A phase I study of docetaxel as a radio-sensitizer for locally advanced squamous cell cervical cancer.

OBJECTIVES: This study was designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly docetaxel with concurrent radiotherapy (RT) for the primary treatment of locally advanced squamous cell carcinoma of the cervix. METHODS: Eligible patients included those with locally advanced squamous cell cervical cancer without para-aortic lymph node involvement. Docetaxel dose levels were 20 mg/m(2), 30 mg/m(2) and 40 mg/m(2) given intravenously weekly for 6 cycles. Three patients were to be treated at each dose level and 6 to receive the MTD. RESULTS: Fifteen patients completed 4-6 cycles of chemotherapy. One of three patients experienced 2 delayed grade 3 severe adverse events (SAE) at the 20 mg/m(2) dose level consisting of colonic and ureteral obstruction. At the 30 mg/m(2) dose level, 1/4 patients had a probable treatment-related celiotomy due to obstipation and a necrotic tumor. Of the 8 patients treated at the 40 mg/m(2) dose level, 1 experienced grade 3 pneumonitis, likely treatment related. Overall, 10/15 (67%) experienced grade 1 or 2 diarrhea, 6 had grade 2 hematologic toxicity, and 2 had grade 2 hypersensitivity. 10 of 16 patients (67%) had no evidence of disease with follow-up ranging from 10-33 months (average 23 months). CONCLUSIONS: The recommended phase II dose of docetaxel administered weekly with concurrent radiotherapy for locally advanced squamous cell carcinoma of the cervix is 40 mg/m(2).

Triple synchronous primary malignancies of the colon, endometrium and kidney in a patient with Lynch syndrome treated via minimally invasive techniques.

Coexisting primary malignancies have been described at length in the literature. While double primary malignancies are relatively common, three synchronous primary malignancies are extremely rare. We describe a case of a 60-year-old woman undergoing surgery for a known endometrial carcinoma. The patient also had a renal mass that was identified as a clear cell renal cell carcinoma and an additional lesion in the colon that was a mucinous adenocarcinoma. Further genetic testing of the patient revealed a deleterious MSH6 mutation suggestive of Lynch syndrome. The patient had all tumors addressed by minimally invasive techniques at the same operative intervention. It is important to consider hereditary cancer syndromes in women with a strong family history presenting with synchronous multiple primary malignancies. A multidisciplinary surgical approach is key to best practices and optimal patient outcomes.

Paclitaxel and carboplatin chemotherapy administered during pregnancy for advanced epithelial ovarian cancer.

BACKGROUND: Ovarian cancer diagnosed during pregnancy is uncommon. Most chemotherapy use reported has been in combination with cisplatinum. Paclitaxel in combination with carboplatin during pregnancy has not yet been reported. CASE: A right adnexal mass was diagnosed during pregnancy at 5 weeks' gestational age in a 30-year-old woman. A laparotomy was performed 2 1/2 weeks later because of the worsening nature of her symptoms and the possibility of ovarian torsion. At surgery, the patient was diagnosed with stage IIIC ovarian papillary serous cystadenocarcinoma. She was treated with six cycles of paclitaxel and carboplatin beginning at 16-17 weeks' gestation. At 35.5 weeks' gestation, a cesarean hysterectomy, left salpingo-oophorectomy, and pelvic and paraaortic nodal sampling with multiple peritoneal biopsies was performed without incident. However, the patient had refractory disease present in the remaining ovary. She was treated with further chemotherapy and is currently doing well. The patient experienced no adverse reactions during her treatment, and the infant has normal growth and development at 15 months of age. CONCLUSION: Paclitaxel used in combination with carboplatin for the treatment of ovarian cancer during pregnancy caused no adverse effects in the infant.

Small bowel obstruction associated with tension-free vaginal tape.

A 73-year-old woman with stress urinary incontinence and uterine prolapse underwent vaginal hysterectomy followed by tension-free vaginal tape (TVT) placement. Postoperatively, she presented with low-grade fever and abdominal distension. Abdominal computed tomography revealed bowel distension and abrupt cutoff of the distended small bowel and normal bowel caliber. Transperitoneal laparotomy demonstrated perforation of the mesentery by the TVT without other injury. The tape was cut in its intraperitoneal portion. The patient resumed normal bowel function and, at last follow-up, remained continent. We advocate that when performing TVT placement in conjunction with vaginal hysterectomy, TVT placement should be performed at the beginning of the procedure.

Radical vaginal trachelectomy after supracervical hysterectomy.

BACKGROUND: Radical vaginal trachelectomy (RVT) is an acceptable approach when applied toward a select group of patients with early stage cervical carcinoma. It is less invasive, can maintain fertility, and can be ideal in patients with significant comorbid factors compared to abdominal approaches. A small subset of patients with a previous supracervical hysterectomy can pose a surgical dilemma. CASE: An 81-year-old woman with a history of severe cardiac disease on routine gynecological examination was found to have adenocarcinoma in situ with a focus suspicious for invasion of the cervical stump diagnosed by cone biopsy. She previously had a supracervical hysterectomy for benign disease of the uterus. A RVT was performed as definitive treatment and the patient recovered without complications. CONCLUSION: In the rare case that presents with a history of supracervical hysterectomy, RVT with some technical modifications can still be considered as a therapeutic option for early stage cervical carcinoma.

Expression of glucose transporter-1 in cervical cancer and its precursors.

OBJECTIVE: Increased glucose uptake and utilization is a known phenomenon exhibited by malignant cells. Overexpression of the glucose transporter protein family is thought to be the principal mechanism by which these cells achieve up-regulation. Our purpose is to determine glucose transporter-1 (GLUT 1) expression in squamous carcinoma of the cervix and precursor lesions. METHODS: Archival histologic sections were obtained from 31 cases of invasive squamous cell carcinoma (SCC) of the uterine cervix, 15 cases of high-grade cervical intraepithelial neoplasia, 5 cases of low-grade, and 9 normal cervices. Immunohistochemistry for GLUT 1 protein was performed using polyclonal GLUT 1 antibody (Dako, Carpinteria, CA) and the labeled streptavidin-biotin procedure. RESULTS: Compared to the internal control, the pattern of staining varied from weak (1+) to strong (3+) reactions. In normal cervix, 1+ GLUT 1 staining was seen in the basal cells of the squamous epithelium. All 31 (100%) cases of SCC were positive for GLUT 1. Positive reactions seemed more intense in tumor cells that were farther away from the stromal blood supply. There was a correlation between intensity of reaction for GLUT 1 and histologic grade of tumor (P = 0.0027) and with progression from normal or dysplastic lesions to invasive cancer (P = 0.0001). Intensity was a predictor of the presence of poorly differentiated tumor type. Low-grade CIN staining was seen in less than one-third of the epithelium, while in high-grade lesions the reaction was present in over one-half of the epithelium. CONCLUSIONS: GLUT 1 is overexpressed in cervical carcinoma. The process appears to be related to grade of tumor but not to the progression from preneoplastic lesions. The results suggest that GLUT 1 overexpression is a late phenomenon in cellular transformation. Furthermore, the possible relation of expression to tumor blood supply suggests that the malignant cells may have an adaptive environmental ability to compensate for a compromised microenvironment.

Continent ileocolonic urinary reservoir (Miami pouch): the University of Miami experience over 15 years.

OBJECTIVE: A patient with a recurrent central pelvic malignancy after radiation will require urinary diversion as part of the reconstructive phase of the pelvic exenteration. The aim of our study was to assess the result of our 15-year experience with a continent ileocolonic urinary reservoir, which is known as the Miami pouch. STUDY DESIGN: Since 1988, all patients who received a continent ileocolonic urinary reservoir in the Division of Gynecologic Oncology, University of Miami School of Medicine, were included in the study. Parameters that were evaluated during the study period include functional outcomes, early and late perioperative complications, and their treatment. RESULTS: A total of 90 patients were identified from February 1988 to December 2002. Seventy-eight patients (87%) had a recurrent central pelvic malignancy, and 82 patients (91%) received radiation before the Miami pouch procedure. The non-reservoir-related morbidities were fever (76%), wound complication (30%), pelvic collection (12%), ileus/small bowel obstruction (12%), and postoperative death (11%). The most common reservoir-related complications were urinary infection (40%), ureteral stricture (20%), and difficulty with self-catheterization (18%). In our study, the overall complication rate that was related directly to the Miami pouch was 53%. Conservative treatment resolved>80% of these cases. The rate of urinary continence that was achieved in our patients was 93% during our 15-year experience with the Miami pouch. CONCLUSION: The Miami pouch is a good alternative for continent urinary diversion during exenteration or radiation-induced damage. The rate of major complications that require aggressive surgical intervention is acceptable. Most postoperative complications (80%) can be corrected with the use of conservative techniques that are associated with fewer deaths than reoperation and thus should be used first. The technique is simple and effective in women who are at high risk, who have undergone previous radiation therapy, and who have a high rate of functional success and is a profound advantage for a woman's psychosocial well-being.