Preoperative chemoradiation for advanced vulvar cancer: a phase II study of the Gynecologic Oncology Group.

PURPOSE: To determine the feasibility of using preoperative chemoradiotherapy to avert the need for more radical surgery for patients with T3 primary tumors, or the need for pelvic exenteration for patients with T4 primary tumors, not amenable to resection by standard radical vulvectomy. METHODS AND MATERIALS: Seventy-three evaluable patients with clinical Stage III-IV squamous cell vulvar carcinoma were enrolled in this prospective, multi-institutional trial. Treatment consisted of a planned split course of concurrent cisplatin/5-fluorouracil and radiation therapy followed by surgical excision of the residual primary tumor plus bilateral inguinal-femoral lymph node dissection. Radiation therapy was delivered to the primary tumor volume via anterior-posterior-posterior-anterior (AP-PA) fields in 170-cGy fractions to a dose of 4760 cGy. Patients with inoperable groin nodes received chemoradiation to the primary vulvar tumor, inguinal-femoral and lower pelvic lymph nodes. RESULTS: Seven patients did not undergo a post-treatment surgical procedure: deteriorating medical condition (2 patients); other medical condition (1 patient); unresectable residual tumor (2 patients); patient refusal (2 patients). Following chemoradiotherapy, 33/71 (46.5%) patients had no visible vulvar cancer at the time of planned surgery and 38/71 (53.5%) had gross residual cancer at the time of operation. Five of the latter 38 patients had positive resection margins and underwent: further radiation therapy to the vulva (3 patients); wide local excision and vaginectomy necessitating colostomy (1 patient); no further therapy (1 patient). Using this strategy of preoperative, split-course, twice-daily radiation combined with cisplatin plus 5-fluorouracil chemotherapy, only 2/71 (2.8%) had residual unresectable disease. In only three patients was it not possible to preserve urinary and/or gastrointestinal continence. Toxicity was acceptable, with acute cutaneous reactions to chemoradiotherapy and surgical wound complications being the most common adverse effects. CONCLUSION: Preoperative chemoradiotherapy in advanced squamous cell carcinoma of the vulva is feasible, and may reduce the need for more radical surgery including primary pelvic exenteration.

Preoperative chemo-radiation for carcinoma of the vulva with N2/N3 nodes: a gynecologic oncology group study.

PURPOSE: To determine if patients with carcinoma of the vulva, with N2/N3 lymph nodes, could undergo resection of the lymph nodes and primary tumor following preoperative chemo-radiation. METHODS AND MATERILAS: Fifty-two patients were entered in the study, but six patients did not meet the criteria of the protocol and were excluded. The remaining 46 patients are the subject of this report. Patients underwent a split course of radiation, 4760 cGy to the primary and lymph nodes, with concurrent chemotherapy, cisplatin/5-FU, followed by surgery. RESULTS: Four patients did not complete the chemo-radiation, because three expired and one refused to complete the treatment. Four patients who completed chemo-radiation did not undergo surgery, because two of them died of non-cancer-related causes, and in the other two patients, the nodes remained unresectable. Following chemo-radiation, the disease in the lymph nodes became resectable in 38/40 patients. Two patients who completed the course of chemo-radiation did not undergo surgery as per protocol because of pulmonary metastasis. One underwent radical vulvectomy and unilateral node dissection and the other radical vulvectomy only. The specimen of the lymph nodes was histologically negative in 15/37 patients. Nineteen patients developed recurrent and/or metastatic disease. The sites of failure were as follows: primary area only, 9; lymph node area only, 1; primary area and distant metastasis, 1; distant metastasis only, 8. Local control of the disease in the lymph nodes was achieved in 36/37 and in the primary area in 29/38 of the patients. Twenty patients are alive and disease-free, and five have expired without evidence of recurrence or metastasis. Two patients died of treatment-related complications. CONCLUSION: High resectability and local control rates of the lymph nodes were obtained in patients with carcinoma of the vulva with N2/N3 nodes treated preoperatively with chemo-radiation.

Pattern of in vivo release of endogenous histamine in the mamillary body and the amygdala.

The mamillary body and the medial amygdaloid nucleus of cats anaesthetized with sodium pentobarbital were bilaterally and simultaneously superfused through push-pull cannulae with CSF and the release of endogenous histamine was determined in the superfusates. Collection of the superfusates in 10 min time periods revealed that histamine was rhythmically released in the two areas with frequencies of one cycle/90 min (mamillary body) or one cycle/135 min (medial amygdaloid nucleus). Collection of the superfusates in time periods of 2 min revealed the existence of an additional ultradian rhythm with a frequency of approximately one cycle/19 min in both areas. Bilateral lesions of the suprachiasmatic nucleus did not seem to influence the pattern of histamine release in the mamillary body and the medial amygdaloid nucleus, but the rate of histamine release was decreased in the mamillary body. It is concluded that the ultradian rhythms of histamine release in the mamillary body and the medial amygdaloid nucleus are not dependent on the integrity of the suprachiasmatic nucleus. The rate of histamine release in the mamillary body seems to be under the influence of excitatory neurons which originate from the suprachiasmatic nucleus.

The release of endogenous histamine in distinct brain areas is modified by electrical stimulation.

In anaesthetized cats, mamillary bodies, hypothalamic areas and medial amygdaloid nuclei were bilaterally superfused through push-pull cannulae and the effects of the electrical stimulation on the release of endogenous histamine were investigated. Electrical stimulation of the mamillary body increased the release of histamine in the stimulated area, as well as in the contralateral mamillary body. Electrical stimulation of the lateral hypothalamic area enhanced the histamine release in the contralateral hypothalamic area. Stimulation of the posterior hypothalamic area led to a delayed increase in the histamine release in the stimulated area. Stimulation of the medial amygdaloid nucleus reduced the release if histamine in the ipsilateral posterior hypothalamic area, while the histamine release in the contralateral lateral hypothalamic area was enhanced. The results demonstrate that electrical stimulation of distinct brain areas rich in histaminergic neurons may either increase, or decrease the release rate of histamine in the stimulated area and/or in remote brain areas.

Semi-preparative gas chromatographic separation of all-trans-perhydrotriphenylene enantiomers on a chiral cyclodextrin stationary phase.

Enantiomers of all-trans-perhydrotriphenylene (PHTP) were separated by gas chromatography using heptakis(6-O-tert.-butyldimethylsilyl-2,3-di-O-methyl)-beta-cyclodextrin (TBDMS-beta-CD) as the chiral selector. Conditions for semi-preparative separations were established using a 2 m x 2 mm I.D. packed column and subsequently extended to a 1.8 m x 4 mm I.D. column which enabled separations on a mg scale. The column packing was TBDMS-beta-CD dissolved in SE-54 coated on Chromosorb P AW-DMCS 80-100 mesh. Optimization of the chromatographic conditions (oven temperature, carrier gas flow, and column load) with respect to better efficiency and peak retention resulted in a system capable of separating up to 10 mg of the racemate per day. Purities of separated enantiomers were determined by capillary gas chromatography. Yields and purities of the fractions obtained by single- and double-step separations are compared. Highly enriched enantiomers with purities of up to 99.6% (99.2% ee) were obtained by a single separation step.

Comparison of the properties of titanium dioxide films prepared by various techniques.

Fourteen university, government, and industrial laboratories prepared a total of twenty pairs of single-layer titanium dioxide films. Several laboratories analyzed the coatings to determine their optical properties, thickness, surface roughness, absorption, wetting contact angle, and crystalline structure. Wide variations were found in the optical and physical properties of the films, even among films produced by nominally the same deposition techniques.