Cardiac events among patients with sarcoma treated with doxorubicin by method of infusion: A real-world database study.

BACKGROUND: Administration of doxorubicin by continuous intravenous (CIV) infusion, versus bolus (BOL) administration, has been proposed to mitigate the risk of cardiac events. This study used real-world data to explore the association between mode of doxorubicin administration and duration of treatment, time-to-treatment failure (TTF), and cardiac events. METHODS: Occurrence of cardiac events after initiation of BOL versus CIV doxorubicin for sarcoma in the International Business Machines MarketScan claims database were compared. Duration of doxorubicin treatment, TTF, and time-to-first-cardiac event (TCE) were evaluated using Kaplan-Meier method and unadjusted and adjusted Cox regression models. RESULTS: A total of 196 patients were included in the BOL group and 399 in the CIV group. In unadjusted analyses, there were significant differences between BOL versus CIV for duration of doxorubicin treatment (median 1.4 vs. 2.1 months, p = .002), TTF (median 8.8 vs. 5.6 months, p = .002), and TCE (medians not reached, p = .03). Adjusting for baseline covariates, only TTF remained significant (hazard ratio: 0.71, 95% confidence interval 0.59-0.86, p = .0004), favoring BOL. CONCLUSIONS: While the risk of cardiac complications was higher with BOL in unadjusted analysis, the risk was no longer present in the adjusted analysis. While we cannot draw causal inferences due to the retrospective, nonrandomized study design, these data suggest that replacing BOL with prolonged CIV administration has not been effective as a strategy to mitigate cardiac events, given community standards of oncologic practice.

Robotic-Assisted Gynecologic Surgery and Perioperative Morbidity in Elderly Women.

STUDY OBJECTIVE: To assess perioperative complications, conversions, and operative times in patients age ≥75 years undergoing robotic-assisted gynecologic surgery. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: High-volume, 2-physician gynecologic oncology practice. PATIENTS: A total of 705 women who underwent any robot-assisted gynecologic procedure for benign (n = 380) or malignant (n = 325) conditions between July 2008 and May 2014. Fifty patients age ≥75 years (elderly group) were compared with 655 patients age <75 years (younger group). INTERVENTIONS: Operative data were gathered prospectively for all robotic-assisted procedures. Demographic and perioperative outcomes were analyzed retrospectively for this study. MEASUREMENTS AND MAIN RESULTS: The mean age was 81.3 ± 4.2 years (range, 75.0-90.5 years) in the elderly group and 52.8 ± 11.5 years (range, 22.9-74.6 years) in the younger group. The elderly group had higher rates of surgery for malignancy (90.0% vs 43.2%; p < .01) and lymphadenectomy (44.0% vs 23.4%; p < .01), and was more likely to have cardiovascular disease (88.0% vs 37.6%; p < .01). There were no between-group differences in body mass index or history of chronic obstructive pulmonary disease, diabetes mellitus, or more than 1 previous abdominal surgical procedure. The elderly group was more likely to have a length of stay greater than postoperative day one (30.0% vs 14.8%; p = .01) and had a higher incidence of postoperative cardiac arrhythmia (8.0% vs 1.2%; p < .01). The elderly group also had a smaller median uterine size (83.0 ± 49.1 g vs 126.0 ± 189.5 g; p < .01), but total operative time, rate of conversion (6.0% vs 1.8%) and rate of blood transfusion (2.0% vs 1.5%) were not significantly different between the 2 groups. Rates of bowel and genitourinary injury were <1% in both groups, and there was no between-group difference in postoperative infectious morbidity, vaginal cuff complications, or reoperation. CONCLUSION: The perioperative complication rates of robotic-assisted surgery are comparable in elderly women and younger women, despite a longer hospital length of stay and greater likelihood of postoperative arrhythmia in elderly women.

Lower limb compartment syndrome as a complication of radical hysterectomy.

•Compartment syndrome is a rare complication of prolonged lithotomy position.•We report a case of compartment syndrome complicating radical hysterectomy.•Prompt diagnosis is crucial to reduce morbidity from compartment syndrome.•Awareness of this complication allows surgeons to address modifiable risk factors.

Hydrothorax after robotic-assisted surgical staging of endometrial cancer.

► Hydrothorax from a pleuroperitoneal leak is a rare complication of laparoscopy. ► First case report of hydrothorax during robot-assisted laparoscopic surgery. ► Consider hydrothorax if new onset respiratory compromise after laparoscopy.

Combined weekly topotecan and biweekly bevacizumab in women with platinum-resistant ovarian, peritoneal, or fallopian tube cancer: results of a phase 2 study.

BACKGROUND: A phase 2 trial was conducted to determine the toxicity and efficacy of combined weekly topotecan and biweekly bevacizumab in patients with primary or secondary platinum-resistant ovarian, peritoneal, or fallopian tube cancer (OC). METHODS: Patients were treated with bevacizumab 10 mg/kg on days 1 and 15 and topotecan 4 mg/m(2) on days 1, 8, and 15 of a 28-day cycle until progressive disease (PD) or excessive toxicity. The primary endpoint was progression-free survival (PFS); secondary objectives included overall survival (OS), objective response, and toxicity. RESULTS: Patients (N = 40) received a median of 8 treatment cycles. Toxicity was generally mild or moderate, with neutropenia (18%), hypertension (20%), gastrointestinal toxicity (18%), pain (13%), metabolic toxicity (15%), bowel obstruction (10%), and cardiotoxicity (8%) being the most common grade 3 and 4 adverse events. No bowel perforations, febrile neutropenia, or treatment-related deaths occurred. Median PFS and OS were 7.8 (95% confidence interval [CI], 3.0-9.4) and 16.6 months (95% CI, 12.8-22.9), with 22 (55%) patients progression-free for ≥6 months. Ten (25%) patients had partial response (PR), 14 (35%) had stable disease (SD), and 16 (40%) had PD. Patients treated with 2 prior regimens received greater benefit than patients treated with 1: PR/SD, 78.9% versus 42.9% (P = .03); median PFS, 10.9 versus 2.8 months (P = .08); median OS, 22.9 versus 12.8 months (P = .02). CONCLUSIONS: A weekly topotecan and biweekly bevacizumab combination demonstrates acceptable toxicity and encouraging efficacy in patients with platinum-resistant OC; further study is warranted.

Leukocytosis after robotic hysterectomy: commonly observed but clinically insignificant.

Laboratory studies are commonly performed after surgery, but with little evidence of clinical utility. We evaluated our experience with measuring a complete blood count (CBC) to determine peripheral blood leukocyte count (WBC) postoperatively following consecutive robotic hysterectomies. From January 2008 through November 2009, two surgeons (KM, HM) performed 204 robotic hysterectomies. Patient age, weight, height, indication for surgery, surgical procedure, operative time, estimated blood loss, hospital length of stay, postoperative fever, and complications were prospectively recorded and correlated with WBC measured on the day after surgery. The postoperative WBC was elevated (>11,000/µl) in 59/204 (29%) patients. Eight (4%) patients had marked leukocytosis (WBC >15,000/µl; maximum 16,600/µl). There was no correlation between postoperative leukocytosis and operative time, BMI, performance of lymphadenectomy, or length of hospitalization. The only factor significantly associated with elevated postoperative WBC was elevated preoperative WBC (P < .001). Also, there was no correlation between postoperative leukocytosis with fever or infectious complications. The mean T max was 37.1ºC and T max over 38ºC was seen in nine patients. Of the five women who developed infectious complications, only one (diagnosed with pneumonia) had a minimally elevated postoperative WBC (11,600/µl); the other four (pneumonia and pelvic abscess, two each) had normal postoperative WBC. Routine measurement of WBC after robotic hysterectomy is not useful. In about 25% of cases there will be a slight leukocytosis, and rarely (about 4%) will the WBC exceed 15,000/µl. In no case was measurement of postoperative WBC clinically relevant.

Robot-assisted total laparoscopic hysterectomy in obese and morbidly obese women.

Total laparoscopic hysterectomy (TLH) in obese patients is challenging. We sought to evaluate whether total laparoscopic hysterectomies using the da Vinci robotic system in obese patients, in comparison with non-obese patients, is a reasonable surgical approach. One-hundred consecutive robot-assisted TLHs were performed over a 17-month period. Obesity was not a contraindication to robotic surgery, assuming adequate respiratory function to tolerate Trendelenburg position and, for cancer cases, a small enough uterus to allow vaginal extraction without morcellation. Data were prospectively collected on patient characteristics, total operative time, hysterectomy time, estimated blood loss, length of stay, and complications. Outcomes with non-obese and obese women were compared. The median age, weight, and BMI of the 100 patients who underwent robot-assisted TLH was 57.6 years (30.0-90.6), 82.1 kg (51.9-159.6), and 30.2 kg/m(2) (19.3-60.2), respectively. Fifty (50%) patients were obese (BMI ≥ 30); 22 patients were morbidly obese (BMI ≥ 40). There was no increase in complications (p = 0.56) or blood loss (p = 0.44) with increasing BMI. While increased BMI was associated with longer operative times (p = 0.05), median time increased by only 36 min when comparing non-obese and morbidly obese patients. Median length of stay was one day for all weight categories (p = 0.42). Robot-assisted TLH is feasible and can be safely performed in obese patients. More data are needed to compare robot-assisted TLH with other hysterectomy techniques in obese patients. Nonetheless, our results are encouraging. Robot-assisted total laparoscopic hysterectomy may be the preferred technique for appropriately selected obese patients.

Phase 2 study of intraperitoneal topotecan as consolidation chemotherapy in ovarian and primary peritoneal carcinoma.

BACKGROUND: Intravenous topotecan is approved for the treatment of ovarian cancer (OC). In intraperitoneal (i.p.) topotecan studies, 20 mg/m(2) dosing was tolerable. This study evaluated the feasibility, safety, and preliminary efficacy of i.p. topotecan as consolidation chemotherapy in patients with OC or primary peritoneal cancers (PPCs). METHODS: Patients with stage III/IV ovarian or PPC in clinical complete response after surgical cytoreduction and intravenous carboplatin/paclitaxel chemotherapy who had benign findings or minimal persistent disease (< or = 1 cm diameter) at second-look surgery were eligible. Intraperitoneal topotecan 20 mg/m(2) was infused once every 21 days for 4 to 6 cycles. Kaplan-Meier estimates were used to calculate progression-free survival (PFS) and overall survival (OS). RESULTS: Twenty patients were enrolled (18 [90%] patients had OC). Sixteen patients received 4 cycles, 3 patients received 6 cycles, and 1 patient withdrew after 1 cycle. The mean delivered dose was 18 mg/m(2). Grade 3/4 toxicities included neutropenia and thrombocytopenia (45% for both). Grade 1/2 abdominal distension and nausea were reported in 60% and 40% of patients, respectively. Median PFS was 24 months from second-look surgery (95% confidence intervals [CI]: +/-10 months). Sixteen patients were alive and median OS was not reached at the time of data analysis. OS estimated at either 30 months from second-look surgery, or 3 years from initial diagnosis, was 84% (95% CI, 68%-100%). CONCLUSIONS: Consolidation i.p. topotecan is a feasible option for women withadvanced ovarian and primary peritoneal cancers. Further investigation of i.p. topotecan is warranted in this patient population.

Ovarian cancer: patterns of surgical care across the United States.

OBJECTIVE: To describe the primary surgical procedures and procedures for intraoperative and postoperative complications, and factors associated with these procedures, in women with ovarian cancer. METHODS: Using hospital discharge data from nine states, obtained from the Heath Care Cost and Utilization Project from 1999 to 2002, we evaluated 10,432 women with a primary diagnosis of ovarian cancer who underwent at least an oophorectomy for additional procedural ICD-9 codes during their initial hospitalization. RESULTS: Surgical procedures performed in addition to oophorectomy included: omentectomy/debulking 81.9%, hysterectomy 73.4%, lymph node dissection 41.4%, appendectomy 23.8%, bowel procedures 19.8%, laparoscopy 5.6%, diaphragmatic procedures 4.9%, colostomy 3.5%, and splenectomy 1.2%. Transfusions were given to 15.5% of patients. Intraoperative and postoperative procedures for complications were coded in 7.4% of patients, including repair of surgical injury 3.5%, procedures for cardiopulmonary complications 2.8%, reoperation 1.1%, and infection treatment 0.3%. In early stage disease 21.4% of women received no additional staging procedures and 46.8% did not have nodal sampling. In bivariate analysis of crude rates, factors associated with lymph node dissection were patient age, race, payer, teaching hospital status, hospital and surgeon volume, and surgeon specialty, p<.01. for all observations. Colostomies were performed by general surgeons in 23.1% of cases, by gynecologic oncologists in 2.7% of cases, and by obstetrician/gynecologists in no cases, p<.001. Complications were associated with age, payer, median household income, and stage, p<.001 for all observations. Complication rates were similar for low- and high-volume hospitals and surgeons. However, in higher volume settings, significantly more patients received debulking procedures, lymph node dissections, and additional surgical procedures, p<.001 for all observations. CONCLUSIONS: A significant percentage of women with ovarian cancer did not receive recommended surgical procedures. Almost 50% of women with early stage disease were not adequately staged and in women with advanced disease, the percentage who had additional surgical procedures such as bowel resections was much lower than in institutions that report high optimal cytoreduction rates.

Incidence and management of abdominal sacrocolpopexy mesh erosions.

OBJECTIVE: This study was undertaken to evaluate the occurrence and management of mesh erosions in patients undergoing abdominal sacrocolpopexy. STUDY DESIGN: A retrospective chart review of the abdominal sacrocolpopexy procedure (n = 92) between 1997 and 2003 was performed. Patients with mesh erosion were identified. Incidence by graft type and treatment required for erosion resolution was analyzed with chi 2 and Fisher exact test. RESULTS: Erosions occurred in 7.6 % (7/92). Erosions were identified only in patients with Gore-Tex (3/33, 9%) or silicone-coated mesh (4/21, 19%) compared with none of 38 patients with polypropylene mesh (n = 24) or fascia (n = 14) grafts ( P = .068.). Partial excision of exposed graft resolved all 3 Gore-Tex erosions, compared with none of the silicone-coated mesh erosions ( P = .03). Complete graft removal was required to resolve silicone-coated mesh erosions. CONCLUSION: We observed a high rate of erosion with Gore-Tex and silicone-coated mesh. Partial graft excision was adequate for Gore-Tex erosions, but complete graft removal was necessary to resolve erosions associated with silicone-coated mesh.

High complication rate identified in sacrocolpopexy patients attributed to silicone mesh.

OBJECTIVES: To report on our experience using a preconfigured Y-shaped silicone-coated polyester mesh and polypropylene mesh for vaginal vault suspension. A variety of materials have been used for both open and laparoscopic sacrocolpopexy in the management of vaginal vault prolapse. Recently, a preconfigured Y-shaped silicone-coated polyester mesh was introduced to facilitate the vaginal cuff suspension to the sacrum. METHODS: We reviewed the data of 45 consecutive patients who underwent abdominal (n = 28) or laparoscopic (n = 17) sacrocolpopexy. Of the 45 patients, 21 underwent silicone mesh suspension of the vaginal cuff to the anterior sacrum, with a mean follow-up of 23 months (range 16 to 41). A comparative analysis was performed of 24 patients who underwent the same procedure with polypropylene mesh. RESULTS: Of the 21 patients in the silicone group, 5 (23.8%) have had a major complication (four vaginal mesh erosions and one mesh infection) after a median follow-up of 9.5 months (range 4 to 20). The presenting symptoms were persistent or new vaginal discharge and/or nonspecific pelvic pain. One patient underwent successful removal of the mesh transvaginally, but the rest required abdominal exploration. To date, the 24 patients who underwent vaginal cuff suspension with polypropylene mesh have had no vaginal mesh extrusions or infections, with a mean follow-up of 12 months (range 1 to 38). CONCLUSIONS: Silicone-coated polyester mesh has recently been associated with a high rate of vaginal erosion when used as a transvaginal suburethral sling. Our experience specifically with vaginal vault suspension corroborates this. We have abandoned the use of silicone mesh because of the unacceptably high extrusion rate and presently use polypropylene mesh.

Frequency of symptoms of ovarian cancer in women presenting to primary care clinics.

CONTEXT: Women with ovarian cancer frequently report symptoms prior to diagnosis, but distinguishing these symptoms from those that normally occur in women remains problematic. OBJECTIVE: To compare the frequency, severity, and duration of symptoms between women with ovarian cancer and women presenting to primary care clinics. DESIGN, SETTING, AND PATIENTS: A prospective case-control study of women who visited 2 primary care clinics (N = 1709) and completed an anonymous survey of symptoms experienced over the past year (July 2001-January 2002). Severity of symptoms was rated on a 5-point scale, duration was recorded, and frequency was indicated as number of episodes per month. An identical survey was administered preoperatively to 128 women with a pelvic mass (84 benign and 44 malignant). MAIN OUTCOME MEASURES: Comparison of self-reported symptoms between ovarian cancer patients and women seeking care in primary care clinics. RESULTS: In the clinic population, 72% of women had recurring symptoms with a median number of 2 symptoms. The most common were back pain (45%), fatigue (34%), bloating (27%), constipation (24%), abdominal pain (22%), and urinary symptoms (16%). Comparing ovarian cancer cases to clinic controls resulted in an odds ratio of 7.4 (95% confidence interval [CI], 3.8-14.2) for increased abdominal size; 3.6 (95% CI, 1.8-7.0) for bloating; 2.5 (95% CI, 1.3-4.8) for urinary urgency; and 2.2 (95% CI, 1.2-3.9) for pelvic pain. Women with malignant masses typically experienced symptoms 20 to 30 times per month and had significantly more symptoms of higher severity and more recent onset than women with benign masses or controls. The combination of bloating, increased abdominal size, and urinary symptoms was found in 43% of those with cancer but in only 8% of those presenting to primary care clinics. CONCLUSIONS: Symptoms that are more severe or frequent than expected and of recent onset warrant further diagnostic investigation because they are more likely to be associated with both benign and malignant ovarian masses.

The significance of psammoma bodies in screening cervical cytologic smears.

OBJECTIVE: Although the presence of psammoma bodies in cervical cytologic smears has been associated previously with gynecologic malignancies, the clinical significance of this finding in asymptomatic women who undergo routine cervical cytologic screening has not been well defined. STUDY DESIGN: For this retrospective clinicopathologic study, a search of the Virginia Mason Medical Center computerized cytology registry from 1993 through March 2002 identified 25 evaluable cervical cytologic smears that contained psammomatous calcifications. Slides were reviewed, and clinical information was obtained from medical records. RESULTS: The median patient age was 36 years (range, 22-72 years). Nine women were postmenopausal. All cytologic smears were obtained for routine screening, and no abnormal cells that were diagnostic of malignancy were identified. Possible explanations for the psammoma bodies was determined for 11 women, including foci of calcifications in benign endometrial or endocervical tissue (4 women), polyps (3 women), marked atrophy (3 women), postpartum (2 women), and follicular cervicitis (1 woman). None of the 25 women had cancer. After excluding 1 woman who was to lost to follow-up, the remaining 24 women were followed up for a median of 3 years (range, 6 months-7 years) without the subsequent detection of cancer. CONCLUSION: Cancers that were reported in previous studies usually were diagnosed in women with malignant background cytology or abnormal symptoms, such as postmenopausal bleeding. In contrast, our study suggests that the presence of psammoma bodies in normal cytologic smears of asymptomatic women is an incidental finding.

Evaluation of p27 in preinvasive and invasive malignancies of the cervix.

OBJECTIVE: p27 is a cell cycle inhibitor whose loss is commonly found in epithelial tumors. Low levels have been associated with poor prognosis. Our goal was to determine if p27 expression could be used to screen for dysplasia and if it is a prognostic factor for cervical malignancies. METHODS: Ten normal cervices, 51 consecutive cone biopsies for preinvasive disease, and 128 consecutive hysterectomies for invasive cervical cancer (1994-1999) were stained for p27 using standard immunocytochemical techniques. All of the cervical cancer patients were managed with radical hysterectomy and lymph node dissection, except for 14 women who underwent adjuvant hysterectomy and lymph node sampling after chemoradiation. RESULTS: There was no significant difference in p27 staining between normal cervices (all stained 4+) and preinvasive lesions (46/51 stained 4+ and 5/51 stained 3+). For the invasive lesions, 47 women had no residual disease in the hysterectomy specimen, due to prior cone biopsy (41) or radiation (6). All had 4+ p27 staining in the residual cervix. None of these women recurred. Eighty-one women had residual disease in the hysterectomy specimen; 25/81 (31%) had p27 staining of <50%. Loss of p27 was not significantly associated with invasion >50% (32 vs 27%), size >4 cm (20 vs 13%), or use of postoperative radiation (36 vs 20%). Loss of p27 was associated with lymphvascular space invasion (LVSI) (44 vs 20%, P = 0.04). Only 4 women had nodal metastasis; all 4 had p27 staining less than 50%; 6/81 (7%) women with residual disease developed recurrences and died. Of the women who died, 3/6 had p27 staining less than 50%. CONCLUSION: p27 is not lost in preinvasive cervical lesions and, therefore, cannot be used to screen for dysplasia. In cervical cancers p27 staining was <50% in 31% of cases, and is associated with increased risk of LVSI. Perhaps, because of the excellent overall survival of this group of women with Stage I cervical cancer, loss of p27 staining was not associated with poor prognosis.