Manuel Penalver

Application of an ATP-bioluminescence assay in human tumor chemosensitivity testing

Intracellular adenosine triphosphate (ATP) is the primary energy unit of living cells, and can be quantitated by measuring the light generated with luciferase-luciferin reagent in a luminometer. The use of an ATP-bioluminescence assay, to determine tumor cell viability after exposure to chemotherapeutic agents, has been adapted to test tumor chemosensitivity in vitro. This presentation will illustrate the method of the ATP-chemosensitivity assay (ATP-CSA) using an ovarian cancer cell line NIHL:OVCAR-3 as an example and present preliminary data on 54/56 successful in vitro ATP-CSAs from 46 patients with pelvic malignancies. Fresh human tumor specimens were generally tested for single and combined drug effects at two drug concentrations (0.2 X and 1 X peak plasma concentrations). Correlation of in vitro drug sensitivity and in vivo patient response was obtained for 23 treatment regimens in 22 patients with ovarian carcinoma. The true positive rate was 100% and the true negative rate 66.7%. Our data demonstrate (a) that the ATP-CSA, measuring total cell viability, is a feasible in vitro assay for human tumor drug testing and (b) that specific criteria of in vitro chemosensitivity for this assay need to be defined by further studies, for single and combined drug exposure at different concentrations, to permit a meaningful correlation with in vivo clinical response.

Guidelines of how to manage vesicovaginal fistula.

Vesicovaginal fistulas are among the most distressing complications of gynecologic and obstetric procedures. The risk of developing vesicovaginal fistula is more than 1% after radical surgery and radiotherapy for gynecologic malignancies. Management of these fistulas has been better defined and standardized over the last decade. We describe in this paper the success rate reported in the literature by treatment modality and the guidelines used at our teaching hospitals, University of Rome Campus Biomedico and University of Miami School of Medicine. In general, our preferred approach is a trans-vaginal repair. To the performance of the surgical treatment, we recommend a minimum of a 4-6 weeks wait from the onset of the fistula. The vaginal repair techniques can be categorized as to those that are modifications of the Latzko procedure or a layered closure with or without a Martius flap. The most frequently used abdominal approaches are the bivalve technique or the fistula excision. Radiated fistulas usually require a more individualized management and complex surgical procedures. The rate of successful fistula repair reported in the literature varies between 70 and 100% in non-radiated patients, with similar results when a vaginal or abdominal approach is performed, the mean success rates being 91 and 97%, respectively. Fistulas in radiated patients are less frequently repaired and the success rate varies between 40 and 100%. In this setting many institutions prefer to perform a urinary diversion. In conclusion, the vaginal approach of vesicovaginal fistulas repair should be the preferred one. Transvaginal repairs achieve comparable success rates, while minimizing operative complications, hospital stay, blood loss, and post surgical pain. We recommend waiting at least 4-6 weeks prior to attempting repair of a vesicovaginal fistula. It is acceptable to repeat the repair through a vaginal approach even after a first vaginal approach failure. In the more individualized management of fistulas associated with radiation, the vaginal approach should still be considered.

Continent urinary diversion in gynecologic oncology

Pelvic exenteration is a salvage procedure used primarily for recurrent gynecologic carcinoma. Up to the present time, an ileal or colon conduit has been used for urinary diversion and the patient remains incontinent of urine. This is a preliminary report of nine patients with gynecologic carcinoma in whom a continent urinary diversion procedure was performed. A segment of distal ileum, the ascending colon, and part of the transverse colon are used to create the colonic reservoir. The segment of colon is opened along the tenia and folded onto itself. The walls of the ascending and transverse colon are anastomosed to detubularize this segment of bowel and eliminate the transient high pressure of the colon. Surgical staples are used for the anastomosis. The segment of ileum is tapered and three purse-string sutures (2-O silk) are placed at the level of the ileocecal valve to achieve continence. The short segment of ileum is then exteriorized as a stoma through which the patient catheterizes. Antirefluxing, non-tunneled ureterocolonic anastomoses are performed. The anterior wall of the reservoir is closed with absorbable staples. Postoperative urodynamic studies have shown maximum capacity of 750 ml and the area of continence to be at the ileocecal valve where the purse-string sutures are placed. All patients are continent and postoperative radiographs were negative for reflux. Follow-up was 6 to 12 months. The colonic reservoir is a capacious low-pressure system and warrants further clinical trials in patients with gynecologic cancer.

The impact of intraoperative autologous blood transfusion during type III radical hysterectomy for early-stage cervical cancer.

OBJECTIVE The aim of this study was to determine the effects on transfusion rates, perioperative complications, and survival of using intraoperative autologous blood transfusions for patients undergoing type III radical hysterectomy and lymphadenectomy. STUDY DESIGN A retrospective analysis was conducted on 156 patients treated with type III radical hysterectomy and lymphadenectomy at the University of Miami School of Medicine from 1990 to 1997. One group of patients (n = 50) had intraoperative autologous blood transfusions and the other (n = 106) did not. RESULTS The group that received intraoperative autologous blood transfusion had a significant reduction in homologous blood transfusions (12% vs 30%; P =.02). Patient demographic data, histologic parameters, and operative factors were similar between the 2 groups. There was a higher percentage of patients with positive pelvic lymph nodes in the group that did not receive intraoperative autologous blood transfusion (10% vs 30%; P =.02). Seven patients in the intraoperative autologous blood transfusion group (14%) died with disease present and all the recurrences in this group were local. CONCLUSION The use of intraoperative autologous blood transfusions during type III radical hysterectomy and lymphadenectomy appears to be safe and effective without compromising rates and patterns of recurrence.

Comparison of bimanual examination with Ultrasound examination before hysterectomy for uterine leiomyoma

OBJECTIVE To correlate the preoperative bimanual examination with ultrasound examination with regard to estimating the size of enlarged nongravid leiomyomatous uteri. METHODS We performed a retrospective review of 161 patients who underwent hysterectomy for uterine leiomyoma between January 1994 and December 1994 and between July 1995 and April 1996. Uterine size was estimated clinically by bimanual examination. Ultrasound reports were reviewed. Uterine weights and dimensions in pathology reports were compared with findings on bimanual examination and ultrasonography. Body mass index (BMI) was calculated and patients were divided into two groups, one with BMIs of more than 30 and another with BMIs of less than or equal to 30. RESULTS Ultrasound examination was ordered in 111 patients (68.9%) preoperatively. There was a strong correlation between the bimanual examination findings and the ultrasound dimensions. The equation for this relationship is ultrasound length (cm)=3.68 + 0.68 x number of weeks (r=.78, P < .001). Ultrasound length also was related strongly to size given in the pathologic reports; the equation for this relationship is ultrasound length (cm)=2.94 + 0.75 x pathology length (cm) (r=.73, P < .001). The correlation between bimanual examination and ultrasound findings was similar in obese and in nonobese patients, when uterine size could be estimated. CONCLUSION There is a strong correlation between bimanual and ultrasound examinations with regard to determining the size of leiomyomatous uteri. Routine ultrasound is not indicated when an experienced examiner can assess uterine size. Ultrasonography may be appropriate when physical assessment is difficult, as in the case of obesity.

Urinary complications of Miami pouch: Trend of conservative management

OBJECTIVE Continent urinary diversions have become popular among gynecologic oncologists. Much information has been gained concerning the complications and current management of patients with continent ileocolonic reservoirs. The high mortality rate associated with reoperation has led clinicians to adopt a trend toward conservative means of management. The purpose of this study was to evaluate the applicability of conservative management of complications related to the creation of the continent ileocolonic reservoir Miami pouch. STUDY DESIGN Patients who underwent creation of the Miami pouch at the Division of Gynecologic Oncology, University of Miami School of Medicine, since 1988 have been included in this study. Management of complications, with particular emphasis on the conservative treatment, has been reviewed in detail for each patient. Open surgery and conservative treatment have been compared. RESULTS Seventy-seven patients underwent creation of the Miami pouch from February 1988 to September 1997. Sixty (77.9%) patients were affected by recurrent cervical cancer; 72 (93.5%) were previously radiated. The perioperative mortality rate was 11.7% (9 patients). Six of these patients died as a result of sepsis; all of them underwent reoperation at least once. The most common urinary complications were ureteral stricture or obstruction (22.1%), difficult catheterization (19.5%), and pyelonephritis (13%). Conservative management strategies used for these complications included percutaneous nephrostomy, stent placement, balloon dilatation, radiologically (ultrasonography, fluoroscopy, computed tomography) guided placement of catheters, and antibiotic treatment. Eighty percent of the complications associated with the ileocolonic reservoir were resolved with conservative treatment, whereas 16.9% required surgical revision. CONCLUSION On the basis of these findings, conservative management of urinary reservoir complications should always be considered before surgical intervention is attempted. The exact time to engage in open revision should be individualized on the basis of the clinical condition of each patient. It is our belief that the conservative approach should be instituted whenever possible but surgical intervention not be delayed when absolutely indicated.

The safety of incidental appendectomy at the time of abdominal hysterectomy

OBJECTIVE The purpose of this study was to assess the complication rates of incidental appendectomies in women who undergo benign gynecologic procedures. STUDY DESIGN This was a retrospective case-controlled study of patients who did (n=100 women) or did not (n=100 women) undergo incidental appendectomies at the time of an abdominal hysterectomy between June 1995 and January 2001. Information was abstracted from hospital and clinic records and a gynecologic oncology database. Data were obtained about age, body mass index, hypertension, diabetes mellitus, the number of days with nothing by mouth, the length of hospital stay, and postoperative complications (cellulitis, fever, ileus, pneumonia, thromboembolic disease). Data were analyzed with the use of two-sample t tests, Wilcoxon Rank sum tests, chi(2) tests, and multiple logistic regressions. RESULTS There was no difference in preoperative diagnosis or operative procedure for either group. The number of patients in the group that did have incidental appendectomy versus the group that did not have incidental appendectomy with additional procedures at the time of abdominal hysterectomy was bilateral salpingo-oophorectomy (66 vs 61 women), unilateral oophorectomy (19 vs 19 women), lysis of adhesions (9 vs 8 women), and others (12 vs 8 women). Compared with the group that did not have incidental appendectomy, the group that did have incidental appendectomy was younger (mean age+/-SD: 44+/-9.6 years vs 48+/-13.6 years, P=.02) and had a lower mean body mass index (26.1+/-6.0 kg/m(2) vs 29.8+/-8.9 kg/m(2), P=.0009). No significant differences were found between the two groups (the group that did have incidental appendectomy vs the group that did not have incidental appendectomy, respectively) with respect to the following postoperative complications: fever (40 vs 27 women), cellulitis (1 vs 2 women), wound collection (4 vs 6 women), wound dehiscence (1 vs 5 women), wound abscess (7 vs 6 women), ileus (3 vs 2 women), and urinary tract infection (4 vs 10 women). The mean length of hospital stay was significantly longer in the group that did have incidental appendectomy than in the group that did not have incidental appendectomy (3.6+/-1.52 days vs 3.1+/-1.1 days, P=.006). However, the difference was no longer significant when patients who were fed electively on the postoperative day 2 were excluded from the analysis (3.16+/-1.13 days vs 3.04+/-1.13 days, P=.507). Thirty-one percent of the histologic specimens were abnormal, with fibrous obliteration being most common, and there was one case of acute appendicitis. CONCLUSION An incidental appendectomy at the time of benign gynecologic procedures does not increase postoperative complication rates or length of hospital stay. The inclusion of incidental appendectomies in all abdominal hysterectomies could potentially decrease the morbidity and mortality rates because of appendicitis in elderly women.

Should sacrospinous ligament fixation for the management of pelvic support defects be part of a residency program procedure? The University of Miami experience

OBJECTIVE The objective of this article is to determine the safety and effectiveness of transvaginal sacrospinous ligament fixation as part of the management of pelvic support defects in a residency program. STUDY DESIGN A retrospective chart review of patients undergoing sacrospinous ligament fixation at the Division of Gynecology, Jackson Memorial Hospital, University of Miami School of Medicine, between July 1990 and December 1995, was performed. Patients with vaginal vault prolapse and uterine prolapse with documented preoperative evaluation were included in this study. Data were obtained using a detailed predetermined flow sheet. RESULTS A total of 160 patients was included in the study. All patients underwent right sacrospinous ligament fixation, anterior and posterior colporrhaphy, and perineorrhaphy. In addition, 31 (19%) underwent enterocele repair, 5 (3%) underwent trachelectomy, and 9 (6%) underwent Burch procedure. Complications included fever 13 (8.1%), urinary tract infection 16 (10%), blood loss requiring transfusion 7 (4.3%), sciatic neuralgia 2 (1.2%), and rectovaginal fistula 2 (1.2%). The mean follow-up was 40 months (range 18 to 78 months). The success of the operation was gauged by recurrence. Ninety-four percent of the patients had no evidence of vaginal vault prolapse on follow-up, and 85% had no recurrence of any pelvic support defect. Eleven of the 24 patients with recurrence underwent repeat surgery, whereas 13 opted for conservative management with pessaries. CONCLUSION Transvaginal unilateral sacrospinous ligament fixation is a safe and successful operation for the treatment of pelvic support defect and should be an essential component in the training of gynecologic residents.

Stage III and stage IV endometrial carcinoma: A review of 41 cases

Forty-one patients with clinical stage III and IV carcinoma of the endometrium presented to Jackson Memorial Hospital between the years 1977 and 1988. These patients were studied as to their presenting symptoms, prognostic factors, therapeutic regimens, and survival. Sixty-one percent of our patients presented with postmenopausal bleeding. Prognostic factors included extent of disease and tumor bulk rather than histologic type, grade, or depth of myometrial invasion. Overall 5-year survival was 7/32 (22%), with 6/22 (27%) for stage III and 1/10 (10%) for stage IV. Those patients who received surgery plus radiation fared better than those who received either alone. Hormonal therapy offered little, if any, benefit. CAP-M chemotherapy was used as adjunctive treatment in 10 patients and its use is discussed. It is our hope that we may later use this study to compare the newer surgical staging in advanced cases of endometrial carcinoma with the previously used clinical staging system.

Continent urinary diversion and low colorectal anastomosis after pelvic exenteration. Quality of life and complication risk

INTRODUCTION Pelvic exenteration is one of the most destructive gynecologic operations performed on an elective basis, with consequent detrimental effects on the quality of life. The use of reconstructive surgery has significantly improved the quality of life of women undergoing this type of procedure. In this paper we review our experience with continent urinary diversion (Miami Pouch) and low colorectal anastomosis at the Division of Gynecologic Oncology of the University of Miami. METHODS Patients who underwent creation of the continent urinary diversion Miami Pouch from 1988 to 1997 and supralevator pelvic exenteration with low colorectal resection and primary anastomosis from 1990 to 1997 have been included in this study. Management of complications, with particular emphasis on the conservative treatment, has been reviewed in detail for each patient. Open surgery and conservative treatment have been compared. Analysis of complications in irradiated and nonirradiated patients was performed. RESULTS 77 patients who underwent creation of the Miami Pouch entered this study. Forty patients underwent total pelvic exenteration, and 37 patients underwent posterior exenteration. The most common urinary complications were ureteral stricture/obstruction (22.1%), difficult catheterisation (19.5%) and pyelonephritis (16.9%). Conservative management strategies were successfully used in 80% of the complications. Analysis of breakdown and fistula formation after low colorectal anastomosis was performed on 77 patients. Thirty-five percent of the irradiated patients developed anastomotic breakdown or fistulas, while the occurrence of this type of complications was only 7.5% in the nonirradiated group. CONCLUSIONS Reconstructive procedures after pelvic exenteration present a significant risk of complications, especially in irradiated patients. Most of the complications related to the creation of continent urinary diversion can safely be treated conservatively. Low colorectal anastomosis carries an acceptable risk of complications in nonirradiated patients, but the risk in irradiated patients is very high, therefore, detailed patient selection and extensive counselling in these groups of patients is mandatory.