Uma K. Devi

Regulatory T cells in a spectrum of HPV-induced cervical lesions: cervicitis, cervical intraepithelial neoplasia and squamous cell carcinoma.

Problem  Thriving of tumors amidst rich immune infiltrates is an unexplained paradox.

Asian society of gynecologic oncology workshop 2010.

This workshop was held on July 31-August 1, 2010 and was organized to promote the academic environment and to enhance the communication among Asian countries prior to the 2nd biennial meeting of Australian Society of Gynaecologic Oncologists (ASGO), which will be held on November 3-5, 2011. We summarized the whole contents presented at the workshop. Regarding cervical cancer screening in Asia, particularly in low resource settings, and an update on human papillomavirus (HPV) vaccination was described for prevention and radical surgery overview, fertility sparing and less radical surgery, nerve sparing radical surgery and primary chemoradiotherapy in locally advanced cervical cancer, were discussed for management. As to surgical techniques, nerve sparing radical hysterectomy, optimal staging in early ovarian cancer, laparoscopic radical hysterectomy, one-port surgery and robotic surgery were introduced. After three topics of endometrial cancer, laparoscopic surgery versus open surgery, role of lymphadenectomy and fertility sparing treatment, there was a special additional time for clinical trials in Asia. Finally, chemotherapy including neo-adjuvant chemotherapy, optimal surgical management, and the basis of targeted therapy in ovarian cancer were presented.

ORIGINAL ARTICLE: Regulatory T Cells in a Spectrum of HPV-Induced Cervical Lesions: Cervicitis, Cervical Intraepithelial Neoplasia and Squamous Cell Carcinoma

Problem  Thriving of tumors amidst rich immune infiltrates is an unexplained paradox.

Accuracy rate of frozen section studies in ovarian cancers: A regional cancer institute experience

BACKGROUND Frozen section is a valuable diagnostic procedure in the categorization of ovarian tumors as benign, borderline and malignant. Thus, it guides in tailoring surgical therapy, particularly in young women. AIM This study was undertaken to determine the accuracy of frozen section in ovarian neoplasms. MATERIALS AND METHODS A retrospective analysis was done of intraoperative frozen sections for suspected ovarian neoplasms. The frozen and permanent section reports were compared and overall accuracy, sensitivity, specificity, positive and negative predictive values were determined. RESULTS The study included 135 patients and the overall accuracy of frozen section in determining malignancy was 84.25%. Twenty cases were incorrectly diagnosed, of which 16 cases were under-diagnosed and four were over-diagnosed. With respect to malignant potential, the sensitivity for malignant tumors was highest (91.5%) with specificity of 98.2%. For benign tumors, the sensitivity and specificity were 90.4% and 82.6%, respectively. Borderline tumors had the lowest sensitivity of 31.2% with specificity of 94%. Sensitivity for benign, borderline and malignant tumors in the non-mucinous group was 91.3%, 60% and 95% respectively, whereas the sensitivity was 75%, 18% and 57%, respectively, for mucinous tumors revealing low sensitivity in borderline, mucinous tumors. The low sensitivity rates were due to restriction in the sampling of an adequate number of bits in the large sized tumors. CONCLUSION The present study concurs that frozen section is an accurate test for diagnosis of benign and malignant tumors. However, accuracy rates for borderline and mucinous tumors are low.

Primary Carcinoma of the Fallopian Tube: A Review of a Single Institution Experience of 8 Cases

Aims and Objectives. To evaluate the clinicopathologic features, response to cytoreductive surgery and adjuvant platinum-based chemotherapy with or without paclitaxel. Materials and Methods. A retrospective observational study of 8 women with a histopathologic diagnosis of primary fallopian tube carcinoma (PFTC) from January 2000 to February 2013. Results. 4/8 (50%) of the women were in the early stage and an intraoperative frozen section was 100% effective in identifying fallopian tube carcinoma and then a staging laparotomy was performed. All 4/8 cases in the early stage had received and responded to single agent carboplatin and all are alive without clinical, radiological, or biochemical evidence of recurrence at the end of 2 years and the longest survivor has completed 13 years. Primary optimal cytoreductive surgery was achievable in 3/4 (75%) in advanced disease. All showed response to adjuvant paclitaxel and carboplatin (T+C), but all had succumbed to the disease following recurrence with mean progression-free survival of 19 months (range 15–21 months) and mean overall survival of 27 months (range 22–36 months). Conclusion. The pivotal role played by a frozen section in diagnosing PFTC which is rare needs to be reemphasized, therefore justifying a primary staging laparotomy in an early stage. Prolonged survival observed in this group following an optimum tailored adjuvant single agent carboplatin is worth noting.

Carcinoma of the vulva: a retrospective review of 37 cases at a regional cancer centre in South India

A retrospective review of 37 cases of carcinoma of the vulva presenting between 1996 and 2000 has been carried out. Thirty-three cases were managed with curative intent and four cases with advanced loco-regional disease were managed with palliative intent. The surgical treatment consisted of wide excision in one case, radical vulvectomy (RV) in six cases, radical vulvectomy and bilateral groin node dissection (RV + BGND) in 25 cases and radical vulvectomy and unilateral groin node dissection in one case. Nine of these 33 women also received adjuvant chemotherapy preoperatively in the hope of achieving better tumour-free surgical margins. Eight cases had a partial response and one case achieved complete response; the surgical margins were free in all these patients. One case received neoadjuvant radiotherapy to the vulva and pelvis followed by RV + BGND, which revealed no residual tumour. Overall, 26/33 cases had groin/inguinal node dissection and 23 (88.4%) of them had groin wound dehiscence. Thirteen of these 26 patients (50%) had inguinal node metastases (Stage III, four patients; Stage IV, nine patients). All the patients with negative nodes were free of disease while three of four patients with Stage III and two of nine patients with Stage IV with nodal metastases remained free of disease. The only patient with Stage III disease plus inguinal node metastases who recurred had multiple positive nodes with extracapsular spread. It appears that although bilateral involvement of the inguinal lymph nodes carries a worse prognosis, unilateral involvement with or without vaginal involvement carries an excellent prognosis provided multiple nodes are not involved. The role of neoadjuvant chemotherapy as compared to neoadjuvant radiotherapy, in locally advanced tumours, needs to be explored further.

Treatment of high-risk gestational trophoblastic neoplasia with weekly high-dose methotrexate–etoposide

OBJECTIVE To assess toxicity and efficacy of weekly high-dose methotrexate-etoposide (HD MTX-ETO) in high-risk gestational trophoblastic neoplasia (GTN). METHODS Retrospective chart review of high-risk GTN patients treated with HD MTX-ETO (methotrexate 1000 mg/m² day 1, etoposide 100 mg/m² days 1 and 2, q 1 wk). RESULTS 134 cycles of HD MTX-ETO were administered to twelve patients; median number of cycles was 8 (range 2-39 cycles). Median follow up was 25.5 months (range 11-69). 7 of these patients switched due to ototoxicity from EP-EMA (etoposide 150 mg/m², cisplatin 75 mg/m² i.v. day 1; etoposide 100 mg/m², methotrexate 300 mg/m², dactinomycin 0.5 mg i.v. day 8, q 14 d) to HD MTX-ETO, after an average of 7 cycles of EP-EMA. Six achieved complete remission without disease recurrence. One patient with a placental site trophoblastic tumour died due to progressive disease. Five patients received HD MTX-ETO primarily; 1 patient with choriocarcinoma presenting with metastases to the brain and liver (WHO score 19) was switched to EP-EMA and died due to complications under EP-EMA. The other 4 achieved complete remission without disease recurrence. HD MTX-ETO was well tolerated; non-haematological toxicity was low except for alopecia and fatigue. Nine patients had grade 2-4 anaemia and received packed cells. Eight patients had grade 3-4 neutropenia and received G-CSF. Two patients developed febrile neutropenia without sepsis. CONCLUSIONS These preliminary results show a better toxicity profile with HD MTX-ETO than EP-EMA and encouraging efficacy. HD MTX-ETO might be a treatment option for some patients with high-risk GTN and needs further investigation.

The role of surgery in locally advanced carcinoma of cervix after sub-optimal chemoradiation: Indian scenario

Background: Standard treatment of advanced cervical cancer is concurrent chemoradiation. Radical radiotherapy for carcinoma cervix includes pelvic external beam radiotherapy (EBRT) with the concomitant platinum based chemotherapy followed by intracavitary brachytherapy (ICBT) to boost central disease. Management of patients who are suboptimally treated, especially, after unsuccessful ICBT insertion is not well-defined. This study explores the role of hysterectomy in these patients. Materials and Methods: From January 2006 to December 2011, 38 patients with locally advanced cervical cancer, in whom ICBT insertion was unsuccessful, were analyzed retrospectively. Operable patients with no parametrial involvement underwent hysterectomy and outcomes (recurrence free and overall survival) were noted. Results: The major complications in post operative period were wound infection, paralytic ileus and bladder atony all of which were conservatively managed with no mortality. At median follow-up of 36 months (range 12-60 months) there was no recurrence in patients with stage 1B2 and stage IIA, 25 out of 38 (65.8%) were event free and the overall survival was 71%. Conclusion: Many patients in Indian scenario receive suboptimal therapy in locally advanced cervical cancer. EBRT with chemotherapy followed by type 1 extra-fascial hysterectomy can be a good alternative for these patients.

EP-EMA regimen (etoposide and cisplatin with etoposide, methotrexate, and dactinomycin) in a series of 18 women with gestational trophoblastic neoplasia.

Objective Evaluation of toxicity and outcome of high-risk gestational trophoblastic neoplasia when treated with EP-EMA (etoposide, 150 mg/m2; cisplatin, 75 mg/m2, intravenous, day 1; etoposide, 100 mg/m2; methotrexate, 300 mg/m2; dactinomycin, 0.5 mg, intravenous, day 8, every two weeks). Materials and Methods We conducted a retrospective chart review of the period 2004–2010. The first-line chemotherapy regimen for high-risk gestational tropholdastic neoplasia was EP-EMA. Results Eighteen patients were treated with EP-EMA, either as first-line chemotherapy for high-risk gestational trophoblastic neoplasia (n = 6), placental site trophoblastic tumor (n = 1), or as salvage chemotherapy for gestational trophoblastic neoplasia after single-agent methotrexate (methotrexate, 1 mg/kg, on days 1, 3, 5, and 7 every two weeks) (n = 10) or high-dose methotrexate-etoposide: methotrexate, 1000 mg/m2, on day 1; etoposide, 100 mg/m2, on days 1 to 2, every week) (n = 1). Median number of cycles of EP-EMA was 8 (range, 3–11). Median follow-up was 19 months (range, 7–77 months). Concerning response rate, 16 patients (89%) achieved complete remission without disease recurrence. Two patients (11%) died: One patient with placental site trophoblastic tumor died of progressive disease; the second patient presented with choriocarcinoma, primarily metastasized to liver, lung, skin, kidney, and brain. She died of sepsis and endocarditis after adding intrathecal methotrexate and switching cisplatin to carboplatin in the EP-EMA regimen. Toxicity was significant. Eight treatment changes were made owing to grade 2 to grade 3 ototoxicity: 7 to high-dose methotrexate-etoposide, 1 change of cisplatin to carboplatin. Fifteen patients (83%) experienced grade 3/4 neutropenia.

Malignant mixed Mullerian tumour of the uterus

Background: A malignant mixed Mullerian tumour (MMMT) of the uterine corpus is an extremely rare and aggressive malignancy. There are very few studies regarding the outcome of MMMT patients in India. Hence, we conducted the present study to analyse the outcome of MMMTs at our institute. Objective: To study the clinical profile, prognostic features, and treatment outcome of MMMT with multimodal therapy. Method: A five-year retrospective study of the MMMT cases diagnosed and treated at our centre was conducted. Twenty patients with pathological proven diagnosis of MMMT treated at our institute from January 2007 to May 2012 were analysed. These patients underwent comprehensive surgical staging followed by adjuvant therapy in the form of chemotherapy alone or chemoradiotherapy. These patients were analysed for event-free survival (EFS), and their outcomes were correlated with histology, therapy, myometrial invasion, and the stage of disease. Results: A majority of these patients presented with postmenopausal bleeding. Endometrial biopsy was diagnostic in only 20% of the patients. Of the 20 patients who underwent surgery, 18 patients received adjuvant therapy. At median follow-up of 16 months (range 3–30 months), the EFS was 30%. No difference in outcome was noted based on tumour histology (heterologous versus homologous). Concurrent chemoradiation improves local control and may delay recurrence but has shown little survival advantage. Conclusion: MMMT is an aggressive tumour of the uterine corpus. A negative endometrial biopsy does not rule out the diagnosis. Poor outcome is noted in patients with advanced-stage disease and myometrial invasion. The optimal adjuvant treatment for this uncommon disease is yet to be established, highlighting the need for larger multicentric studies on MMMTs.