The impact of pre-therapy extraperitoneal surgical staging on the evaluation and treatment of patients with locally advanced cervical cancer.

OBJECTIVE: The use of extraperitoneal surgical staging prior to treatment in patients with bulky or locally advanced cervical cancer allows the detection and treatment of disease beyond the standard pelvic radiation fields. This study was conducted to evaluate the impact of extraperitoneal surgical staging in the treatment and outcome of patients with locally advanced cervical cancer. METHODS: 51 patients with locally advanced cervical cancer treated between 1985 and 1998 were retrospectively reviewed. Information on morbidity, usefulness, and results of surgery and patterns of disease recurrence were obtained. Survival distributions were calculated by the Kaplan-Meier product limit method and compared with the log-rank test. RESULTS: All 51 women were surgically staged by an extra-peritoneal approach. Preoperative CT scans (n=27) when compared with surgical findings showed sensitivity for pelvic and para-aortic lymph node metastasis of 39%, specificity of 88%, positive predictive value of 39% and negative predictive value of 88%. Lymph node metastases were found in 30/51 patients (59%). There were no significant treatment delays or surgical morbidity as a result of extra-peritoneal surgical staging. In 21 patients (41%), the highest level of involved nodes was in the pelvis and they were treated with pelvic radiation. The para-aortic nodes were involved in nine patients (18%) and were treated with extended field radiation. All patients also received concurrent radiosensitization with chemotherapy. The estimated survival for the entire group was 60% at 5 years. For node negative patients, estimated 5-year survival was 67% while it was 54% for all node positive patients (p=0.17). Analysis according to anatomic site of involved nodes showed that the estimated 2-year and 5-year survival for those with pelvic nodal involvement was 81% and 64%, respectively. However, in the group of nine patients with para-aortic nodal disease, the estimated 2-year survival was 44%. Five (56%) were dead of disease with a median time to death of 16.0 months and four patients (44%) were alive with a median duration of follow up of 16.1 months. There was a statistically significant difference in survival for the group of patients with positive pelvic nodes only compared to the group with positive para-aortic nodes (p=0.03). The estimated 5-year survival by FIGO stage was 80%, 70% and 51% for stages Ib, II, III, disease, respectively. Factors that did not significantly affect survival included age, histology and type of chemotherapy. CONCLUSIONS: Pre-therapy extra-peritoneal surgical staging resulted in treatment modification in 18% of patients with locally advanced cervical cancer. The morbidity from surgery and subsequent radiation therapy was acceptable. The procedure is recommended to allow for individualization of treatment in patients with local-regional cervical cancer.

Evaluation of the possible protective role of adeno-associated virus type 2 infection in HPV-associated premalignant disease of the cervix.

OBJECTIVE: Our objective was to examine the prevalence of adeno-associated virus (AAV) infection in women with normal cervical smears and those with HPV-associated cervical intraepithelial neoplasia (CIN). METHODS: HPV typing was performed on DNA from cervical smears of 211 women with CIN (CIN 1 = 83, CIN 3 = 128) and 433 healthy women who had a normal cervical smear. HPV typing was performed on all cases and controls using type-specific oligonucleotide primers (HPV 16, 18, 31, 33). AAV DNA was amplified by nested PCR from the same samples. The amplified DNA were separated on 2% agarose gels, blotted, and hybridized to AAV-2 DNA labeled by random priming with [alpha-(32)P]dCTP to confirm specificity of amplification. RESULTS: A total of 131 cases of CIN were positive for one of the HPV types either alone or in combination. HPV 16 was present in 120 (57%) cases, HPV 18 in 15 (7%), HPV 31 in 27 (13%), and HPV 33 in 15 (7%) and there were multiple HPV types detected in 34 (16%) cases. All of the controls were selected to be negative for HPV. A total of 6/433 (1.4%) control cervical smears and 4/211 (1.9%) of CIN (CIN1 = 2; CIN3 = 2) contained AAV DNA. No correlation between AAV and any clinical feature was observed. CONCLUSIONS: These results are different from some that have been previously published and suggest that AAV DNA is not frequently present in either normal control cervical samples or cervical intraepithelial neoplasia. This does not support the hypothesis that AAV may be protective against cervical cancer. Further research is necessary to understand the natural history of AAV infection and its role in human disease.

Serous adenocarcinoma of the uterus presenting as paraneoplastic cerebellar degeneration.

Paraneoplastic cerebellar degeneration is a rare complication of cancer and is most frequently associated with lung, ovary, and breast cancers as well as Hodgkins lymphoma. A 74-year-old female with a past history of breast cancer presented with vomiting, ataxia, slurred speech, and dizziness. Her serum chemistry, thyroid and liver function tests, acetylcholine antibodies, serum cortisol, CT, and MRI imaging were all normal. Serum testing for anti-YO antibodies was positive. Further evaluation including CT of the abdomen and pelvis revealed endometrial thickening. Subsequently, an endometrial biopsy showed a poorly differentiated serous adenocarcinoma. Surgical staging was consistent with a stage IIIc serous adenocarcinoma of the uterus. The risk factors, symptoms, signs, differential diagnosis, and clinical and antibody associations of the paraneoplastic cerebellar degeneration syndrome are reviewed. In addition, an efficient approach to the diagnostic evaluation of such patients is proposed.

Necrosis of myometrial choriocarcinoma with fulminating sepsis complicating chemotherapy for trophoblastic tumor.

We report a patient who developed metastatic gestational choriocarcinoma following delivery of a normal, healthy child that, however, was anemic and required blood transfusion. The patient developed secondary postpartum hemorrhage over a period of several weeks and required curettage and myometrial contractants to control the bleeding. At the time of diagnosis the patient had extensive pulmonary metastases and ultrasound showed full penetration of the myometrium by tumor. Immediately following the second course of chemotherapy with etoposide, methotrexate, and actinomycin D, alternating with cyclophosphamide and vincristine, the patient developed sepsis associated with a uteroperitoneal fistula and required hysterectomy. The sepsis was associated with disseminated intravascular coagulopathy and adult respiratory distress syndrome. However, the patient's tumor was exquisitely sensitive to chemotherapy and with good intensive care unit support and chemotherapy the survived without residual scar except for the loss of reproductive function. There are two lessons to be learned from these events: (1) The syndrome of secondary postpartum hemorrhage with a fetus that is anemic spells a diagnosis of choriocarcinoma; and (2) color Doppler flow vaginal ultrasound performed at the time of presentation of trophoblastic tumors may be useful to show full penetration of the myometrium by tumor which may be a warning of possible scar rupture in a subsequent pregnancy.

Evidence-based medicine: how do we find the evidence?

Applying evidence-based medicine in clinical practice is an important advance in the attempt to improve clinical care. However, if appropriate evidence is unobtainable, it obviously cannot be used. Several resources are available to find quality studies in our field, detailing successes as well as shortcomings with respect to many aspects of patient care. Databases such as MEDLINE and EMBASE are helpful, but they require specific strategies to maximize the efficiency and comprehensiveness of literature searches. In addition, they are incomplete and thus do not allow access to many good studies. In an attempt to remedy this dilemma, the Cochrane Library was created. This database contains systematic reviews on a large number of subjects as well as a controlled trial registry. It approaches the criteria of an ideal database, and has proved to be an invaluable tool in the practice of evidence-based medicine.