Overexpression of VEGF165 is associated with poor prognosis of cervical cancer.

BACKGROUND: Cervical cancer is a major health hazard to Indian women. Human papillomavirus (HPV) infection is an established risk factor for cervical carcinogenesis. However, understanding the cervical cancer biology beyond HPV infection is very crucial to predict aggressive behavior, prognosis, treatment response and survival. In the present study, we explored the role of vascular endothelial growth factor A (VEGFA) isoforms, VEGFC and VEGFD in cervical cancer progression and its association with HPV 16 and 18 infections. MATERIAL AND METHODS: A total of 110 cervical cancer tissues and 50 normal cervical tissues were collected for the study. Reverse transcription-polymerase chain reaction was employed to analyze tissue VEGFA isoforms, VEGFC and VEGFD expression. RESULTS: VEGF165 was significantly higher, whereas VEGFC and VEGFD were significantly lower in malignant cervical carcinoma tissues as compared to normal cervix tissues. Expression levels of VEGF121 and VEGFC were significantly associated with type of tumor growth while VEGF165 was significantly associated with lymph node metastasis. VEGF165 transcript levels were significantly higher in patients with squamous cell carcinoma (SCC) and developed recurrence. Most strikingly, higher VEGF165 expression was significantly associated with worst disease-free survival (DFS) specifically in patients with SCC. CONCLUSION: Association of VEGF165 with lymph node metastasis, disease recurrence and worst DFS indicated that VEGF165 is an important prognostic factor in cervical carcinogenesis.

Retrospective Analysis of 32 Cases of Ovarian Granulosa Cell Tumours.

INTRODUCTION: Granulosa cell tumour (GCT) comprises 2-5% of ovarian malignancies. They are hormonally active tumours and may present with menstrual complaints, abdominal distension or infertility. Prognosis is generally favourable because of the early stage at diagnosis and less aggressive behaviour. MATERIALS AND METHODS: Medical records of 32 cases presenting from January 2008 to December 2014 were retrospectively analysed for the patient characteristics, tumour characteristics and the treatment received. RESULTS: The mean age was 42.75 ± 10.25 years (range: 22 to 70 years). The most common presenting symptom was abdominal distension (50.00%) followed by menstrual complaints. The mean tumour diameter was 15.24 cm (range: 4-25 cm). Endometrial pathology was found in 4 patients (12.50%), and all had simple hyperplasia without atypia. Twenty-four patients underwent primary staging surgery; one patient underwent interval debulking surgery after neo-adjuvant chemotherapy. Seven patients had undergone surgery elsewhere of which 4 underwent re-staging and three were given chemotherapy. All patients had the final histopathology of adult granulosa cell tumour except one patient with juvenile granulosa cell tumour. Most patients had stage I disease (81.25%). Post-operative chemotherapy was administered to 22 patients. The most commonly used regimen was paclitaxel and carboplatin. The overall 5-year survival rate was 90%. The mean overall survival was 36.95 ± 34.08 months (range: 0.50 to 112.00 months). Two patients had recurrence at 38 and 44 months, respectively. CONCLUSION: GCT of the ovary is a rare tumour with a tendency for late relapse. Survival is generally excellent as majority of the patients present in early stages.

Does preoperative CA-125 cutoff value and percent reduction in CA-125 levels correlate with surgical and survival outcome after neoadjuvant chemotherapy in patients with advanced-stage ovarian cancer? - Our experience from a tertiary cancer institute.

AIM: The aim of the study is to evaluate percent fall in CA-125 levels after neoadjuvant chemotherapy (NAC) and preoperative CA-125 value to predict surgical and survival outcomes in women with advanced-stage epithelial ovarian cancer (EOC). METHODS: A retrospective review of 406 women receiving NAC for advanced-stage EOC from January 2012 to July 2015 was conducted. Data were collected for demography, radiographic profile, CA-125 levels before and after NAC, chemotherapy, and surgicopathological information. Percent fall in CA-125 was categorized into two groups: <95% (R < 95) and >95% (R > 95) fall from prechemotherapy to preoperative levels. Similarly, women were also categorized using preoperative CA-125 levels of <100 and >100 U/ml. A subset of women from January 2012 to December 2013 was followed to June 2015 for evidence of any recurrence to determine survival outcomes. RESULTS: About 56% women had R > 95 and 44% had R < 95. As compared to R < 95, R > 95 group was more likely to have complete cytoreduction (P = 0.00). Furthermore, women with R > 95 had significant better progression-free survival (PFS) as compared to women with R < 95 (P = 0.009) but no difference in overall survival (OS) (P = 0.28). Women with preoperative CA-125 <100 had significant higher number of complete cytoreduction (55% vs. 40%; P = 0.00) and were associated with both PFS (P = 0.007) and OS benefit (P = 0.02). CONCLUSION: Our data showed that >95% fall in CA-125 and an absolute preoperative CA-125 value of <100 U/ml is associated with better surgical and survival outcome in women with advanced EOC. These data are important in patient counseling and treatment planning.

Prevalence of high-risk human papillomavirus type 16 and 18 in oral and cervical cancers in population from Gujarat, West India.

BACKGROUND: Oral and cervical cancers are major malignancies in men and women, respectively, in India. This study evaluated occurrence of human papillomavirus (HPV) 16 and 18 infections in oral and cervical cancers to estimate HPV-associated burden of these cancers in the population from Gujarat, West India. METHODS: A total of 97 malignant oral carcinoma tissues and 52 cervical carcinoma tissues were analyzed by type-specific PCR for the presence of HPV type 16 and 18 infections. RESULTS: None of the oral cancer patients revealed the presence of HPV type 16 and 18 infection. In cervical cancer, 31 (59.6%) patients were infected with HPV 16 and 18. Of these 31 HPV-positive cervical cancer patients, 28 (90.3%) were infected with HPV 16 and 3 (9.7%) were infected with HPV 18. CONCLUSION: The results suggested that HPV 16 and 18 do not play an important role in oral carcinogenesis in the population from Gujarat, West India. However, HPV 16 is highly prevalent in the cervical cancer patients, which may be considered for planning of prevention programs such as screening and vaccination in women from this region.

Ovarian carcinoma or abdominal tuberculosis?-A diagnostic dilemma: study of fifteen cases.

OBJECTIVE: To evaluate the clinical, laboratory, and diagnostic features in women with abdominal tuberculosis that resembled advanced ovarian malignancy. METHODS: A retrospective review of women with abdominal tuberculosis who were managed at GCRI Ahmedabad from 1996 to 2001 was undertaken. RESULTS: Fifteen patients (3.06 %) with suspected ovarian cancer cases, finally diagnosed as abdominal tuberculosis over a 6-year period (1996-2001), are analyzed. During this period, 492 patients were operated for suspected ovarian malignancy. Pre-operatively, ultrasound-guided biopsies were inconclusive in 14 cases and hence, exploratory laparotomy was planned. They underwent laparotomy and biopsy for final diagnosis. Frozen sections-of peritoneal/omental biopsies in 11 cases and ovarian tumour in three cases-were indicative of tuberculosis in all the 14 cases. CONCLUSION: The data of this study indicate that the majority of the cases with peritoneal tuberculosis can be diagnosed intra-operatively through the use of frozen section in conjunction with clinical features. Ascites and high levels of Ca125 do not necessarily indicate that the clinical picture is malignant in reproductive women. Laparoscopic tissue biopsy may be a fundamental tool in the management of such cases to avoid extended surgery.

Management of drug resistant gestational trophoblastic neoplasia.

OBJECTIVE: To determine the outcome of secondary management in drug-resistant gestational trophoblastic neoplasia (GTN). STUDY DESIGN: Sixteen of 60 patients with GTN (8 low-risk and 8 high-risk) who developed resistance to primary chemotherapy were studied retrospectively. Primary chemotherapy was methotrexate-folinic acid rescue (MTX-FA) for low risk and etoposide/methotrexate/actinomycin D/cyclophosphamide/vincristine (EMA-CO) for high risk. Secondary chemotherapy for the low-risk group was either actinomycin D or EMA-CO, depending on serum beta human chorionic gonadotropin (hCG) levels at resistance. For the high-risk group, etoposide/methotrexate/actinomycin D/cisplatinum (EMA-EP) or bleomycin/etoposide/cisplatin (BEP) was given. Third-line chemotherapy was vincristine/actinomycin D/cyclophosphamide (VAC) or vincristine/ iphosphamide/cisplatin (VIP). Surgery and radiotherapy were used in selected patients. RESULTS: Survival after salvage therapy in low-risk patients was 100%: 2 with EMA-CO and 6 with actinomycin D. Of high-risk cases 75% were cured with EMA-EP or BEP. Third-line chemotherapy was given in 2 patients: 1 was lost to follow-up and the other died. Survival was significantly influenced by both hCG level at the start of secondary therapy and site of metastasis. CONCLUSION: Prognosis in GTN is excellent. Optimization of treatment strategies for those who develop drug resistance remains a key challenge.

High-risk gestational trophoblastic neoplasia at Gujarat Cancer and Research Institute: thirteen years of experience.

OBJECTIVE: To evaluate and analyze the results of chemotherapy (EMA-CO [etoposide, methotrexate, actinomycin D-cyclophosphamide, vincristine]) in high-risk gestational trophoblastic neoplasia (GTN). STUDY DESIGN: A total of 97 women with high-risk GTN were evaluated for a period of 13 years (1995-2008). All women received EMA-CO as a first-line chemotherapy. EMA-EP (etoposide, methotrexate, actinomycin and cisplatinum), PVB (cisplatin, vinblastine and bleomycin), and BEP (bleomycin, etoposide and cisplatin) were the chemotherapies used as second-line therapy in women who experienced resistance to primary chemotherapy. Intrathecal methotrexate was given in women with brain metastasis and also as prophylaxis in pulmonary metastasis. Eleven women had brain metastasis and received cranial radiotherapy. The most common toxicity was hematologic. . RESULTS: Of 97 women, 78 (80.4%) were evaluable and 19 (19.6%) were lost to follow-up with incomplete treatment. Of the 78 patients, 6 women developed resistance and had progression of disease. Seven women had died (5 due to disease, 2 due to chemotherapy toxicity). Overall 65 of the 78 (83.3%) women achieved remission. Of the 78 women, 66.7% (52/78) had complete remission with first-line chemotherapy, and an additional 16.6% (13/78) achieved remission with second-line chemotherapy, resulting in a total of 83.3% (65/78) attaining remission. A total of 46% (30/ 65) had follow-up of > 3 years, and 32.4% (21/65) had follow-up of 1-3 years. Three of 9 women with brain metastasis achieved remission. Sixty percent (39/65) resumed normal menstrual function (had remission for at least 2 years). Twelve women became pregnant since the completion of the chemotherapy, with 10 live births of healthy infants without any congenital abnormalities. CONCLUSION: High-risk GTNs are highly curable if properly treated, and patients can anticipate a normal future reproductive outcome. EMA-CO remains the preferred chemotherapy for management.

Role of percutaneous nephrostomy in advanced cervical carcinoma with obstructive uropathy: a case series.

AIMS AND OBJECTIVE: Over 70% of the cases present in advanced stages of the disease and are associated with poor prognosis and high mortality rates. In many of them, it is difficult to offer definitive treatment as they present in uremia due to associated obstructive uropathy. There are no clear-cut guidelines for performing percutaneous nephrostomy (PCN) in patients of advanced cervical cancer. The results are unpredictable in terms of benefits achieved in these cases. Thus, we evaluated our experiences with PCN in the management of cervical cancer patients presenting with obstructive uropathy. MATERIAL AND METHODS: 15 patients of cervical cancer with obstructive uropathy and deranged renal functions were retrospectively evaluated for the role of PCN in their management RESULTS: PCN was done in 15 patients of advanced cervical cancer. The mean age of patients was 44.5 years. Twelve (80%) patients presented primarily with advanced cervical carcinoma and obstructive uropathy. Three (20%) were already treated. Symptomatic improvement and significant fall of mean serum creatinine value from 7.5 mg% to 0.9 mg% over a period of 1-3 weeks was noted post PCN. Out of 12 patient with primary untreated advanced disease, curative treatment was possible in 3, palliative radiotherapy/chemo-therapy in 7 and only symptomatic treatment in 2 cases, after obstructive uropathy was managed with PCN insertion. Out of 3 already treated patients, 2 were disease free after curative radiotherapy/surgery. PCN was done to prevent permanent kidney damage in them. One patient was defaulter of curative radiotherapy. She had progressive residual disease. Complications like hemorrhage (20%), infection (26%), reinsertion for dislodgment/misplacement (53%), percutaneous leak or perinephric leak (20%), blockage of PCN (33%) were noticed. CONCLUSION: In spite of inherent, albeit manageable complications, PCN is a simple and safe technique. One of the major benefits observed was ability to administer either curative/palliative radiotherapy or chemotherapy in 85% of patients (11 out of 13 with disease). There was no active disease in remaining 2 patients. Therefore, the decision to attempt PCN in carefully selected cervical cancer patients is justified.