Utilization of primary health care services among Syrian refugee and Lebanese women targeted by the ICRC program in Lebanon: a cross-sectional study.

BACKGROUND: The Syrian crisis has put tremendous strain on the Lebanese health system, particularly in the historically underserved border region. The ICRC Primary Health Care program has focused on refugee and host communities in these areas. This study objectives were: 1) to determine whether the ICRC program was reaching the most vulnerable populations; 2) to understand the key perceived health needs in the catchment areas of the ICRC supported facilities; and 3) to identify barriers to utilization of health care services. METHODS: Between July and September 2017 we conducted two cross-sectional studies - one randomized household survey and one clinic-based - in the catchment areas of three ICRC-supported facilities, targeting women of reproductive age and caretakers of children under five. Differences between groups were analysed with t-test or chi-squared test. RESULTS: In the household survey, similar socio-demographic profiles were observed between Syrian refugee women and vulnerable Lebanese hosts. With regard to the study objectives:The most vulnerable populations were those seen in the ICRC-supported facilities.For both populations, the most common reasons for seeking care were non-communicable diseases (40.6%) and sexual and reproductive health issues (28.6%). Yet the people reaching the ICRC supported facilities were more likely to seek care for communicable diseases affecting their children (37.8%), rather than for the most common reasons expressed in the household survey.In the catchment areas, reported gaps included low immunization coverage and low levels of antenatal care and family planning both for Syrian and Lebanese. Dental care also emerged as an issue. Out of pocket expenditures was reported as a critical barrier for utilization of primary health care services for both populations, while the most important barrier for utilization of ICRC-supported services was lack of awareness. CONCLUSIONS: Despite the ICRC reaching the most vulnerable Syrian and Lebanese communities, the population-based survey revealed that important gaps exist in terms of utilization of health care services among women of reproductive age and their children. A stronger outreach component is needed to address lack of awareness. Innovative solutions are also needed to address cost barriers at the levels of both facility and individual user.

Ten-year follow-up of a phase 2 study of dose-intense paclitaxel with cisplatin and cyclophosphamide as initial therapy for poor-prognosis, advanced-stage epithelial ovarian cancer.

BACKGROUND: The objective of this study was to assess activity and toxicity in patients with newly diagnosed, advanced-stage epithelial ovarian cancer (EOC) who were receiving dose-intense paclitaxel, cyclophosphamide, cisplatin, and filgrastim delivered with a flexible dosing schedule. METHODS: Patients with stage III/IV EOC received cyclophosphamide 750 mg/m(2), followed by a 24-hour infusion of paclitaxel 250 mg/m(2) and cisplatin 75 mg/m(2) on Day 2. Filgrastim began on Day 3 at 10 microg/kg daily for 9 days. Patients received 6 cycles of all drugs. Those who achieved a pathologic complete response or had microscopic residual disease at the conclusion of 6 cycles of therapy received an additional 2 to 4 cycles of paclitaxel with cyclophosphamide. Patients who had an objective response continued on cyclophosphamide and paclitaxel. RESULTS: Sixty-two patients were enrolled. Thirty-two of 62 patients had stage IIIC disease, and 26 of 62 patients had stage IV disease. According to an intent-to-treat analysis, 55 patients (89%) experienced a clinical complete remission. At a median potential follow-up of 11.4 years, the median progression-free survival was 18.9 months, and the median survival was 5.4 years. The most serious toxicity was grade 3/4 neutropenic fever (35%). Although all participants developed peripheral neuropathy, improvement in neuropathic symptoms began with the decrease or cessation of paclitaxel. CONCLUSIONS: The studied regimen yielded a high response rate and encouraging overall survival. The current data and those reported by the Japanese Gynecologic Oncology Group suggest that further study is warranted of dose-dense or dose-intense paclitaxel regimens in women with newly diagnosed, advanced-stage EOC.

Surgical management of the subdiaphragmatic mass: a sequential combined approach with laparoscopy followed by posterior thoracotomy.

Recurrent ovarian cancer in the upper abdomen involving the liver parenchyma and diaphragmatic muscle traditionally requires a major abdominal surgical procedure; this involves pubis to xyphoid incision and complete mobilization of the liver. We present a strategy for evaluating 4 cases with apparently isolated recurrence to the diaphragm and liver approached by a sequential 2-phase procedure, involving diagnostic laparoscopy and subsequent posterior lateral thoracotomy. Preliminary diagnostic laparoscopy was performed to distinguish candidates for either definitive laparoscopic treatment or posterior thoracotomy. Two patients with disease confined to the diaphragm were successfully treated by laparoscopy alone, whereas full-thickness diaphragmatic resection and liver metastasis excision with cavitational ultrasonic surgical aspirator was performed in the other 2 patients. Argon beam coagulation was used to control local hemostasis and to fulgurate any possible residual tumor at the margin of resection. This is a multidisciplinary approach that is technically feasible and safe, requiring a short hospital stay.

Epithelioid angiosarcoma of the uterus: a review of management.

BACKGROUND: Uterine epithelioid angiosarcoma is extremely rare. Evidence-based advice regarding optimal management is lacking. METHOD: We report the 22nd case in the world literature and review all the cases reported in English since 1900. An attempt is made to generate information that may help in the management based on the available literature. RESULTS: A 54-year-old woman was found to have an enlarged uterus on routine clinical examination. Although, she had no other symptoms, an endometrial biopsy was performed, which indicated a high-grade sarcoma. She was taken for a total abdominal hysterectomy and bilateral salpingo-oophorectomy and final histology returned a diagnosis of epithelioid angiosarcoma of the uterus. Two months later, she had tumor recurrence and was started on gemcitabine and taxotere later changed to albumin-bound paclitaxel (ABI-007, Abraxane) and bevacizumab. She was still alive with no evidence of disease at the time of this report, 12 months after diagnosis. Literature review suggests that surgical resection followed by chemotherapy is a reasonable management approach. CONCLUSION: Uterine epithelioid angiosarcoma is an uncommon but very aggressive disease. Surgical resection followed by sequential chemotherapy is a reasonable management approach, and modern chemotherapy and anti-angiogenic agents may have merit.

PET-CT vs. CT alone in ovarian cancer recurrence.

BACKGROUND: To compare fusion, positron emission tomography-computed tomography (PET-CT) with CT alone in detecting ovarian carcinoma recurrence. METHODS: Fifty-one consecutive patients underwent 53 restaging PET-CT scans with a concurrent diagnostic quality CT scan. Two body imaging radiologists independently assessed the CT's; each then teamed with a nuclear medicine specialist to review the PET-CT's. Two teams conferred for consensus on the presence of disease in the chest, abdomen, and body overall with CT alone and with PET-CT, using a six-point reader confidence metric to determine accuracy and receiver operating characteristic (ROC) curves. Reader agreement was compared using kappa. Recurrence was determined by two gynecologic oncologists reviewing clinical records from time of presentation to at least 13 months (mean 22.7) after imaging. RESULTS: Recurrence was based on histopathology in 17% (9/53). Seventy-two percent (38/53) cases had recurrence, with two cases showing isolated chest recurrence. PET-CT accuracy exceeded CT for body 92% (49/53) vs. 83% (44/53), chest 96% (51/53) vs. 89% (47/53), and abdomen 91% (48/53) vs. 79% (42/53). ROC curves for PET-CT dominated that for CT alone; this difference was statistically significant for abdomen and for body overall (P < 0.01). Interobserver agreement was better for PET-CT than for CT alone. CONCLUSIONS: PET-CT demonstrates greater accuracy and less interobserver variability than CT alone.

Hope.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery that provides hope to the patient, support to caregivers, and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. A patient with recurrent ovarian cancer, now in a 12-year remission after recurrence, and her surgeon, discussed their experiences and feelings around the hopes and fears of cancer and its treatment. Hope sustains many through dark times, and is at the core of the wonderful resilience of many who wrestle with cancer. Concerns about false hope, unrealistic expectations, assumptions, engaging in realistic hopefulness, and the joys and stresses embodied in hope and how they frame the caregiver-patient relationship are discussed. The literature and limited evidence base are reviewed.

Uterine smooth-muscle tumors with unusual growth patterns: imaging with pathologic correlation.

OBJECTIVE: This essay illustrates the salient features of variant smooth-muscle tumors on multiple imaging techniques with correlative pathology. We describe how recognition of these features allows the radiologist to distinguish a uterine leiomyoma variant from the classic fibroid or a leiomyosarcoma. Finally, we highlight the role of the radiologist in triaging these patients to surgical versus medical management and in surgical planning. CONCLUSION: Parasitic leiomyoma, intravenous leiomyomatosis, disseminated peritoneal leiomyomatosis, and benign metastasizing leiomyoma show key features on multiple imaging techniques that correlate with pathology findings. In the appropriate clinical setting, the radiologist should include these unusual lesions in the broader differential diagnosis of smooth-muscle tumors and, in certain cases, aid in surgical planning.

Long-acting octreotide for the treatment and symptomatic relief of bowel obstruction in advanced ovarian cancer.

Symptoms of malignant bowel obstruction in patients with recurrent ovarian cancer lead to a poor quality of life. Sandostatin LAR Depot (LAR) is an intramuscular, monthly administered, long-acting form of octreotide. LAR's safety and utility were evaluated in a pilot study enrolling 15 advanced ovarian cancer patients with bowel dysfunction. Once safety with subcutaneous (SQ) octreotide was assessed, patients were given 30 mg LAR on Day 1 and octreotide SQ for 2 weeks. Of 13 evaluable patients, three patients had a major response to LAR treatment with reduction in bowel obstruction symptoms, two had a minor response, four had no response, and four had progressive symptoms. Three patients remained on LAR for more than 9 months. No significant toxicities were attributable to octreotide or LAR. Because three patients received nine or more monthly injections of LAR, possible direct antitumor effects of LAR or synergy with chemotherapy needs to be explored.

Phase I trial of escalating doses of topotecan in combination with a fixed dose of pegylated liposomal doxorubicin in women with müllerian malignancies.

BACKGROUND: Topotecan and pegylated liposomal doxorubicin (Doxil) interact with topoisomerase I and II (topo I and II), respectively, with schedule dependent, and potentially synergistic cytotoxicity. OBJECTIVES: Define dose-limiting toxicity (DLT) and determine the maximum tolerated dose (MTD) of topotecan delivered by 72-h infusion administered immediately after Doxil delivered at a fixed dose (30 mg/m(2)) in a cohort of women with recurrent müllerian malignancies. METHODS: Topotecan dose was escalated from 0.5 mg/m(2)/day for 3 days in 0.2 mg/m(2)/day increments with treatment repeated every 21 days. Eligibility criteria required ECOG < or = 2 and no more than four prior lines of chemotherapy. No dose reductions were allowed in the first two cycles to allow evaluation of cutaneous toxicity. RESULTS: Between November 2000 and August 2002, 18 patients were enrolled. Median age 59 (40-71) years. Patients received a median 1 (1-6) cycles of chemotherapy, with 39 cycles of treatment delivered at DL 1. All patients were evaluable for toxicity and 12 for response. At dose level 2, dose-limiting toxicity consisted of nausea and vomiting, mucositis, cutaneous toxicity, and neutropenia. There was no clinically significant cardiac toxicity. There were no radiologically confirmed partial responses. CONCLUSIONS: Doxil 30 mg/m(2) and topotecan 0.5 mg/m(2)/day by 72-h infusion (total dose 1.5 mg/m(2)), although a rational combination of cytotoxic therapies, have limited clinical activity.

Expression of multidrug resistance-1 protein inversely correlates with paclitaxel response and survival in ovarian cancer patients: a study in serial samples.

OBJECTIVES: The role of MDR1 in clinical paclitaxel resistance remains poorly characterized. This study sought to identify the incidence and significance of P-glycoprotein (P-gp) over-expression on survival, tumor response to paclitaxel and the effect of prior cytotoxic exposure on P-gp expression in patients with paired primary and recurrent ovarian cancer samples. METHODS: Retrospective survival analysis. P-gp expression was evaluated immunohistochemically with antibodies c494 and c219. RESULTS: Thirty-two patients were identified from the tumor registry. Median interval between primary and secondary surgery was 17.9 (5.7-40.9) months. Only five primary tumors (16%) demonstrated +++ staining for P-gp. First-line treatment contained paclitaxel in 17 patients (53%) and 26 patients (81%) had been exposed to P-gp exportable chemotherapy before second surgery. Only seven of the recurrent tumors (22%) were +++. Only one of seven (14% (95% CI 0-46%)) recurrent tumors with ++ or +++ staining responded to subsequent paclitaxel, while 8 of 10 (80% (CI 46-100%)) recurrent tumors with 0/+ staining responded (P = 0.025). In multivariate analysis of outcome following second surgery, response to paclitaxel (P = 0.004) and P-gp over-expression (P < 0.001) were significant predictors of survival. CONCLUSIONS: De novo strong P-gp over-expression is uncommon, appears to change little over time or with prior exposure to chemotherapy. However, P-gp over-expression is a significant prognostic factor, and at the time of disease, relapse is inversely correlated with tumor response to paclitaxel.

The treatment of uterine leiomyosarcoma. Results from a 10-year experience (1990-1999) at the Massachusetts General Hospital.

OBJECTIVE: Uterine leiomyosarcomas (LMS) are rare tumors with a poor prognosis. The purpose of this study is to review the presentation, therapy and outcome of patients with leiomyosarcoma originating from the uterus treated at the Massachusetts General Hospital from 1990 to 1999. METHODS: A retrospective chart review was done to patients treated for uterine leiomyosarcoma during the study period. One author reviewed all available histologic specimens. Statistical analysis was done to determine whether there is an association between histologic criteria or therapy used and overall survival. RESULTS: Forty-seven charts were reviewed to identify 27 patients with leiomyosarcoma arising from the uterus treated in the decade from 1990 to 1999. Most patients received multimodality therapy with surgery followed by chemotherapy and/or radiotherapy. Patients who had no visible disease at the conclusion of primary surgery had a better overall survival than patients who did not achieve surgical remission (P < 0.0003). There is a trend toward improved survival in patients with lower number of mitotic figures per 10 high-power fields (P = 0. 062). Current chemotherapy drugs were minimally effective with 80% of treated patients having progression of disease. Adjuvant therapy after optimal cytoreduction does not decrease the rate of recurrence. CONCLUSION: Uterine leiomyosarcoma continues to be a deadly disease. Aggressive surgical cytoreduction at the time of initial diagnosis offers the possibility of prolonged survival or cure.

Phase II trial of anastrozole in women with asymptomatic müllerian cancer.

OBJECTIVE: To evaluate the efficacy and toxicity of the selective aromatase inhibitor anastrozole (Arimidex), we conducted a phase II trial in 53 women with asymptomatic recurrent/persistent müllerian cancer. METHODS: Patients with ovarian, peritoneal, or fallopian tube carcinoma were eligible for enrollment. Eligible patients had an ECOG PS < or = 1 and no clinical indication for immediate systemic chemotherapy. Patients were assigned to measurable (cohort 1) or evaluable disease (cohort 2) cohorts, respectively. Patients were treated with anastrozole 1 mg po daily. Monthly follow-up included interim history, physical exam, and CA-125 with radiologic evaluation every 3 months. Estrogen, progesterone, and Her-2/neu receptor status was also evaluated in archived tumor samples. RESULTS: Fifty-three women with a median age of 63 (range, 46-86) years were enrolled. Twenty-nine women enrolled in cohort 1 and 24 in cohort 2. Included were 43, 7, and 3 women with ovarian, primary peritoneal, and fallopian tube carcinoma, respectively. All 53 patients were evaluable for treatment toxicity and response. The median time to disease progression was 85 days (85 days for cohort 1 and 82 days for cohort 2). A partial response was documented in a single patient with measurable disease. Forty-two percent of patients had stable disease (measured as time to treatment termination) for >90 days, 15% for >180 days, 7% for >270 days, and 4% for >360 days. One patient remained on anastrozole at 15 months. Toxicity was modest (grade I) and infrequent, with the most common toxicities being fatigue and hot flashes. There were no thrombotic complications. Median time to progression for patients with estrogen receptor-positive tumors was 72 days as compared to 125 days for those with tumors negative for the estrogen receptor (P = 0.95, log-rank test). The median time to progression in patients with progesterone-positive tumors was 77 days and 91 days for patients with progesterone-negative tumors. CONCLUSION: In summary, anastrozole is a well-tolerated oral agent but with minimal tumoricidal activity in women with recurrent/persistent müllerian cancers. A minority of patients demonstrated prolonged stable disease while on this agent.

Phase II study of liposomal doxorubicin and weekly paclitaxel for recurrent Müllerian tumors.

OBJECTIVE: Pegylated liposomally encapsulated doxorubicin (Doxil. Ortho-Biotech) and paclitaxel (Taxol, Bristol Myers Squibb) are both active against Müllerian malignancies. A phase II trial was performed to determine the toxicity and efficacy of these agents when administered in combination. METHODS: Patients were initially treated with 30 mg/m(2) of liposomal doxorubicin every 21 days and 70 mg/m(2) of paclitaxel every week for 18 weeks. The plasma pharmacokinetics of paclitaxel was determined when administered alone and concurrently with liposomal doxorubicin. RESULTS: Forty women with recurrent gynecologic malignancies of Müllerian origin including 34 with ovary and primary peritoneal cancer (85%) were enrolled. Toxicity was evaluated for all 508 cycles of therapy. Paclitaxel and liposomal doxorubicin were delivered at 95% (66.4 mg/m(2)/week) and 77% (7.65 mg/m(2)/week) of their intended weekly dose intensities, respectively. Reductions in the dose of liposomal doxorubicin were frequently required for palmar plantar erythrodysesthesia during the latter cycles of therapy. There were 4 patients with a complete response and 7 with partial responses, for an overall objective response rate of 29%, among the 38 evaluable patients. Response rates for the subset of 13 women with tumor recurrence occurring at least 6 months after prior platinum-based therapy was 54%. The concurrent administration of liposomal doxorubicin did not alter the pharmacokinetic disposition of paclitaxel. CONCLUSION: Liposomal doxorubicin with weekly paclitaxel is active in Müllerian malignancies. The concurrent delivery of the weekly paclitaxel with liposomal doxorubicin may increase liposomal doxorubicin skin toxicity. Liposomal doxorubicin does not alter the pharmacokinetics of paclitaxel.

Intraoperative radiation therapy in the management of gynecologic and genitourinary malignancies.

Women with locally advanced primary or recurrent gynecologic malignancies have a poor prognosis. The doses of external radiation necessary to treat gross or microscopic recurrent disease in patients previously irradiated exceed the doses tolerated by normal tissue [1,3-5]. IORT has been added to the treatment armamentarium in this group of patients to maximize local control and minimize the radiation exposure to dose-limiting surrounding structures. In addition, IORT may improve the long-term local control and the overall survival rates in women with pelvic sidewall or para-aortic nodal recurrence [1,4,5]. The most encouraging results are seen in cases of microscopic residual disease following surgical debulking [4,6]. In gynecologic malignancies, IORT has served to reiterate the importance of optimal surgical resection. Higher 5-year disease-free and overall survival rates have been documented in women who have microscopic residual disease, compared with those who have gross residual disease [1,3-6]. IORT in the management of GU malignancies has not been used extensively. In RCC, where surgery alone often results in suboptimal treatment results, IORT seems to be well tolerated and controls local disease [2,27,29,30]. Because of the chemoresistant nature of RCC, IORT may play an important role in the future in the management of locally advanced and recurrent RCC. In bladder cancer, IORT had been used in combination with chemotherapy and EBRT, as part of bladder-sparing protocols. The data suggest that IORT in this patient population is also well tolerated, and may become more widely used as less radical surgical procedures gain clinical importance. IORT in the treatment of prostate and testicular cancers has not been used frequently, given the highly efficacious treatment modalities currently available to treat these malignancies. A review of institutional experiences with IORT may allow the establishment of guidelines for patient selection. These criteria, in turn, may be useful in the design of clinical trials. The construction, execution, and evaluation of clinical trials are mandatory to adequately assess the role of IORT in the treatment of patients with gynecologic and GU malignancies.

Paclitaxel and platinum chemotherapy for malignant mixed müllerian tumors of the ovary.

OBJECTIVE: Malignant mixed müllerian tumor (MMMT) of the ovary is a rare tumor with a dismal prognosis. The most effective therapy is unknown. The current study was undertaken to characterize a group of patients treated as if they had aggressive epithelial ovarian tumors, with cytoreductive surgery and combination paclitaxel/platinum chemotherapy. METHODS: Retrospective analysis of data obtained from tumor registry and hospital records of cases of malignant mixed müllerian tumor between January 1, 1992 and January 1, 2000 treated at the Massachusetts General Hospital, Brigham and Women's Hospital, and University of Vermont was performed. Only patients treated with combination paclitaxel and platinum therapy were included in the analysis. Data were collected regarding cytoreduction, response to chemotherapy, disease-free interval, and survival. RESULTS: Fifty-five patients were identified with MMMT. Twenty-eight patients with a clearly ovarian primary had received treatment with combination paclitaxel and platinum. Paclitaxel and carboplatin was given as second-line therapy in 2 patients who had chemoresponsive but incurable disease; the remaining patients were treated with paclitaxel and platinum therapy as first-line therapy. These 28 patients had a median (range) age of 66 (46-84 years) and stage was I in 2 patients, II in 3, III in 18, and IV in 5. Treatment was generally well tolerated. Sixteen patients of 26 treated with paclitaxel and platinum as first-line therapy achieved a complete clinical response (55%) and 6 patients achieved partial response for a total response rate of 72%. Optimal cytoreduction was associated with increased time to recurrence (P = 0.001) but not with survival. Overall median survival for the 28 patients is 27.1 months. CONCLUSION: Although treatment fails many patients, a minority of patients with MMMT in this highly selected population do unexpectedly well. An aggressive approach with surgery and combination paclitaxel-platinum chemotherapy appears to offer very effective therapy.