Laparoscopic, robotic and open method of radical hysterectomy for cervical cancer: A systematic review.

BACKGROUND: Over the last two decades, numerous studies have indicated the feasibility of minimally invasive surgery for early cervical cancer without compromising the oncological outcome. OBJECTIVE: Systematic literature review and meta analysis aimed at evaluating the outcome of laparoscopic and robotic radical hysterectomy (LRH and RRH) and comparing the results with abdominal radical hysterectomy (ARH). SEARCH STRATEGY: Medline, PubMed, Embase, Cochrane library and Reference lists were searched for articles published until January 31(st) 2011, using the terms radical hysterectomy, laparoscopic radical hysterectomy, robotic radical hysterectomy, surgical treatment of cervical cancer and complications of radical hysterectomy. SELECTION CRITERIA: Studies that reported outcome measures of radical hysterectomy by open method, laparoscopic and robotic methods were selected. DATA COLLECTION AND ANALYSIS: Two independent reviewers selected studies, abstracted and tabulated the data and pooled estimates were obtained on the surgical and oncological outcomes. RESULTS: Mean sample size, age and body mass index across the three types of RH studies were similar. Mean operation time across the three types of RH studies was comparable. Mean blood loss and transfusion rate are significantly higher in ARH compared to both LRH and RRH. Duration of stay in hospital for RRH was significantly less than the other two methods. The mean number of lymph nodes obtained, nodal metastasis and positive margins across the three types of RH studies were similar. Post operative infectious morbidity was significantly higher among patients who underwent ARH compared to the other two methods and a higher rate of cystotomy in LRH. CONCLUSIONS: Minimally invasive surgery especially robotic radical hysterectomy may be a better and safe option for surgical treatment of cervical cancer. The laparoscopic method is not free from complications. However, experience of surgeon may reduce the complications rate.

Endometrial stromal sarcoma: A review of the literature.

Endometrial stromal sarcomas are rare malignant tumors of the uterus, and most of the information available in literature is based on small series or case reports. A proper preoperative diagnosis is difficult and in most cases the diagnosis is confirmed after hysterectomy for a presumed benign disease. Endometrial sampling, ultrasound, and magnetic resonance imaging can provide diagnostic clues. Total hysterectomy with bilateral salpingo-oopherectomy is the main line of management and for early disease complete cure is a reality. Ovarian conservation may be possible in young women with early stage disease and the role of lymphadenectomy is controversial. Adjuvant hormone therapy in the form of progesterone, gonadotropin releasing hormone analogues, and aromatase inhibitors are found to be effective in preventing recurrences. Hormone therapy, radiotherapy and surgical excision of the metastasis are recommended for recurrences.

Granulosa cell tumours of the ovary.

Granulosa cell tumours are rare, potentially malignant sex cord stromal tumours of the ovary. They are unique in their presentation and histological features. Many of them are hormone-producing and this property helps them to present early unlike other epithelial ovarian cancers. As a result, most of them will be in an early stage at the time of initial diagnosis. The tumour can manifest in young girls as a juvenile form and conservative management with unilateral salpingo-opherectomy may be an option in them as 95% are unilateral. Surgery is the treatment of choice and initial staging laparatomy a determinant recurrence. Advance stage of the tumour, its size (>5 cm), mitotic figures (>10/hpf), nuclear atypia and absence of call-exner bodies are poor prognostic factors. Such tumours are characterised by late recurrences and this necessitates a prolonged follow-up. Tumour markers such as inhibin and estradiol are useful in follow-up. Chemotherapy, radiotherapy and hormone replacement therapy have very little role in the initial treatment and may be suggested in case of recurrences. With appropriate treatment, a better survival rate can be achieved as against other ovarian malignancies. Methods used for locating, selecting and synthesising data: A search of Medline and Cochrane data base for the period from 1999 to 2010 was carried out to include relevant systematic reviews, meta-analysis, randomised controlled and other clinical and rare case reports. The date of the last search was January 2010.

A nested case-control study of female breast cancer in Karunagappally cohort in Kerala, India.

Lifestyle factors related to breast cancer risk were examined in a case-control study nested in a cohort in Karunagappally, Kerala, South India. We sought interviews with all the residents in Karunagappally with the population of 385,103 (191,149 males and 193,954 females) in the 1991 census and established a cohort of 359,619 (93% of the population in 1991) in 1990. For analysis 264 breast cancer cases with age > or = 20 years were selected from 438 breast cancer cases reported during the period 1990-2004 and for each case 3 non-cancer controls were randomly selected matched for age, religion and place of residence through the Cancer Registry, Karunagappally. Conditional logistic regression was used for the analysis. In the present study, in addition to a low number of pregnancies (P <0.001 and P for trend <0.001), more frequent intake of roots and tubers except tapioca (cassava) (OR for > or = 5 times =1.56, 95% CI=1.09, 3.09, P for trend <0.05), milk drinking (OR=1.78, 95% CI=1.17-2.69, P<0.01) and consumption of chicken meat (OR=1.84, 95% CI=1.09-3.09, P<0.05) were found to increase breast cancer risk. The present study further showed that consumption of tapioca which is a commonly used food item in South India, particularly in Kerala, reduced breast cancer risk (OR=0.55, 95% CI=0.37-0.83, P<0.01). Risk analysis was attempted among pre- and post-menopausal women separately and similar odds ratio were obtained. Consumption of tapioca (cassava) decreased risk of developing breast cancer among premenopausal women (P<0.001 and OR=0.35, 95% CI=0.18, 0.65) and a low number of pregnancies (P<0.01), consumption of roots & tubers (P<0.05), usage of chicken meat (P=0.05) increased the risk of breast cancer among post-menopausal women. Further studies seem warranted to confirm the possible protective effect of tapioca consumption. There is an increasing need of breast cancer prevention programs responsive to the cultural practices of the people and the study results should provide leads to cancer control programs especially in rural areas.

Background radiation and cancer incidence in Kerala, India-Karanagappally cohort study.

The coastal belt of Karunagappally, Kerala, India, is known for high background radiation (HBR) from thorium-containing monazite sand. In coastal panchayats, median outdoor radiation levels are more than 4 mGy y-1 and, in certain locations on the coast, it is as high as 70 mGy y-1. Although HBR has been repeatedly shown to increase the frequency of chromosome aberrations in the circulating lymphocytes of exposed persons, its carcinogenic effect is still unproven. A cohort of all 385,103 residents in Karunagappally was established in the 1990's to evaluate health effects of HBR. Based on radiation level measurements, a radiation subcohort consisting of 173,067 residents was chosen. Cancer incidence in this subcohort aged 30-84 y (N = 69,958) was analyzed. Cumulative radiation dose for each individual was estimated based on outdoor and indoor dosimetry of each household, taking into account sex- and age-specific house occupancy factors. Following 69,958 residents for 10.5 years on average, 736,586 person-years of observation were accumulated and 1,379 cancer cases including 30 cases of leukemia were identified by the end of 2005. Poisson regression analysis of cohort data, stratified by sex, attained age, follow-up interval, socio-demographic factors and bidi smoking, showed no excess cancer risk from exposure to terrestrial gamma radiation. The excess relative risk of cancer excluding leukemia was estimated to be -0.13 Gy-1 (95% CI: -0.58, 0.46). In site-specific analysis, no cancer site was significantly related to cumulative radiation dose. Leukemia was not significantly related to HBR, either. Although the statistical power of the study might not be adequate due to the low dose, our cancer incidence study, together with previously reported cancer mortality studies in the HBR area of Yangjiang, China, suggests it is unlikely that estimates of risk at low doses are substantially greater than currently believed.

Phenotypic alterations in Rb pathway have more prognostic influence than p53 pathway proteins in oral carcinoma.

The two well-defined pathways that are shown to be prominently altered in a variety of cancers are the cell cycle regulatory pathways led by either p53 or Rb genes. The present study is undertaken to find the pathway that is more altered in oral carcinoma at protein level, with special emphasis on its prognostic significance. The expression pattern of key molecules of the Rb and p53 pathways, such as Rb, cyclin D1, CDK4, p16, p53, p21 and Bcl-2 and the proliferative marker PCNA were analysed in 348 oral carcinoma specimens by immunohistochemical technique. The expression index of these molecules and various clinicopathological factors were statistically correlated with treatment end points to assess its prognostic efficacy after following up these patients up to a maximum of 48 months with a median of 23 months. Rb pathway proteins, Rb (P=0.016), cyclin D1 (P=0.0001) and p16 (P=0.012) showed significant association with disease-free survival, and p16 (P=0.041) and cyclin D1 (P=<0.0001) with the overall survival. Among p53 pathway proteins studied, only p53 expression index showed association with both disease-free survival and overall survival. Multivariate analyses confirmed that the biological variables, cyclin D1 and p16 and the clinical variable, 'stage of disease' were independent predictors of disease-free survival and overall survival. Subgrouping of the patients on the basis of p16 and cyclin D1 expression revealed that the subgroup having downregulation of p16 and overexpression of cyclin D1 exhibited the worst disease-free survival and overall survival compared to the other subgroups. The present data showed that disabling of the Rb and p53 pathways were frequent events in oral carcinoma. The study also demonstrated that the Rb pathway proteins are comparatively more important than p53 pathway proteins for the prognostication of oral carcinoma patients. The combined evaluation of p16 and cyclin D1 in oral carcinoma could identify a group of patients with the worst survival who might therefore need alternate or more intense treatment strategies.

Squamous cell cancer of the buccal mucosa in young adults.

BACKGROUND: Squamous cell carcinoma of the buccal mucosa is predominantly a cancer of elderly people and is seen rarely in young adults. Although many aetiological factors have been postulated, tobacco alone has been implicated as the main factor in the aetiology of such cancers at any age. PATIENTS AND METHODS: A retrospective analysis of 46 patients with cancer of the buccal mucosa who were under the age of 35 years at the time of presentation was made to evaluate their survival and predictors of survival. The details were extracted from the computerised records and case records of the Regional Cancer Centre, Trivandrum, India. These were analysed with particular emphasis on risk factors, clinical extent, and treatment. Survival was analysed by the Kaplan-Meier method, and differences in survival were compared using the log-rank test. RESULTS: The male:female ratio was 6.7:1. Almost all the patients (n = 42, 91%) used either tobacco or alcohol, with tobacco chewing being the most common. The 3 and 5 years disease-free survival were 72 and 61%, respectively. Non-smokers and patients with an advanced T stage at presentation had significantly worse prognoses.

p53, p16 and cyclin D1: molecular determinants of radiotherapy treatment response in oral carcinoma.

Management of oral cancer by radiotherapy has witnessed promising advances in the past few years, with patient-tailored radio fractionation regimens. Different fractionation schedules, conventional and altered regimes, have been used in curative radiotherapy. Although contribution of biological markers on radio response has been evaluated, its unique influence on various radio fractionation schemes has not been accounted so far. Our study analyses a set of proteins that previously demonstrated radio response influence for their possible prognostic value in decision-making process between the respective fractionation schemes. Expression patterns of regulatory proteins such as p53, cyclin D1, p16, Cdk4, p21, Rb, bcl-2 and PCNA were determined by immunohistochemistry utilizing monoclonal antibodies in 125 patients who received curative radiotherapy dose. Among these 125 patients, 90 (72%) received altered fractionation, whereas 35 (28%) received conventional fractionation. p53 over-expression correlated with local treatment failure among the patients treated with conventional fractionation whereas cyclin D1 over-expression and p16 underexpression were associated with local treatment failure as well as overall survival in altered fractionation treated cases. Our findings suggest that wild-type p53 status may be an important parameter for achieving high local control in those patients undergoing conventional fractionation, where as intact p16 and cyclin D1 status may be beneficial for effective local control in patients who are treated with altered fractionation. Furthermore, it can be assumed that conventional fractionation employs p53-mediated apoptosis, whereas altered fractionation activates the functional G1 cell-cycle checkpoint for tumor growth suppression.

Interim results from a cluster randomized controlled oral cancer screening trial in Kerala, India.

A cluster randomized controlled oral cancer screening trial is on-going in the Trivandrum district, India, to evaluate the efficacy of screening in reducing oral cancer mortality. Subjects, aged 35 years and above, in 13 clusters in the Trivandrum district, India, were randomized to the intervention (screening) group (7 clusters, 78969 subjects) to receive three rounds of screening by oral visual inspection by trained health workers at 3-year intervals or to a control group (6 clusters, 74739 subjects). Two rounds of screening were completed between 1995 and 2002 during which 69896 (88.5%) subjects were screened at least once, and 59.7% of the 4408 screen-positive subjects were further investigated. In the intervention group, 344404 person-years were accrued and 329326 person-years were in the control group. In the intervention group, 149 incident oral cancer cases and 65 deaths from oral cancer were observed, and 106 incident cases and 62 deaths from oral cancer were observed in the control group. The programme sensitivity for detection of oral precancerous lesions and cancer was 81.5% and the programme specificity was 84.8%; the programme positive predictive value was 39.6%. In the intervention group 37.6% of the cases were in stages I-II, as opposed to 18.9% in the control group. The 3 year survival rate was 57.5% in the intervention and 38.8% in the control group (P<0.05). The age standardized oral cancer mortality rates were 21.2/100000 person-years in the intervention and 21.3/100000 in the control group. After completing two rounds of screening, oral cancer mortality rates were similar in both study groups.

Antitumour property and toxicity of Barringtonia racemosa Roxb seed extract in mice.

Ethnomedical survey has shown that the seeds of Barringtonia racemosa Roxb are traditionally used in certain remote villages of Kerala (India) to treat cancer like diseases. So the seed extracts were tested for their antitumour activity and toxicity. Intraperitoneal (i.p.) daily administration of 50% methanol extract of this seed to mice challenged with 1 million Dalton's Lymphoma Ascitic (DLA) cells resulted in remarkable dose dependent anti-DLA activity in mice. The optimum dose was found to be 6 mg/kg. This dose protected all the animals challenged with the tumour cells. The efficacy of the drug was found to be better than that of a standard drug, vincristine in this tumour model. However, the oral administration showed only marginal activity compared to i.p. administration. The extract was found to be devoid of conspicuous acute and short-term toxicity to mice, when administered daily, (i.p.) for 14 days up to a dose of 12 mg/kg (which was double the concentration of optimum therapeutic dose). The treated mice showed conspicuous toxic symptoms only at 24 mg/kg. The LD(50) to male mice for a single i.p. dose was found to be 36 mg/kg. The seed extract is an attractive material for further studies leading to drug development.

Epstein-Barr virus-associated gastric carcinoma in southern India: A comparison with a large-scale Japanese series.

Epidemiological and clinicopathological features of Epstein-Barr virus (EBV) associated gastric carcinoma was compared in India and Japan, two countries differing markedly in gastric cancer incidence. Using in situ hybridization assay, the presence of EBV-encoded small RNA (EBER) was examined in 215, and 2,011 gastric cancer cases in Kerala, India, and Japan, respectively. Ten cases (5%), all males, in the Indian series were EBER-positive. This frequency was similar to that in the Japanese series (6.2%). As was the case with Japanese series, the EBV-associated gastric carcinoma in the Indian series was observed most frequently in the middle part of the stomach (1 in antrum, 4 in middle part, 2 in cardia, and 3 unknown), and, histologically, the diffuse type Lauren's classification (8 cases) was more common than the intestinal type (2 cases). Virus subtyping by PCR-RFLP revealed that all of the 10 EBV strains isolated from the EBER-positive Indian cases were subtype A, and wild-type F for Bam HI F region. In Bam HI I region, 8 cases were type C and the remaining 2 cases were type D. In either series, there was no significant difference in the frequency of tumors with p53 overexpression between EBER-positive and -negative cases. However, the proportion of cells with p53 overexpression in EBER-negative tumors was significantly higher than that in EBER-positive tumors regardless of histological type in both series. In conclusion, the frequency and major clinicopathological features of EBV-associated gastric carcinoma in south India were similar to those observed in Japanese series although gastric cancer incidence in these two countries differs markedly.

Germline BRCA1 mutation analysis in Indian breast/ovarian cancer families.

Most of the predisposition to hereditary breast and ovarian cancer has been attributed to inherited defects in two tumor suppressor genes BRCA1 and BRCA2. To explore the contribution of BRCA1 mutations to hereditary breast cancer among Indian women, we examined the coding sequence of the BRCA1 gene in 14 breast cancer patients with a positive family history of breast and/or ovarian cancer. Mutation analysis was carried out using conformation sensitive gel electrophoresis (CSGE) followed by sequencing. Three mutations (21%) in the BRCA1 gene were identified. Two of them are novel mutations of which one is a missense mutation in exon 7 near the RING finger domain, while the other is a one base pair deletion in exon 11 which results in protein truncation. The third mutation, 185 delAG, has been previously described in Ashkenazi Jewish families. To our knowledge this is the first report of a study of germline BRCA1 mutation analysis in familial breast cancer in India. Our data from 14 different families suggests a lower prevalence but definite involvement of germline mutations in the BRCA1 gene among Indian women with breast cancer and a family history of breast cancer.