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We report the surgical-pathologic findings in 15 adults who had a history of irradiation of the head and neck in childhood. These patients we selected for thyroid surgery because of a "cold" area or areas detected on 99mTc thyroid scan, with or without palpable thyroid abnormalities. Eight of the fifteen patients had thyroid cancer, and 3 had atypical adenomas. We found multiple lesions in 12 patients. Macroscopic and microscopic malignancy in a location different from the cold area or areas occurred in 5 of the 8 cancer patients. In vitro of these findings, we recommend that adults who received irradiation to the head and neck in childhood and who have been found to have an abnormal thyroid scan or thyroid examination, or both, have a total thyroidectomy... [ABSTRACT FROM AUTHOR]

The impact of laparoscopic cholecystectomy (LC) on the operative experience of surgical residents was assessed in a series of 787 cholecystectomies. During an initial 18-month period, residents participated in LC as operating surgeon and as first assistant or camera operator in 33% and 97% of cases, respectively. Operative time, cholangiography rate, conversion rate, and complications were not adversely affected by resident operators. Residents performed 87% of concurrent planned open cholecystectomies (OC). In comparison to the 6 months preceding LC: (1) The mean number of resident OCs decreased significantly while the total number of resident cholecystectomies was unchanged; (2) the proportion of OCs performed by PGY5 residents significantly increased at the expense of junior resident cases. LC can be safely integrated into surgical resident training by standard methods as for open procedures. Although resident operative experience has been redistributed, initial experience does not suggest that qualification in open biliary surgery has been compromised. [ABSTRACT FROM AUTHOR]

Fractionated radiation therapy after liver resection for metastatic cancer has traditionally been a palliative procedure. Here, we consider that radiation may be an appropriate adjuvant therapy for cure after liver resection for metastases. This pilot study in rats establishes a model for evaluating the effects of fractionated irradiation posthepatectomy. Sixty Sprague-Dawley rats were randomized to four groups. The groups underwent laparotomy, laparotomy and radiation, hepatectomy, and hepatectomy and radiation. We found that the rats treated with radiation had statistically significant (P < 0.0001) clinical radiation change by liver function tests at 6 months. This damage was resolved to normal at 1 year regardless of hepatectomy. In fact, we demonstrate the possibility of a protective effect from radiation damage in the regenerated liver. We also demonstrate statistically significant histologic change at 8 months (P < 0.01) in the radiation-treated rats which does not resolve at 1 year.

Sixty-four patients (mean age, 51 years) had mastectomies which were synchronous and bilateral. Sixty-one premastectomy biopsies (bilateral, 34 and unilateral, 27) demonstrated the following: invasive carcinoma, 17; noninvasive carcinoma, 24; combination of above, 10; and benign disease, 10. Twenty-two patients had bilateral mastectomy because of bilateral positive biopsy. Twenty-nine patients with unilateral carcinoma on biopsy had bilateral mastectomy. Thirteen patients had bilateral mastectomy despite benign disease only on biopsy (10) or no biopsy (3). Ten unexpected carcinomas (34%) were found in the contralateral breast in the 29 patients with carcinoma diagnosed on unilateral biopsy. The biopsy pathology of these 10 specimens was invasive ductal carcinoma in 1 and multifocal, noninvasive carcinoma (ductal, 3 and lobular, 6) in 9. An unexpected carcinoma may be found in the contralateral breast in a significant number of patients who are selected for bilateral mastectomy, particularly if the selection is on the basis of a noninvasive, lobular histology. Bilateral mastectomy may be appropriate for such patients, particularly when complicated by a strong family history and breasts which are difficult to assess by physical or mammographic examination.

Fine-needle aspiration (FNA) biopsy of a thyroid nodule was performed in 797 patients. Ninety-six patients had resection of the thyroid nodule performed subsequent to a one-time FNA biopsy. The surgical pathology of these 96 cases demonstrated a 5.8% false-negative rate and a 9.9% false-positive rate. As a consequence, we prospectively evaluated the routine practice of repeat FNA of cytologically benign thyroid nodules. Repeat FNA confirmed the original benign cytology in 183 (93%) of 196 patients. Seventeen of these 183 patients with benign FNA on both biopsies had resection of the nodule performed because of the development of suspicious clinical signs or in response to the patient's choice; 1 recurrent cyst was found to be carcinomatous. Of the 13 patients demonstrating a change in cytology on repeat FNA biopsy, 9 had a nodule that was classified as possibly malignant (suspicious); 6 of these patients underwent resection, and 1 patient was found to have a carcinomatous nodule. Four patients had nodules that were classified as probably malignant on repeat FNA biopsy; all of their nodules were resected, and three of them were found to be carcinomatous. This study demonstrates that, although one-time FNA biopsy of thyroid nodules is highly accurate, with a relatively low false-negative rate, repeat fine-needle biopsy improves on this diagnostic accuracy, thereby decreasing the risk of misdiagnosing a thyroid nodule that is malignant.

Between 1978 and 1990, 23 patients underwent 35 thoracotomies for metastatic colorectal cancer. The pulmonary disease was diagnosed within an interval of 0 to 105 (average, 33.4) months after colon resection. Fifteen patients underwent a single thoracotomy; 12 patients had solitary lesions, and three patients had multiple nodules. Eight patients underwent multiple thoracotomies. The median survival following thoracotomy was 28 months; three-year survival was 45 percent, and five-year survival was 16 percent. Factors that had no significant bearing on survival included origin and stage of the primary tumor and patient age and sex. An interval before thoracotomy of three years had an impact on survival approaching statistical significance (P = 0.17). Patients who underwent multiple thoracotomies had a significantly prolonged survival (P = 0.04). Patients who underwent a single thoracotomy for a solitary lesion had a significantly prolonged survival compared with patients who had a single thoracotomy for multiple metastases. After thoracotomy, 14 patients eventually developed recurrent disease, which was confined to the lung in only four patients. Of these 14 patients, 11 subsequently died of cancer. We conclude that thoracotomy for metastatic disease should be considered when the primary tumor is controlled, the lungs are the only site of metastatic disease, and there is adequate lung reserve to withstand surgery. Survival following thoracotomy may be influenced by the interval before diagnosis, the number of pulmonary nodules, and the number of thoracotomies performed.

Complications of laparoscopic cholecystectomy were evaluated by a survey of surgical department chairpersons at 4,292 US hospitals. The 77,604 cases were reported by 1,750 respondents. Laparotomy was required for treatment of a complication in 1.2% of patients. The mean rate of bile duct injury (exclusive of cystic duct) was 0.6% and was significantly lower at institutions that had performed more than 100 cases. Bile duct injuries were recognized postoperatively in half of the cases and most frequently required anastomotic repair. Intraoperative cholangiography was practiced selectively by 52% of the respondents and routinely by 31%. Bowel and vascular injuries, which occurred in 0.14% and 0.25% of cases, respectively, were the most lethal complications. Postoperative bile leak was recognized in 0.3% of patients, most commonly originating from the cystic duct. Eighteen of 33 postoperative deaths resulted from operative injury. These data demonstrate that laparoscopic cholecystectomy is associated with low rates of morbidity and mortality but a significant rate of bile duct injury.

Approximately three-fourths of open biopsies of the breast performed for mammographically detected suspicious lesions are shown histologically to be benign. Under the narrow conditions described herein, stereotaxic fine-needle aspiration (FNA) can identify these lesions with an accuracy of more than 90 per cent and a false-negative rate of 5 per cent. In an effort to reduce this failure rate, the mammographic appearance and stereotaxic FNA results of these lesions each were given scores on a scale of zero (benign) to five (malignant), to derive an over-all risk score prospectively applied to 264 suspicious occult lesions of the breast prior to open, biopsy. While all 264 lesions could be assigned a mammographic score, adequate tissue for assignment of a cytologic score could be obtained from 150 lesions. Of the 150 evaluable lesions, 53 were malignant and 97 were benign, historically. With a total score of two as the threshold for open biopsy, 21 of 150 (14 per cent) were proved to be benign, with no false-negative findings. If the total threshold score mandating an open biopsy was raised to four, the comparable figures were 61 of 150 (40 per cent) benign lesions and two false-negative instances of carcinoma in situ. Provided adequate tissue is aspirated for cytologic examination, we conclude that this algorithm has practical value in the management of nonpalpable lesions of the breast in that it can reliably identify a fraction of the benign lesions and spare these patients an operation.

The diagnosis of "poorly differentiated" carcinoma was made in 47 of 683 colon cancers on the basis of conventional light microscopy which showed poorly defined glands, solid architecture or variable admixtures thereof. Samples from 44 of these 47 tumors were assessed by immunohistochemical analysis for the presence of neuroendocrine (NE) antigens. Paraffin sections were immunostained with antibodies to NSE, chromogranin, serotonin, VIP, substance P and somatostatin. Additional sections were also stained with monoclonal antibody (Mab) A-80 that recognizes a glycoprotein related to exocrine (EX) differentiation. Based on our findings, the tumors were phenotypically reclassified as follows: I) pure EX (n = 8), II) pure NE (n = 4), III) mixed EX-NE carcinomas (n = 23), and IV) predominantly EX carcinomas with occasional NE cells (n = 9). Survival among groups II and III appeared to be less than group I and survival in group IV was significantly less than group I. Survival among the four pure NE (group II) and 11 predominantly NE mixed carcinomas (group III) taken together was significantly less than the pure EX carcinomas. This study indicates: 1) The incidence of NE differentiation in tumors of the colon and rectum is higher than previously believed. 2) The poorly differentiated colon carcinomas comprise four distinct groups: pure EX, pure NE, mixed EX-NE carcinomas, and predominantly EX carcinomas with a NE cell subpopulation. 3) The presence of NE differentiation or of a NE cell subpopulation in colon carcinoma appears to be associated with a poorer prognosis.

Topically applied chitosan fails to improve the control of bleeding in a liver laceration model when compared to pressure alone in both normal and heparinized rats, and both chitosan and pressure alone are significantly less effective in controlling bleeding than the application of thrombin. In addition, our histologic results suggest that there may be an increased inflammatory response by the healing liver following topical application of chitosan.

Three cases of lateral neck tumors caused by thrombosis of the external jugular vein have been presented. Microscopic examination of the excised thrombosed veins revealed all of them to have a dilated architecture with somewhat degenerated vessel walls much like an aneurysm. Such a dilatation would cause some stasis and eddy currents and make the vessels more susceptible to thrombus formation. The final factor which induced these thrombi remains unknown. Indeed, when the interrelation of the factors discussed previously is considered, multiple etiologic factors appear most likely. Some form of minor trauma, although not documented, would still seem the most likely cause of thrombosis of a vein in a patient with no previous symptoms. In case III, trauma of inflammatory changes in a mass already noted to be present for some time could have induced thrombosis within the dilated vessel. Thrombosis of the external jugular vein is yet another lesion in the extensive differential diagnosis of a mass in the lateral neck.

Recent studies in animals have shown prolonged survival of endocrine allografts after treatment of the graft with Ia antibody prior to transplant. In this study, we documented the presence of Ia bearing passenger cells in human parathyroid and islets of Langerhans. Furthermore, we characterized these cells with regard to their expression of HLA-DQ and HLA-DR molecules using indirect immunofluorescence. We found that passenger cells in parathyroid express both HLA-DQ and HLA-DR. In contrast, islets express only HLA-DR. Parathyroid tissue treated first with polyclonal anti-DR or anti-DQ and complement eliminated cells that reacted with monoclonal anti-DR or -DQ probes, respectively. Similarly, islets treated with polyclonal anti-DR and complement eliminated cells that reacted with monoclonal anti-DR reagents. We believe that further characterization of Ia+ cells in human endocrine tissue will provide information that could be used to enhance allograft survival.

Neuroendocrine carcinomas were diagnosed in 13 of 683 patients who had colon cancers removed from January 1980 to June 1987 for an incidence of 1.9%. The patients were 28 to 89 years of age (median, 72 years). There were seven male and six female patients. The treatment was as follows: right hemicolectomy, 5; transverse colectomy, 1; left hemicolectomy, 1; low anterior resection, 2; abdominal-perineal resection, 1; and in 3 patients with rectal tumors, biopsy examination only was performed. Microscopic stages were as follows: Dukes' stage B, 1; stage C, 6; stage D, 5; and stage indeterminate, 1. By light microscopy, the tumors showed solid clusters or ribbons of round to fusiform, small to intermediate-sized cells with variably abundant mitoses. Eight tumors had foci of glandular and/or squamous differentiation. By immunohistochemistry, all tumors showed one or more neuroendocrine markers, including neuron-specific enolase, chromogranin, synaptophysin, serotonin, and various neuropeptides. By electron microscopy, single membrane-bound neurosecretory granules were noted. The sites of metastases included regional nodes, 8; liver, 5; bone, 1. Four patients were treated with a combination of chemotherapy and radiation therapy. These tumors were, as a group, aggressive, with eight patients dead within 12 months of diagnosis. Median survival was 7 months, with three patients alive at 2, 38, and 68 months, respectively. Specifically, small- and intermediate-cell neuroendocrine carcinomas of the colon and rectum behaved very aggressively and displayed numerous structural and functional similarities with their bronchopulmonary counterparts.

Benign non-parasitic cysts of the spleen are very uncommon, with a total of 651 cases having been described in the literature to date. Because of their uncommon nature, and the fact that their symtoms may be vague, a high index of suspicion is necessary if they are to be diagnosed. The therapy of choice is surgical excision by splenectomy and the accompanying cystectomy. The prognosis following such therapy is excellent.

It is proposed to identify histologically indeterminate human cancers by comparing their qualitative content of stained proteins, separated by two-dimensional electrophoresis, with patterns of proteins from a series of identified human cancers of comparable or different stem cell origin. The hypothesis to be tested is that in cancer, biochemical ontogeny, reflected in the distribution of cellular and tissue proteins, will recapitulate phylogeny, albeit in a manner less organized than normal. Patterns of protein from cancer cells, whether histologically identified or not but originating from embryologically similar stem cells, are expected to exhibit greater homology, compared with protein profiles of cancer cells derived from stem cells of different embryologic origin. Normal or cancer cell proteins common or unique to one or more cell sources can be identified, and subsets of proteins that characterize cancer cells of specific stem cell origin identified. There are reasons to believe that cancer cells rarely, if ever express properties inconsistent with the basic cellular commitment of their stem cell of origin. Photo-optical scanning and computer-assisted analysis will greatly facilitate collating the many hundreds of discrete proteins, among which those used to characterize different cancer cells are to be found.

Twenty Parkinsonian patients and 20 control subjects were compared with respect to their electrooculographic findings. It was found that Parkinsonian patients are distinguished from controls by their significantly lower mean EOG ratios. L-dopa treatment restored EOG ratios to control values. The findings are interpreted as indicating an association of Parkinson's disease with metabolic changes in the melanin-containing cells of the pigment epithelium.

Radionuclide scanning is usually contraindicated in pregnancy because of the danger of fetal radiation exposure. Radionuclide bone scanning with Tc-99m MDP is a sensitive indicator of early osseous metastases in breast cancer. Three cases of breast cancer during pregnancy are reported; modified bone scanning was utilized for staging and decision analysis. Modifications of bone scanning techniques to minimize fetal radiation exposure and fetal dosimetry calculations are described.

Sequential hormone therapy for advanced breast cancer can offer significant and prolonged disease control with minimal morbidity. Predictors of response to sequential hormone therapy have not previously been identified. Sixty postmenopausal women with advanced or recurrent breast cancer treated with sequential megestrol acetate and tamoxifen were evaluated to identify factors which predict response to sequential therapy. The response rate to first-line therapy was 28% (17/60). Forty-seven percent of patients who responded to the first therapy responded to the second (8/17). Four of 16 patients (25%) who failed the first hormone therapy responded to the second. The response rate to a second hormone therapy was 25% (15/60). Chi-square tests were used to test the association between a response to sequential hormonal therapy and prior chemotherapy, age at first hormone trial, number of sites of disease, dominant site of disease, sequence of hormonal therapy, second response on the basis of first response, presence of soft tissue disease or bone disease alone, and receptor value. A one-tailed Fisher exact probability test revealed that a greater proportion of receptor-positive patients exhibited positive responses to sequential hormonal therapies than did receptor-negative patients. All of the patients who responded to a second hormonal therapy were estrogen receptor (ER)- and progestogen receptor (PgR)-positive. Fisher exact probability tests revealed a statistically significant association between response to initial hormone therapy and response to a subsequent hormone trial. This study suggests that patients who fail their initial hormone trial should be considered for a second hormonal trial if they are ER- and PR-positive.

We studied 28 patients who had undergone 30 operations for pheochromocytoma since 1964. The tumor types included bilateral, extra-adrenal, malignant, recurrent, and multiple endocrine neoplasia, with 20 tumors confined to the adrenal gland. The preoperative studies used to localize the tumor included ultrasonography, intravenous urography, angiography, and computed tomography. Patients underwent exploratory operations via flank, subcostal, bilateral subcostal, midline, or thoracoabdominal approaches. In one case, that of a recurrence after bilateral adrenalectomy, surgical exploration discovered a tumor that had not been localized during the preoperative workup. Two patients underwent splenectomy because of injury incurred during operative exploration. Our experience suggests that preoperative localization is highly reliable, and therefore the benefits of extensive surgical exploration may be outweighed by its risks. We believe that with the exception of tumors that occur in association with childhood or pregnancy, multiple endocrine neoplastic syndromes, or recurrent disease, a direct approach to the tumor, possibly via the flank, is justified. Our results suggest that exploration of the contralateral adrenal or periaortic area is not so important as to be worth jeopardizing the spleen or other organs by a complex or extensive dissection.

The results of our experience have demonstrated that patients who undergo hepatic resection for primary or metastatic carcinomas have survival rates considerably higher than those reported in the literature for patients who do not undergo resection. Morbidity rates as well as survival rates among the patients we studied lie within the reported values of the major institutions. It is certainly clear that, within the past five years, metastatic disease to the liver from a primary carcinoma of the colon and rectum has become a treatable disease. We, therefore, advocate the aggressive approach to carcinoma of the liver and look forward to further advancement in the treatment of this disease.

Megestrol acetate (160 mg/day) produced a response rate of 44% in a retrospective series of 39 evaluable patients with advanced breast cancer. The estrogen-receptor (ER) level was greater than 10 fmols/mg of protein in 28 patients, and the progesterone-receptor (PR) level was greater than 10 fmols/mg of protein in 26 patients. ER and PR levels, age, and disease-free interval were analyzed for their relationship to response. The PR was the single best predictor of response to megestrol acetate; the addition of ER added 2% to the predictive accuracy rate of PR alone.

Methods that avoid long-term immunosuppression must be developed for human parathyroid allotransplantation to be feasible. Pretransplant treatment of the graft to eliminate passenger cells is one such method. An alternative approach is short-term treatment of the recipients with cyclosporine (CsA). In this study, parathyroid glands from Lewis X Brown Norway rats were cultured for 1 week and treated with antiserum directed against class II major histocompatibility complex antigens. Treated glands were transplanted into hypocalcemic Wistar-Furth recipients that previously received 30 mg/kg of CsA once a day for 3 days before transplantation. At 280 days after transplantation, 67% of the recipients had functional parathyroid allografts. Control rats (no CsA; fresh, untreated glands) rejected these grafts within 28 days. Control rats given 3 days of CsA and transplanted with fresh, untreated glands had functional grafts for greater than 56 days (median survival, 80.5 days). Prolongation of allograft survival with short-term, preoperative CsA demonstrates the efficacy of immunosuppression given at the time of antigen presentation. This course of CsA is even more effective when the recipient receives a graft whose passenger cells are eliminated.

Distinct glomerular ultrastructural lesions in the form of nodular subepithelial and intramembranous, as well as discrete and band-like subendothelial deposits are described in a patient suffering from mixed IgG-IgM essential cyoglobulinemic glomerulonephritis. It is suggested that the deposits may represent immune complexes which are belived to play a central role in the pathogenesis of the glomerulonephritis.

We performed a prospective, randomized, double-blind study of continuous epidural analgesia for 72 hours after major abdominal procedures. Patients were randomly assigned to one of five treatment groups: epidural morphine, epidural bupivacaine, a combination of morphine and bupivacaine, epidural saline solution, and no epidural catheter. All patients received supplemental morphine sulfate or meperidine hydrochloride, intramuscularly or intravenously, as needed. Epidural infusion was begun at 2 to 4 ml/hr, depending on age and height, with two increments of 1 ml/hr allowed if pain relief was insufficient. All pain management decisions were made by nurses, who also monitored epidural function. Performance was measured four ways: pain as measured at regular intervals in the 72-hour period with a visual analog, pain as measured after 72 hours with the McGill Pain Questionnaire, amount of supplemental narcotics needed, and recovery of respiratory function and ambulation as percent of preoperative levels. The group that received the combination of morphine and bupivacaine did best on all measures; in most instances the difference between the results seen with the combination regimen and those seen with saline solution or no catheter were significant at the 0.05 level. With the exception of pruritus, complications were evenly distributed among all treatment groups, including noncatheterized controls. We conclude that epidural analgesia with the combination of morphine and bupivacaine is safe, is easily managed, and gives pain relief superior to that provided by traditional, systemic administration of narcotics.

Methods that avoid chronic immunosuppression of transplant recipients must be developed to eliminate the various risk factors associated with such treatment (e.g., increased infections and malignancies). Pretransplant treatment of the graft with anti-Ia serum plus complement to eliminate "passenger cells" is one such method. An alternative approach is short-term treatment of the recipients with cyclosporine (CsA). In this study, parathyroid glands from Lewis X Brown Norway rats were cultured for one week at 37 degrees C and treated with anti-Ia and complement. Treated glands were transplanted into parathyroidectomized, hypocalcemic Wistar-Furth recipients that had received 30 mg/kg of CsA once a day for the three days prior to transplant. At 1 year posttransplant, 67% of the recipients had functional parathyroid allografts. Control rats (no CsA; fresh, untreated glands) rejected their grafts within 28 days. Controls given three days of CsA and transplanted with fresh, untreated glands all had functional grafts for greater than 56 days (median survival: 80.5 days). Prolongation of allograft survival with short-term, preoperative CsA demonstrates the efficacy of immunosuppression given only at the time of antigen presentation. This course of CsA allowed for indefinite graft survival when the recipient received a graft previously cultured and treated with Ia antiserum. These results are encouraging and should be evaluated further to determine whether similar approaches will be useful in human transplants.

Prolonged l-phenylalanine mustard (L-PAM) administration as an adjuvant to mastectomy in the management of patients with primary breast cancer and pathologically positive axillary nodes was evaluated by a prospective, randomized, clinical trial. Treatment failures occurred in 22 per cent of 108 patients receiving placebo and 9.7 per cent of 103 women given L-PAM (p = 0.01). A statistically significant difference (p = 0.02) existed in favor of L-PAM relative to disease-free interval. In premenopausal women, the difference with respect to disease-free interval of treated and control groups was highly significant (p = 0.008). A treatment failure occurred in 30 per cent of premenopausal patients receiving placebo and 3 per cent of those treated with L-PAM (p = 0.008). Whereas a similar trend was observed in postmenopausal patients, the difference is not statistically significant. Thus, L-PAM has been demonstrated to be effective in the treatment of women with primary breast cancer, particularly those who are premenopausal. Results were achieved with minimal undesirable side effects.

Megestrol acetate as initial hormonal therapy produced a 40% objective response rate in 53 patients with advanced breast cancer; another 26% achieved stable disease. For 19 patients with visceral-dominant disease, the response rate was 42%. To investigate the effect of the order of sequential hormonal therapy, records of 66 patients treated with tamoxifen before megestrol acetate or with megestrol acetate before tamoxifen were reviewed retrospectively. Of the 24 patients who were given megestrol acetate first, nine (38%) had objective response to primary therapy, and four (17%) to secondary therapy. Among the 42 patients treated with tamoxifen first, there were nine (21%) objective responses to primary therapy and eight (19%) responses to secondary therapy. Results show that megestrol acetate is effective first-line hormonal therapy for advanced breast cancer. Megestrol acetate can be used as primary hormonal therapy and tamoxifen as secondary hormonal therapy, as an alternative to the more usual reverse order. One may also consider megestrol acetate for some advanced breast cancer patients with visceral-dominant disease.