The effects of melatonin prophylaxis on sensory recovery and postoperative pain following orthognathic surgery: a triple-blind randomized controlled trial and biochemical analysis.

Post-surgical neuropathy is a known complication of many surgical procedures for which few remedies are effective. This study used neurosensory assessments and biochemical assays to evaluate the efficacy of melatonin on nerve healing following orthognathic surgery. Thirty randomly allocated orthognathic patients were prophylactically administered either oral melatonin or identical placebo for 21 consecutive days. Pre- and post-surgical clinical parameters included subjective pain, numbness, and objective neurosensory function. Pre- and post-surgical biochemical parameters were serum hydrogen peroxide and antioxidant enzyme levels. Melatonin was found to significantly reduce subjective pain perception by 50% in the early postoperative days. A 30% reduction in subjective numbness perception was observed at 1-week postoperative, increasing to an over 80% reduction by 3 months postoperative (P<0.00001). Objective neurosensory testing showed a significant improvement in healing profile in the melatonin group. Postoperatively, the hydrogen peroxide concentration was lower in the melatonin group (P<0.00001), and the levels of antioxidant enzymes were higher (P<0.00001). The strong correlations between clinical outcomes and biochemical changes suggest a link between antioxidant effects and reduced postsurgical pain and sensory recovery. The study findings suggest that the prophylactic administration of melatonin confers significant clinical benefits in terms of reduced postoperative pain and opioid use and improved sensory recovery following surgery.

Adrenal insufficiency after laparoscopic hysterectomy in a patient with primary antiphospholipid syndrome.

BACKGROUND: We report a case of bilateral adrenal hemorrhage and subsequent adrenal insufficiency after a laparoscopic hysterectomy in a patient with anticardiolipin antibody syndrome. CASE: A 55-year-old woman with a history of anticardiolipin antibody syndrome presented with nausea and vomiting 1 week after laparoscopic hysterectomy and staging for endometrial adenocarcinoma. Based on a diagnosis of adrenal insufficiency, the patient was started on oral hydrocortisone 20 mg in the morning and 10 mg in the afternoon, and fludrocortisone 0.05 mg twice daily on day 5. Her symptoms resolved completely within 24 hours of beginning steroids. CONCLUSION: The diagnosis of adrenal insufficiency should be entertained in any patient with a history of thrombophilias presenting with general abdominal complaints.

Paclitaxel in the treatment of carcinosarcoma of the uterus: a gynecologic oncology group study.

OBJECTIVE: The goal of this study was to estimate the clinical activity of paclitaxel in patients with persistent or recurrent carcinosarcoma of the uterus who have failed other treatments. METHODS: The Gynecologic Oncology Group (GOG) conducted a phase II study of paclitaxel 170 mg/m(2) (135 mg/m(2) in those with prior irradiation) intravenously every 3 weeks in patients with histologic confirmation of carcinoma and measurable disease who had failed appropriate local therapy. RESULTS: A total of 53 patients were entered into the study between September 1994 and January 1997; 44 patients were evaluable for response. The median age of the patients treated was 65 years (range: 38-79). Twenty-six patients had heterologous mixed mesodermal tumors (MMTs) and 18 patients had homologous tumors. A median of three courses were administered (range: 1-18). Fifteen patients had previous radiation therapy and 33 patients had failed prior chemotherapy. Eight patients (18.2%) had a response to paclitaxel: four patients had a complete response and four had a partial response. Neutropenia was the most common toxic effect. CONCLUSIONS: Paclitaxel had moderate activity in patients with carcinosarcoma of the uterus. The GOG is currently studying the combination of paclitaxel and ifosfamide versus ifosfamide alone for patients with advanced or recurrent carcinosarcoma of the uterus.

Radical surgical resection and high-dose intraoperative radiation therapy (HDR-IORT) in patients with recurrent gynecologic cancers.

OBJECTIVE: To determine the outcome for patients with recurrent gynecologic tumors treated with radical resection and combined high-dose intraoperative radiation therapy (HDR-IORT). METHODS AND MATERIALS: Between November 1993 and June 1998, 17 patients with recurrent gynecologic malignancies underwent radical surgical resection and high-dose-rate brachytherapy. The mean age of the study group was 49 years (range 28-72 years). The site of the primary tumor was the cervix in 9 (53%) patients, the uterus in 7 (41%) patients, and the vagina in 1 (6%) patient. The treatment for the primary disease was surgery with or without adjuvant radiation in 14 (82%) patients and definitive radiation in 3 (18%) patients. The current surgery consisted of exenterative surgery in 10 (59%) patients and tumor resection in 7 (41%) patients. Complete gross resection was achieved in 13 (76%) patients. The mean HDR-IORT dose was 14 Gy (range 12-15). Additional radiation in the form of permanent Iodine-125 implant was given to 3 of 4 patients with gross residual disease. The median peripheral dose was 140 Gy. RESULTS: With a median follow-up of 20 months (range 3-65 months), the 3-year actuarial local control (LC) rate was 67%. In patients with complete gross resection, the 3-year LC rate was 83%, compared to 25% in patients with gross residual disease, p < 0.01. The 3-year distant metastasis disease-free and overall survival rates were 54% and 54%, respectively. The complications were as follows: gastrointestinal obstruction, 4 (24%); wound complications, 4 (24%); abscesses, 3 (18%); peripheral neuropathy, 3 (18%); rectovaginal fistula, 2 (12%); and ureteral obstruction, 2 (12%). CONCLUSION: Radical surgical resection and combined IORT for patients with recurrent gynecologic tumors seems to provide a reasonable local-control rate in patients who have failed prior surgery and/or definitive radiation. Patient selection is very important, however, as only those patients with complete gross resection at completion of surgery appear to benefit most from this radical approach in the salvage setting.

Paclitaxel, an active agent in nonsquamous carcinomas of the uterine cervix: a Gynecologic Oncology Group Study.

PURPOSE: A phase II trial of paclitaxel was initiated in advanced nonsquamous carcinoma of the cervix to determine its activity in patients who had failed standard chemotherapy. PATIENTS AND METHODS: Eligible patients had at least one measurable lesion. The starting dose of paclitaxel was 170 mg/m(2) (135 mg/m(2) for patients with prior pelvic radiation) given as a 24-hour continuous intravenous infusion with courses repeated every 3 weeks. Dose escalation to 200 mg/m(2) and de-escalation to 110 mg/m(2) were allowed based on adverse effects. RESULTS: In this trial, 42 assessable patients were initially entered onto the study, and 13 responses were seen; four patients had a complete response, and nine patients had a partial response. The overall response rate was 31%. The primary and dose-limiting toxicity was neutropenia. CONCLUSION: The response rate to paclitaxel exceeds the rates reported using other single agents in nonsquamous carcinoma of the cervix.

The role of laparoscopy in second-look evaluations for ovarian cancer.

BACKGROUND: The aim of this study was to evaluate the accuracy and safety of laparoscopic second-look operations in patients with ovarian cancer. METHODS: We retrospectively reviewed the medical records of all patients who have undergone laparoscopic second-look procedures for ovarian cancer at our institution. RESULTS: From July 1993 to December 1998, 150 patients underwent laparoscopic second-look operations. The mean age of patients was 53 years (range, 25-78 years). The majority of patients (87%) had Stage III or IV disease at initial surgery; the remainder were Stage II or unstaged. Eighty-two patients (54%) had had optimal cytoreduction at the time of their initial surgery. All patients had completed primary chemotherapy and were clinically disease-free based on imaging studies and CA-125 levels at the time of second look. Sixty-nine patients (46%) were found to have pathologically negative second looks; thus, the rate of positive second-look evaluations was 54%. The rate of conversion to laparotomy was 18/150 (12%). In 3 cases this was secondary to bowel injury; one patient sustained a bladder injury; the remainder of conversions to laparotomy were for secondary cytoreduction. There was only 1 case where the patient was found to have extensive adhesions and laparoscopy was abandoned. The overall rate of major complications was 2.7%. CONCLUSIONS: In our experience, laparoscopy is a safe and accurate method of second-look assessment in patients with ovarian cancer. The incidence of complications is low, particularly in this group of patients, all of whom have undergone prior abdominal surgery. The rate of negative evaluations and the rate of recurrences in patients with negative second looks are equivalent to those described in studies of second-look assessment by laparotomy.

Clinicopathologic features of BRCA-linked and sporadic ovarian cancer.

CONTEXT: Most hereditary ovarian cancers are associated with germline mutations in BRCA1 or BRCA2. Attempts to define the clinical significance of BRCA mutation status in ovarian cancer have produced conflicting results, especially regarding survival. OBJECTIVE: To determine whether hereditary ovarian cancers have distinct clinical and pathological features compared with sporadic (nonhereditary) ovarian cancers. DESIGN AND SETTING: Retrospective cohort study of a consecutive series of 933 ovarian cancers diagnosed and treated at our institution, which is a comprehensive cancer center as designated by the National Cancer Institute, over a 12-year period (December 1986 to August 1998). PATIENTS: The study was restricted to patients of Jewish origin because of the ease of BRCA1 and BRCA2 genotyping in this ethnic group. From the 189 patients who identified themselves as Jewish, 88 hereditary cases were identified with the presence of a germline founder mutation in BRCA1 or BRCA2. The remaining 101 cases from the same series not associated with a BRCA mutation and 2 additional groups (Gynecologic Oncology Group protocols 52 and 111) with ovarian cancer from clinical trials (for the survival analysis) were included for comparison. MAIN OUTCOME MEASURES: Age at diagnosis, surgical stage, histologic cell type and grade, and surgical outcome; and response to chemotherapy and survival for advanced-stage (II and IV) cases. RESULTS: Hereditary cancers were rarely diagnosed before age 40 years and were common after age 60 years, with mean age at diagnosis being significantly younger for BRCA1- vs BRCA2-linked patients (54 vs 62 years; P=.04). Histology, grade, stage, and success of cytoreductive surgery were similar for hereditary and sporadic cases. The hereditary group had a longer disease-free interval following primary chemotherapy in comparison with the nonhereditary group, with a median time to recurrence of 14 months and 7 months, respectively (P<.001). Those with hereditary cancers had improved survival compared with the nonhereditary group (P=.004). For stage III cancers, BRCA mutation status was an independent prognostic variable (P=.03). CONCLUSIONS: Although BRCA-associated hereditary ovarian cancers in this population have surgical and pathological characteristics similar to those of sporadic cancers, advanced-stage hereditary cancer patients survive longer than nonhereditary cancer patients. Age penetrance is greater for BRCA1-linked than for BRCA2-linked cancers in this population.

Long-term experience in the surgical management of cancer of the uterine cervix.

Cancer of the uterine cervix is the seventh most common malignancy among women and the fifth most common cause of cancer mortality worldwide. In the United States, the use of the Papanicolaou (Pap) smear for screening has meant a significant decline in the incidence and mortality from cervical cancer over the past five decades. However, there are still approximately 12,800 new cases diagnosed per year in the U.S. and 4,800 deaths are estimated in 1999. Both surgery and radiation therapy have long-established roles in management. Surgery has the advantages of shorter treatment time, removal of the primary tumor, more limited tissue injury, and the potential to preserve ovarian function; radiation therapy has the capacity to treat tumor that involves the bladder and/or rectum while preserving their function. Therefore, the role of surgery is more suited to the management of early-stage disease and centrally located recurrences that occur after radiation therapy. Studies from our institution have played an integral role in the development of the modern surgical approach to cervical cancer. Reviews on early-stage disease helped define the role of conization and simple hysterectomy for microinvasive cervical cancer and identified patients who were at high risk for recurrence after radical hysterectomy. The classic work of Brunschwig has given gynecologic surgeons the ability to offer hope and life to select patients who previously could have expected only pain and death. Future investigation into the techniques of intra-operative radiation therapy may increase the pool of patients for whom surgically based salvage therapy may be offered.

Pelvic exenteration for recurrent endometrial cancer.

Pelvic exenteration is generally not considered an operation with curative value for women with recurrent endometrial carcinoma. We reviewed our experience with pelvic exenteration performed in patients with recurrent endometrial adenocarcinoma from 1947 through 1994. A total of 44 patients were identified, with a mean age of 60 years (range 35-69 years). Primary therapy usually consisted of total abdominal hysterectomy with bilateral salpingo-oophorectomy, with most receiving either pre- or postoperative radiotherapy. Prior to exenteration, 10 of 44 (23%) patients had never received any form of radiotherapy. The median interval between initial surgery and exenteration was 28 months (range 2-189 months). The type of exenteration performed was total in 23 patients (52%), anterior in 20 patients (46%), and posterior in 1 patient. Major postoperative complications occurred in 35 patients (80%) and included urinary/intestinal tract fistulas, pelvic abscess, septicemia, pulmonary embolism, and cerebrovascular accident. Median survival for the entire group of patients was 10.2 months. Nine patients (20%) achieved long-term survival (>5 years). Pelvic exenteration for recurrent endometrial cancer is associated with a high operative morbidity and poor overall survival. Although only 20% of patients achieved long-term survival, this procedure remains the only potentially curative option for the few patients with central recurrence of endometrial cancer who have failed surgical and radiation therapy.

Gynecologic cancer and laparoscopy.

Numerous technologic and surgical advances have led to the application of operative laparoscopic techniques to gynecologic cancers. Operative laparoscopy has been described in the surgical staging and treatment of patients with ovarian, cervical, and endometrial cancers. it seems to be a very promising approach with the potential to revolutionize numerous aspects of the management of gynecologic malignancies. Since 1996, the SGO has offered an operative laparoscopy course to all gynecologic oncology fellowship programs. Boike and colleagues report that faculty and fellows from 25 different fellowship programs have attended the 2-day course. In questionnaires filled out at the completion of the course, more than 85% of respondents believed that operative laparoscopic procedures were equivalent to open techniques and should be taught in fellowship programs. Despite the enthusiasm for the use of endoscopy in patients with gynecologic malignancies, its potential is unconfirmed and its hazards unknown. Reports regarding complications and long-term results are just now beginning to be published. More clinical data must be collected before the minimally invasive techniques can be accepted as new surgical standards. Ongoing prospective clinical trials will help to answer many of the questions regarding safety and efficacy. Pending the completion of additional trials, operative laparoscopy will remain a promising but unproven tool in the management of patients with gynecologic cancer.

Laparoscopic-assisted vaginal hysterectomy for endometrial cancer: clinical outcomes and hospital charges.

OBJECTIVE: Our objective was to compare the clinical outcomes and associated hospital charges between two methods of hysterectomy for patients with early-stage endometrial cancer. METHODS: Retrospective chart review of 320 patients with early-stage endometrial cancer treated by laparoscopic-assisted vaginal hysterectomy (LAVH) or total abdominal hysterectomy (TAH) was performed for the period of July 1, 1991, to September 30, 1996, at Memorial Sloan-Kettering Cancer Center. RESULTS: Sixty-nine patients (22%) were treated by LAVH, and 251 (78%) were treated by TAH. The majority of the patients (80%) had Stage I disease. The mean age was similar for both groups: 60 years for the LAVH vs 61 years for TAH. The mean weight was significantly lower for the LAVH group, 71 kg (range 43-117 kg), than for the TAH group, 82 kg (range 38-200 kg), (P < 0.05). Overall complication rates were lower among patients treated by LAVH. Operating room time was longer for the LAVH group (214 min) than for the TAH group (144 min) (P < 0.05). The median length of stay was significantly shorter for patients treated by LAVH (2.0 days) compared to TAH (6.0 days) (P < 0.05). Room charges were significantly higher for the TAH patients ($6960) compared to the LAVH patients ($3130) (P < 0.05). Overall mean total charges were significantly less for the LAVH group ($11,826) than for the TAH group ($15,189) (P < 0.05). With a median follow-up of 30 months for the TAH group and 18 months for the LAVH group, there was no significant difference in disease recurrence (P = 0.91). CONCLUSION: Patients treated by LAVH for early-stage endometrial cancer had significantly shorter hospitalization and fewer complications, resulting in less overall hospital charges when compared to patients treated by TAH. Long-term outcome was similar. Laparoscopic-assisted vaginal hysterectomy is an attractive alternative for selected patients with early-stage endometrial cancer.

Splenectomy in recurrent epithelial ovarian cancer.

OBJECTIVE: To report a series of patients with recurrent epithelial ovarian cancer who underwent splenectomy for isolated parenchymal metastases. METHODS: We performed a retrospective review of all patients who had a splenectomy for ovarian cancer at our institution during the period 1991 to 1997. RESULTS: Six patients were identified who had a splenectomy performed for recurrent epithelial ovarian cancer confined to the splenic parenchyma. All had initial cytoreductive surgery for Stage III disease followed by platinum-based chemotherapy. Five patients underwent second-look surgery and four of them had pathologically confirmed persistent disease. All five patients who underwent second-look surgery had an intraperitoneal (ip) port placed and received platinum-based ip chemotherapy. Computed tomography (CT) scan performed during the posttreatment surveillance period demonstrated recurrent disease confined to the spleen in all six patients. Splenectomy was performed at a median of 57 months (range 28-88 months) after the initial surgery. The only major complication was a diaphragmatic tear necessitating chest tube placement. With a median follow-up of 25.5 months (range 6-65 months), all six patients are alive and free of disease. CONCLUSION: Splenectomy is a safe and feasible procedure in recurrent epithelial ovarian cancer. Isolated parenchymal splenic metastasis may occur as a late recurrence in epithelial ovarian cancer and splenectomy should be considered a part of the management of this group of patients.

A phase II trial of intraperitoneal cisplatin and etoposide as consolidation therapy in patients with Stage II-IV epithelial ovarian cancer following negative surgical assessment.

PURPOSE: To determine the efficacy of three courses of intraperitoneal (i.p.) cisplatin (CDDP) and etoposide (VP-16) as consolidation therapy following pathologically negative second-look surgical reassessment for Stage IIC-IV epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Between September 1988 and April 1996, 40 patients were treated with three cycles of i.p. CDDP (100 mg/m2)/VP-16 (200 mg/m2) as consolidation therapy. Survival was compared to that of a group of 46 contemporaneous patients undergoing observation only. RESULTS: Median age of the 36 eligible patients was 52 years (range 30-70 years). Stage distribution was II (3), III (31), and IV (2); histologic grade was 1 (2), 2 (7), 3 (25), and not recorded (2); and residual disease at completion of initial surgery was none/microscopic in 13/36 (36%) patients. Median age of the 46 patients who did not receive consolidation was 52 years (range, 27-80 years); stage distribution was II (18), III (26), and IV (2); histologic grade was 1 (5), 2 (12), 3 (28), and not recorded (1). With a median follow-up of 36 months in both groups, 14/36 (39%) of the protocol group have recurred compared with 25/46 (54%) of those undergoing observation alone. Median disease-free survival (DFS) for the observed patients is 28.5 months and has not been reached in the consolidation group. Disease-free survival distribution between the two groups was compared using the log-rank test and was found to be significant (P = 0.03). Multivariate analysis revealed that the only significant predictor of improved DFS was protocol treatment (P < 0.01). CONCLUSION: Intraperitoneal consolidation with CDDP/VP-16 following negative second-look reassessment in patients with advanced EOC resulted in a significant increase in DFS compared to nonprotocol patients treated concurrently who underwent observation alone.

Cigarette smoking and cervical dysplasia among non-Hispanic black women.

This is the first case-control study to determine whether smoking is associated with cervical dysplasia, after adjustment for human papillomavirus (HPV) infection, among a group of non-Hispanic black women. Subjects were interviewed and asked questions about smoking and other risk factors for cervical cancer. HPV infection was determined by hybrid capture. Thirty-two women with histologically confirmed incident dysplasia and 113 control women with normal cytologic smears were enrolled; all women were HIV negative. Smoking was more strongly associated with dysplasia among women with high-grade lesions than among all case women combined. After adjustment, women with high-grade lesions were roughly four times more likely to be ever (odds ratio [OR]: 3.8; 95% confidence interval [CI]: 0.76-18.4) or current (OR: 4.3; 95% CI: 0.83-21.9) smokers, compared with control women. Larger studies among black women that control for HPV infection are needed to confirm these findings and to explore associations among black women with low-grade lesions.

Perineural fibrous thickening within the dental pulp in type 1 neurofibromatosis: a case report.

A case of type 1 neurofibromatosis is presented that illustrates oral manifestations and their role in the diagnosis of this condition. The oral lesions may be overlooked in the diagnosis of intraoral swellings. This case documents the finding of perineural fibrous thickening within the dental pulp. Such changes may indicate pulpal involvement in neurofibromatosis and the effect of a genetically transmitted disorder upon the pulp.

Adjuvant therapy in gynecologic malignancies. Ovarian, cervical, and endometrial cancer.

While surgery is the primary treatment for the management of gynecologic malignancies, adjuvant chemotherapy and radiation therapy play a critical role in survival for many patients. In this article, we discuss the feasibility and effectiveness of adjuvant therapy for ovarian, cervical, and endometrial cancers, and discuss current recommendations.

Regression of uterine low-grade smooth-muscle tumors metastatic to the lung after oophorectomy.

BACKGROUND: Metastatic uterine low-grade smooth-muscle tumors may present with pulmonary symptoms and radiographic lung abnormalities consistent with metastatic neoplasms. Ovarian hormone stimulation of these smooth-muscle tumors has been suggested, but the role of surgical or medical oophorectomy has not been established in patients with metastatic disease. CASES: Two women with histologically confirmed uterine low-grade smooth-muscle tumors metastatic to the lung had progressive and complete tumor regression after oophorectomy and no further therapy. CONCLUSION: Some uterine low-grade smooth-muscle tumors metastatic to the lung regress after oophorectomy. Removing ovarian hormone stimulation may result in complete tumor regression without the need for further therapy.

Carboplatin as a radiation sensitizer in locally advanced cervical cancer: a pilot study.

Radiation therapy is the mainstay in treatment of locally advanced cervical carcinoma. Several chemotherapeutic agents have been used as radiation sensitizers in the treatment of cervical cancer in an effort to improve local response and survival. A prospective study was designed to evaluate carboplatin as a radiosensitizer in advanced cervical cancer. Standard radiotherapy techniques were used to treat patients with Stage IIA-IIIB cervical cancer. Intravenous carboplatin was administered twice weekly concurrent with external beam radiation. Of 22 evaluable patients, there were 19 complete responders of whom 15 remain alive: 11 patients were alive and disease free at last visit for a median duration of 15 months follow-up (range, 4-43 months) and 4 patients remain alive with disease for a median duration of 17 months (range, 3-55 months). Seven have died, one of whom was without evidence of disease. There were no treatment-related deaths and no grade 4 toxicity. The most significant adverse effect was hematologic resulting in four patients with grade 3 neutropenia or anemia. There were no fistulae or late gastrointestinal or genitourinary complications. This pilot study suggests that carboplatin administered with standard radiation is safe, well-tolerated, and thus may be useful as a radiation sensitizer in the treatment of locally advanced cervical cancer.

Normalization of the tumor marker CA-125 after oophorectomy in a patient with paraneoplastic cerebellar degeneration without detectable cancer.

A 61-year-old woman developed severe subacute cerebellar degeneration in association with a neuronal antinuclear autoantibody. Neurologic investigations were remarkable only for mild CSF leukocytosis. Despite no radiographic evidence of cancer, a salpingo-oophorectomy was performed on the basis of an increased gynecologic cancer marker (CA-125) and the neurologic symptoms that were strongly suggestive of paraneoplastic cerebellar degeneration. Although no tumor was detected in the surgical specimen, CA-125 levels normalized after surgery. The patient remains stable 12 months after surgery with a severe cerebellar syndrome, no evidence of cancer, and persistent circulating antineuronal autoantibodies. An elevated tumor marker in a patient with a presumed paraneoplastic neurologic disorder should suffice as evidence of an occult neoplasm, and guide definitive treatment.