Outcome assessment of home parenteral nutrition in patients with gynecologic malignancies: what have we learned in a decade of experience?

Recent improvements in parenteral nutrition and home care delivery systems have made home parenteral nutrition (HPN) a reality for patients with gynecologic malignancies. The records of 61 patients with gynecologic cancers who received HPN between 1981 and 1990 were retrospectively reviewed for outcome, complications, survival, and quality of life. Indications for HPN included mechanical bowel obstruction, short bowel syndrome, malnutrition during cancer therapy, or complications of cancer therapy. Ninety-two percent of patients had disease present at initiation of HPN. Fifty-six percent of patients had ovarian cancer; the remainder had other gynecologic malignancies. The vast majority of patients had prior surgery, radiotherapy, or chemotherapy before receiving HPN. Sixty-four percent of patients underwent cancer treatment (chemotherapy, surgery, or radiation) during HPN. Median survival for ovarian cancer patients on HPN was 72 days and 52.5 days for nonovarian patients (not statistically significant, P = 0.95). Minimal complications were noted from HPN with 9% of hospitalizations due to HPN. Nutritional parameters initially improved in most patients on HPN but then decreased prior to death. Quality of life parameters improved significantly in patients on HPN as compared to pre-HPN status (P < 0.05). In conclusion, HPN is a viable option in gynecologic cancer patients and offers improved quality of life even during the terminal phase of their illness.

Uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis: the University of Minnesota experience.

OBJECTIVE: To present the experience of a large referral center with patients with the rare but specific syndrome of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. DESIGN, PATIENTS: Between 1953 and 1991, 15 patients with the syndrome were evaluated by the authors; each patient's records were carefully reviewed. MAIN OUTCOME MEASURES: For each patient, the clinical course, specific anatomic findings, treatment(s) offered, and obstetrical outcome are presented. RESULTS: The specificity of the association of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis was confirmed by our series, the largest in the literature to date. The findings suggest a specific development anomaly of the müllerian ductal system, probably secondary to a wolffian duct anomaly. The most common clinical presentation was that of the onset of pelvic pain and/or dysmenorrhea shortly after menarche, in association with the finding of a vaginal/pelvic mass. When a communication between the two sides existed, symptoms of abnormal vaginal discharge and bleeding were common. Optimal outcome appears to have occurred for patients initially managed using a conservative surgical approach, i.e., simple vaginal septum resection combined with conservative treatment of associated endometriosis. Obstetrical outcome in our patients was similar to that in patients with the more common combination of uterus didelphys and sagittal vaginal septum. CONCLUSION: A greater awareness of the syndrome of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis should lead to its prompt diagnosis, allowing for early and appropriate surgical intervention as well as decreased long-term morbidity.

Serum levels of macrophage colony-stimulating factor in patients with ovarian cancer undergoing second-look laparotomy.

OBJECTIVE: The purpose of this study was to evaluate the prognostic significance of macrophage colony-stimulating factor serum levels in patients with ovarian cancer undergoing second-look laparotomy. STUDY DESIGN: The presurgical serum levels of macrophage colony-stimulating factor from 33 consecutive patients with ovarian cancer undergoing second-look laparotomy were determined and compared with those of 50 healthy control subjects. Mean differences in groups were evaluated with the Student t test. RESULTS: Sixteen of 33 patients had a positive result at second look and a mean serum macrophage colony-stimulating factor level of 2.31 +/- 1.45 ng/ml. Seventeen of 33 patients had a negative result at second look and a mean macrophage colony-stimulating factor level of 1.90 +/- 0.86 ng/ml (p greater than 0.05). The mean macrophage colony-stimulating factor level in the control group was 1.20 +/- 0.51 ng/ml. This was statistically lower than the mean level found in patients with a negative second-look result (p less than 0.05). CONCLUSION: Regardless of tumor status, serum macrophage colony-stimulating factor levels tend to be elevated at the time of second-look laparotomy.

Pseudomyxoma peritonei--experience from a tertiary referral centre.

Pseudomyxoma peritonei is a clinical diagnosis of massive abdominal swelling by a gelatinous material, produced usually from an ovarian or appendiceal primary. It is a rare entity that is usually histologically benign but behaves clinically in a malignant fashion with recurrent growth, although not demonstrating histological stromal invasion. The disease remains localized to the peritoneal cavity and the clinical course is one of repeated episodes of intestinal obstruction caused by extrinsic compression that seem only to be relieved by surgical debulking. Variable responses have been obtained with adjuvant chemo-, radio- and immunotherapy, but these isolated responses are unable to be reproduced and so there is no accepted adjuvant treatment for this disease.

Multimodality therapy for advanced and recurrent vulvar squamous cell carcinoma. A pilot project.

From 1985 to 1989 eight women with advanced or recurrent vulvar carcinoma were treated at the Women's Cancer Center of the University of Minnesota Hospital and Clinic. Each received a combination of 5-fluorouracil, mitomycin C and cisplatin during radiotherapy. Five of the eight women who underwent posttreatment radical vulvectomy had acceptable operative morbidity. Six patients experienced a complete clinical response. Of them, one had microscopic residual disease in the surgical specimen. One patient with recurrent vulvar carcinoma experienced progression of disease on therapy. One death was attributable to chemotherapy toxicity, and two patients died of intercurrent disease. The overall survival rate at 27 months was 33%. This multimodality approach to the treatment of advanced vulvar carcinoma should be considered when designing a therapeutic approach to treating extensive or resistant vulvar carcinoma.

Surgical intervention following multimodality therapy for advanced cervical cancer.

From 1978 through 1986, 183 women with cervical carcinomas underwent pretreatment extraperitoneal surgical staging followed by definitive radiation therapy. Overall 10-year actuarial relapse-free and survival rates were both 64%. There were a 20.2% overall incidence and 31.6% actuarial incidence of patients with subsequent abdominal surgery. Of the 47 total surgical procedures, most frequent were 15 repairs of radiation-related bowel injury (11 patients), 11 colostomies for tumor-related obstruction or fistula and 10 explorations for possible exenteration. Only one exenteration could be performed. Other operations consisted of 5 hysterectomies, 3 negative explorations for suspected recurrence, 1 cholecystectomy, 1 small bowel obstruction following surgical staging, and 1 sigmoid resection for colon cancer. Seven patients had multiple operations. Logistic analysis revealed cervix size, pelvic node status, periaortic lymph node status, and thin physique to be significant predictors of overall recurrence, while cervix size was the only significant predictor of exploration for exenteration. Tumor-related colostomies and radiation complications tended to occur in lower and higher clinical stages, respectively. There was a trend toward greater survival in patients with surgery for radiation complications.

Primary malignant melanoma of the vagina: a clinicopathological analysis of 10 cases.

We retrospectively analyzed clinicopathological findings in 10 cases of primary malignant melanoma of the vagina. The main presenting symptoms were vaginal bleeding, vaginal discharge, and feeling of a mass. The tumors were predominantly located in the lowest one-third and in the anterolateral aspect of the vagina. Patients underwent various surgical procedures, radiation therapy, and chemotherapeutic modalities. The mean survival time and the recurrence time from the time of diagnosis were 15 and 8 months, respectively. The tumors were examined for histological characteristics of cell type, presence of melanin pigment, depth of invasion, vascular invasion, intraepithelial spread, junctional activity, and mitotic count. Of all these histological variables, the mean survival time had a significant correlation to mitotic count (P less than 0.04). We concluded that patients with lower mitotic counts (less than 6 per 10 HPF) had better survival (21 months) compared to patients with mitotic counts greater than 6 per 10 HPF who had a mean survival of only 7 months.

Prognostic significance of steroid receptors measured in primary metastatic and recurrent endometrial carcinoma.

Forty-two cases of recurrent and 14 cases of advanced clinical stage (III and IV) endometrial carcinoma are presented, in which progesterone and estrogen receptors from the metastatic sites were measured. Mean survival time (time from recurrence or, in advanced stages, from the time of diagnosis to death or last follow-up), mean total survival time (time from diagnosis to death or last follow-up), and mean time to recurrence (time from diagnosis of primary tumor to the time of recurrence) were positively correlated with positive progesterone and estrogen receptor status and with histologic grade of tumor. No correlation was found with age, clinical stage, depth of myometrial invasion, or site of metastasis. However, when multiple variables were considered with the Cox regression model, the combination most highly correlated with survival included progesterone receptor, grade of tumor, and site of metastasis (pelvis vs. other sites). All differences were statistically significant (p less than 0.05). We conclude that measurement of progesterone and estrogen receptors in metastatic or recurrent endometrial tumors may be used as an additional prognostic variable.

The role of surgical debulking in cancer of the uterine cervix.

From 1978 to 1985, 159 women with advanced cervical cancer received definitive radiation therapy following extraperitoneal surgical staging including pelvic lymph node dissection and periaortic lymph node sampling. Relapse-free survival was a strong function of peritoneal and nodal metastases but was independent of clinical stage. The 5-year relapse-free rate fell from 86% in women without pelvic node metastases to 0% in those with unresectable pelvic node metastases. Women with microscopically positive pelvic node metastases had virtually the same (56%) relapse-free rate as those with grossly positive but completely resected metastases (57%). The overall pelvic failure rate was 16.4% and was significantly higher in women with unresectable pelvic node metastases. Periaortic and peritoneal metastases substantially increased the probability of recurrence. Although histologic grade was prognostically significant, histopathologic category was not. Severe enteric morbidity occurred in 3.6% of patients treated solely to the pelvis and in 7.9% of patients treated to the pelvis and periaortics. Therapeutic implications of debulking pelvic node metastases are discussed.

Resection of the pubic bone as an adjunct to management of primary, recurrent, and metastatic pelvic malignancies.

Patients with locally advanced vulvovaginal carcinomas with pubic bone encroachment or fixation pose a treatment dilemma. The purpose of this study was to evaluate the outcome in 12 patients who have undergone pubic bone resection at the University of Minnesota as part of treatment of locally extensive primary, recurrent, or metastatic vulvovaginal carcinomas. Six patients with primary vulvar carcinomas and six patients with recurrent or metastatic vulvovaginal carcinomas underwent bone resection as part of their surgical therapy. Survival in the primary treatment group was 50%, with no local recurrences. Survival in the recurrent/metastatic disease group was 83%, with a follow-up time of 9 months to 15 years. One vulvar and one groin recurrence have occurred in the recurrent/metastatic group. Pubic bone resection added little to surgical morbidity and gave good functional results. Pubic bone resection, in combination with radical extirpative procedures, is an option for treatment of patients with locally extensive vulvovaginal carcinomas, particularly those with previous radiation therapy.

Pretreatment surgical staging in cervical carcinoma: therapeutic efficacy of pelvic lymph node resection.

Pretreatment surgical staging in cervical carcinoma has been studied extensively to define a group for extended field radiation or adjuvant chemotherapy. A theoretical, but as yet unproved, benefit from this surgery is the resection of large, presumably radioresistant, pelvic nodal metastases before radiation therapy. One hundred fifty-six patients were divided by pelvic nodal status after surgical staging with excision of pelvic lymph nodes: group A, negative (n = 81); group B, microscopic metastases only (n = 18); group C, macroscopic nodal metastases resected (n = 48); and group D, unresectable nodal metastases (n = 9). The 5-year recurrence-free survival in group C (51%) approached that of group B (57%) and was significantly better than that of group D (0%). The groups are compared by International Federation of Gynecology and Obstetrics stage, grade, histology, and incidence of paraaortic metastases. Patterns of recurrence imply improved pelvic control in patients undergoing resection of pelvic nodal metastases. Surgical removal of pelvic nodal metastases before radiation therapy is recommended.

Prognostic significance of the presence of human papillomavirus DNA in patients with invasive carcinoma of the cervix.

Cases of invasive carcinoma of the uterine cervix were analyzed to determine whether the presence or absence of human papillomavirus (HPV) DNA in the neoplasms was a contributing factor to their outcome. The presence of HPV DNA was evaluated using in situ hybridization on formalin-fixed, paraffin-embedded tissue sections. Eighty-five patients with cervical carcinoma who had been surgically evaluated were included in the study. Data from these patients was analyzed retrospectively to determine survival, recurrence, presence of nodal metastases, tumor grade, mode of therapy, peritoneal fluid cytologic results, and age in relation to presence or absence of HPV DNA. No significant statistical differences were found between the HPV-16-positive, HPV-18-positive, and HPV DNA-negative patients.

Tolerance and preliminary results of simultaneous therapy with radiation and cisplatin for advanced cervical cancer.

From 1982 through 1985, 49 women with advanced cervical cancer were treated with concurrent radiation and cisplatin to assess tolerance to the combined modality regimen and its efficacy in comparison to historical controls at the same institution. Eligibility criteria included clinical stage IV disease; para-aortic lymph node metastases; and bilateral, unresectable, and/or multiple (greater than 3) pelvic node metastases. Nodal status was assessed by extraperitoneal surgical staging in the majority of patients with clinical stage I-IVA disease. There was no increase in acute or chronic toxicity compared to historical controls. No patient required reduction of the planned dose of radiation because of acute toxicity. Comparison with historical controls suggests a modest improvement in relapse-free survival in the cisplatin-treated group with positive para-aortic nodes (59% vs. 54% at 2 yr and 59% vs. 42% at 3 yr). We conclude that adjuvant cisplatin can be given simultaneously with radiation for advanced cervical cancer without excessive toxicity or compromise of the radiation regimen. However, confirmation of the modest improvement in relapse-free survival rates for patients with positive para-aortic nodes and identification of other subsets of patients who may benefit will require a prospective randomized trial.

Infectious morbidity in gynecologic cancer.

A retrospective investigation of infectious morbidity in gynecologic oncology patients documented that 54 (11%) of 494 patients and 68 (6%) of 1204 patient admissions were complicated by a serious infection. The highest rate of infectious morbidity by admission was 21%, occurring in patients admitted for cancer of the vulva. The highest surgical infectious morbidity, 22%, occurred in patients admitted for cervical cancer. Important factors in determining infection risk include multiple host factors, radical surgical procedures, factors inherent in the tumor itself, and additional irradiation and chemotherapy. These serious polymicrobial infections dictate intelligent selection of antimicrobials and appropriate monitoring to anticipate complications inherent in antimicrobial therapy. beta-Lactamase induction, superinfection, nephrotoxicity, and necrotizing enterocolitis are documented problems in these patients.

Effect of cis-platinum on tolerance to radiation therapy in advanced cervical cancer.

Women with advanced carcinoma of the uterine cervix are at high risk for the development of local, regional, and distant metastases. Thus, both effective systemic agents and radiosensitizers could be useful adjuvants. However, because a substantial fraction of women with advanced cervical neoplasms are cured with radiation therapy, such experimental agents must not compromise the administration of conventional therapy. Cis-platinum is particularly appealing as it has both radiosensitizing properties and activity in metastatic cervical cancer. The present study examined the effect of weekly cis-platinum on radiation tolerance in 29 women with advanced cervical cancers. Although toxicity was acceptable, no marked enhancement in survival could be demonstrated.

Prognostic importance of progesterone and estrogen receptors in cancer of the uterine cervix.

Tissue levels of cytosolic estrogen receptors (ERc) and progesterone receptors (PRc) have been shown to have prognostic meaning in hormonally responsive cancers arising in the breast and endometrium. Although carcinomas of the uterine cervix rarely respond to hormonal manipulation, the normal cervical stroma and epithelia contain ERc and PRc. To study the prognostic value of these receptors, 65 cervical carcinomas for ERc and PRc were assayed before initiation of surgical or radiation therapy. In premenopausal women, logistic models demonstrated that clinical stage, surgical stage, and receptor level independently predict survival. If confirmed in further studies, ERc and PRc may prove to be useful prognostic factors in the management of cervical carcinomas.

Concurrent weekly cis-platinum and radiotherapy in advanced cervical cancer: a preliminary dose escalating toxicity study.

Concurrent weekly cis-platinum in a dose escalating manner and conventional radiotherapy was evaluated in advanced cervical cancer. The toxicity of weekly cis-platinum given 2 hr before standard fractionation of radiotherapy was assessed using the modified GOG toxicity criteria. Sixteen patients having parameters indicating high risk for conventional therapy failure including positive pelvic and paraaortic nodes and intraperitoneal spread were entered. There was no life-threatening toxicity. The toxicity of the administered chemotherapy was only moderate. Patient compliance was good as at the 20 mg/m2 dose level, 79% of the prescribed doses were administered. The use of adjuvant cis-platinum in poor prognosis advanced cervical cancer merits further study.

Cytoplasmic estrogen and progesterone receptors as prognostic parameters in primary endometrial carcinoma.

Eighty-six cases of primary endometrial carcinoma were assayed for the presence or absence of cytoplasmic estrogen and progesterone receptors by the saturation point dextran-coated charcoal assay. The levels of cytoplasmic progesterone receptors and estrogen receptors were analyzed according to clinical stage, histologic type and grade of the tumor, presence or absence of lymph node metastases, myometrial invasion, and survival. The cases were divided into positive and negative receptor groups with levels chosen of greater than 10 fmol/mg of cytosol protein for progesterone receptor and 5 fmol/mg of cytosol protein for estrogen receptor as discrimination points. Statistically significant survival differences were found between estrogen receptor positive versus estrogen receptor negative patients, progesterone receptor positive versus progesterone receptor negative patients, and estrogen positive-progesterone receptor positive versus estrogen negative-progesterone receptor negative patients. Mean cytoplasmic estrogen and progesterone receptor levels were inversely proportional to grade. This report suggests that treatment protocols should be devised to reflect the prognostic significance of receptor status.