of men with Klinefelter's syndrome.

Cowden's disease: a further indication for prophylactic mastectomy.

Cowden's disease (multiple hamartoma syndrome) is a syndrome involving abnormalities of multiple organ systems. Transmitted in an autosomal dominant pattern, it carries a high frequency of mammary carcinoma in early middle age in affected women. The hyperkeratotic cutaneous and gingival markers of the disease are its principal overt manifestations. Prophylactic bilateral total mastectomy with optional immediate reconstruction is recommended for women Cowden's disease. An illustrative family with the disease is presented in which one affected young woman was found to have invasive mammary carcinoma with regional metastasis at the time of prophylactic mastectomy.

Secretory component in breast cancer. Analysis of the levels in primary and metastatic disease.

Levels of secretory component (SC) were measured in breast tumors from 95 patients with primary or metastatic cancer. Tumor cytosols were prepared by polytron disruption and high speed centrifugation (105,000 g X 30 min) and SC was measured using a sensitive radioimmunoassay which detects primarily free SC. In frozen samples stored for up to 5 months SC resisted degradation and could be measured quantitatively without interference. In primary tumors from patients between ages 28 and 97, SC positive samples ranged from 4 ng/mg protein to 600 ng/mg protein. In metastatic lesions, SC positive samples ranged no higher than 46 ng/mg protein. The studies indicate that SC can be measured quantitatively in both primary and metastatic tumors and that prolonged storage does not interfere with measurements of SC. The wide variation in SC levels in primary tumor samples may be related to a susceptibility to metastasis. Further, the low levels of SC in metastatic lesions could indicate a potential for SC involvement in immune regulation of tumor growth.

Primary carcinoma of the gallbladder.

Data from 6,222 patients with primary carcinoma of the gallbladder reported upon in the past 15 years have been analyzed. The disease occurs predominately in elderly females who often present with extremes of clinical symptoms, suggesting, on one hand, benign calculous disease or, on the other, advanced incurable malignant disease. Laboratory and x-ray data tend to confirm the clinical diagnosis of incurable disease, but do not aid in determining those patients with early, potentially curable lesions. The biologic nature of the tumor makes most carcinomas unsuspected findings at the time of operation and limits those patients presenting with resectable disease to about 25 per cent. The over-all five year survival of patients with carcinoma of the gallbladder is only 4.1 per cent. Furthermore, virtually the only survivors are those with lesions resected early that were not apparent to the operating surgeon and of the papillary cell type without significant invasion of the wall of the gallbladder. If the tumor is recognized and believed to be resected, survival is only 2.9 per cent, with failures caused by locally recurrent tumor. Despite the obvious failure of management of carcinoma of the gallbladder, therapeutic advantage has not been taken of the tumor's propensity to remain locally invasive by extending the scope of the traditional cholecystectomy to include en bloc hepatic wedge resection and regional lymphadenectomy in treating patients with recognized malignant tumors. Reoperation for delayed hepatic resection and lymph node dissection should be considered in selected patients with carcinoma unsuspected at operation but noted in the resected specimen. Selected application of this approach might offer the chance of cure to a small, but definite, group of patients who are currently being undertreated.

Obstruction due to malignant tumors.

An overview of the causes, the clinical pictures and the management of obstruction in three major organ systems due to primary and secondary malignant neoplasms has been presented. Such obstruction often produces dramatic clinical pictures that require careful, appropriate, and often aggressive therapy if patients are to receive the quality of palliation they deserve or the attendant improvement in survival that may result.

Prevention of vesicoureteral reflux with Fogarty catheters during formalin therapy.

Vesicoureteral reflux during formalin therapy of intractable hemorrhagic cystitis can be prevented with Fogarty catheters inserted cystoscopically into the lower ureters. With this technique formalin instillation and cystography can be done through the cystoscope at the same time. Topical intravesical vasopressin did not, in our experience, lessen the bladder hemorrhage.

Primary carcinoma of the gallbladder.

The clinical records of 48 patients with primary carcinoma of the gallbladder seen at the Dartmouth-Hitchcock Medical Center over the past 25 years were reviewed. Of the 37 patients with unresected tumors, there were no survivors. Of the 11 patients with resected tumors, one survived five years, two died before five years without evidence of recurrence, and the remainder died with locally recurrent tumor. This experience reemphasizes the inadequacy of the present surgical approach to the disease. The tendency of carcinoma of the gallbladder to spread initially by local invasion of the liver bed and by metastases to regional lymph nodes has often been neglected by those treating the disease. Wedge resection of the liver and regional lymphadenectomy in addition to cholecystectomy are theoretically advantageous and should be striven for in the case of resectable tumors, even if reoperation is required.

Neoplasms of the small bowel.

Small bowel tumors are unusual lesions exhibiting nonspecific clinical features often diagnosed at an advanced stage. In the cases studied at the Hospital of the University of Pennsylvania nearly all the 32 patients with malignancies were symptomatic whereas in the 34 patients with benign lesions the condition was discovered as an incidental finding in about half of the patients. Weight loss, palpable mass or anemia usually indicated malignancy. Small bowel radiography was the most useful diagnostic aid in the present series. While the etiology of these lesions is unknown, villous adenomas probably bear a relationship to carcinoma. The association between chronic regional enteritis and small bowel tumors is unestablished but suggestive. An analysis of reported series reveals a disproportionate incidence of additional primary tumors in patients with small bowel neoplasms. Surgical extirpation is indicated for curative treatment. In the present series, resection in hope of cure was carried out in 25 of 32 malignant tumors resulting in eight five-year survivals. One of these latter lived nine years with disseminated malignant carcinoid reflecting the occasional indolent course of this tumor.