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Between 1968 and 1976, 175 patients with severe dysplasia or carcinoma in situ were treated at the University of California, San Francisco. One hundred fourteen underwent therapeutic conization while 61 were treated definitely by hysterectomy. Bleeding was the main complication of cone biopsy. It occurred in 9.9% of all conizations, but only 2% of patients required transfusion. Although follow-up has been relatively short, two patients treated by therapeutic conization, who were lost to follow-up, subsequently developed recurrent invasive cancer and four have developed recurrent carcinoma in situ or severe dysplasia. One patient treated by hysterectomy has developed metastatic cancer and one has had a recurrence of severe dysplasia at the vaginal vault. There have been 32 pregnancies following cone biopsy with no increase in abortion or prematurity.

The effect of cone biopsy for cervical intraepithelial neoplasia on subsequent fertility and pregnancy was evaluated for 314 reproductive age women. Excluding patients lost to follow-up and those who had therapeutic hysterectomy, two study groups totaling 166 patients were obtained. The first consisted of 105 patients who did not become pregnant following conization. We found no evidence of secondary infertility caused by cervical conization. The second group of 61 patients achieved 88 pregnancies following conization. Comparison of these pregnancies with the outcome of 106 pregnancies by these same women prior to conization showed no effect of the operation on spontaneous abortions, preterm delivery, or cesarean section rates. The sole sequela of conization was to alter the duration of the first stage of labor.

The evidence concerning those factors related to prognosis in endometrial carcinoma has been reviewed and age, histologic differentiation of the tumor, depth of myometrial invasion and extent of disease have been found to be definitely correlated with survival. The development of different treatment methods has been traced and various modern treatment techniques have been discussed. On the basis of these prognostic indicators and reported experience with alternative methods of therapy, a plan of management for patients with endometrial carcinoma has been proposed. Although we believe this is a logical method with proven effectiveness, we wish to emphasize the importance of individualized therapy based on an understanding of the clinical-pathological findings.

Study Objective: To determine the efficacy of a 6-month course of combination chemotherapy with hexamethylmelamine, cyclophosphamide, doxorubicin, and cisplatin (H-CAP) in the treatment of advanced ovarian carcinoma., Design: Prospective, non-randomized, single-institution trial with a 6-month course of chemotherapy, followed by second-look laparotomy for restaging. Minimum follow-up after completion of therapy is 83 months., Patients: Fifty-five patients with advanced (stage III or IV), intermediate- or high-grade epithelial carcinoma of the ovary. Twenty patients had limited residual tumor (3 cm or less maximal tumor diameter) after initial cytoreductive surgery; 35 had extensive residual disease., Interventions: All patients received chemotherapy with hexamethylmelamine (150 mg/m2 body surface area orally on days 1 to 14), cyclophosphamide (350 mg/m2 intravenously on days 1 and 8), doxorubicin (20 mg/m2 intravenously on days 1 and 8), and cisplatin (60 mg/m2 intravenously on day 1). Courses were repeated at 4-week intervals; 41 patients (75%) received six courses; 10 patients received five courses, 3 patients received four courses, and 1 patients received three courses. Forty-seven patients underwent second-look laparotomy after completion of therapy; 8 had their disease restaged clinically., Results: Fifty-three of fifty-five patients (96%) had either partial or complete response to treatment. Nineteen of forty-seven patients who had a second-look laparotomy had a surgically documented complete response; 17 of these 19 patients began chemotherapy with limited residual tumor. Ten patients (18%) remain disease-free 83 to 108 months after therapy, whereas three additional patients died of other diseases without clinical evidence of recurrent ovarian cancer. Nine of twenty patients who began chemotherapy with limited residual tumor remain disease-free, as compared to only 1 of 35 patients with more extensive tumor (P less than 0.001). All long-term, disease-free survivors had surgically documented complete response at second-look laparotomy., Conclusions: Treatment with cisplatin-based combination chemotherapy after aggressive cytoreductive surgery should be considered standard treatment for advanced ovarian carcinoma. Our intensive, 6-month course of treatment produced results comparable to those previously reported with prolonged treatment.

A review of the literature and the experience of a residency program in internal medicine indicate that house officers have special problems during training. Some are shared by all residents, whereas others are unique to certain groups. These problems are caused by historical and cultural factors that have led to the current structure of many residency programs and often interfere with the parallel development of professional, personal and family growth. Program directors and chiefs of service need to be flexible and humane and should negotiate clear expectations with house staff to allow efficient functioning of the residency program and insightful personal growth.

The authors in this article present assessments by attending physicians of a seminar method to improve clinical teaching. An experimental study was conducted to determine whether or not the seminar method (a) is perceived by attending physicians as beneficial, (b) modifies the physicians' attitudes toward teaching, (c) enables attending physicians to define needed teaching changes, (d) motivates them to improve their teaching performance, and (e) is perceived as having long-term benefits. Forty-six inpatient attending physicians from four California institutions participated in the study. The physicians were randomly assigned to an experimental group which attended a seminar on clinical teaching or to a control group which received no such intervention. Questionnaires completed by the physicians indicated that the teachers who experienced the seminar method perceived it as beneficial, improved their attitudes toward clinical teaching, determined needed teaching changes, attempted to implement new teaching approaches, and perceived long-term benefits.

Six patients with poor prognosis carcinoma of the cervix were treated with external radiation therapy simultaneously with cisplatin, bleomycin, and vincristine. Toxicity was very mild with nausea and vomiting and mild myelosuppression being the major toxicities. At a median of 36 months follow-up, four of six patients are alive, three with no evidence of disease. The median survival after diagnosis is 25+ months. The data suggest that radiation therapy and cytotoxic therapy administered together in patients with advanced cervix carcinoma is well tolerated. Further study to determine therapeutic efficacy is warranted.

Graduate medical education in the setting of a large health maintenance organization (HMO) is a challenging enterprise with surmountable problems and tangible rewards. Ten years ago an independent residency program in internal medicine was begun at one of the largest medical centers in the Kaiser-Permanente Medical Care Program in Northern California. The residency program, at the Kaiser-Permanente Medical Center in Santa Clara, is described and compared with other graduate medical programs. Included are discussions of curriculum development, faculty, funding, medical school affiliation, and the role of HMOs in graduate training.

A patient developed recurrence of squamous carcinoma of the cervix in the episiotomy scar after vaginal delivery through the involved cervix. At the time of her radical hysterectomy, all margins and nodes were free of tumor, suggesting implantation at delivery as the etiology of the recurrence. Review of the literature revealed three other cases of episiotomy recurrence. All cases were either clinically unsuspected or had negative Papanicolaou tests during pregnancy. Careful surveillance and early therapy appear to give a more favorable prognosis for this unusual type of recurrence.

Sonograms of 27 patients with gestational trophoblastic disease were evaluated and categorized to newer concepts regarding the pathology and pathogenesis of this disorder. The patients were assigned to the following subgroups: 1) classical or complete mole; 2) partial or incomplete mole; 3) coexistent mole and fetus; 4) hydropic degeneration of the placenta; 5) locally invasive mole; and 6) metastatic trophoblastic disease, including choriocarcinoma. The utility of this categorization and of ultrasound in the diagnosis and subsequent management of these patients is presented.

From 1963 through 1977, 108 patients with stage IB cervical carcinoma were treated with radical hysterectomy and pelvic lymphadenectomy at the University of California, San Francisco. Forty-four of 48 patients followed for 5 or more years after surgery are known to be alive (5-year survival rate, 91.7%). The 5-year survival rate of all 108 patients using the life-table method is 93.4%. Complications in this series were few; only 1 patient developed a ureterovaginal fistula.

We evaluated the size-selective properties of the glomerular barrier in 30 patients in whom diabetic nephropathy was associated with urinary IgG losses. Neutral dextrans of graded size were used to characterize glomerular membrane-pore structure. A fractional IgG clearance (relative to freely permeable inulin) smaller or greater than 0.001 was used to distinguish patients with minor (group 1, N = 14) and major (group 2, N = 16) urinary IgG leakage, respectively. Fractional clearances of dextrans (theta D) of smaller size (radii 20-40 A) were similar, but those of larger dextrans (radii 42-60 A) were elevated in group 2 relative to group 1 patients. When plotted on log-normal probability coordinates, the correlation between theta D and radius in healthy subjects is linear, suggesting that glomerular pores form one population with a normal distribution. In diabetic nephropathy with urinary IgG leakage, however, theta D for large molecules was elevated and departed from linearity, suggesting a bimodal pore size distribution within the glomerular membrane. A pore model of solute transport revealed (1) the upper pore mode was highly permeable to large dextrans equivalent in size to IgG and (2) the fraction of glomerular filtrate permeating the large pores was greater in group 2 than in group 1 patients with diabetic nephropathy, 6% versus 3%, respectively. We conclude that urinary IgG leakage in diabetic nephropathy is determined by the development of a subpopulation of enlarged pores. The magnitude of urinary IgG losses appears to be a function of the membrane area-fraction occupied by the enlarged pores.

Twelve patients with malignant mixed mullerian tumors were treated with combination chemotherapy at Vanderbilt University Hospital from 1977 through 1981. Nine patients, all of whom received combination chemotherapy with hexamethylmelamine, cyclophosphamide, doxorubicin, and cisplatin (HCAP), were evaluable for response. Objective responses (all partial responses) were noted in 3 (33.3%) (response rate greater than 10% and less than 55% with 90% confidence limits), a minimal response was noted in one patient, and stable disease in four (50%) patients. Responders survived longer (calculated from the initiation of HCAP) than nonresponders (median 112 vs 19 weeks). These results are not at present statistically different from previous studies utilizing doxorubicin alone, cisplatin alone, the combination of doxorubicin and DTIC, or the combination of vincristine, actinomycin D, and cyclophosphamide.

The presence and/or depth of myometrial invasion of endometrial adenocarcinoma has important prognostic and therapeutic implications. Fifteen patients with histologically proven endometrial cancer underwent preoperative evaluation with sonography (US) and magnetic resonance imaging (MRI) to assess depth of invasion. Using criteria of greater than or equal to 50% of myometrial wall involvement as representing deep invasion, and less than 50% as superficial invasion, US was more accurate than MRI in five cases; in three MRI was more accurate than US; both MRI and US were equally accurate in four; neither was accurate in three. Polypoid lesions caused the greatest number of false positive reports of deep invasion with both MRI and US. Preliminary results indicate that US and MRI have promise as preoperative tests to assess the extent of myometrial invasion.

Two patients with resistant gestational trophoblastic neoplasms were treated with vinblastine, bleomycin, and cisplatin (Einhorn regimen). Both patients had failed multiple conventional therapeutic regimens including methotrexate, dactinomycin, high-dose methotrexate, and the modified Bagshawe regimen. Both patients achieved complete remissions and remain free of disease at 20 and 33 months following completion of therapy. The combination of vinblastine, bleomycin, and cisplatin is highly active in patients with resistant gestational trophoblastic neoplasms, and should be used as second-line therapy for poor-prognosis patients failing initial treatment.

Six women with Bowen's disease of the anogenital area were treated by total excision of the anal mucosa, perianal skin and, in some cases, partial vulvectomy. Two patients had foci of microinvasive squamous carcinoma. Adequate tumor margins were determined by frozen sections. The resulting mucosal and cutaneous defects were grafted with medium split-thickness skin grafts applied to the anal canal and sutured circumferentially to the rectal mucosa. Grafts were held in place by a finger cot inserted in the anal canal and stuffed with cotton balls. Patients were constipated five or six days with codeine. The skin grafts healed per primam. One additional patient was similarly treated for a chronic herpetic ulceration of the anus and healed. Contrary to dire predictions, all patients were able to distinguish between gaseous and solid rectal contents and sphincter function was preserved. In one patient, Bowen's disease has recurred in the grafted perianal skin.

Charts of 36 patients with clinical stage II endometrial adenocarcinoma over ten years were reviewed. All were staged before any treatment, in accordance with International Federation of Gynecology and Obstetrics (FIGO) guidelines. Although details of treatment varied, two main protocols were used. Fourteen patients were treated with the "standard" protocol involving external whole-pelvis radiation, followed by intracavitary cesium and then hysterectomy. In 1981, a "modified" protocol was introduced, which called for a hysterectomy immediately following intrauterine and vaginal cesium. External radiation therapy was given only to those patients found to have deep myometrial invasion or cervical involvement. Of 14 patients treated by this protocol, seven had no surgical indication for postoperative external radiation. There was no increase in recurrence in these patients, and the five-year survival rate was 76% for patients treated with the modified protocol compared with 65% for those who had standard therapy. Morbidity related to external radiation therapy occurred in two patients with the standard protocol and one patient who received pelvic radiation on the modified protocol.

The effects of a seminar method to improve the teaching of ward attending physicians were evaluated. Forty-six attending physicians from four institutions were randomly assigned to experimental and control groups. The method was evaluated to assess its effects on attending physicians' performances and attitudes, and impact on learners. Evaluation methods included ratings of videotapes of ward rounds, teachers' subjective assessments of both their teaching performances and their experiences in the study, and trainee ratings. Videotape ratings, the teachers' own assessments, and the trainees' assessments of the attending physicians' impact on learning were significantly different, favoring the experimental group (p less than 0.05). It is concluded that the seminar method can provide the basis for effective and feasible approaches for improving clinical teaching by attending physicians.

Two patients with alveolar soft part sarcoma of the uterus are described. One of the sarcomas was a submucosal nodule of the cervix, and the second was a minuscule, incidentally discovered lesion in the corpus. Both lesions contained periodic acid-Schiff-positive, diastase-resistant cytoplasmic granules, and characteristic membrane-bound crystalline inclusion bodies were demonstrated in the cervical lesion.

Fourteen patients with advanced ovarian carcinoma previously treated with chemotherapeutic agents including cisplatin were treated with vinblastine 0.1 mg/kg intravenously every week. There were no responses in 13 evaluable patients. The median survival was 19+ weeks following the initiation of vinblastine (VBL) therapy. Toxicity consisted of minimal myelo-suppression (WBC count less than 2500/microliter in 8/78 courses, WBC count less than 1500/microliter in 0/78 courses, platelets less than 150,000/microliter in 0/78 courses), nausea (4/13 patients), vomiting (2/13 patients), neuropathy (4/13 patients), and weakness and fatigue (6/13 and 5/13 patients, respectively). Although data derived from the human tumor stem cell assay (HTSCA) suggest that VBL may be an active agent against previously treated ovarian carcinoma, this study in patients with refractory advanced disease suggests that VBL is inactive (less than 20% response rate with 90% confidence levels) in that setting. Whether significant durable benefit can be achieved with VBL therapy in patients whose tumor is sensitive in the HTSCA remains to be seen.

Epidermoid carcinoma of the cervix was treated in 120 patients by means of exploratory celiotomy (with semitherapeutic excision of involved lymph nodes) followed by irradiation. The size of the field used for irradiation was determined by the presence and site of lymph involvement. Of 64 patients, metastatic cancer in pelvic nodes was found in 40, and in common iliac or aortic nodes in 24. Of the 2 groups, 8 and 3 patients, respectively, survived for 2 years or more. Irradiation to extended fields (using 5500 rads at 850 rads per week) controlled the cancer satisfactorily within the treated area, but the incidence of bowel complications was high. Recurrent carcinoma usually appeared as distant metastases outside the treatment area which suggests that patients with bulky primary lesions and positive nodes actually already have systemic disease as treatment is started. A safe yet effective dosage level for radiation therapy to extended fields has not yet been established.

Analysis of 4458 patients evaluated by cytology at the Department of Obstetrics and Gynecology, Kasr El-Einy Hospital, Cairo University, during the years 1981 to 1985 revealed that only 1.07% of these women had abnormal cytology. The prevalence rate for cervical intraepithelial neoplasia (CIN) was remarkably low, corresponding to 3.59/1000 for CIN grade I, 2.28/1000 for CIN II, and 1.16/1000 for CIN III. The mean age for CIN was 44.23 years while that for cervical cancer was 54.32. This low prevalence rate of CIN among Egyptian females, together with the late onset of the disease in comparison with other populations, calls for further study of the epidemiologic characteristics of this low-risk community.

Seventeen patients with advanced ovarian carcinoma who had minimal residual intraabdominal disease after six months of combination chemotherapy were treated with abdominopelvic irradiation. All 17 patients had residual intraabdominal tumor nodules with a cross-sectional diameter of less than 2 cm. Eleven had only microscopic residual disease at the time of irradiation. Fourteen have relapsed at a median of eight months after the completion of radiotherapy. All but two had intraabdominal recurrences. Myelosuppression was common and severe, causing marked delays or discontinuation of radiotherapy in ten of 17 patients. Patients receiving the entire planned dose of radiotherapy had longer disease-free survival (14 months median) than did patients receiving only partial doses (seven months median). However, six of seven patients receiving full dose irradiation have relapsed. Abdominopelvic irradiation in the schedule employed here is poorly tolerated and is not an effective salvage treatment in patients with limited or microscopic residual tumor following initial combination chemotherapy.

The milk-alkali syndrome is the association of hypercalcaemia and renal failure, with or without alkalosis, in the presence of absorption of excessive quantities of calcium, alkali, or both. Two patients with the milk-alkali syndrome are described, one representing an acute, reversible disorder and the other demonstrating a chronic syndrome with only partially reversible renal disease. Differential diagnosis is not difficult and is usually aided by the initial clinical evaluation as well as rapid response to conservative therapy. Because the initial stages of renal insufficiency are often fully reversible, the early identification and treatment of the milk-alkali syndrome can prevent progression to irreversible, chronic renal failure. Although non-absorbable antacids, H2 blockers, and sucralphate are the basis of modern treatment of peptic ulcer disease, the syndrome may still occur, especially in patients who self-treat symptoms of dyspepsia.

Sixteen patients with metastatic or recurrent carcinoma of the cervix were treated with combination chemotherapy consisting of mitomycin-C, vincristine, bleomycin, and cisplatin. Seven of 14 (50%) evaluable patients responded. In 2 patients all measurable disease resolved. Median duration of response was 4.5 months. Toxicity was severe and consisted of myelosuppression, pulmonary fibrosis, nausea, vomiting, stomatitis, asthenia, and fever. Two treatment-related deaths occurred. This combination chemotherapy regimen appears to have a response rate similar to other cisplatin containing regimens. Response durations were short and toxicity was severe.

Study Objective: To define the clinical features and results of systemic treatment in women with adenocarcinoma of unknown primary site involving predominantly the peritoneal surfaces., Design: Retrospective analysis of 18 patients treated at a single institution between 1978 and 1984., Patients: All 18 women had abdominal carcinomatosis and had no primary site identified at laparotomy. Nine patients had limited residual tumor (maximal tumor diameter, 3 cm or less) after initial cytoreductive surgery, and 9 patients had extensive residual disease., Interventions: In general, patients were treated according to standard guidelines for treatment of advanced ovarian carcinoma. All patients had initial laparotomy with attempted cytoreduction; of these 18 patients, 16 subsequently received cisplatin-based chemotherapy. Patients were restaged either clinically (10 patients) or with second-look surgery (8 patients)., Results: The median survival for all patients was 23 months. Five patients had complete response to chemotherapy, and three patients remain disease-free 41, 59, and 77 months after diagnosis. Patients with limited residual disease had longer median survival than did those with extensive residual disease (31 months compared with 11 months)., Conclusions: Women with adenocarcinoma of unknown primary site involving predominantly the peritoneal surface should be distinguished from other patients with adenocarcinoma of unknown primary site because they have a more indolent disease course, a higher response rate to systemic therapy, and a chance for long-term, disease-free survival after therapy. Although optimal treatment is undefined, we recommend that these patients be treated using the guidelines established for therapy of advanced ovarian carcinoma, including initial surgical cytoreduction followed by cisplatin-based combination chemotherapy.