Sentinel lymph node detection and microstaging in vulvar carcinoma.

OBJECTIVE: To determine the efficacy of using complementary techniques for detecting sentinel lymph nodes (SLNs) in vulvar carcinoma and to evaluate the utility of microstaging techniques. STUDY DESIGN: Patients with invasive vulvar carcinoma underwent sentinel lymph node detection (SLND) using preoperative lymphoscintigraphy, intraoperative isosulfan blue dye injection and an intraoperative hand-held gamma-detecting probe. Eleven patients were included and a total of 16 groins evaluated. Sentinel nodes identified were excised, bisected and examined in surgical pathology using hematoxylin and eosin (H&E) staining. Pathologically negative SLNs were subjected to additional microstaging via serial sectioning and immunohistochemical staining for cytokeratin. Surgical management of the vulvar cancer and extent of inguinal-femoral lymphadenectomy were individualized based on clinicopathologic parameters, including depth of invasion, location of the tumor and patient performance status. RESULTS: Lymphoscintigraphy, dye and gamma-detector methods led to the total detection of 16, 19 and 17 SLNs, respectively. In two cases the isosulfan blue dye assisted in the isolation of an additional sentinel node over that of the gamma probe. Each method individually identified SLNs in 10/11 patients (91%). A total of 19 sentinel nodes were isolated. One SLN (5%) was positive for metastatic disease using H&E staining. Of the 18 negative SLNs, 2 (11%) had micrometastases (< 0.2 mm) upon serial sectioning and immunohistochemical staining. CONCLUSION: Combined-modality mapping enhances detection of SLNs in vulvar carcinoma. Histologic microstaging improves the detection of micrometastases within SLNs.

Deep venous thrombosis associated with large leiomyomata uteri. A case report.

BACKGROUND: The association of deep venous thrombosis (DVT) with uterine leiomyomata has been reported only rarely in the English-language literature. These concomitant findings occurred in a woman with no other known risk factors for development of DVT. CASE: A 49-year-old, Caucasian woman, gravida 3, para 3, with a past medical history significant for large uterine leiomyomata, menorrhagia and anemia, presented with acute edema of the left lower extremity. Doppler studies revealed compression of the left iliofemoral vein with associated thrombosis. No risk factors for DVT were identified. Intravenous heparin was initiated, with eventual preoperative placement of an inferior vena cava Greenfield filter. A total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed without complications. CONCLUSION: Large uterine leiomyomata are a potential cause of lower extremity venous stasis and resulting thrombosis and can be treated with hysterectomy.

Intraperitoneal photoimmunotherapy of ovarian carcinoma xenografts in nude mice using charged photoimmunoconjugates.

OBJECTIVE: The objective of this study was to compare the efficacy of photoimmunoconjugates with cationic and anionic molecular charges on intraperitoneal photoimmunotherapy of ovarian cancer xenografts in nude mice. METHODS: The photosensitizer chlorin(e6) (c(e6)) was conjugated via a poly-l-lysine linker to the F(ab')(2) fragment of the murine anti-ovarian cancer monoclonal antibody OC125, resulting in a photoimmunoconjugate with a pronounced cationic charge. Alternatively, by succinylating the poly-l-lysine conjugate, a photoimmunoconjugate with a pronounced anionic charge was obtained. A murine model of ovarian cancer derived from intraperitoneal inoculation of NIH:OVCAR-5 cells was employed. The conjugate was injected intraperitoneally followed after 3 h by red light delivered through a fiber into the peritoneal cavity. These photoimmunotherapy treatments were repeated three times, and the results obtained with the anionic and cationic photoimmunoconjugates were compared with those obtained with free c(e6) and control. The extent of residual macroscopic disease and death from disease were the evaluable outcomes for tumoricidal and survival studies, respectively. RESULTS: In contrast to other intraperitoneal photosensitizers, mice showed no systemic toxicity or morbidity from the treatment. In this initial study the mean residual tumor weights in all treatment groups ranged from 33 to 73 mg, as compared with 330 mg in untreated controls (P < 0.0001), and the response to the cationic conjugate was significantly better than that to the anionic conjugate or free c(e6) (P < 0.005). The median survival for mice treated with cationic photoimmunoconjugate was 41 days, compared with 35 days in controls (P = 0.009). CONCLUSION: Photoimmunotherapy with a cationic photoimmunoconjugate produces results superior to those obtained with an anionic conjugate, and further optimization of the treatment regimen may lead to a potential treatment for advanced ovarian cancer.

Vaginal small cell carcinoma mimicking a Bartholin's gland abscess: a case report.

We report a case of a 32-year-old woman with a lesion in the vagina which clinically mimicked a Bartholin's gland abscess, but was demonstrated to be a small cell carcinoma by light microscopy. This tumor is very rare and to our knowledge there are 13 reported cases of primary vaginal small cell carcinoma in the English literature. The mean age of presentation of this neoplasm in the 13 reported cases is 61 with a median survival of 12 months. This case stresses the importance of considering this unusual diagnosis when confronted with a large or recurrent "Bartholin's gland lesion," and underlines the need for careful pathological examination of such specimens.

Recurrent psammocarcinoma of the peritoneum with complete response to tamoxifen therapy.

Psammocarcinoma is a rare type of serous carcinoma arising from the ovary or peritoneum, characterized by massive psammoma body formation, invasiveness, and low-grade cytological features. A case of primary peritoneal psammocarcinoma is presented. Aspects of clinical presentation, diagnosis, and management are described. Emphasis is placed on successful management of recurrent disease using tamoxifen therapy.

Postoperative pelvic irradiation in early stage uterine mixed mullerian tumors.

PURPOSE OF INVESTIGATION: To review our management experience with uterine mixed mullerian tumors (MMTs) in order to evaluate potential prognostic indicators, and assess the efficacy of various treatment modalities. METHODS: A retrospective, clinicopathologic evaluation of 43 patients presenting for treatment of uterine MMTs between 1982 and 1992 was conducted. Diagnostic criteria for inclusion was the presence of both a malignant glandular or squamous epithelial component, and a homologous or heterologous stromal component. RESULTS: Overall 2- and 5-year cancer related Kaplan-Meier survival estimates with 95% confidence intervals were 44 (.28, .59) and 26% [.12, .39], respectively. Survivals were 83 [.62, .99] and 58% [.31, .85] when disease was confined to the uterus, and 22 [.03, .41] and 7% [.01, .20] when disease extended beyond the uterus. Clinical staging was often inaccurate, with 29% of clinical stage I or II disease being upstaged at laparotomy. A significant survival advantage was found in patients with stage I or II disease treated with surgery plus pelvic irradiation (p = 0.001), as compared to those treated with surgery alone. The prognosis after disease recurrence was poor, irrespective of secondary therapy, with a median survival of 11 months. CONCLUSIONS: A therapeutic advantage may be gained from postoperative pelvic irradiation in the treatment of surgical stage I or II uterine MMT.

Stage IB and IIA cervical cancer with negative lymph nodes: the role of adjuvant radiotherapy after radical hysterectomy.

The records of 171 patients with lymph node-negative stage IB and IIA cervical cancer primarily treated with radical hysterectomy and pelvic lymphadenectomy from 1974 to 1992 were retrospectively reviewed to identify poor prognostic factors and evaluate the role of adjuvant pelvic radiotherapy. One hundred sixteen patients (68%) were treated with radical hysterectomy alone (RH) and 55 patients (32%) received adjuvant radiotherapy (RH + RT). Factors predictive of recurrence for the entire group of patients included lymph-vascular space invasion (LVSI) (P = 0.003) and grade 3 histology (P = 0.04). Patients receiving RH + RT were older and more likely to have outer third cervical wall invasion, LVSI, positive margins, > or =2 cm pathologic tumor size, and >4 cm clinical tumor size (all P < 0.05). Overall, 28 patients (16%) developed recurrent disease with no difference between RH and RH + RT groups. After controlling for confounding variables, patients with LVSI who received RH + RT were less likely to develop disease recurrence than patients receiving RH alone (P = 0.04). LVSI is an important prognostic variable in lymph node-negative stage IB and IIA cervical cancer. Although adjuvant pelvic radiotherapy may decrease the risk of recurrence in patients with LVSI, the majority of patients with negative lymph nodes may be treated with radical surgery alone.

Characterization of a xenograft model of human ovarian carcinoma which produces intraperitoneal carcinomatosis and metastases in mice.

A new xenograft model for human epithelial ovarian carcinoma, with extensive intraperitoneal (i.p.) carcinomatosis as the predominant disease manifestation, is described. Cells from the established NIH:OVCAR-5 cell line were injected i.p. into 6- to 8-week-old Swiss nude mice. Comparative analyses between cells cultured in vitro and tumor cells derived ex vivo were performed to assess histologic features, immunohistochemical cell markers, hormonal receptor expression, adhesion to extracellular matrix molecules and chromosomal constitution. Macroscopically, the extent of tumor development appeared to be site-dependent and tumor cell survival was dose-dependent. Advanced disease was characterized by extensive solid tumor burden and ascites with parenchymal invasion, lymphatic metastases and vascular dissemination. Individual tumor nodules exhibited developing neovasculature characterized by the absence of mature basement membrane. Despite some histologic loss of cellular differentiation in advanced disease, antigenic expression was preserved, distinguishing these cells as epithelial in origin. Karyotyping of tumor cells demonstrated multiple numeric and structural chromosomal abnormalities. Serum and ascites CA 125 levels were consistently elevated only in tumor-bearing mice. This new murine model closely resembles the aggressive disease process of human epithelial ovarian carcinoma, in which the efficacy of i.p. and systemic therapeutic modalities can be investigated.

The effect of postsurgical therapy on stage III endometrial carcinoma.

The records of 86 pathologic stage III endometrial carcinoma patients treated at Massachusetts General Hospital between 1974 and 1992 were retrospectively reviewed to identify predictors of poor outcome and to determine the effect of postsurgical therapy on recurrence and survival. Patients underwent TAH/BSO with selective lymphadenectomy and peritoneal washings. Cases prior to 1988 were retrospectively restaged using the FIGO surgical staging criteria. Postoperatively, patients received individualized regimens of EBRT (external beam radiotherapy), brachytherapy, and cytotoxic or hormonal chemotherapy. The 5-year survival and 5-year disease-free survival (DFS) for all patients were 54 and 44%, respectively. Forty-two percent of stage IIIA/B patients recurred in a median time of 14 months. Fifty-four percent of stage IIIC patients recurred in a median time of 16 months. Of patients who recurred, 90% stage IIIA/B and 71% stage IIIC patients recurred at extrapelvic sites. Age greater than 70, high-grade lesions, and fallopian tube metastases were predictive of poor outcome in stage IIIA/B by multivariate analysis. Vascular invasion was the only poor prognostic factor identified by multivariate analysis in stage IIIC disease. No benefit from pelvic EBRT in stage IIIA/B could be identified. Stage IIIC patients had increased DFS and a trend for increased survival with pelvic EBRT. Chemotherapy did not improve survival in either group.

Intraperitoneal photodynamic therapy of human epithelial ovarian carcinomatosis in a xenograft murine model.

The objective of this investigation was to determine the efficacy of i.p. photodynamic therapy (PDT) against solid, multifocal ovarian carcinoma using a newly described NIH:OVCAR-5 induced murine model. PDT was initiated when diffuse microscopic disease and small multifocal tumor nodules were present, similar to the extent of residual carcinoma that may persist clinically after laparotomy and tumor debulking. The photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA), was administered in a dose of 0.25 mg/kg body weight i.p. 90 min prior to light exposure. An argon-pumped dye laser was used to deliver low intensity light (20 J) i.p. through a cylindrically diffusing fiberoptic tip. Treatment regimens consisted of a series of three to five treatments at 3-7 day intervals, with the extent of macroscopic disease or death from disease being the evaluable outcome parameters for tumoricidal and survival studies, respectively. The mean tumor burden at necropsy for treated animals was 0.034 +/- 0.014 g compared to 0.379 +/- 0.065 g in untreated controls (P<0.001). Survival studies were initiated in two groups at day 7 and day 14 following cell inoculation. The first group received either three or five treatments at 5-day intervals, and both had a significant increase in median survival compared to untreated controls (57 and 53 days, respectively, compared to 43 days, P<0.05). The second group was treated every 7 days until death and also had a significant survival advantage over controls (57 days compared to 47 days, P<0.05). These studies suggest that benzoporphyrin derivative mono acid ring A-mediated PDT is a feasible, well-tolerated, experimental treatment approach that elicits a tumoricidal response against diffuse, solid i.p. disease in tumor-bearing mice, with concomitant prolongation of survival and needs careful optimization.