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This article illustrates one agency's attempt to enhance communication between physicians and home health care providers. Elmhurst Memorial Home Health and Hospice developed four interdisciplinary care teams, each of which cover their entire geographic service area. Patients are assigned to these care teams based on their referring physician. This method of assignment allows the physician to establish contact with one team coordinator and a core group of caregivers. This model provides the opportunity for increased communication-and case conferencing at regularly established intervals. Physicians, staff, and patients are extremely satisfied with this model; it has proven to be a win-win strategy for all involved. Copyright © 2000 by Aspen Publishers, Inc. [ABSTRACT FROM AUTHOR]

Currently, three prediction models are used to predict a patient's risk of having Lynch syndrome (LS). These models have been validated in probands with colorectal cancer (CRC), but not in probands presenting with endometrial cancer (EMC). Thus, the aim was to determine the performance of these prediction models in women with LS presenting with EMC. Probands with EMC and LS were identified. Personal and family history was entered into three prediction models, PREMM(1,2), MMRpro, and MMRpredict. Probabilities of mutations in the mismatch repair genes were recorded. Accurate prediction was defined as a model predicting at least a 5% chance of a proband carrying a mutation. From 562 patients prospectively enrolled in a clinical trial of patients with EMC, 13 (2.2%) were shown to have LS. Nine patients had a mutation in MSH6, three in MSH2, and one in MLH1. MMRpro predicted that 3 of 9 patients with an MSH6, 3 of 3 with an MSH2, and 1 of 1 patient with an MLH1 mutation could have LS. For MMRpredict, EMC coded as "proximal CRC" predicted 5 of 5, and as "distal CRC" three of five. PREMM(1,2) predicted that 4 of 4 with an MLH1 or MSH2 could have LS. Prediction of LS in probands presenting with EMC using current models for probands with CRC works reasonably well. Further studies are needed to develop models that include questions specific to patients with EMC with a greater age range, as well as placing increased emphasis on prediction of LS in probands with MSH6 mutations.

Background: Granulosa cell tumors of the ovary are rare, primarily treated surgically. In advanced or recurrent disease, data are inconclusive regarding the benefit of either primary or adjuvant chemotherapy. Hormonal therapy has been suggested as an alternative treatment., Case: Our patient had three recurrences of estrogen receptor negative and progesterone receptor positive GCT, the first two treated by surgery with or without adjuvant chemotherapy. For the third recurrence, the patient received alternating biweekly cycles of megestrol and tamoxifen. Computed tomography showed stable disease at 6 months, partial response at 18 months, and complete response at 22 months. The patient continues on hormonal therapy and has been disease-free for 5 years., Conclusion: This study and others suggest that hormonal therapy may provide another option for treating these relatively rare tumors.

Purpose: To determine whether the addition of paclitaxel to doxorubicin plus cisplatin improves overall survival (OS) in women with advanced or recurrent endometrial carcinoma. Secondary comparisons included progression-free survival (PFS), response rate (RR), and toxicities., Patients and Methods: Eligible, consenting patients received doxorubicin 60 mg/m(2) and cisplatin 50 mg/m(2) (AP), or doxorubicin 45 mg/m(2) and cisplatin 50 mg/m(2) (day 1), followed by paclitaxel 160 mg/m(2) (day 2) with filgrastim support (TAP). The initial doxorubicin dose in the AP arm was reduced to 45 mg/m(2) in patients with prior pelvic radiotherapy and those older than 65 years. Both regimens were repeated every 3 weeks to a maximum of seven cycles. Patients completed a neurotoxicity questionnaire before each cycle., Results: Two hundred seventy-three women (10 ineligible) were registered. Objective response (57% v 34%; P <.01), PFS (median, 8.3 v 5.3 months; P <.01), and OS (median, 15.3 v 12.3 months; P =.037) were improved with TAP. Treatment was hematologically well tolerated, with only 2% of patients receiving AP, and 3% of patients receiving TAP experiencing neutropenic fever. Neurologic toxicity was worse for those receiving TAP, with 12% grade 3, and 27% grade 2 peripheral neuropathy, compared with 1% and 4%, respectively, in those receiving AP. Patient-reported neurotoxicity was significantly higher in the TAP arm following two cycles of therapy., Conclusion: TAP significantly improves RR, PFS, and OS compared with AP. Evaluation of this regimen in the high-risk adjuvant setting is warranted, but close attention should be paid to the increased risk of peripheral neuropathy.

Purpose: To determine whether pegylated liposomal doxorubicin (PLD) has antitumor activity in pretreated patients with persistent or recurrent endometrial carcinoma and to define the nature and degree of toxicity of PLD., Patients and Methods: Women with histologically documented recurrent or persistent measurable endometrial carcinoma and with failure of one prior treatment regardless of prior anthracycline therapy were enrolled. PLD was administered intravenously over a 1-hour period at a dose of 50 mg/m(2) every 4 weeks; the dosage was modified in accordance with observed toxicity., Results: Of 46 patients entered, 42 were assessable for response, as three were declared ineligible on central pathology review and one was not assessable for response. Forty had received prior chemotherapy, 11 hormonal therapy, and 29 radiation therapy. Doxorubicin had been given to 32 patients, carboplatin with paclitaxel to six, carboplatin to one, and fluorouracil to one. Four patients had partial responses lasting 1.1, 2.1, 3.3, and 5.4 months; the overall response rate was 9.5% (95% confidence interval, 2.7% to 22.6%). Three of these responses (in liver and in lymph node) occurred in patients who had progressed after doxorubicin with either paclitaxel or cisplatin. The median number of courses was 2.5 (range, one to 14). Toxicity was generally mild: only 25 patients experienced leukopenia, with a median WBC count of 2,900 (range, 800 to 3,900) at nadir. The only grade 4 toxicities were one episode each of esophagitis, hematuria, and vomiting. The median overall survival was 8.2 months., Conclusion: PLD has only limited activity in pretreated advanced, recurrent endometrial cancer, but further trials in anthracycline-naive patients and in previously untreated patients are ongoing. Its toxicity profile should permit its use in combination with myelosuppressive drugs.

Objective: The goal of this study was to assess the local groin recurrence of vulvar carcinoma in patients treated by complete groin node dissection with preservation of the fascia lata (GNDPFL)., Methods: This study is a retrospective chart review of 60 patients with Stage I-IV vulvar carcinoma who underwent radical vulvectomy and GNDPFL between 1990 and 1998. All superficial inguinal nodes and the deep femoral nodes on the anterior and medial surfaces of the femoral vein within the fossa ovalis were removed en bloc while sparing the fascia lata and the cribriform fascia over the femoral artery., Results: Of the 60 study patients, 14 patients had Stage I disease, 20 Stage II, 21 Stage III, and 5 Stage IV. The mean number of nodes removed was 10 per groin. Thirty-nine patients had benign nodes on groin dissection. None of these 39 patients developed cancer recurrence in the dissected groins. Twenty-one of the sixty study patients (34%) had malignant nodes on groin dissection. Of these 21 patients, 2 experienced cancer recurrence in the groins. Our study describes a groin recurrence rate of 7.6% in patients with fewer than three malignant unilateral groin nodes. Postoperatively, 13% of patients developed lymphedema and 15% formed lymphoceles., Conclusions: The zero groin recurrence rate in patients with negative nodes and the low rate of recurrence in patients with positive nodes indicate that groin lymphadenectomy with preservation of fascia lata is complete, therapeutic, and comparable to radical techniques of lymphadenectomy involving skeletonization of femoral vessels, resection of fascia lata, and muscle transposition., (Copyright 2000 Academic Press.)

Objectives: The search for effective systemic chemotherapy for endometrial cancer is ongoing. Complete responses to current drugs or regimens are infrequent, and overall survival for patients with disease not amenable to surgery or radiation therapy is poor. Dactinomycin has proven activity against a wide variety of solid tumors but has not been tested against endometrial cancer. Using pharmacokinetic data supporting an intermittent, single-dose schedule, this Phase II Gynecologic Oncology Group study was conducted to determine the antitumor activity and toxicity of dactinomycin in patients with persistent or recurrent endometrial adenocarcinoma., Methods: Eligibility was limited to patients with measurable disease, adequate renal, hepatic, and bone marrow function, and no more than one prior chemotherapy regimen. Treatment consisted of 2 mg/m(2) slow intravenous push of dactinomycin over 15 min with courses repeated every 4 weeks., Results: A total of 27 patients were entered in this study between April 1996 and September 1996; all were evaluable for toxicity and 25 were evaluable for response. Overall, 12/25 (48%) patients had received prior radiation therapy and all had received prior chemotherapy. Sites of measurable disease were pelvis (9 patients) and distant (16 patients). There was 1 complete response and 2 partial responses for an overall objective response rate of 12%. Aside from emesis (grade 3, 2 patients; grade 4, 2 patients) significant nonhematologic toxicity was rare. The most common toxicity was neutropenia (grade 3, 2 patients; grade 4, 10 patients)., Conclusion: Toxicity was deemed acceptable but the limited effectiveness of dactinomycin precludes further clinical development in this patient population., (Copyright 1999 Academic Press.)

From January 1993 through January 1996, 37 patients with unresectable squamous carcinoma of the cervix were entered on study and scheduled to receive oral isotretinoin 1 mg/kg per day with subcutaneous alpha interferon 6,000,000 units/day. A course was defined as 4 continuous weeks of therapy. The mean number of four-course cycles delivered was 1.8. One patient was ineligible because of wrong cell type and two were never treated. Thus, 34 patients were evaluable for toxicity. Eight patients were inevaluable for response. Five did not receive a complete 4-week course and three did not have additional tumor measurements; thus 26 were evaluable for response. Prior radiotherapy had been given to 25 patients and prior chemotherapy to 23 patients. There was no grade 4 neutropenia. The incidence of Gynecologic Oncology Group (GOG) grade 3 granulocytopenia and thrombocytopenia was 8.8% and 5.8%, respectively. Six patients (17.6%) developed grade 3 or worse nausea and vomiting. Four (11.7%) patients developed grade 3 neurologic symptoms. There were no complete responses and one partial response. The overall response rate was 3.8% (95% confidence interval, 0.1-19.6%). In this pretreated population, isotretinoin and alpha interferon in the dose and schedule employed exhibit minimal activity.

Twenty-nine evaluable patients with endometrial cancer were treated with amonafide 300 mg/m2 for 5 consecutive days every 3 weeks. Two partial responses (8%) were seen. Hematologic toxicity was severe or life-threatening in 13 patients occurring as follows: leukopenia in 13 patients (45%); thrombocytopenia in 10 patients (34%); granulocytopenia in 13 patients (45%); and anemia in four patients (14%). In view of the low response rate and high toxicity, this dose schedule of amonafide does not warrant further investigation in endometrial cancer.

Objective: To determine if DNA ploidy, hormone receptors, vascular space invasion (VSI), perivascular lymphocytes (PVL), and the oncogenes HER-2/neu, p53, and bcl-2 are independent prognostic indicators for lymph node metastasis and cancer recurrence in clinical stage I endometrial carcinoma., Methods: Among 349 patients with clinical stage I endometrial cancer 31 patients either had lymph node metastases when surgically staged or developed recurrent cancer. Using a case-control matched-pair technique, controls were selected for each of 24 cases by matching for age, histological grade, depth of myometrial invasion, performance of node dissection, and use of adjuvant radiation therapy. In a blinded fashion a pathologist reviewed all histopathology, and all molecular tests were performed on paraffin-embedded tissue samples. Statistical analysis was performed by chi2 and McNemar's tests., Results: VSI was the only histopathological factor significantly related to positive lymph nodes and cancer recurrence (P = 0.01), independent of grade and myometrial invasion. Aneuploidy, oncogene expression (p53, HER-2/neu, bcl-2), and hormone receptors were not significantly related to lymph node metastasis and cancer recurrence., Conclusions: The presence of vascular space invasion is a pathological factor independently associated with a risk of nodal metastasis and cancer recurrence in clinical stage I endometrial cancer. DNA ploidy, oncogene expression, and hormone receptor status do not have more predictive value than standard staging pathological criteria., (Copyright 1997 Academic Press.)

Purpose: Progestins represent the most widely used form of endocrine therapy in advanced or recurrent endometrial carcinoma. Based on encouraging response rates in breast cancer with high-dose megestrol acetate (MA) 800 mg/d, this phase II trial assessed response rates in patients with endometrial carcinoma treated with high-dose MA., Patients and Methods: Sixty-three patients with recurrent or advanced endometrial carcinoma were entered into this Gynecologic Oncology Group (GOG) study. Patients had either failed to respond to or were considered incurable with local therapy and had not received prior cytotoxic or hormonal therapy. MA 800 mg/d was administered orally in divided doses. Standard GOG toxicity criteria were used., Results: Of 63 patients entered, 58 were assessable for toxicity and 54 for response. Of 13 responders (24%), six (11%) had a complete and seven (13%) a partial response. Four of the responses lasted greater than 18 months. Twelve patients (22%) had stable disease. The response rate of patients with grade 1 or 2 lesions (11 of 30, 37%) was significantly higher (P = .02) than that of patients with more poorly differentiated tumors (two of 24, 8%). There was no difference in response rates comparing advanced versus recurrent disease, cell type, including papillary serous lesions, site of disease, prior radiation, age, or weight. The median progression-free survival (PFS) and overall survival intervals were 2.5 and 7.6 months, respectively. Grade 3 weight gain (> 20%) was seen in three patients and grade 3/4 hyperglycemia in three. Three deaths secondary to cardiovascular events were possibly related to therapy; diabetes was also a contributing factor in all three cases., Conclusion: High-dose MA is active in endometrial carcinoma, but appears to have no advantage over lower-dose progestins.

Background: An analysis of survival and complications related to the type of radical vulvectomy operation performed is reported., Methods: Clinical records and pathology reports were reviewed for the time period 1975-1989. The operation, complications, and site of recurrent disease were recorded., Results: The following types of surgical vulvectomies were used: radical vulvectomy (28 cases), the technique with three separate incisions (42 cases), and en bloc radical vulvectomy (94 cases). There was no significant difference in survival between the patients receiving en bloc radical vulvectomy or three separate incisions when analyzed by stage of disease. The following numbers of local/regional recurrences occurred among patients receiving the following treatment regimens: radical vulvectomy, seven; the technique with three separate incisions, six; and en bloc radical vulvectomy, five. Three patients treated by the separate-incision technique had a bridge recurrence. Complications were more frequent in those receiving the en bloc technique compared with those receiving the technique with three separate incisions: wound breakdown, 64% versus 38%, respectively (P = 0.005); wound infection, 20% versus 12%, respectively (P = 0.4); wound cellulitis, 21% versus 14%, respectively (P = 0.4); and lymphocyst formation, 28% versus 14%, respectively (P = 0.08). Drain placement or prophylactic antibiotics did not reduce wound infection or wound breakdown significantly. The most common sites of metastatic disease were the lungs and subcutaneous tissues of the leg. Hypercalcemia occurred in four patients, with the sites of metastatic disease being the subcutaneous tissue of the thigh (three patients) and pubic bone (one patient)., Conclusions: The technique with three separate incisions provides satisfactory survival results with less morbidity compared with the en bloc technique of radical vulvectomy.

A prospective phase II clinical treatment trial of 13 patients with previously untreated optimal surgically resected (< or = 1 cm stage III ovarian carcinoma was conducted at the University of Michigan Hospitals. The treatment regimen after surgical resection consisted of chemotherapy followed by whole abdomen and pelvic radiation therapy. Chemotherapy consisted of four cycles of 50 mg/m2 cisplatin and 1000 mg/m2 cytoxan. This was followed by whole abdomen radiation therapy with a planned total dose of 30 Gy to the whole abdomen and then a 20-Gy boost to the pelvis. Six of 13 patients received a paraaortic radiation boost. There was minimal acute toxicity, but delayed toxicity was encountered with 38% of patients developing a bowel obstruction. Nine patients had reassessment laparotomy: 5 second-look laparotomies and 4 laparotomies for bowel obstruction. Two of these 9 patients died of septic complications after surgery. Nine patients died with disease, 1 patient is alive with advanced disease, and only 3 patients are alive with no evidence of disease. Actuarial 3-year survival and progression-free interval was 26 and 20%, respectively. Primary treatment consisting of sequential chemotherapy and whole abdomen radiation in the dose and scheme utilized did not improve the survival over what could be expected utilizing one of these treatments alone. It was associated with increased delayed toxicity.

A review of 172 patients with squamous cell cancer of the vulva treated at the University of Michigan Medical Center from 1975-1989 was performed to compare the 1988 FIGO Staging System to the 1970 FIGO Staging System. The stage distribution according to the 1970 FIGO Staging System was stage I, 65; stage II, 44; stage III, 50; and stage IV, 13. The cumulative 5-year survival under the old system was stage I, 94%; stage II, 91%; stage III, 36%; and stage IV, 26%. The distribution changed under the 1988 FIGO system to stage I, 58; stage II, 36; stage III, 49; stage IVA, 16; and stage IVB, 13. The cumulative survival also changed to stage I, 94%; stage II, 89%; stage III, 71%; stage IVA, 19%; and stage IVB, 8%. The new FIGO stage distribution shifted for the worse due to the influence of positive lymph nodes found at the time of surgery. The survival was then analyzed for death from all causes. This was markedly decreased when compared to the cumulative corrected survival. This relates to the high number of other primary malignancies and the age of the patients. Among these 172 patients, other primary malignancies included squamous cell cancer of the cervix (11), squamous cell cancer of the vagina (2), endometrial cancer (3), squamous cell cancer of the lung (2), colon cancer (3), and others (6). An additional 5 patients died from myocardial infarction within 2 years of diagnosis. The new 1988 FIGO Staging System provides for better discrimination of survival between stages than the 1970 FIGO Staging System.

Ten patients with squamous cell carcinoma of the cervix metastatic to periaortic lymph nodes were treated with external-beam radiation therapy and synchronous infusion of intravenous 5-fluorouracil (5-FU) chemotherapy at doses of 350 mg/m2/day. The overall response rate was 90% with four complete responses (CR) and five partial responses (PR). The median duration of response was 11.8 months for CRs and 3.6 months for PRs. Toxicity was tolerable, with gastrointestinal symptoms and myelosuppression being noted most frequently. No patient experienced life-threatening toxicity. Median survival was 7.6 months, with only one patient being alive and free of disease at 2 years. In this pilot study we were unable to demonstrate a beneficial effect of continuous infusion of low doses of 5-FU chemotherapy concurrent with radiation therapy when compared to conventional radiotherapy in patients with advanced squamous cell carcinoma of the cervix.

Measurement from Christmas Island (2 degrees N, 157 degrees W) of long-term mean vertical motions in the tropical atmosphere using very-high-frequency wind-profiling Doppler radar show that there is a transition from downward motion in the free troposphere to upward motion in the upper troposphere and lower stratosphere. The observations in the free troposphere are consistent with a balance between adiabatic and diabatic heating and cooling rates in a clear atmosphere. Comparison of the results at Christmas Island during El Niño and non-El Niño conditions with earlier results obtained for stratiform rain conditions over Pohnpei, Federated States of Micronesia, show that cirrus clouds in the vicinity of the tropopause likely play an important role in determining the sense and magnitude of vertical motions in this region. These results have implications for the exchange of mass between the troposphere and stratosphere over the tropics.

One hundred seventy-two cases of patients with squamous cell cancer of the vulva treated at the University of Michigan Medical Center from 1975 to 1988 are reported. The mean age was 66 years with a range of 21 to 101 years. The distribution by stage included Stage I, 65; Stage II, 44; Stage III, 50; and Stage IV, 13 patients. Groin node dissections performed on 145 patients showed negative nodes, 58%; unilateral positive nodes, 28%; and bilateral positive nodes, 14%. The distribution of patients with positive nodes was influenced by stage: Stage I, 14%; Stage II, 23%; Stage III, 72%; Stage IV, 92%. The overall cumulative 5-year survival was 71% and this was significantly influenced by stage of disease: Stage I, 94%; Stage II, 91%; Stage III, 36%; Stage IV, 26%. Stages I/II and III/IV were combined for analysis. In Stages I/II, survival was significantly influenced by tumor grade while size, patient age, and lymph node status did not influence survival. In Stage III/IV, survival was significantly influenced by tumor size, node status, and number of positive nodes while grade, patient age, and tumor location did not influence survival. Squamous cell cancer of the vulva is effectively treated with radical surgery but advanced-stage disease with regional metastases significantly alters survival.

Thirty-four patients with recurrent/persistent squamous cell carcinoma of the vulva were treated at the University of Michigan Medical Center from 1975-1988. At follow-up, 19 patients (56%) were free of disease and 15 were dead of disease. Three patients developed a "bridge" recurrence, one patient each with original stages I, II, and IV. Two of these patients were free of disease and one patient died of disease. Ten patients had metastatic disease to the groin lymph nodes at the time of recurrence, and all of these patients are dead of disease. Therapy for the recurrence consisted of five radical vulvectomies (80% survival), four pelvic exenterations (25% survival), and 25 wide radical excisions (56% survival). The lymph node status was highly significant in predicting outcome, with zero of ten patients remaining free of disease when the lymph nodes were involved and 19 of 24 free of disease when the lymph nodes were uninvolved (P less than .0001). Factors that did not influence survival included the institution where the initial surgery was performed and the interval from initial therapy to recurrence. Twenty patients received their initial therapy at the University of Michigan and 12 (60%) were free of disease. Fourteen patients were referred from outside institutions for their recurrence and seven (50%) were free of disease. Nineteen patients had a recurrence within 2 years and nine were free of disease, ten patients recurred between 2-10 years of whom seven were free of disease, and five patients recurred after 10 years with three free of disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Although incontinence has been reported after radical vulvectomy, its relationship to operative technique, anatomy, and treatment has not been defined. Twenty-one patients having vulvectomies for vulvar cancer were prospectively evaluated preoperatively and postoperatively with urodynamic function studies. A portion of the urethra was removed in four patients undergoing radical vulvectomy, and 14 had a vulvectomy excision that came within 1 cm of the distal urethra. Six patients (28%) developed a change of continence, with three developing total incontinence, two stress incontinence, and one urge incontinence. All four patients who had a portion of the urethra excised developed stress or total incontinence. The other two patients with incontinence (one total, one urge) had the vulvectomy excision that came close to the urethra. No patient had a change in continence when surgery did not involve or come close to the urethra. When the four patients with a distal urethral resection were compared with patients in whom the urethra was not excised, there was a significant decrease postoperatively in functional urethral length (P less than .0001), anatomical urethral length (P less than .0001), and distal urethral pressure transmission ratios in Q3 (P = .004), Q4 (P = .02), and Q5 (P = .005); but no difference in urethral support (Q-tip test), flow rates, residual urine, bladder capacity, maximal urethral pressure, resting closure pressure, or squeeze pressure. Histologic examination of urethral specimens demonstrated that a portion of the compressor urethrae muscle was often excised. Radical vulvectomy by itself does not cause incontinence, but it would appear that removal of a portion of the urethra increases the chance of incontinence.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary melanoma of the vagina is a rare tumor associated with a poor prognosis. The clinical and pathologic features of 15 patients treated at the University of Michigan Medical Center and Bowman Gray School of Medicine are reviewed. The presenting symptom of bleeding was noted in 80% of the patients. The cumulative 5-year survival was 17.4%. Two patients survived more than 5 years. All melanoma tumors were of the nodular type, 66% were located in the lower one-third of the vagina, and all patients were found to have invasion greater than 3 mm at the time of diagnosis. The majority of recurrences were located in the pelvis, with the lung being the most common metastatic site. Data from the literature were incorporated with these patients' data in a meta-analysis. Tumor thickness (6 mm or less) significantly (P = .015) affected the disease-free interval. Tumor size (less than 3 cm) significantly (P = .024) influenced survival, whereas age, stage, tumor location, and tumor thickness did not. There was no significant difference in survival among patients treated by surgical resection, irradiation, or surgical resection plus irradiation. The type of surgery, whether radical or conservative, also did not influence survival. One patient had a complete response to high-dose irradiation fractions (greater than 400 cGy), and this form of irradiation in conjunction with surgical resection is presented as a treatment option.

In a retrospective study conducted at the University of Alabama at Birmingham, the University of Michigan, and the Mayo Clinic, 185 patients with previously untreated FIGO stage IB and IIA squamous cell carcinoma of the cervix were found to have nodal metastasis at the time of radical hysterectomy and pelvic lymphadenectomy. Of these patients, 103 received adjuvant pelvic irradiation. Cancer recurred in 76 patients; the median time to recurrence was 3.1 years. The prognostic significance of patient age, clinical stage, lesion diameter, number and location of nodal metastases, and use of adjuvant radiation therapy was determined by multivariate analysis. Only patient age (P = 0.0006), lesion diameter (P less than 0.0001), and number of nodal metastases (P = 0.0004) were noted to be significant factors in determining overall survival. Rates of recurrence were also related to these factors. Employment of these significant variables led to identification of four risk groups. In general, patients with small cervical lesions (diameter less than 1 cm) and no more than two nodes with metastases fell into the low-risk category; those patients with large cervical lesions (diameter greater than 4 cm) and more than two involved nodes fell into the high-risk category. All other patients were categorized into intermediate-risk groups. Ten-year survival was 92% in the low-risk group (n = 13), 70% in the low-intermediate-risk group (n = 66), 56% in the high-intermediate-risk group (n = 66), and 13% in the high-risk group (n = 20). This risk group classification identifies subgroups of early-stage cervical carcinoma patients found to have nodal metastasis at the time of radical hysterectomy that warrant appropriately selected adjuvant therapy.

Between 1964 and 1987 ten patients with vaginal melanoma were treated at The University of Michigan Hospital. Five of the six patients who underwent radical surgery had adequate information concerning the first site of relapse, and in four of these five, pelvic sites or locoregional lymph nodes were the first sites of recurrent disease. One of these patients developed a 17-cm pelvic recurrence, which responded with a 75% reduction in size 3 months after completion of radiotherapy given in high individual fractions (400 cGy X 11). Three patients were managed with local resection, and all developed recurrent locoregional disease. One patient presented with metastatic disease. We conclude that locoregional control of vaginal melanoma is difficult to achieve with surgery alone. We hypothesize that preoperative radiotherapy to the pelvis (500 cGy X 6 given 3 days a week to the whole pelvis with subsequent consideration for a vaginal boost field) may improve the poor rate of locoregional control of vaginal melanoma that is seen when surgery alone is used.

Inferior myocardial infarction results in Q waves in the inferior leads of the electrocardiogram (ECG). Left anterior hemiblock results in initial r waves in these leads. Thus the diagnosis of one in the presence of the other is difficult. It has been reported that inferior infarction can be diagnosed in the presence of left anterior hemiblock when there is a q wave or q equivalent in lead II, and that part of the inferior wall must be spared, to result in the initial r waves of left anterior hemiblock in leads III and aVF. We examined these concepts in 18 patients with such an ECG, by means of resting myocardial perfusion (thallium-201) scintigraphy. In 15 there were defects in the inferior left ventricular wall consistent with inferior infarction. In all of these patients there was sparing of part of the inferior wall: in nine, sparing of the posterior part, and in six, sparing of the anterior part. We conclude that in apparently isolated left anterior hemiblock, a q wave or q equivalent in lead II is an important sign, indicating the likelihood of associated inferior infarction.

High levels of angiotensin II were found in umbilical venous blood of babies delivered vaginally (40.3 pg-ml-1) and vaginally with epidural anaesthesia (66.8 pg-ml-1); low levels of angiotensin II were found in umbilical venous blood of babies delivered by Caesarian section (7.5 pg-ml-1) and in the peripheral blood of normal adults (7.92 pg-ml-1). There were no significant differences between these groups in the levels of plasma renin activity (PRA), although the mean values of PRA showed trends similar to those described for angiotensin II. It is suggested that the increase in PRA may account, in part, for the high levels in angiotensin II seen following vaginal delivery, but additional factors may also be involved.

Vibrio alginolyticus produces an extracellular collagenase which requires specific induction by collagen or its high-molecular-weight fragments. Peptone also induces collagenase during the late exponential and early stationary growth phases. The peptone inducers have been shown to have a broad molecular weight range between 1,000 and 60,000. The peptone inducers supported slow growth of V. alginolyticus when supplied as the sole nitrogen source in minimal medium. Digestion of the peptone inducers with purified V. alginolyticus collagenase resulted in a decrease in their inducing ability, whereas digestion with trypsin or alpha-chymotrypsin did not. This indicated that induction by the inducers required the presence of collagenase-sensitive bonds. Prolonged digestion of the inducers with collagenase did not completely eliminate the inducing ability of the inducers. The peptone inducers acted as inhibitors of collagenase. A minimal medium induction system has been developed which involves resuspending cells at high density in a medium containing succinate, (NH(4))(2)SO(4), KH(2)PO(4), and the peptone inducer. Cells grown in minimal medium induce earlier than cells grown on peptone, Casamino Acids, or tryptone. Collagenase production was shown to occur for 30 to 60 min in the presence of rifampin at levels which completely inhibit the incorporation of [(3)H]uracil into trichloroacetic acid-precipitable material. Chloramphenicol completely and immediately abolished collagenase production, which together with labeling studies has confirmed that collagenase production involves de novo synthesis of the enzyme. Both glucose and Casamino Acids repressed collagenase production, although synthesis of the enzyme continued for 30 to 60 min after their addition. The repression of collagenase production by glucose and Casamino Acids was more severe than the inhibition of enzyme formation due to addition of rifampin.

The production of nitric oxide (NO) in the stratosphere during each of the solar proton events of November 1960, September 1966, and August 1972 is calculated to have been comparable to or larger than the total average annual production of NO by the action of galactic cosmic rays. It is therefore very important to consider the effect of solar proton events on the temporal and spatial distribution of ozone in the stratosphere. A study of ozone distribution after such events may be particularly important for validating photochemical-diffusion models.

In a retrospective study, 185 patients with previously untreated stage IB or IIA (International Federation of Gynecology and Obstetrics) squamous cell carcinoma of the cervix were found to have pelvic nodal metastasis at the time of Wertheim hysterectomy and bilateral pelvic lymphadenectomy. Of these patients, 103 received adjuvant whole-pelvis irradiation and 82 received no adjuvant therapy. Median dose of pelvic irradiation was 5000 cGy. Among the irradiated patients, in 75% the dose was 5000 cGy or greater. Matching irradiated and nonirradiated patients according to stage, tumor size, and number and location of positive nodes yielded 60 pairs. Mean length of follow-up was 3.9 years for the 60 irradiated patients and 5.8 years for the non-irradiated patients. Kaplan-Meier overall and cancer-specific survival estimates for the two groups were not significantly different (P greater than 0.30). During the follow-up period, 21 surgery-only patients and 22 patients treated with adjuvant radiotherapy had recurrence, but adjuvant radiotherapy decreased the proportion of recurrences occurring in the pelvis alone--27% compared with 67% in the surgery-only group (P = 0.01).

Pelvic exenteration, although performed most frequently for recurrent squamous cell carcinoma of the cervix and vagina, has been used in selected patients with pelvic sarcoma. Nine patients with various histologic types of sarcoma treated by pelvic exenteration are reported. During this 23-year time period, 46 patients with sarcoma were evaluated for possible exenteration. Patients with embryonal rhadomyosarcoma (sarcoma botryoides) were excluded because these pediatric tumors are now treated with less radical operative procedures, plus radiation and chemotherapy. Six patients had exenteration as primary treatment, and three patients had exenteration as secondary treatment. Four patients developed recurrent disease (mean 5.2 months), and all four died of disease. Five patients were alive at 5 and 10 years, for an absolute survival of 55%. All three patients with mixed mesodermal tumors died of recurrent disease, compared with 83% survival for patients with other sarcoma types. Pelvic exenteration may play a limited but important role in the therapy of pelvic sarcoma.