Emery Salom

Management of recurrent ovarian cancer: evidence-based decisions

In this era of advanced medical technology, recurrent ovarian cancer continues to be a therapeutic dilemma. Most of these patients will succumb to their disease process. For this reason, it is of paramount importance for all clinicians to recognize that the primary goal of salvage therapy is to maximize disease-free survival and quality of life. With this goal in mind, they can offer patients a variety of different modalities to control disease, including second-look surgery, secondary or interval cytoreduction, second-line chemotherapy, hormonal therapy, and immunotherapy. The role of second-look surgery has yet to be delineated, but the modality can be helpful in evaluating disease status and guiding further therapy in patients receiving first-line platinum-based chemotherapy or in research protocols. Interval cytoreductive surgery has been shown to confer a survival advantage in a small subset of patients with localized resectable disease proven to be platinum sensitive. The choice of chemotherapeutic agents and the prognosis depend directly on whether the patient is a platinum-sensitive responder. Many agents are approved for the treatment of recurrent ovarian cancer, and the treatment of each patient should be individualized depending on the cumulative toxicities and performance status. Extensive ongoing research trials are underway to elucidate the best salvage therapy.

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.

Pelvic exenteration and reconstruction

For the past six decades, pelvic extenteration has been utilized in the treatment of localized central pelvic recurrences after chemo/radiotherapy. The radicality of the procedure that includes resection of the bladder, vulva/vagina, and rectum, although with curative intent, results in comprehensive changes for the patient. For this reason, all patients should undergo extensive psychosocial counseling to prepare them for the changes in body image and lifestyle. Extirpation of the pelvic viscera has undergone a number of modifications since Brunschwig first described it in 1948 to maximize survivability and minimized anatomical distortion. Most of the advancements have been focused on the reconstructive phase after pelvic exenteration. A few select patients can be free of any external appliances such as a colostomy bag with utilization of a low colorectal anastomosis, and can maintain sexual intimacy with creation of a neovagina. In addition, reconstruction of the pelvic floor with omental flaps, dura mater grafts and myocutaneous flaps have decreased postoperative morbidity. In this article, we provide a review of pelvic exenteration in gynecologic oncology, emphasizing preoperative evaluation, surgical techniques and their postoperative management.

The Microculture-Kinetic (MiCK) Assay: The Role of a Drug-Induced Apoptosis Assay in Drug Development and Clinical Care

A drug-induced apoptosis assay, termed the microculture-kinetic (MiCK) assay, has been developed. Blinded clinical trials have shown higher response rates and longer survival in groups of patients with acute myelocytic leukemia and epithelial ovarian cancer who have been treated with drugs that show high apoptosis in the MiCK assay. Unblinded clinical trials in multiple tumor types have shown that the assay will be used frequently by clinicians to determine treatment, and when used, results in higher response rates, longer times to relapse, and longer survivals. Model economic analyses suggest possible cost savings in clinical use based on increased generic drug use and single-agent substitution for combination therapies. Two initial studies with drugs in development are promising. The assay may help reduce costs and speed time to drug approval. Correlative studies with molecular biomarkers are planned. This assay may have a role both in personalized clinical therapy and in more efficient drug development.

Correlation of pretreatment drug induced apoptosis in ovarian cancer cells with patient survival and clinical response

BackgroundThis study was performed to determine if a chemotherapy-induced apoptosis assay (MiCK) could predict the best therapy for patients with ovarian cancer.MethodsA prospective, multi-institutional and blinded trial of the assay was conducted in 104 evaluable ovarian cancer patients treated with chemotherapy. The MiCK assay was performed prior to therapy, but treating physicians were not told of the results and selected treatment only on clinical criteria. Outcomes (response, time to relapse, and survival) were compared to the drug-induced apoptosis observed in the assay.ResultsOverall survival in primary therapy, chemotherapy naïve patients with Stage III or IV disease was longer if patients received a chemotherapy which was best in the MiCK assay, compared to shorter survival in patients who received a chemotherapy that was not the best. (p < 0.01, hazard ratio HR 0.23). Multivariate model risk ratio showed use of the best chemotherapy in the MiCK assay was the strongest predictor of overall survival (p < 0.01) in stage III or IV patients. Standard therapy with carboplatin plus paclitaxel (C + P) was not the best chemotherapy in the MiCK assay in 44% of patients. If patients received C + P and it was the best chemotherapy in the MiCK assay, they had longer survival than those patients receiving C + P when it was not the best chemotherapy in the assay (p = 0.03). Relapse-free interval in primary therapy patients was longer if patients received the best chemotherapy from the MiCK assay (p = 0.03, HR 0.52). Response rates (CR + PR) were higher if physicians used an active chemotherapy based on the MiCK assay (p = 0.03).ConclusionThe MiCK assay can predict the chemotherapy associated with better outcomes in ovarian cancer patients. This study quantifies outcome benefits on which a prospective randomized trial can be developed.

Personalized Cancer Care: A New Paradigm in Oncology

Oncology Issues March/April 2010 ersonalized cancer care is an emerging strategy in medical oncology. The theme of the 2009 American Society of Clinical Oncology (ASCO) meeting—chosen by ASCO’s then-president Richard Schilsky, MD, was personalized cancer care, highlighting the importance of this issue.1 Bottom line: improved outcomes for patients—including better survival and higher clinical benefit rates— warrant individualization of therapy whenever possible. One national oncology blog (Medscape, September 2, 2009) emphasized that this new paradigm implies that oncologists should consider how implementation of personalized cancer care could impact the nature of their practice and relationships with their colleagues and referring physicians, as well as their staff and patients. The lay press is also exhibiting an emerging awareness about personalized medicine.2 Patients are beginning to come for cancer consultations with an expectation that their care will be personalized. Patients also expect that their physicians will implement all of the appropriate testing and treatment decisions to allow patients to access the most individualized treatment available. Indeed, many patients, disappointed in the discussion about personalized medical care, seek second opinions elsewhere, usually from academic medical centers. Because of this emerging trend, physicians need to re-evaluate the way in which they care for cancer patients. Community cancer centers and oncology practices should optimally and appropriately incorporate all of the validated technologies of personalized cancer treatment advances so that their care is state-of-the-art, effectively meeting the needs of their patients. This article addresses several timely issues related to personalized cancer care, including:

Should Leiomyoma Morcellation Be Banned?: Risk of Sarcoma in 2,248 Patients Referred to a Gynecologic Oncologist [129]

INTRODUCTION: To determine the incidence of uterine leiomyosarcoma in patients undergoing total abdominal hysterectomy (TAH) and total robotic and laparoscopic hysterectomies for benign uterine leiomyomas. METHODS: We reviewed the medical records of 2,248 patients referred to a gynecologic oncology practice who underwent hysterectomies for symptomatic leiomyomas between 1995 and 2014. The patients ages, admitting diagnosis, operative, and pathologic findings were analyzed. The incidence of leiomyosarcomas, endometrial stromal sarcomas, and mixed mesodermal tumors were calculated. All myomectomies and all known sarcomas preoperatively were excluded from the study. RESULTS: Nearly half of the 2,248 patients underwent a laparoscopic and robotic hysterectomy (51%). A total of four (0.17%) patients with presumed benign disease were found to have a uterine leiomyosarcomas. The TAH group had a high rate—0.26% (3/1,136) compared with only 0.08% (1/1,112) in the total robotic and laparoscopic hysterectomy group. Eighty percent were postmenopausal women with an average age of 60 years. One (0.04%) patient in the TAH group was found to have endometrial stromal sarcoma. CONCLUSION: The incidence of all leiomyosarcomas in patients undergoing surgery for uterine leiomyomas is extremely rare (0.17%), more so in minimally invasive surgery (1/1,112) with more than 80% of patients being postmenopausal. Based on our study, the probability of morcellating an unknown sarcoma in a premenopausal woman not accounting for other high-risk factors would be 1 in 2,500–5,000. Based on the low incidence of leiomyosarcomas in our study, which is similar to others, banning morcellation would lead to increased morbidity and mortality as a result of laparotomy.

Radical Robotic and Abdominal Hysterectomy: Perioperative and Oncologic Outcomes of 175 Cases of Cervical Cancer [238].

INTRODUCTION: The purpose of this study was to investigate the perioperative, postoperative, and oncologic outcomes regarding radical robot laparoscopic-assisted, and radical abdominal hysterectomy±pelvic or paraaortic lymphadenectomies in early-stage cervical carcinoma. METHODS: A total of 175 patients underwent radical hysterectomy for early-stage cervical carcinoma management between January 2005 and July 2014. All cases were retrospectively reviewed to compare demographics, perioperative and postoperative, such as mean operative time, estimated blood loss, lymph node counts, intraoperative and postoperative complications, and follow-up results. RESULTS: A total of 175 patients were divided equally between radical robot laparoscopic-assisted (53.8%) and radical abdominal hysterectomy (46.2%) groups. The groups did not differ in age, body mass index, and combined medical problems. The mean operating times were similar for both groups: radical robot laparoscopic-assisted 189±65.6 compared with radical abdominal hysterectomy 184±48.9 minutes, respectively. Estimated blood loss was significantly reduced in the radical robot laparoscopic-assisted group compared with radical abdominal hysterectomy (100±125 compared with 400±475 mL, P<.001) as well as length of stay radical robot laparoscopic-assisted=1 day compared with radical abdominal hysterectomy=3 days (P<.001). There was no difference in average paraaortic lymph nodes (3.7 compared with 3.9), pelvic lymph node count (18 compared with 14), intraoperative complications (4.7 compared with 4.3), postoperative complications (24.1 compared with 23.9) between radical robot laparoscopic-assisted compared with radical abdominal hysterectomy, respectively. Intraoperative complications included venotomy (n=2, one in each group), colostomy (radical robot laparoscopic-assisted=1), and cystotomy (radical abdominal hysterectomy=1). No cases of wound infections or incisional hernias in the radical robot laparoscopic-assisted group compared 4.0% and 1.3% among the radical abdominal hysterectomy group, respectively. Vaginal dehiscence was 3.5% in the radical robot laparoscopic-assisted and none in the radical abdominal hysterectomy group. There was no statistically significant difference in rates of readmission, postoperative fever, vaginal cuff complications overall, pelvic collections, and ileus or small bowel obstruction between the two groups. Recurrence rates were also similar 11% (radical robot laparoscopic-assisted) compared with 7.5% (radical abdominal hysterectomy). CONCLUSION: Minimally invasive surgery is associated with decreased hospital length stay, less blood loss, and postoperative complications in the treatment of early-stage cervical carcinoma patients compared with radical abdominal hysterectomy, making it a safe alternative with fewer complications.

The treatment of fecal incontinence after traumatic vaginal delivery: overlapping sphincteroplasty, internal anal sphincter imbrication, levatorplasty, culdoplasty, and perineorrhaphy

Abstract Objective: To assess the operative procedure used in the treatment of fecal incontinence after traumatic vaginal delivery and the functional outcome after surgery. Methods: Between 1995 and 1998, a prospective nonrandomized study was conducted on 22 patients, all of whom had complete fecal incontinence of gaseous, liquid, and solid stool. Preoperatively, all patients were found to have anterior rupture of the external anal sphincter after vaginal deliveries. All patients underwent overlapping sphincteroplasty, culdoplasty, levator ani plication, and perineorrhaphy. Results: Incontinence to gas was found in only one woman (6%). Liquid incontinence was reported in 3 of 22 patients (13.7%). One patient (6%) experienced incontinence to solid stool. A total of four patients (18.2%) suffered constipation, but in only three patients (17%) did the constipation persist after 1 month. Ninety-five percent of the patients had no incontinence to solid stool. The mean follow-up period was 20 months. Conclusion: Ninety-five percent of patients are continent to solid stool. A total of 82% of patients suffer no fecal incontinence and experience excellent functional status, maintaining Grade III and IV continence.