Tumor-reactive antibodies evolve from non-binding and autoreactive precursors.

The tumor microenvironment hosts antibody-secreting cells (ASCs) associated with a favorable prognosis in several types of cancer. Patient-derived antibodies have diagnostic and therapeutic potential; yet, it remains unclear how antibodies gain autoreactivity and target tumors. Here, we found that somatic hypermutations (SHMs) promote antibody antitumor reactivity against surface autoantigens in high-grade serous ovarian carcinoma (HGSOC). Patient-derived tumor cells were frequently coated with IgGs. Intratumoral ASCs in HGSOC were both mutated and clonally expanded and produced tumor-reactive antibodies that targeted MMP14, which is abundantly expressed on the tumor cell surface. The reversion of monoclonal antibodies to their germline configuration revealed two types of classes: one dependent on SHMs for tumor binding and a second with germline-encoded autoreactivity. Thus, tumor-reactive autoantibodies are either naturally occurring or evolve through an antigen-driven selection process. These findings highlight the origin and potential applicability of autoantibodies directed at surface antigens for tumor targeting in cancer patients.

Neoadjuvant Chemotherapy for Elderly Patients with Advanced Stage Ovarian Carcinoma.

BACKGROUND: The treatment of elderly patients with advanced stage ovarian carcinoma is challenging due to a high morbidity. OBJECTIVES: To evaluate the clinical course and outcome of elderly patients with advanced stage ovarian carcinoma receiving neoadjuvant chemotherapy (NACT). METHODS: A retrospective study of all patients with stage IIIC and IV ovarian carcinoma receiving NACT in one medical center (between 2005 and 2017). The study group criteria age was above 70 years. The control group criteria was younger than 70 years old at diagnosis. Demographics and treatment outcomes were compared between groups. Primary outcomes were progression-free survival (PFS) and overall survival (OS). RESULTS: Overall, 105 patients met the inclusion criteria, 71 patients (67.6%) were younger than 70 years and 34 patients (32.4%) older. Rates of interval cytoreduction were significantly higher in younger patients (76.1% vs. 50.0%, P = 0.01). Of those who underwent interval cytoreduction, no difference was found in rates of optimal debulking between groups (83.35% vs. 100%, P = 0.10). Using a Kaplan-Meier survival analysis, no significant differences were observed between groups in PFS or OS, P > 0.05. Among the elderly group alone, patients who underwent interval cytoreduction had significantly longer PFS than those without surgical intervention (0.4 ± 1.7 vs. 19.3 ± 19.4 months, P = 0.001). CONCLUSIONS: Elderly patients with ovarian carcinoma who received NACT undergo less interval cytoreduction than younger patients, with no difference in PFS and OS. However, among the elderly, interval cytoreduction is associated with significantly higher PFS.

Neutrophil-to-lymphocyte ratio as a prognostic factor in advanced stage ovarian carcinoma treated with neoadjuvant chemotherapy.

OBJECTIVES: To evaluate the prognostic significance of neutrophil-to-lymphocyte ratio (NLR) upon diagnosis, and its impact on surgical outcome, among patients with advanced stage ovarian carcinoma treated with neoadjuvant chemotherapy (NACT). METHODS: A retrospective cohort study included all women with stage IIIC and IV ovarian carcinoma receiving NACT in Rabin Medical Center, Petah-Tikva, Israel; January 1, 2005, to June 30, 2017. Demographics and treatment outcome were compared between patients with NLR at diagnosis ≥6.0 and those with NLR <6.0. Primary outcome was optimal debulking (<1 cm largest residual disease). Overall survival was compared between groups using Kaplan-Meier survival analysis. RESULTS: Of 111 patients, 33 (29.7%) had NLR ≥6.0 at diagnosis, and 78 (70.3%) had NLR <6.0. No difference was found in rates of optimal debulking between the group with NLR ≥6.0 and that with NLR <6.0 (78.9% vs 84.7%, respectively, P=0.555). Using Kaplan-Meier survival analysis, NLR ≥6.0 was associated with significantly worse overall survival (P<0.05). In a multivariate Cox proportional hazard model, elevated NLR was not statistically associated with poor overall survival (P=0.080). CONCLUSIONS: In advanced stage ovarian carcinoma, NLR ≥6.0 at diagnosis did not predict surgical outcome, however it was a predictive factor for poor overall survival.

Neoadjuvant Chemotherapy Treatment Modifications in Ovarian Carcinoma: The Impact on Surgical Outcome and Progression-free Survival.

OBJECTIVE: Little is known on the impact of neoadjuvant chemotherapy (NACT) treatment modifications on surgical outcome and progression-free survival (PFS) in patients with ovarian carcinoma. We aimed to report the changes we made during NACT and to evaluate its impact on patient outcome. METHODS: A retrospective cohort study of all women with advanced stage ovarian carcinoma treated with NACT followed by interval cytoreduction in one university-affiliated medical center (January 2005 to June 2017). We excluded those who were treated with NACT without any surgical intervention. NACT modifications included delay in treatment, change in chemotherapy, and dose reduction. Demographics, tumor characteristics, surgical outcome, and PFS were compared between patients exposed to NACT treatment modifications and those who received standard treatment. RESULTS: Seventy-nine patients met inclusion criteria of whom, 59 patients received standard, nonmodified treatment and 20 patients modified NACT. There were no intergroup differences with respect to age at diagnosis (59.5±11.6 vs. 64.70±8.09, P=0.09) and stage of disease (P=0.13). Radiologic complete response rates (25.0% vs. 32.2%, P=0.545) and optimal cytoreduction rates (75.0% vs. 86.4%, P=0.23) were similar in both treatment groups. Mean PFS (in months) was comparable between patients receiving standard treatment and those who required NACT modifications (18.5 vs. 12.2, P=0.125). CONCLUSIONS: NACT treatment modifications did not affect surgical outcome and PFS. We conclude that when clinically indicated, dose alteration and scheduling can be implemented without apparent detriment to outcome.

Malignant Ascites: Validation of a Novel Ascites Symptom Mini-Scale for Use in Patients With Ovarian Cancer.

BACKGROUND: Ascites is a common finding in patients with ovarian cancer. Paracentesis is a relatively simple, safe, and effective procedure for draining fluid from the peritoneum, but valid quality-of-life tools are needed to determine its subjective value for alleviating symptoms and improving patient quality of life. The objective of this study was to prospectively evaluate the performance of a novel Ascites Symptom Mini-Scale (ASmS) and compare it with a previously available questionnaire. METHODS: Patients with ovarian cancer-related ascites presenting for paracentesis were asked to complete the newly devised ASmS before the procedure and 1 and 24 hours after. Patients also completed a pain assessment scale and a previously validated ascites questionnaire at the same time points. RESULTS: The cohort included 28 patients of median age 68 years (range, 51-86 years), 13 (46.4%) with primary ovarian cancer and 15 with recurrent disease. A median of 3300 mL of ascites was drained. The median score on the ASmS decreased significantly from 21.5 before paracentesis to 11.0 at 1 hour after paracentesis (P < 0.001) and remained low at 24 hours. No demographic factor predicted greater benefit from the procedure. Patients with both mild and severe symptoms reported significant relief. CONCLUSIONS: The ASmS is a robust quality-of-life tool for the specific assessment of symptoms of ovarian cancer-related malignant ascites. It can be used in the clinical trial setting assessing interventions aimed at treating ascites and in the clinic to identify those patients with mild symptoms, who may benefit from paracentesis.

Simple Hysterectomy for Residual Cervical Intraepithelial Neoplasm.

OBJECTIVE: Many patients undergo hysterectomy for the treatment of cervical dysplasia. Factors that correlate with residual high-grade squamous intraepithelial lesions (HGSIL) at hysterectomy are not clear. We set out to determine preoperative features that may predict residual disease for patients treated for cervical dysplasia. MATERIALS AND METHODS: A retrospective database was reviewed for women who underwent simple hysterectomy for HGSIL between 1990 and 2013. Clinical data included age, history of dysplasia, initial treatment, follow-up colposcopy, indications for surgery, time elapsed between initial treatments, and pathology findings after hysterectomy. Significant residual disease was defined as HGSIL or cervical carcinoma. Statistical analyses were performed with the SPSS, independent Student t test, and Pearson χ test. Significance was set at p < .05. RESULTS: Eighty-three women met the study criteria. The indication for hysterectomy was residual histological finding at conization pathology in 30 women and patients' request in 53 women. Residual disease was found in 42 hysterectomy specimens: in 16 of 30 with residual histological finding and in 26 of the 53 patients' request. Reason for the hysterectomy was not statistically significant for residual disease (p = .708). Median age of patients with residual disease was 46.5 years versus 44.1 years for those without residua (p = .02). Postmenopausal patients had a higher rate of residual disease, 12 (32.4%) of the 28 premenopausal patients and 25 (67.6%) of the 54 postmenopausal patients (p = .04). Conization margin status was not associated with residual disease (p = .878). CONCLUSIONS: Older women and those in menopause are at significantly higher risk of residual disease at hysterectomy.

Axillary lymph node metastasis in ovarian carcinoma: Two case reports and review of literature.

•Extra-peritoneal metastasis is uncommon in epithelial ovarian carcinoma.•Metastasis of epithelial ovarian carcinoma to axillary lymph node is rare.•Lymphatic drainage system can explain the rout of this distant metastasis.•Tissue diagnosis is the mainstay in identifying the origin of axillary metastasis.

Diagnosis of deep pelvic masses on a gynaecology service: Trans-vaginal ultrasound-guided needle aspiration of pelvic solid and cystic lesions.

OBJECTIVES: Women with undiagnosed pelvic lesions are often referred for evaluation and treatment. Transvaginal ultrasound-guided fine needle aspiration (TVUS-FNA) biopsy can assist in making management decisions. We describe our experience with this modality. METHODS: We performed a retrospective chart review of all women who had a TVUS-FNA biopsy between January 2004 and December 2014. Charts were reviewed for clinicopathologic information. The pathologic results of the TVUS-FNA were compared with the final diagnosis. RESULTS: Fifty-nine women underwent TVUS-FNA; the median age was 66 years (range 27-85). Thirty-three lesions were evaluated by fine-needle aspiration biopsy of the solid structure and 26 by aspiration of fluid for cytology. Pathologic feasibility rate was 88% (52/59). Of those with evaluable tissue, the sensitivity of the procedure was 100% and the specificity 92%. Considering the seven inconclusive results, the procedure had sensitivity of 88% (29/33) and specificity of 88% (23/26). Overall accuracy of TVUS-FNA for this patient cohort was 85%. No patient characteristics were found to distinguish between accurate and inaccurate or inconclusive TVUS-FNA result. No complications were noted. CONCLUSIONS: TVUS-FNA offers an excellent modality for the diagnosis and management of deep pelvic lesions otherwise not amenable for histologic evaluation.

A Dedicated Follow-Up Clinic for BRCA Mutation Carriers.

BACKGROUND: Women who carry the BRCA gene mutation have an up to 80% chance of developing cancer, primarily of breast and ovarian origin. Confirmation of carrier status is described by many women as an overwhelming, life-changing event. Healthy individuals harboring a BRCA mutation constitute a high risk population with unique needs, often overlooked by health authorities. As such, we felt the need to create a specialized service dedicated specifically to this high risk population. The clinic staff comprises an experienced multidisciplinary team of health professionals who can support the medical and emotional needs of this population. Since its inception in 2001 the clinic has served 318 women. The mean age of patients is 46 years. With a median follow-up of 46 months, 21 women have developed malignancies, including 17 breast cancers, 1 ovarian cancer and 3 additional cancers. All but one of the patients above the age of 40 underwent bilateral salpingo-oophorectomy (BSO). The median and mean ages at BSO were 46.5 and 48 years, respectively (range 33-68). However, only 28.3% underwent bilateral preventive mastectomy. A multidisciplinary clinic for BRCA mutation carriers provides a "home" for this unique population with unmet needs. The high rate of BSO in women before natural menopause indicates that both the medical community and this population are aware of international guidelines supporting this procedure. We believe that a dedicated clinic, with a multidisciplinary team, is likely to contribute to the health, quality of life and survival of BRCA carriers.

Endometrial Cancer Surgery for Elderly Women--The Early Postoperative Period.

OBJECTIVE: The aim of this study was to examine the early postoperative period and assess whether elderly patients recuperate differently than do their younger counterparts after surgery for endometrial cancer. METHODS: This retrospective chart review comprised all women older than 75 years who underwent laparotomy for endometrial cancer staging at our center from January 2005 through December 2010 and a consecutive control group of women younger than 74 years. Parameters included demographic variables, surgical procedure/findings, postoperative morbidity, and pathology. RESULTS: Ninety patients older than 75 years and 88 younger patients were identified. The elderly patients had a statistically significant prolonged wait for bowel movement (5.9 vs 3.1 days, P = 0.002) and ambulated later (4.1 vs 1.1 days, P < 0.001). Postoperative hospital stay was similar in both groups (5.8 vs 4.2 days, P = 0.37). Early postoperative complications (fever, bowel, wound, eventration, cardiopulmonary) occurred at a similar rate in both groups. CONCLUSIONS: Elderly patients after laparotomy for endometrial cancer staging ambulated later and recovered bowel function later than did the younger patients. This did not translate into prolonged hospital stay or excessive complications. Earlier intervention with physical therapy and stool softeners can possibly close this gap in recovery.

Uterine papillary serous carcinoma pre-operatively diagnosed as endometrioid carcinoma: Is omentectomy necessary?

BACKGROUND: Uterine papillary serous carcinoma (UPSC) is a relatively rare but aggressive uterine malignancy comprising approximately 10% of endometrial cancers. Many women pre-operatively misdiagnosed as having endometrioid carcinoma have ultimately UPSC on final pathology. These women receive inadequate surgical staging without omentectomy. AIM: To assess the value of omentectomy on disease-free interval and overall survival in women with UPSC who had an initial diagnosis of endometrioid carcinoma. METHODS: This retrospective study included all women treated for the final diagnosis of UPSC in our centre from January 2007 to December 2012. Data regarding patient demographics, staging procedures, histology results, adjuvant therapy and follow-up outcomes were recorded. RESULTS: Of the 52 women with a final diagnosis of UPSC, more than 45% had an initial diagnosis of endometrioid carcinoma. All women underwent hysterectomy and removal of the adnexa. Lymph node evaluation was performed in 75% of women. Omentectomy was performed in 30/52 women (58%). Of those, three women (10%) had omental involvement. Mean disease-free interval with omentectomy was 24.5 months versus 30.5 months without (P = 0.29). Mean overall survival was 33 months with an omentectomy and 29 months without (P = 0.32). Recurrence patterns did not differ between groups. CONCLUSION: Women diagnosed pre-operatively with endometrioid carcinoma and eventually found to have UPSC can expect no change in prognosis despite not having undertaken a full staging procedure. Repeat surgery for omentectomy is probably of no benefit.

The significance of paracardiac lymph-node enlargement in patients with newly diagnosed stage IIIC ovarian cancer.

OBJECTIVE: Extra-abdominal metastases in epithelial ovarian cancer (EOC) are relatively rare. Interpreting computed tomography (CT) scans, during initial work-up, little attention is focused on enlargement of paracardiac lymph nodes (PCLN) and their significance is not clear. We aimed to examine whether the presence of PCLN during initial diagnosis of EOC influences prognosis. METHODS: A retrospective study comparing patients with stage 3 EOC who were diagnosed with PCLN on CT scan during initial evaluation to stage 3C patients without PCLN. Scans were reviewed by a single radiologist for peritoneal involvement, distal metastases and presence of PCLN. Disease status at diagnosis, results of surgery, chemotherapy and response, disease-free interval (DFI) and overall survival (OS) were recorded. RESULTS: Thirty one patients with stage 3C EOC with PCLN on initial CT scan were included and compared with 41 controls. There was no significant difference between groups in abdominal optimal cytoreduction rate. Lower rates of complete response (CR) to initial treatment were detected in the study group (45.2% vs. 78.0%, p=.004). In survival analysis, the DFI for patients with PCLN was shorter (median 9.0 vs. 24.0 months, p=.0097) and overall survival was shorter (median 31.7 vs. 61.3 months, p=.001). Multivariate analysis showed that PCLN was significantly associated with a lower rate of CR, a shorter DFI and a shorter OS. CONCLUSION: The presence of enlarged PCLN at presentation appears to be associated with poor prognosis in stage 3C EOC. Further attention should be given to detection and follow-up of such findings when considering treatment.

Clinical course of patients treated for advanced ovarian carcinoma without surgical intervention.

OBJECTIVE: To describe the clinical course and outcome of patients with non-surgically-treated advanced ovarian cancer attending a single institute. METHODOLOGY/PRINCIPAL FINDINGS: We reviewed the medical charts of all patients with advanced epithelial ovarian cancer who underwent chemotherapy at a tertiary medical center between January 2005 and December 2010 but were never operated. Data on patient characteristics, disease course, and outcome were collected from patient files. Sixteen patients met the inclusion criteria. Eight (50%) were diagnosed with apparent FIGO stage IIIC disease, and 8 with stage IV. Five patients (31%) achieved a complete clinical response, and 11 (69%) achieved a partial response. Among the complete responders, the median disease-free interval was 8 months (range 7-11 months). In all of them, the disease recurred and second-line chemotherapy was administered. Of them, four (80%) achieved a second complete response. Partial responders had up to four lines of chemotherapy, with continued disease progression. The median overall survival of the whole group was 19.5 months, and of the complete responders, 28 months. CONCLUSIONS/SIGNIFICANCE: Most patients with advanced ovarian carcinoma who will not undergo surgery respond only partially to first-line chemotherapy. Having no surgery is associated with a short disease-free interval.

The use of Fluorouracil (5-FU) and leucovorin in women with heavily pretreated advanced ovarian carcinoma.

BACKGROUND: Women suffering from recurrent platinum-resistant ovarian carcinoma go through several lines of chemotherapy, but eventually fail all conventional chemotherapy options. After failing multiple other regimens, we offer patients fluorouracil (5-FU) in a weekly regimen with leucovorin. For those women who failed to react to multiple lines of treatment, 5-FU has been shown to be a reasonable option with reported response rates of 10% to 33%. We report our experience with 5-FU+leucovorin in this patient population. METHODS: This is a retrospective chart review of women treated for recurrent ovarian carcinoma between January 2003 and December 2009. Women with recurrent ovarian carcinoma who had been treated with at least 3 previous chemotherapy regimens and had received 5-FU were eligible for the study. 5-FU and leuocovorin are given at 600 mg/m weekly for 6 weeks of an 8-week cycle. Patient charts were reviewed for demographics and disease history relevant to the administration of 5-FU. Response was assessed clinically and by CA125 levels. RESULTS: Fifty-three patients matching inclusion criteria received 5-FU during the study period. Twenty-five percent of patients achieved a partial response and 17% stable disease for an overall response rate of 42%. A median of 4 weekly doses was administered (range, 1 to 26). The median survival of the whole cohort was 10 weeks after the last dose of 5-FU was administered. CONCLUSIONS: In this population of heavily pretreated patients, a significant response to 5-FU can be achieved. Unfortunately, the response is short lived and mostly partial.

Burkitt's lymphoma of the ovary: case report and review of the literature.

Primary Burkitt's lymphoma of the ovary is extremely rare. We report the case of a 39-year-old woman who presented with a 1-month history complaints of night sweats, abdominal pain and dyspnea. Physical examination demonstrated pleural effusions, ascites and an abdominal mass. Imaging showed enlargement of both ovaries extending to the surrounding tissue. Frozen sections on explorative laparotomy suggested granulosa cell tumor of the ovary, and thus extensive debulking was carried out. The final pathological report was compatible with Burkitt's lymphoma. A systematic literature review revealed another 16 cases of ovarian Burkitt's lymphoma. Characteristics predictive for the diagnosis of Burkitt's lymphoma were: younger age, bilateral ovarian involvement, a rapidly progressive course and high LDH levels.

Should simple hysterectomy be added after chemo-radiation for stage IB2 and bulky IIA cervical carcinoma?

BACKGROUND AND AIMS: Management of bulky cervical tumours is controversial. We describe the addition of high dose rate brachytherapy with concomitant chemotherapy to an attenuated protocol of radiation followed by simple hysterectomy in the management of bulky cervical tumours. METHODS: Between January, 2003 and December, 2006, 23 patients diagnosed with bulky cervical tumours underwent a fixed chemo-radiation protocol followed by simple hysterectomy. Fractionated external beam pelvic radiation (4500 cGy) followed by two high-dose rate applications of brachytherapy (700 cGy - prescription dose to point A) was given with weekly concomitant cisplatin (35 mg/m(2)). Patients then underwent simple hysterectomy. Clinical information was prospectively collected and patient charts were then further reviewed. RESULTS: Twenty patients had stage IB2 and three bulky IIA. Median tumour size was 5 cm. Sixteen patients (70%) achieved a clinical complete and seven (30%) a clinical partial response. All patients had a total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH BSO). On final pathology, 12 patients (52%) had a pathological complete response, whereas 11 patients (48%) had residual carcinoma in the cervix. Surgical margins were not involved. With a median follow-up time of 20 months (range 10-50 months), four patients (17.4%), all from the pathological partial response group, have suffered a pelvic recurrence, within 6 months from therapy; nineteen patients (82.6%) remain free of disease. CONCLUSIONS: This attenuated protocol of chemo-radiation using HDR brachytherapy followed by simple hysterectomy is a viable option in the treatment of bulky cervical carcinomas. The rate of residual cervical disease after chemo-radiation is substantial, but simple hysterectomy achieved negative surgical margins in all cases.

Tumor microRNA expression patterns associated with resistance to platinum based chemotherapy and survival in ovarian cancer patients.

BACKGROUND: Ovarian cancer, the leading cause of gynecologic cancer deaths, is usually diagnosed in advanced stages. Prognosis relates to stage at diagnosis and sensitivity to platinum based chemotherapy. We aimed to assess the expression of microRNAs in ovarian tumors and identify microRNA expression patterns that are associated with outcome, response to chemotherapy and survival. METHODS: Patients, who were surgically treated for ovarian cancer between January 2000 and December 2004 were identified. Patient charts were reviewed for clinicopathologic information, follow-up and survival. Total RNA was extracted from tumor samples and microRNA expression levels were measured by microarrays. Expression levels were compared between groups of samples and statistically analyzed. RESULTS: Fifty-seven patients were identified to fit study criteria. Of them, 19 patients had stage I disease at diagnosis, and 38 patients, stage III. All patients received platinum based chemotherapy as first line treatment. 18 microRNAs were differentially expressed (p<0.05) between stage I and stage III disease. Seven microRNAs were found to be significantly differentially expressed in tumors from platinum-sensitive vs. platinum-resistant patients (p<0.05). Five microRNAs were associated with significant differences (p<0.05) in survival or recurrence-free survival. High expression of hsa-mir-27a identified a sub-group of patients with very poor prognosis. CONCLUSIONS: We have found an array of tumor specific markers that are associated with response to platinum based first line chemotherapy. Expression of some of these miRNAs also correlated closely with prognosis. This approach can potentially be used to tailor chemotherapy and further management to specific patient needs.

Labial edema following treatment of condyloma acuminata with CO(2) laser in an adolescent: a case report and literature review.

PURPOSE: To describe a case of bilateral labial edema in an adolescent patient and review the literature on this rare occurrence. MATERIAL: A 16-year-old girl was treated for widespread genital condyloma acuminata with CO(2) laser under general anesthesia and local lidocaine injections. Severe bilateral labial edema occurred after 48 hours. RESULTS: Lidocaine and Latex dermal patch tests for delayed hypersensitivity were negative. The edema resolved following treatment with local ice packs and magnesium sulfate compresses for 2 weeks. CONCLUSION: This is the first description of severe bilateral labial edema after CO(2) laser treatment for condyloma acuminata. We suggest that transient local lymphatic obstruction was the reason for this complication. The literature on this rare occurrence is reviewed.

Granular cell tumor of the vulva: six new cases.

Granular cell tumors are rare neoplastic skin and soft tissue lesions: only 1-2% are malignant. Five to sixteen percent occur in the vulva. We present our experience with granular cell tumors of the vulva in six patients, all of whom had wide local excisions and were followed-up in our outpatient clinic for 3-171 months. One died of an unrelated cause. None of the others has evidence of the disease.