Sunesh Kumar Jain

Mutations in the mitochondrial DNA D-loop region are frequent in cervical cancer

BackgroundMitochondrial DNA (mtDNA) is known for high mutation rates caused by lack of protective histones, inefficient DNA repair systems, and continuous exposure to mutagenic effects of oxygen radicals. Alterations in the non-coding displacement (D) loop of mitochondrial DNA are present in many cancers. It has been suggested that the extent of mitochondrial DNA mutations might be useful in the prognosis of cancer outcome and/or the response to certain therapies. In order to investigate whether a high incidence of mutations exist in mitochondrial DNA of cervical cancer patients, we examined the frequency of mutations in the D-loop region in 19 patients of cervical cancer.ResultsMutations, often multiple, were detected in 18 of 19 (95%) patients. The presence of mutations correlated with Human Papilloma Virus (HPV) infection in these patients. Mutations were also detected in normal samples and lymphocytes obtained from cervical cancer patients, but their frequency of occurrence was much lower as compared to the cervical cancer tissues.ConclusionOur findings indicate that D-loop alterations are frequent in cervical cancers and are possibly caused by HPV infection. There was no association of mtDNA D-loop mutations with the histopathological grade and tumor staging.

Molecular variants of HPV-16 associated with cervical cancer in Indian population.

Human papilloma virus is a causative factor in the etiology of cervical cancer with HPV16 being the most prevalent genotype associated with it. Intratype variations in oncogenic E6/E7 and capsid L1 proteins of HPV 16 besides being of phylogenetic importance, are associated with risk of viral persistence and progression. The objective of this multicentric study was to identify HPV‐16 E6, E7 and L1 variants prevalent in India and their possible biological effects. Squamous cell cervical cancer biopsies were collected from 6 centres in India and examined for the presence of HPV 16. Variants of HPV‐16 were characterized by full length sequence analysis of L1, E6 and E7 genes in 412 samples. Similar distribution of the variants was seen from the different centres/regions, with the European variant E350G being the most prevalent (58%), followed by American Asian variant (11.4%). Fifty six changes were seen in E6 region, 31 being nonsynonymous. The most frequent being L83V (72.3%), Q14H (13.1%) and H78Y (12.1%). Twenty‐nine alterations were seen in E7 region, with 12 being nonsynonymous. The most frequent being F57V (9%). L1 region showed 204 changes, of which 67 were nonsynonymous. The most frequent being 448insS (100%), and 465delD (100%), H228D (94%), T292A (85%). The identified variants some new and some already reported can disrupt pentamer formation, transcriptional regulation of the virus, L1 protein interface interaction, B and T cell epitopes, p53 degradation, and thus their distribution is important for development of HPV diagnostics, vaccine, and for therapeutic purpose.

Corpus luteum hemorrhage: Rare complication of congenital and acquired coagulation abnormalities

Women taking anticoagulants or those with a clotting factor deficiency are at increased risk of corpus luteum rupture due to coagulation abnormalities and three such cases are described here. Case 1 was a 35‐year‐old woman with prosthetic mitral valve replacement who was on anticoagulant therapy, in whom hemoperitoneum secondary to ruptured corpus luteum was seen. Emergency laparotomy revealed 1.2 L of massive hemoperitoneum. Left salpingo‐oophorectomy was performed. Case 2 was two episodes of hemoperitoneum from luteal cyst rupture in a young patient with the rare congenital factor X deficiency. This patient was managed conservatively with fresh frozen plasma and blood transfusion. This is the first case of congenital factor X deficiency manifested as luteal rupture to be managed conservatively. Case 3 was two episodes of hemoperitoneum from luteal cyst rupture in a patient with antiphospholipid antibody syndrome who was on oral anticoagulants. Laparotomy was done twice with left salpingo‐oophorectomy in the first instance and partial excision of the right ovary in the second instance. Hemoperitoneum secondary to rupture of the corpus luteum should be considered in the differential diagnosis of acute abdominal pain in women with congenital and acquired coagulation deficiencies.

Role of FDG PET-CT in detecting recurrence in patients with uterine sarcoma: comparison with conventional imaging.

PurposeThe purpose of the present study was to evaluate the role of 18F-fluorodeoxyglucose (FDG) PET-CT in detecting recurrent disease in posttherapy patients of uterine sarcoma and compare the same with conventional imaging (CI). MethodsA total of 15 FDG PET-CT studies were acquired in 12 posttherapy uterine sarcoma patients. The images were evaluated by two experienced nuclear medicine physicians in consensus. Clinical/imaging follow-up (minimum 6 months) and histopathology were taken as the reference standard. All the patients had also undergone CI (CT or MRI or ultrasonography) of the chest, abdomen, and pelvis. The diagnostic accuracy of FDG PET-CT was calculated and compared with that of CI. ResultsThe median age of the patients was 51.5 years (interquartile range: 47.5–53). Histopathology was leiomyosarcoma in six, carcinosarcoma in five, and endometrial stromal sarcoma in one patient. Six FDG PET-CT studies were carried out for suspected recurrence and nine for posttherapy surveillance. Six FDG PET-CTs were positive and nine were negative for recurrence. The sensitivity, specificity, and accuracy of FDG PET-CT were 85.7, 100, and 93.3%, respectively, on per study-based analysis, and 80, 100, and 83.3% on per lesion-based analysis. PET-CT showed higher sensitivity and specificity compared with CI for both study-based and lesion-based analysis. However, no significant difference was found between FDG PET-CT and CI either in the study-based or in the lesion-based analysis (P not significant). ConclusionFDG PET-CT is a highly sensitive and specific modality for detecting recurrence in posttherapy patients with uterine sarcoma. However, it provides no significant advantage over CI for this purpose.

A prospective randomized trial comparing the efficacy of Letrozole and Clomiphene citrate in induction of ovulation in polycystic ovarian syndrome

OBJECTIVES: To compare the efficacy of letrozole and clomiphene citrate (CC) in patients of anovulatory polycystic ovarian syndrome (PCOS) with infertility. MATERIALS AND METHODS: This prospective randomized clinical trial included 204 patients of PCOS. 98 patients (294 cycles) received 2.5–5 mg of letrozole; 106 patients (318 cycles) received 50–100 mg of CC (both orally from Days 3–7 of menstrual cycle). The treatment continued for three cycles in both the groups. Main outcome measures: ovulation rate, endometrial thickness, and pregnancy rate. Statistical analysis was done using SPSS 13 software. P value less than 0.05 was considered significant. RESULTS: The mean number of dominant follicles in letrozole groups and CC groups was 1.86±0.26 and 1.92±0.17, respectively (P=0.126). Number of ovulatory cycle in letrozole group was 196 (66.6%) versus 216 (67.9%) in CC group (P=0.712). The mean mid-cycle endometrial thickness was 9.1±0.3 mm in letrozole group and 6.3±1.1 in CC group, which was statistically significant (P=0.014). The mean Estradiol [E2] level in clomiphene citrate group was significantly higher in CC group (364.2±71.4 pg/mL) than letrozole group (248.2± 42.2 pg/mL). 43 patients from the letrozole group (43.8%) and 28 patients from the CC group (26.4%) became pregnant. CONCLUSION: Letrozole and CC have comparable ovulation rate. The effect of letrozole showed a better endometrial response and pregnancy rate compared with CC.

High prevalence of Fitz-Hugh-Curtis Syndrome in genital tuberculosis.

Perihepatitis with violin string adhesions between the liver and the anterior abdominal wall in association with gonococcal or chlamydial salpingitis constitutes Fitz-Hugh-Curtis Syndrome (FHCS). It manifests as pain and tenderness in the right upper quadrant of abdomen pleuritic pain exacerbated by breathing coughing laughing and movement probably due to irritation of Glissons capsule of the liver. There are two phases of the syndrome; acute and chronic. In the acute phase perihepatitis and focal peritonitis result from the transport of inflammatory peritoneal fluid either directly or by lymphatic vessels to the subphrenic and subdiaphragmatic spaces. In the chronic phase violin string adhesions are observed between the anterior surface of the liver and the anterior abdominal wall. Recently genital and abdominal tuberculosis has been observed to be associated with FHCS in a report of three cases. From June 2004 to December 2006 a total of 82 women were found to have genital tuberculosis.The ages ranged between 19 to 46 years (mean age 25.6 years). Most women were from rural areas (n=60 75.6%) with the majority of poor or low socioeconomic status (n=72 87.8%). (excerpt)

Hysterosalpingographic findings in infertile women with genital tuberculosis

To evaluate the hysterosalpingographic findings from infertile women who were subsequently diagnosed with genital tuberculosis.

Telomerase--a potential molecular marker of lung and cervical cancer.

Abstract Telomerase, a ribonucleoprotein enzyme that adds hexameric TTAGGG nucleotide repeats onto telomeres is reactivated in most malignancies. Lung cancer is a common malignant disease worldwide as well as in India. Most patients present in advanced stages. As noninvasive diagnostic techniques are preferred, we assayed the telomerase activity in pre-bronchoscopy sputum and compared it with that of bronchial washings and bronchoscopic biopsies by telomeric repeat amplification protocol (TRAP) in 53 cases of lung cancer. These were corroborated with cytopathological/histopathological examinations. Telomerase activity was detected in 58.5% of sputum samples, 70% of bronchial washings and 74% of bronchoscopic biopsies thereby making it a good noninvasive diagnostic marker of lung cancer. Cervical cancer is the 7th most common cancer worldwide, with 100,000 new cases being reported annually in India. It is routinely screened by Papanicolaous (Pap) smear. Human papilloma virus (HPV) is one of its etiological agents. We have assayed telomerase activity in relation to HPV-16/18 in cervical samples from 93 subjects ranging from normal to precancerous to frank cancers in tissue biopsies and cervical scrapings. HPV infection was detected by polymerase chain reaction (PCR) in 81% of tumor samples, in 6% of control hysterectomy samples and in 2% of cervical scrapings of normal healthy controls with HPV-16 being the predominant type. Telomerase activity was detected in 96.5% of cervical tumor samples, in 68.7% of premalignant cervical scrapings but was not detected in control hysterectomy samples, or in cervical scrapings of normal healthy controls. There was 71% correlation between telomerase activity and HPV-16/18 infection.

Increased complication rates associated with laparoscopic surgery among patients with genital tuberculosis

To compare the complications and surgical difficulties encountered during laparoscopy between women diagnosed with and without genital tuberculosis (TB).

Human papilloma virus genotyping, variants and viral load in tumors, squamous intraepithelial lesions, and controls in a north Indian population subset.

A study of human papilloma virus (HPV) types and variants is important for developing preventive protocols and appropriate intervention targets. The presence of HPV types, their variants, and viral load in a population subset from North India was studied. Polymerase chain reaction (PCR) and line blots were used for HPV genotyping; HPV 16 and 18 viral loads were measured using real-time PCR. Variant analysis was done by sequencing of the PCR-amplified E6/E7regions of HPV 16 and the long control region and E6/E7 regions of HPV 18. The 93.6%, 78.6%, and 10% of tumors, squamous intraepithelial lesions (SILs), and controls were HPV-positive, respectively. The most commonly observed type was HPV 16. Human papilloma virus 73 which is uncommonly observed was seen in 2 tumors. Multiple infections were more common in controls and SILs than tumors. The majority (86.4%) of the HPV 16-positive and all of the HPV 18-positive samples belonged to the European variant class. Five novel nonsynonymous changes were seen in the HPV 16-positive and 2 in HPV 18-positive samples. There was a significant increase in viral loads from controls through SILs to tumors, but no significant differences in viral loads were observed between different stages of cancer. In tumors, a significant increase in HPV 16 viral loads was seen with increasing age. The study shows a similar HPV type and variant distribution to European studies, with some differences in type distribution. Viral load does not appear to be good marker for stage wise progression and intralesional variability may affect its use as a differentiating parameter between high-grade squamous intraepithelial lesion and low-grade squamous intraepithelial lesions.