The opinions and practices of providers toward the sexual issues of cervical cancer patients undergoing treatment.

OBJECTIVES: Cervical cancer and its treatments impair women's sexual function. These complications may or may not be regarded when clinicians develop treatment plans. We aim to investigate the considerations of providers toward the sex life of cervical cancer patients. METHODS: All members of the Society of Gynecologic Oncology received a questionnaire assessing their opinions and practices toward specific questions regarding the sexual functioning of their patients. RESULTS: Of the 124 providers who completed the survey, the majority were Board Certified Gynecologic Oncologists (56%) with an average of 15years in training. Approximately 23% received training about sexual dysfunction. Providers without formal training were more likely to agree that: "Information regarding sexual function in patients undergoing treatment for cervical cancer is lacking" (p=0.02). Providers with over 10years of experience were more likely to agree that "sex is private and discussing it with patients will interfere with our provider-patient relationship" (p=0.03). International clinicians were more likely to agree that: "I feel uncomfortable initiating discussions regarding sexual function with patients" (p=0.03), "Sex is private and discussing it with patients will interfere in our provider-patient relationship" (p=0.02), and "If a patient has a sexual problem, they will raise the subject" (p=0.009). CONCLUSIONS: Years of clinical experience, provider age, a history of training on regarding sexual dysfunction and an international setting of practice affect providers' opinions and practices toward sexual issues of cervical cancer patients. More formal, relevant training regarding sexual dysfunction is warranted for clinicians who treat cervical cancer patients.

Factors influencing primary treatment of midline vulvar cancers.

OBJECTIVES: Advanced vulvar cancers involving midline structures pose a therapeutic challenge. Our objectives were to review the management and outcomes, and identify factors influencing primary treatment modality. METHODS: Patients with midline vulvar cancers diagnosed from 1985 to 2012 were included in the analysis. Medical records were abstracted for demographics, clinico-pathological findings, treatment, and outcomes. Groin node status was defined by clinical findings or pathology. Survival was analyzed by Kaplan-Meier method and differences by log-rank test and Cox proportional hazards model. Factors influencing treatment modality were evaluated using stepwise logistic regression. RESULTS: Forty-two patients were identified. Twenty-one underwent primary radical vulvectomy and 21 underwent primary radiation. Median tumor diameter was 3.4cm (range 2-9cm) for primary radical vulvectomy and 5cm (range 2.3-15cm) for primary radiation. Primary radiation was significantly associated with a tumor diameter ≥5cm (p=0.02), or when 2 or more midline (p=0.008) or 1 or more mucosal structures (p=0.03) were involved. On multivariate analysis, age and tumor diameter were predictors of progression-free survival (PFS) (p=0.02 and p=0.0004, respectively) and overall survival (OS) (p=0.03 and p=0.0005, respectively). Thirty-month OS for primary surgery and primary radiation was 74% and 71% (p=0.78), respectively. There were no differences in PFS or recurrence rates between the two treatment groups. CONCLUSIONS: Clinical tumor diameter and the number of midline or mucosal structures involved influence selection of primary treatment modality. Survival outcomes and recurrence rates did not differ between treatment groups. Age and tumor diameter are important prognostic factors for survival.

Reconstruction of Large Perineal and Pelvic Wounds Using Gracilis Muscle Flaps.

BACKGROUND: The reconstruction of large defects after abdominoperineal resections and pelvic exenterations has traditionally been accomplished with vertical rectus myocutaneous flaps (VRAMs). For patients requiring two ostomies, robot-assisted abdominoperineal resections (APRs), and to avoid the morbidity of a VRAM harvest, the authors have used the gracilis muscle flap to reconstruct the large dead space in these patients. METHODS: A retrospective analysis of 16 consecutive APRs (10 with concomitant pelvic exenterations) reconstructed with gracilis flaps during a 2-year period was performed. Gracilis muscle flaps were used to obliterate the dead space after primary skin closure was ensured with adduction of the legs. RESULTS: All 16 patients had locally advanced cancers and had received neoadjuvant chemotherapy and radiation. Of these 16 patients, 10 had pelvic exenterations. All the patients had reconstruction with gracilis flaps (6 bilateral flaps). One major wound complication in the perineum occurred as a result of an anastomotic leak in the pelvis, but this was managed with conservative dressing changes. Three patients had skin separation in the perineum greater than 5 mm with intact subcutaneous closure. No patients required operative debridement or revision of their perineal reconstruction. No perineal hernias or gross dehiscence of the skin closure occurred. CONCLUSIONS: Large pelvic and perineal reconstructions can be safely accomplished with gracilis muscle flaps and should be considered as an alternative to abdominal-based flaps.

Ovarian involvement in endometrioid adenocarcinoma of uterus.

OBJECTIVE: Ovarian preservation is an option for some premenopausal patients with early stage endometrial cancer. Studies have shown that ovarian preservation in selected patients does not negatively impact survival outcomes. The objective of this study is to determine the frequency and characteristics of ovarian involvement when endometrial cancer is clinically confined to the uterus. METHODS: Patients with endometrioid adenocarcinoma of uterus treated at our institution between 2000 and 2013 were identified. Patients with ovarian metastasis or synchronous primary ovarian cancer were included. Patients were excluded if there was gross extrapelvic disease on examination or imaging. RESULTS: Seven hundred and fifty-nine patients were found to have endometrial cancer with the disease confined to the pelvis (stages I, II, and III). Fifteen patients (2%) had ovarian metastasis. Twenty-three patients (3%) had synchronous uterine and ovarian cancer. Most ovarian lesions (32 out of 38) were either enlarged or had abnormal appearing surface involvement. Six patients had microscopic ovarian involvement, accounting for 0.8% of the endometrial cancer patients with pelvis-confined disease. All of the patients were greater than 50 years of age. For those patients with microscopic ovarian metastasis, all had FIGO grade 3 disease, deep myometrial invasion, and extrauterine involvement of either cervix or lymph nodes. CONCLUSIONS: Microscopic ovarian involvement occurred in 0.8% of patients with endometrial cancer. For premenopausal patients with endometrial cancer, normal appearing ovaries may be considered for preservation in the absence of extrauterine spread, grade 3 disease and deep myometrial invasion.

Recurrence patterns and survival endpoints in women with stage II uterine endometrioid carcinoma: a multi-institution study.

OBJECTIVE: There is paucity of data in regard to prognostic factors and outcome of women with 2009 FIGO stage II disease. The objective of this study was to investigate prognostic factors, recurrence patterns and survival endpoints in this group of patients. METHODS: Data from four academic institutions were analyzed. 130 women were identified with 2009 FIGO stage II. All patients underwent hysterectomy, oophorectomy and lymph node evaluation with or without pelvic and paraaortic lymph node dissections and peritoneal cytology. The Kaplan-Meier approach and Cox regression analysis were used to estimate recurrence-free (RFS), disease-specific (DSS) and overall survival (OS). RESULTS: Median follow-up was 44months. 120 patients (92%) underwent simple hysterectomy, 78% had lymph node dissection and 95% had peritoneal cytology examination. 99 patients (76%) received adjuvant radiation treatment (RT). 5-year RFS, DSS and OS were 77%, 90%, and 72%, respectively. On multivariate analysis of RFS, adjuvant RT, the presence of lymphovascular space invasion (LVSI) and high tumor grades were significant predictors. For DSS, LVSI and high tumor grades were significant predictors while older age and high tumor grade were the only predictors of OS. CONCLUSIONS: In this multi-institutional study, disease-specific survival for women with FIGO stage II uterine endometrioid carcinoma is excellent. High tumor grade, lymphovascular space invasion, adjuvant radiation treatment and old age are important prognostic factors. There was no significant difference in the outcome between patients who received vaginal cuff brachytherapy compared to those who received pelvic external beam radiation treatment.

Outcomes of Treatment of Gestational Trophoblastic Neoplasia in a Primarily Indigent Urban Population.

OBJECTIVE: To review outcomes of women with gestational trophoblastic neoplasia (GTN) who presented to an inner-city hospital system, given that the rigorous treatment and follow-up for GTN is often problematic for certain women of low socioeconomic status with limited resources and social support. STUDY DESIGN: A retrospective review was performed with IRB approval of patients diagnosed with GTN based on the revised WHO scoring system from 1999-2010 at our institution. SPSS Statistics software was used to perform univariate and multivariate analyses. RESULTS: Forty-nine patients were treated for GTN: 32 low-risk and 17 high-risk. Low-risk patients received an average of 5 cycles of initial single-agent chemotherapy. Six patients had persistent disease and were switched to a second single-agent regimen. One patient required multiagent chemotherapy for normalization of human chorionic gonadotropin levels. No patient had recurrence of disease. All high-risk patients were initially treated with multiagent chemotherapy, averaging 8 cycles. Two of the 17 patients persisted; 1 recurred. All 3 currently have no evidence of disease. No patient died of disease. CONCLUSION: Excellent treatment outcomes in patients with GTN may be achieved in disadvantaged populations when compliance to regimens is optimized.

Factors associated with clinical trial screening failures in gynecologic oncology.

OBJECTIVE: Low enrollment of adult cancer patients in clinical trials is an ongoing challenge in cancer research. We sought to determine factors associated with clinical trial screening failures in women with gynecologic malignancies at a large urban university health system. METHODS: A retrospective review was conducted of women with gynecologic malignancies who presented to an urban university system between 12/2009 and 12/2012. Data collected included demographic, clinico-pathologic and trial-related factors, as well as reasons for non-participation. RESULTS: Two hundred twenty-one patients were eligible for a clinical trial. Of these, 44% participated while 56% did not. There were more screening failures when trials were offered at the time of primary treatment than at recurrence (62% vs. 38%, p=0.001). There was no significant difference in participation based on age, ethnicity, hospital setting, payor status, family history, comorbidities, prior treatment, substance abuse, recent surgery or trial type. Of the non-participants, 62% declined the study due to perceived harm and 10% due to socio-economic barriers while 20% were excluded due to co-morbidities and 8% due to noncompliance. CONCLUSIONS: Significantly more screening failures for clinical trials occurred when trials were offered at the time of primary treatment. The majority of patients declined based on perceived harm from enrolling in a clinical trial, although 20% of eligible patients were not offered enrollment despite not meeting any exclusion criteria. Our findings underscore the importance of appropriate counseling when offering clinical trials, as well as overcoming physician biases in deciding who is an appropriate candidate.

Malignant ovarian germ cell tumor - role of surgical staging and gonadal dysgenesis.

OBJECTIVE: To evaluate the effect of comprehensive surgical staging and gonadal dysgenesis on the outcomes of patients with malignant ovarian germ cell tumor. METHODS: We performed a retrospective review of patients with ovarian germ cell tumors who were treated at our institution between 1976 and 2012. RESULTS: Malignant ovarian germ cell tumors (MOGCTs) were identified in 50 females. The median age was 24 years (range 13 to 49). Of all MOGCT patients, 42% had dysgerminoma, 20% immature teratoma, 16% endodermal sinus tumor, and 22% mixed germ cell tumor. Univariate analyses revealed that the lack of surgical staging (p=0.048) and endodermal sinus tumor (p=0.0085) were associated with disease recurrence, while age at diagnosis, ethnicity, and stage of the disease were not. Multivariate analyses revealed that the lack of surgical staging (p=0.029) and endodermal sinus tumor (p=0.016) were independently associated with disease recurrence. In addition, 7 patients (14%) had 46 XY karyotype, including 6 with pure dysgerminoma and 1 with mixed germ cell tumor. Five had Swyer syndrome and 2 had complete androgen insensitivity syndrome. Concurrent gonadoblastoma was found in 5 of the patients. No difference was found in the mean age at presentation, stage distribution, or recurrence rate for MOGCT patients with or without XY phenotype. CONCLUSIONS: Comprehensive surgical staging was associated with a lower rate of recurrence. Fourteen percent of phenotypic females with MOGCT and 29% of those with dysgerminoma had XY karyotype. The clinical outcome of these patients is similar to that of MOGCT patients with XX karyotype.

Adnexal masses requiring surgical intervention in women with advanced cervical cancer.

OBJECTIVE: Surgical evaluation of adnexal masses in patients with cervical cancer can be considered in order to optimize treatment outcomes and rule out a second pathologic process. Our objective was to review treatment patterns and outcomes in women with advanced cervical cancer (ACC) and an adnexal mass. METHODS: A retrospective review was performed with IRB approval of patients treated for advanced cervical cancer at our institution between 1990 and 2011. Patients were identified using institutional databases and tumor registries. Descriptive statistics were performed using Microsoft Excel 2011 and Instat was used to perform Fisher's exact test and student T-tests. RESULTS: Two hundred twenty eight patients with stage IIB-IVB cervical cancer were identified, 50 (22%) of whom had an adnexal mass on initial imaging studies (31 stage IIB, 15 stage IIIB, 3 stage IVA, 3 stage IVB). The mean follow up time of patients with adnexal masses was 22 months (range 3-128 months). Thirteen of 50 (26%) patients underwent surgical evaluation of the adnexal mass. Six were found to have cervical cancer metastatic to the adnexae, while seven had benign adnexal lesions. Thirty-seven of 50 (74%) patients were conservatively managed. All 37 women had cystic masses <8 cm or complex masses <5 cm in size. Thirty-four of the 37 (92%) patients had resolution of their adnexal mass and 3 were deemed stable on follow up imaging. Twenty three percent of surgically managed patients and 57% of conservatively managed patients had disease recurrence (p=0.05). There were no recurrences in the adnexa. CONCLUSION: Twelve percent of women with ACC and an adnexal mass have ovarian metastases. Patients with cystic masses less than 8 cm and complex masses less than 5 cm in size can be expectantly managed.

Illness perceptions matter: understanding quality of life and advanced illness behaviors in female patients with late-stage cancer.

BACKGROUND: Patients with late-stage cancer are living longer, making it important to understand factors that contribute to maintaining quality of life (QOL) and completing advanced illness behaviors (eg, advance directives). OBJECTIVE: To examine whether illness perceptions-the cognitive beliefs that patients form about their cancer-may be more important guides to adjustment than clinical characteristics of the cancer. METHODS: In a cross-sectional study, 105 female patients diagnosed with stage III (n = 66) or IV (n = 39) breast (n = 44), gynecological (n = 38), or lung (n = 23) cancer completed self-report measures of illness perceptions, QOL, and advanced illness behaviors. Clinical data was obtained from medical records. RESULTS: Despite modest associations, patients' beliefs about the cancer were clearly unique from the clinical characteristics of the cancer. Illness perception variables accounted for a large portion of the variance (PS < .01) for QOL and advanced illness behaviors, whereas clinical characteristics did not. QOL scores were predicted by patients' reports of experiencing more cancer related symptoms (ie, illness identity), believing that their cancer is central to their self-identity, and higher income. Higher completion of advanced illness behaviors was predicted by higher income, the cancer being recurrent, and participants perceiving their cancer as more severe but also more understandable. LIMITATIONS: This study was limited by a cross-sectional design, small sample size, and focus on female patients. CONCLUSION: Addressing patients' beliefs about their cancer diagnosis may provide important targets for intervention to improve QOL and illness behaviors in patients with late-stage cancer.

Lymph node metastasis in endometrioid adenocarcinomas of the uterine corpus with occult cervical involvement.

OBJECTIVE: Surgical-pathologic studies have defined the risk of lymphatic metastasis in clinical stage I endometrial cancers. However, data on the risk of lymph node metastasis in endometrial cancers involving the uterine cervix are less robust. The aim of this study was to determine the risk of lymphatic metastasis in patients with endometrial cancers with occult tumor extension to the uterine cervix. METHODS: Our institutional tumor registry identified all patients with endometrioid endometrial cancers who underwent comprehensive surgical staging. Patients with gross involvement of the cervix and patients with extra-uterine disease were excluded. The risk of lymphatic metastasis associated with cervical involvement was analyzed in the context of known uterine risk factors for lymphatic metastasis such as age, depth of invasion, grade, and lymphovascular space invasion (LVSI). RESULTS: We identified 169 patients who met inclusion and exclusion criteria. Univariate analyses revealed that LVSI (p<0.01), tumor grade (p<0.01), depth of myometrial invasion (p<0.01), tumor free distance (p<0.01), tumor size (p=0.02), and cervical involvement (p<0.01) were associated with lymphatic metastasis while age at diagnosis (p=0.85) was not. Multivariate analyses revealed that only LVSI (p<0.01), tumor grade (p=0.02), and depth of myometrial invasion (p=0.03) were independently associated with lymphatic metastasis. CONCLUSION: Cervical involvement is not an independent predictor of lymphatic metastasis in endometrial cancer. In an unstaged patient, decisions regarding adjuvant treatment or additional diagnostic procedures such as lymphadenectomy should be based on uterine factors.

Correlation of cone biopsy with findings at radical hysterectomy and use of adjuvant radiation therapy.

OBJECTIVE: To determine if pathologic findings in cone biopsy specimens correlate with residual invasive disease in radical hysterectomy specimens and the need for adjuvant chemo-radiation therapy. STUDY DESIGN: We identified 65 patients who underwent a cone biopsy and subsequent radical hysterectomy. Clinico-pathologic parameters in the cone specimens were correlated with the presence of residual invasive disease in the radical hysterectomy specimens and the need for adjuvant chemo-radiation. RESULTS: A positive endocervical margin, a positive deep margin, a positive post-cone ECC, and positive LVSI were significantly associated with the presence of residual disease in the radical hysterectomy specimen, while positive LVSI, a positive ECC, a positive deep cone margin, and greater than 1 positive margin were significantly associated with the use of adjuvant chemo-radiation therapy. CONCLUSION: Pathologic parameters in cone biopsy specimens can estimate the risk of residual invasive disease in radical hysterectomy specimens and the use of adjuvant chemo-radiation.

Patterns of first recurrence following adjuvant intraperitoneal chemotherapy for stage IIIC ovarian cancer.

OBJECTIVE: Adjuvant intraperitoneal (IP) platinum-based chemotherapy has been shown to improve outcome for patients with advanced ovarian cancer. We hypothesize that patients who have received adjuvant IP chemotherapy more commonly recur first at extraperitoneal sites than patients who have received adjuvant intravenous (IV) chemotherapy. METHODS: Patients with newly diagnosed stage IIIC optimally debulked serous ovarian cancer were identified from institutional databases. Patterns of recurrence were compared between patients who received IV and IP chemotherapy using standard two-sided statistical tests. RESULTS: Of the 104 patients who met inclusion criteria, 60 received IV chemotherapy and 44 received IP chemotherapy. Patients in the IV group had a first recurrence more commonly in the lower abdomen or pelvis than the IP group. Patients in the IP group more commonly recurred in the upper abdomen and extra-abdominal lymph nodes. More patients in the IP group than the IV group recurred at extra-abdominal sites (45.5% versus 23.3%, P=0.018). CONCLUSIONS: Patients receiving adjuvant IP chemotherapy are less likely to first recur in the lower abdomen or pelvis and more likely to recur outside of the abdominal cavity. The data suggest that IP chemotherapy is highly effective in the anatomic areas of peritoneal distribution.

Translational randomized phase II trial of cabozantinib in combination with nivolumab in advanced, recurrent, or metastatic endometrial cancer.

BACKGROUND: Combining immunotherapy and antiangiogenic agents is a promising treatment strategy in endometrial cancer. To date, no biomarkers for response have been identified and data on post-immunotherapy progression are lacking. We explored the combination of a checkpoint inhibitor (nivolumab) and an antiangiogenic agent (cabozantinib) in immunotherapy-naïve endometrial cancer and in patients whose disease progressed on previous immunotherapy with baseline biopsy for immune profiling. PATIENTS AND METHODS: In this phase II trial (ClinicalTrials.gov NCT03367741, registered December 11, 2017), women with recurrent endometrial cancer were randomized 2:1 to nivolumab with cabozantinib (Arm A) or nivolumab alone (Arm B). The primary endpoint was Response Evaluation Criteria in Solid Tumors-defined progression-free survival (PFS). Patients with carcinosarcoma or prior immune checkpoint inhibitor received combination treatment (Arm C). Baseline biopsy and serial peripheral blood mononuclear cell (PBMC) samples were analyzed and associations between patient outcome and immune data from cytometry by time of flight (CyTOF) and PBMCs were explored. RESULTS: Median PFS was 5.3 (90% CI 3.5 to 9.2) months in Arm A (n=36) and 1.9 (90% CI 1.6 to 3.4) months in Arm B (n=18) (HR=0.59, 90% CI 0.35 to 0.98; log-rank p=0.09, meeting the prespecified statistical significance criteria). The most common treatment-related adverse events in Arm A were diarrhea (50%) and elevated liver enzymes (aspartate aminotransferase 47%, alanine aminotransferase 42%). In-depth baseline CyTOF analysis across treatment arms (n=40) identified 35 immune-cell subsets. Among immunotherapy-pretreated patients in Arm C, non-progressors had significantly higher proportions of activated tissue-resident (CD103+CD69+) ɣδ T cells than progressors (adjusted p=0.009). CONCLUSIONS: Adding cabozantinib to nivolumab significantly improved outcomes in heavily pretreated endometrial cancer. A subgroup of immunotherapy-pretreated patients identified by baseline immune profile and potentially benefiting from combination with antiangiogenics requires further investigation.

The role of lymphadenectomy in endometrial cancer.

The role of lymphadenectomy in the management of endometrial cancer is rapidly evolving. Although retrospective reports have suggested that lymphadenectomy is associated with a therapeutic benefit, recent prospective trials have questioned the therapeutic effect of lymphadenectomy. Lymphadenectomy remains the gold standard for detecting metastatic disease to the regional nodes. In this review, we discuss the controversies surrounding lymphadenectomy for endometrial cancer.

Clinicopathologic features of bone metastases and outcomes in patients with primary endometrial cancer.

OBJECTIVE: Patients with advanced or recurrent endometrial cancer often have distant metastases found within the lymph nodes, liver, and/or lung. However, there have been reported cases of primary endometrial cancer with metastasis to the bone. The objective of this study was to describe the clinical and pathologic features of endometrial cancer metastatic to bone. METHODS: A retrospective chart review of our clinical and pathology database was performed to identify women diagnosed with endometrial cancer metastatic to the bone between 1990 and 2007. Clinical data and outcomes were obtained from medical records. Slides were re-reviewed to confirm the diagnosis. RESULTS: Twenty-one patients with endometrial cancer metastatic to the bone were identified; in 12 patients (57%), the diagnosis was confirmed by a bone biopsy. The median age of diagnosis of primary endometrial cancer was 60 years (range, 32-84). Fourteen patients (67%) had FIGO stage III/IV disease. Six patients (29%) had a bone metastasis at the time of diagnosis while 15 patients (71%) had a bone lesion as a recurrence. The median time to a diagnosis of bone metastasis recurrence was 10 months (range, 3-148). The overall survival of those patients with bone metastases at primary diagnosis was 17 months (95% CI: 2-32) compared to 32 months (95% CI: 14-49) for those with a recurrent bone metastasis. CONCLUSION: Although a rare event, endometrial cancer can metastasize to the bone. If a bone lesion is identified, treatment using a multimodality approach is reasonable, especially if found as an isolated recurrence.

Endometrial sampling diagnosis of FIGO grade 1 endometrial adenocarcinoma with a background of complex atypical hyperplasia and final hysterectomy pathology.

OBJECTIVE: The purpose of this study was to determine posthysterectomy pathologic findings in patients with a preoperative endometrial sampling diagnosis of International Federation of Gynecology and Obstetrics (FIGO) grade 1 endometrial adenocarcinoma with a background of complex atypical hyperplasia (CAH). STUDY DESIGN: We reviewed 1423 consecutive cases of endometrial cancer to identify cases with a preoperative endometrial biopsy that demonstrated FIGO grade 1 endometrial adenocarcinoma. Final uterine pathologic findings were grouped into low- and high-risk based on FIGO and Gynecologic Oncology Group criteria. RESULTS: We identified 123 cases with a background of CAH and 367 cases without a background of CAH. FIGO grade in the hysterectomy specimen was more than FIGO grade 1 in 11 of 123 cases (8.9%) with a background of CAH, compared with 60 of 359 cases (16.7%) without a background of CAH (P = .04). CONCLUSION: An endometrial sampling diagnosis of FIGO grade 1 endometrial adenocarcinoma with a background of CAH is more likely to correlate with final posthysterectomy grade than a diagnosis not arising with a background of CAH.

Taurine modulates neutrophil function but potentiates uropathogenic E. coli infection in the murine bladder.

Eradication of a urinary tract infection (UTI) appears to be related to a number of innate host defence mechanisms and their interactions with invading bacteria. Recurrent UTIs (rUTIs) pose a difficult problem in that these bacteria use both host and bacterial factors to evade elimination. Neutrophil bactericidal function is depressed, both systemically and in urine, in patients with a history of recurrent UTI. Taurine is a semi-essential amino acid and is successful in preserving neutrophil bactericidal function in urine. Taurine may preserve neutrophil function at the urothelium and thus aid UTI resolution. Adult female (6 weeks old) C57Bl/6 mice were randomised into three groups: a saline gavage only control group, a saline gavage + E. coli group, and a taurine gavage + E. coli group [21 g/70 kg taurine in 0.9% normal saline (N/S) for 5 days]. Whilst taurine gavage pre-treatment resulted in increased serum neutrophils respiratory burst activity, at the urothelial-endothelial interface it caused higher colony forming units in the urine and a higher incidence of E. coli invasion in the bladder wall with no evidence of increased bladder wall neutrophils infiltration on MPO assay of histological assessment. Histologically there was also evidence of reduced bladder inflammation and urothelial cell apoptosis. In conclusion, taurine effectively increases neutrophils activity but given its anti-inflammatory properties, at the expense of decreased urothelial-endothelial activation thus preventing clearance of active E. coli infection in the bladder. Despite the negative results, this study demonstrates the importance of modulating interactions at the urothelial interface.

Incidence and management of pancreatic leaks after splenectomy with distal pancreatectomy performed during primary cytoreductive surgery for advanced ovarian, peritoneal and fallopian tube cancer.

OBJECTIVE: To determine the incidence, management, and outcome of patients diagnosed with a pancreatic leak after a distal pancreatectomy during primary surgical cytoreduction for ovarian, peritoneal, or tubal cancer. METHODS: We performed a retrospective chart review of all patients who had a distal pancreatectomy at the time of primary surgery. Charts were reviewed to identify those patients who developed a persistent left upper quadrant abdominal fluid collection with elevated amylase levels. RESULTS: A total of 17 patients had a distal pancreatectomy; of these, 4 patients (24%) developed a postoperative pancreatic leak. In these patients, persistent leukocytosis prompted evaluation with a computed tomography scan, which subsequently revealed a fluid collection. The median time from surgery to drainage of this collection was 9 days (range, 8-66). The drain remained in situ for a median of 29 days (range, 22-82). The median amylase level of the fluid was 22,945 U/L (range, 763-47,250). The median length of hospital stay for those patients with a leak was 33 days (range, 25-44), which was longer than those without a leak. However, the median time from surgery to treatment with systemic chemotherapy was 31 days (range, 16-43), which was equivalent to those without a pancreatic leak. CONCLUSION: Twenty-four percent of patients who had undergone a distal pancreatectomy developed a pancreatic leak. This complication, which usually presents early in the postoperative period, can be managed conservatively with percutaneous drainage. Oral intake may be resumed, and total parenteral nutrition is not needed in the majority of cases. Systemic chemotherapy can be administered without significant delay.

Incidence of intestinal obstruction following intraperitoneal chemotherapy for ovarian tubal and peritoneal malignancies.

OBJECTIVES: To report the incidence of intestinal obstruction after intraperitoneal chemotherapy (IP) in women with ovarian, tubal, or peritoneal malignancies, and determine the frequency of malignant versus adhesion-related obstruction. METHODS: Patients who were treated with at least one dose of IP chemotherapy between 1986 and 1997, and who had at least 3 month follow-up, were included. Data regarding admissions for gastrointestinal obstruction complaints, radiologic diagnosis of intestinal obstruction and medical or surgical management of obstruction were recorded. RESULTS: We identified 334 patients; 307 met our inclusion criteria. A total of 104 (34%) patients developed symptomatic intestinal obstruction after IP therapy commenced. The overall incidence of adhesion-related or mechanical bowel obstruction was only 4%. In the group of patients with a mechanical bowel obstruction, the median time to diagnosis of obstruction was 21 months (range, 2-51) after initiation of IP treatment. Surgical intervention to relieve the obstruction was performed in 6 (50%) patients diagnosed with adhesion-related bowel obstruction. Similarly, in those diagnosed with a malignant bowel obstruction, 42 (48%) were taken to the operating room in an attempt to relieve the obstruction. CONCLUSION: Intestinal obstructions developed in a third of patients who received IP therapy as part of their treatment for advanced ovarian, tubal, or peritoneal cancer. However, the majority of the obstructions are related to progression of malignant intra-abdominal disease. Only 4% of the patients develop intestinal obstruction due to intestinal adhesions after IP treatment.