Robotic management of endometriosis: where do we stand?

The progressive and chronic nature of this disease can have a substantial impact on both quality of life and functioning of women who suffer from the disease. While medical treatment can be sufficient therapy for many women with endometriosis, medical therapies are often inadequate for the severest cases. The anatomic changes of adhesions/fibrosis and smooth muscle metaplasia that are associated with endometriosis, however, can be substantial and surgery for this disease can be technically challenging. Historically, the severest cases of endometriosis were managed using a laparotomy approach. Traditional laparoscopy has gained popularity for the management of this disease but has limitations in the surgical treatment of the most difficult cases of endometriosis. With the introduction of the robotic surgical platform, experience has gradually accumulated regarding its application for surgical management of deeply infiltrating endometriosis (DIE). It has been suggested that the robotic platform enables more complex dissections and may be the ideal modality for the surgical management of endometriosis. As both experience and technology expand, the robotic platform is being utilized by an increasing number of surgeons and for increasingly complex minimally invasive pelvic surgery. The literature analyzing its actual performance in the management of DIE, however, is only just manifesting. This review focus on the surgical management of endometriosis by robotic laparoscopy. Specifically we describe the unique surgical challenges of this disease. We also highlight the current state of the literature that analyzes the application of robotic laparoscopy to the various anatomic and clinical manifestations of endometriosis and critique outcomes as they apply to the safety, efficacy and cost of this modality for the management of endometriosis.

Total laparoscopic hysterectomy versus laparoscopic-assisted vaginal hysterectomy in endometrial cancer: surgical and survival outcomes.

STUDY OBJECTIVE: To compare surgical and survival outcomes of patients with early-stage endometrial cancer (EC) who underwent total laparoscopic hysterectomy (TLH) or laparoscopic-assisted vaginal hysterectomy (LAVH) +/- lymphadenectomy. DESIGN: Retrospective, nonrandomized clinical study (Canadian Task Force classification II-2). SETTING: Two tertiary care academic medical centers. PATIENTS: Patients with EC treated by TLH or LAVH from 1998 through 2006. INTERVENTIONS: TLH and LAVH were performed in 80 and 24 patients, respectively. Patient demographics and clinical variables were collected, and surgical and survival outcomes were determined. MEASUREMENTS AND MAIN RESULTS: Median operating time was significantly higher for patients undergoing LAVH than for those undergoing TLH (212.5 and 183.5 minutes, respectively; p = .039). EBL was also greater in patients undergoing LAVH (median 220 mL) compared with those undergoing TLH (median100 mL; p = .001). After a median follow-up time of 51.5 months, there was no difference in recurrence or survival rates between the groups. CONCLUSION: Early-stage EC can be treated effectively with either TLH or LAVH. TLH patients may experience shorter operating times and less blood loss. When performed by experienced laparoscopists, TLH may be more feasible than LAVH in this cohort of patients.

Prevention and management of antineoplastic-induced hypersensitivity reactions.

Acute hypersensitivity reactions (HSRs) are an unpredictable and potentially catastrophic complication of treatment with chemotherapeutic agents. Reactions may affect any organ system in the body and range widely in severity from mild pruritus to systemic anaphylaxis. Certain classes of chemotherapeutic agents, such as the taxanes, platinum compounds, asparaginases, and epipodophyllotoxins are commonly associated with HSRs. The clinical characteristics of these high risk agents with respect to HSRs are discussed in this review. Protocols to prevent or reduce the severity of these reactions have been developed, but despite these attempts, HSRs will still happen. Should a reaction occur, it is imperative that it be recognised quickly in order to minimise exposure to the inciting agent and implement appropriate therapeutic and supportive measures. When a patient becomes sensitised to a chemotherapeutic agent, avoidance of re-exposure is the mainstay of future prevention. For sensitised patients who have derived clinically meaningful benefit from a particular agent, however, continuation of treatment with the agent is desirable. Options may include attempting a trial of desensitisation or treatment with a related compound. Virtually all patients demonstrating HSRs to paclitaxel and docetaxel are able to successfully tolerate re-treatment following discontinuation and administration of diphenhydramine and hydrocortisone. Re-treatment has generally been less successful with platinum compounds. with recurrent HSRs occurring in up to 50% of patients following desensitisation protocols. Patients sensitised to asparaginase are often able to tolerate the alternative preparations, Erwinia carotovora asparaginase or polyethylene glycol-modified Escherichia coli asparaginase. There is very little experience with re-treatment following sensitisation to the epipodophyllotoxins. As re-treatment may have serious consequences, careful consideration of the risks and benefits of these strategies is imperative when deciding among these options.

Carboplatin skin testing: a skin-testing protocol for predicting hypersensitivity to carboplatin chemotherapy.

PURPOSE: A high incidence of moderate to severe hypersensitivity reactions (HRs) is noted in patients who have been treated with multiple courses of carboplatin. Presently, there is no reliable way to predict which patients may be at risk for this potentially severe adverse reaction. We developed a skin-test protocol to identify patients at high risk for HR to carboplatin chemotherapy. PATIENTS AND METHODS: Patients undergoing more than seven courses of carboplatin received a 0.02-mL intradermal injection of an undiluted aliquot of their planned carboplatin infusion 1 hour before each course of the agent. A positive skin test was prospectively defined as that resulting in a wheel of at least 5 mm with a surrounding flare. We recently reported a 27% incidence of HRs in patients receiving more than seven courses of carboplatin. These patients served as historical controls for the current study. RESULTS: Forty-seven patients with recurrent ovarian or primary peritoneal carcinoma receiving carboplatin were skin tested. Thirteen of 47 patients (28%) manifested a positive skin test at a median of nine total courses of carboplatin (range, eight to 17 courses). This rate of skin-test positivity was not significantly different from the incidence of documented HR reported in a historical control group (P =.89), suggesting comparable populations. A negative skin test accurately predicted the absence of HR in 166 of 168 courses of chemotherapy. Only two of 47 patients (4%) experienced a HR after a negative skin test. Thus, administering carboplatin only to patients with a negative skin test may result in a significant reduction in HRs relative to historical controls (P =.002). CONCLUSION: An easily performed skin test appears to predict patients in whom carboplatin may be safely administered. Treatment modifications based on the results of skin testing may reduce the incidence of HRs in patients receiving repeated courses of carboplatin.

Treatment of gynecologic cancers in pregnancy.

Gynecologic cancers are among the most common malignancies in reproductive-age women. Approximately 3% of women diagnosed with a malignancy of the reproductive tract will have a coexisting pregnancy. A pregnant woman with a gynecologic malignancy presents a significant challenge for the clinician for many reasons. Considerable diagnostic delay is common due to confusion of symptomatology with the physiologic changes associated with the pregnant state. The diagnostic options available for a patient suspected of having an invasive gynecologic malignancy may also be compromised by the pregnancy. In addition, difficult medical, ethical, and religious issues arise when the treatment of these malignancies is incompatible with continuation of the pregnancy. Unfortunately, a relatively limited experience with reproductive tract cancers in pregnancy has prevented the development of universally accepted management algorithms for many of the complex issues regarding their treatment. A literature review of diagnostic and treatment strategies for cervical, ovarian, endometrial, and vulvar carcinoma complicated by pregnancy is presented.

Treatment of relapsed carcinoma of the ovary with single-agent paclitaxel following exposure to paclitaxel and platinum employed as initial therapy.

OBJECTIVES: The aim of this study was to evaluate the ability of paclitaxel to achieve a second clinical response in patients with recurrent epithelial ovarian carcinoma who responded to standard therapy with platinum and paclitaxel in the initial setting. METHODS: Thirty-four patients with epithelial ovarian who demonstrated a complete response to paclitaxel and platinum in the initial treatment setting were retreated with paclitaxel as a single agent for relapse of their disease. Paclitaxel was given at a dose of 135-175 mg/m(2) over 3 h at 21-day intervals. Fifteen patients had platinum-resistant disease and 19 had potentially platinum-sensitive disease. Response was documented by physical examination, serial serum CA125 measurement, or radiologic evaluation. RESULTS: An objective response to paclitaxel retreatment was demonstrated in 15 patients (44%), with a median progression-free interval (PFI) of 8.6 months (range 4-17 months). An additional 14 patients (41%) demonstrated disease stabilization, with a median PFI of 7.4 months (range 3-13 months). Overall, retreatment with paclitaxel was well tolerated, with minimal cumulative toxicities, despite repetitive dosing. CONCLUSION: These results demonstrate that patients with ovarian cancer who relapse after initial treatment with paclitaxel often have disease that is still responsive to the agent. Given its relative lack of cumulative toxicity, retreatment with paclitaxel as a single agent is a reasonable therapeutic option for patients with recurrent ovarian cancer.

Screening for gynecologic cancer.

Screening for cervical cancer with the Pap test has significantly reduced mortality from the disease. Although screening for ovarian and endometrial cancer is desirable, suggested strategies have not demonstrated efficacy. For the present time, educating patients with regard to the symptoms associated with these diseases and prompt evaluation of women who present with these symptoms helps limit unnecessary diagnostic delay.

The use of paclitaxel and platinum-based chemotherapy in uterine papillary serous carcinoma.

OBJECTIVE: Uterine papillary serous carcinoma (UPSC) is an aggressive malignancy with a histologic appearance and pattern of spread that resembles that of papillary serous adenocarcinoma of the ovary. The current standard therapy for advanced ovarian cancer, cisplatin or carboplatin plus paclitaxel, results in high objective response rates for that tumor. This regimen has thus far not been evaluated in UPSC. METHODS: Twenty-four patients with UPSC treated with platinum-based chemotherapy and paclitaxel were retrospectively evaluated. Eighteen patients received these agents in the adjuvant setting (n = 9) or for disease persistent after initial surgical management (n = 9). Eleven patients received one or more courses of this drug combination for recurrent disease, 5 of whom had prior exposure in the initial setting. RESULTS: Mean follow-up was 35 months (range 6-72+). A median progression-free interval (PFI) of 30 months (range 8-61+) was seen in patients treated in the adjuvant setting. Objective response, indicated by normalization of an elevated prechemotherapy CA125 level, was seen in 8 of 9 patients treated for residual disease after initial surgery (median PFI of 13 months, range 5-38+). Objective response of both measurable and/or evaluable disease was seen in 7 of 11 patients treated for recurrent disease (median PFI of 9 months, range 4-18). Six patients had retreatment with one or both agents and 4 responded a second time. Overall, the regimen was well tolerated. CONCLUSION: Paclitaxel and platinum-based chemotherapy has demonstrated activity in UPSC with acceptable toxicity. These results merit further investigation of the possible role of these agents in patients with this aggressive histologic subtype.

Allelic imbalance on chromosome 17p13 in borderline (low malignant potential) epithelial ovarian tumors.

Borderline epithelial ovarian tumors (BEOTs) possess clinical and pathologic features intermediate between cystadenomas and cystadenocarcinomas. Although the clinical and pathologic characteristics of BEOTs are well described, the molecular aspects are poorly understood. Three regions of loss of heterozygosity (often referred to as allelic imbalance [AI] when identified by polymerase chain reaction) on chromosome 17p13, one of which includes the p53 gene, have been implicated in the development of ovarian and breast cancers. To provide evidence that genes in these regions also may be involved in the development of BEOTs, we undertook a detailed analysis of AI at all three loci in BEOTs from 21 patients. Seventeen of the BEOTs were serous and four were mucinous. Five of 21 tumors (24%) had AI at one or more loci. Four tumors had AI using the D17S695 marker, two of which showed AI only at this locus. In addition, three tumors exhibited AI at the D17S654 locus, one of which showed AI only at this locus. These data suggest that there may be two tumor suppressor genes distal to p53 involved in the development of at least a subset of BEOTs. Peritoneal implants from a subset of serous BEOTs also were evaluated for AI and were found to be concordant with the primary tumor in all cases. Their genetic similarity is consistent with the implantation theory of peritoneal spread of serous BEOTs in these cases.

Analysis of allelic imbalance on chromosome 17p13 in stage I and stage II epithelial ovarian cancers.

OBJECTIVES: To determine whether there is evidence for allelic imbalance (AI) on chromosome 17p13 in early-stage epithelial ovarian tumors. METHODS: Studies of allelic imbalance were performed on 29 stage I or stage II epithelial ovarian cancers using 5 short tandem repeat polymorphic markers (STRPs) on chromosome 17p13 by polymerase chain reaction (PCR) amplification. RESULTS: Sixteen of 29 (55%) tumors showed AI at one or more loci, including 7 of 29 (24%) tumors that showed distinct regions of AI. AI at p53 was present in only 9 of 25 (36%) informative tumors. A region of AI, defined by marker D17S654, close to candidate genes OVCA1 and OVCA2, was identified distal to p53 and occurred in 11 of 23 (48%) informative tumors. This region of AI also extended more distal to this locus, and included marker D17S695 where AI occurred in 11 of 26 (42%) informative tumors. Microsatellite instability was observed in 2 of 29 tumors. CONCLUSIONS: This study supports the presence of at least one tumor suppressor gene on chromosome 17p13 distal to p53 that is involved in the early development of epithelial ovarian cancer. This study also suggests that the molecular analysis of early-stage epithelial ovarian cancers can provide important information on the genetic etiology of ovarian cancers.