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Biomedical subjects

K S Raju

Publications and source records attributed to K S Raju.

At least 19 recordsLinked to original sources
PubMed2006

A comparative study of the risk of malignancy index and the ovarian crescent sign for the diagnosis of invasive ovarian cancer.

OBJECTIVE: To compare the value of the risk of malignancy index (RMI) and the ovarian crescent sign (OCS) in the diagnosis of ovarian malignancy. METHODS: This was a prospective observational study of women with ultrasonographic diagnosis of an ovarian cyst. The RMI was calculated in all cases using a previously published formula (RMI = U (ultrasound score) x M (menopausal status) x serum CA125 (kU/L)). A value > 200 was considered to be diagnostic of ovarian cancer. The OCS was defined as a rim of visible healthy ovarian tissue in the ipsilateral ovary. Its absence was taken as being diagnostic of invasive cancer. RESULTS: A total of 106 consecutive women were included in the study, of whom 92 (86.8%) had a benign ovarian tumor, five (4.7%) had borderline lesions and nine (8.5%) had an invasive ovarian cancer. The absence of an OCS diagnosed invasive ovarian cancer with a sensitivity of 100% (95% CI, 70-100%), specificity of 93% (95% CI, 86-96%), positive predictive value (PPV) of 56%, negative predictive value (NPV) of 100% and positive likelihood ratio (LR+) of 13.86 (95% CI, 6.79-28.29). This compared favorably with a sensitivity of 89% (95% CI, 57-98%), specificity of 92% (95% CI, 85-96%), PPV of 50%, NPV of 99% and LR+ of 10.78 (95% CI, 5.34-21.77), which were achieved using RMI > 200 (P < 0.01). CONCLUSIONS: The RMI and the OCS are useful tests for discriminating between invasive and non-invasive ovarian tumors. The application of these tests in a sequential manner might improve the overall accuracy of ovarian cancer diagnosis.

Algorithms↗
PubMed2004

The value of detection of normal ovarian tissue (the 'ovarian crescent sign') in the differential diagnosis of adnexal masses.

OBJECTIVE: The aim of the study was to evaluate whether the presence of normal ovarian tissue adjacent to an adnexal tumor (the 'ovarian crescent sign') could assist in the preoperative differential diagnosis of adnexal lesions. METHODS: This was a prospective observational study including 100 women with a preoperative diagnosis of an adnexal mass. Demographic and biochemical data were collected and all women underwent a detailed transvaginal ultrasound scan. Tumor volume, morphological characteristics and Doppler features were recorded in each case. In addition, the tissue adjacent to the cyst was systematically examined for the presence of normal ovarian tissue. All the findings were compared to the final histological diagnosis. RESULTS: Sixty-seven (67%) of the cysts removed were benign, nine (9%) were borderline and 24 (24%) women had invasive malignant lesions. Normal ovarian tissue was seen in 58/76 (76%) women with non-invasive lesions, and in one woman (4%) with an invasive malignancy. In the absence of normal ovarian tissue, ovarian cancer was diagnosed with a sensitivity of 96% and specificity of 76%. CONCLUSION: The presence of normal ovarian tissue adjacent to an ovarian cyst is a useful morphological feature that may be used to help exclude an invasive ovarian malignancy in women with adnexal masses detected on ultrasound scan.

Adnexal Diseases↗
PubMed2004

Implementing the 2-week wait rule for cancer referral in the UK: general practitioners' views and practices.

The 2-week wait rule for cancer referrals became effective in December 2000 for all cancers treated by the National Health Service in the UK. Attainment of this target depends initially on appropriate and timely referral by general practitioners (GPs). General practitioners' views and referral practices under the 2-week wait rule were examined based on a postal survey of 508 GPs in an inner London area (65% response). Data on mode of referral indicated that 90% of GPs used the urgent suspected cancer form, although 38% also sent a letter with further information. General practitioners generally regarded the 2-week wait rule as working well in terms of improving patients' initial access, and 50% thought communication with the hospital had improved. However, 46% expressed some concerns, including problems arising from the different sets of forms required by local cancer networks, the lack of a dedicated referral form for breast cancer, and feelings of a loss of autonomy. General practitioners also acknowledged an element of over-referral under this rule due to the effects of clinical uncertainty and patient pressure and their concerns about increased waiting times for non-target referrals. The survey therefore indicates that GPs are generally positive about the 2-week wait rule but identified some problems of implementation including a need for standardized national cancer referral forms.

Attitude of Health Personnel↗
PubMed2003

Development of an evidence-based algorithm for the management of ovarian cancer.

OBJECTIVE: To describe the management of ovarian cancer to be undertaken by a gynaecologist and to describe the highest level of primary research evidence supporting it. DESIGN: Use of regional guidelines and semi-structured interviews with gynaecological oncologists to devise a flow-chart algorithm for management. Use of an algorithm to identify the key research questions and to define search strategies for primary research, which was assessed using pre-defined criteria for validity. MAIN OUTCOME MEASURES: Highest level of evidence for each research question based on the design of the valid studies. RESULTS: Prospective cohort studies (level II-2A) support the algorithm's diagnostic procedures. The evidence for accurate staging is derived from case series data (level II-2B). Preserving the uterus in young women wishing to maintain fertility is supported by prospective cohort studies (level II-2A) and by case series data (level IV) for women with germ cell tumours. Prospective cohort studies (level II-2A) support surgical management with hysterectomy, bilateral oophorectomy and debulking. The evidence for chemotherapy comes from randomised controlled trials (level I), except for germ cell tumours where the evidence was from case series data (level IV). CONCLUSIONS: The management of ovarian cancer and the level of evidence supporting it can be described using a flow-chart algorithm. Evaluations of whether this presentation helps consultants follow guidelines are required.

Adolescent↗
PubMed2003

National guidance on gynaecological cancer management: an audit of gynaecological cancer services and management in the South East of England.

OBJECTIVE: To evaluate the appropriateness of the structure and the process of care for gynaecological cancer against national guidelines. SETTING & SAMPLE: Incident cases of ovarian and cervical cancer managed between 1 January, 1999 and 31 December, 2000 in the South East of England. METHODS: Completion of an audit form, by a researcher, using the clinical record. Qualitative interviews with gynaecologists at each hospital. MAIN OUTCOME MEASURES: Whether hospitals meet the requirements for being a 'centre' or a 'unit' for gynaecological cancer and whether gynaecologists manage ovarian or cervical cancer according to the guidelines. RESULTS: Stage was recorded in the notes of 53% (262/492) of women with ovarian cancer but information to assist in determining stage was recorded in 86%. Of women who had a stage recorded by the consultant, who should have had a laparotomy and be referred for chemotherapy, 81% (169/209) were managed according to the guidelines, ignoring whether there was removal of disease to nodules of less than 1 cm. Stage was recorded in the notes of 60% (188/315) of women with cervical cancer, although information relevant to staging the patient was recorded in 66%. Overall 76% (142/188) of women with stage recorded in the notes were managed according to the guidelines but 40% (127/315) of women audited were not assessable. Only one site met the criteria for being a cancer centre. Of the remaining sites, most striking was the inability to assemble a team of professionals, including a radiologist, a pathologist and an oncology nurse to discuss individual patient care. CONCLUSIONS: Retrospective note audits will be hampered by missing data in the clinical record until systems are developed to improve the quality of notes. This research suggests that guidelines based on FIGO staging for the management of ovarian and cervical cancer are not followed and that this may be associated with incomplete cancer management teams.

Adult↗
PubMed2003

Development of an evidence-based algorithm for the management of cervical cancer.

OBJECTIVE: To develop a description of the management of cervical cancer to support locally developed, regional guidelines and to identify the level of primary research evidence to support it. DESIGN: Development of a flow-charted algorithm, using regional guidelines and clinician consensus. A Medline literature search for primary research was done to validate the algorithm and selection of papers, to verify if they were valid according to pre-defined criteria and to compare algorithm management with an alternative. MAIN OUTCOME MEASURE: The highest level of evidence for algorithm management was based on the design of the supporting research. RESULTS: Twenty percent of the algorithm is supported by level I evidence (randomised controlled trials), 70% by level II evidence (cohort studies) and 10% by level IV evidence (expert opinion or case series). Level II evidence supports the management of Stage Ia, squamous cell carcinoma by cone biopsy or a simple hysterectomy. This level of evidence also applies to research on the management of Stages Ib-IIa, by radical hysterectomy and pelvic lymphadenectomy followed by radiotherapy, if the lymph nodes are positive. Radiotherapy to treat Stages IIb-IV cervical cancer is supported by level I evidence. The management of Stage I adenocarcinoma is supported by level II evidence. CONCLUSIONS: Evaluations of the effect of informing clinicians of the strengths of the proposed management are now required, as constructing evidence-based algorithms is worthwhile, only if they are likely to affect clinical practice.

Adenocarcinoma↗
PubMed1999

IL-2 enhances standard IFNgamma/LPS activation of macrophage cytotoxicity to human ovarian carcinoma in vitro: a potential for adoptive cellular immunotherapy.

OBJECTIVE: The objective was to evaluate the enhancement of human peritoneal macrophage cytotoxic in vitro activity by the addition of interleukin-2 (IL-2) to the standard interferon gama (IFNgamma) and lipopolysaccharide (LPS) activation procedure used for cellular adoptive immunotherapy in a human ovarian cancer system. This cytotoxic effect of these activated macrophages was tested on cells from ovarian cancers of various stages, histology type, and grade, both prior to chemotherapy and at recurrence, in ovarian carcinoma cells lines and normal cells. Increased activation of the macrophage may make it a better candidate for intraperitoneal cellular adoptive immunotherapy as a component of ovarian cancer therapy. This was not a study of the mechanism of macrophage killing. METHODS: Ascites specimens were collected from 24 ovarian cancer patients at the time of surgery or by paracentesis. The mononuclear cell fraction was isolated by discontinuous density gradient centrifugation and used as a cellular source of peritoneal macrophages (PMs) and primary cultured ovarian cancer cells. PMs were separated by 1-h adhesion followed by intensive washing to remove floating cells. The floating cells were cultured for 24 h which left the cancer cells attached after unattached cells were removed by washing. These cells formed a monolayer of cancer cells, which could be subcultured in 22 patients. The cells from the third to fifth passages were used as target cells without coculture with other cells. PMs were identified by latex ingestion, and their purity after isolation by adhesion culture was tested by flow cytometry and immunofluorescence. PMs were activated by culturing in the presence of IFNgamma, with or without IL-2, for 18 h followed by the addition of LPS 6 h prior to use as effector cells in cytotoxicity assays. Ovarian cancer cells of both established cell lines and primary cultures were labeled with (51)Cr and utilized as target cells to quantitatively measure PM-mediated cytotoxicity. Ovarian cancer cells were also cocultured with PMs for morphologic observations to provide supporting evidence to the cytotoxicity assays. RESULTS: IL-2 enhances the cytotoxicity of the standard IFNgamma/LPS macrophage activation in this system. Peritoneal macrophages so activated are cytotoxic to autologous and allogenic primary cultured ovarian tumors and to ovarian carcinoma cell lines. The macrophages are cytotoxic to cells both prior to treatment and at recurrence, but the data from the few recurrent patients did reach statistical significance. This cytotoxicity is not MHC associated. Normal cells are minimally affected. CONCLUSIONS: IL-2 augmented the standard IFNgamma/LPS method of activating peritoneal macrophage cell killing of human ovarian cancer cells in this in vitro system. The cell killing occurred with autologous and allogenic tumor cells from patients with primary and possibly recurrent tumors. Activated PMs minimally affected the normal cells tested. This enhanced activation may improve the disappointing results of previous adoptive cellular immunotherapy human trials and should be considered for ovarian cancer clinical trials.

Adult↗
PubMed1999

Cholera toxin-induced alteration of the phenotype and behaviour of an ovarian carcinoma cell line, SR8.

Cholera toxin (CT) has been reported to cause a variety of effects on several different cell types. Recently, CT has been shown to increase the susceptibility of ovarian carcinoma cells to cytotoxicity mediated by a variety of effector cells (natural killer, lymphokine-activated killer cells and tumour-associated lymphocytes derived from ascites of ovarian cancer patients) of both autologous and allogenic background. In the present study, CT demonstrated several effects on a newly established ovarian carcinoma line (SR8)1 when added to the culture medium at a concentration of 12.5 ng/mL for 2 days. Cholera toxin altered SR8 morphology to a uniform polygonal cellular shape, with less cell dispersion than the non-CT treated cells. Cholera toxin prolonged the population doubling time by approximately 10 h. The CT-treated SR8 cells exhibited reduced epidermal growth factor receptor expression (39 versus 50%), and increased carbohydrate antigen 125 expression (45 versus 2%) in both immunocytochemical and quantitative flow cytometric analyses. These changes in morphology and tumour marker expression were reversible when CT was removed from the culture. The CT-treated SR8 cells showed reduced capacity to generate tumours in female nude mice in comparison with non-CT treated cells, which produce both subcutaneous and intraperitoneal xenografts with local invasion in an animal model. Cytogenetic analysis of the cell line SR8 before and during treatment with CT showed no new clonal rearrangements. The possible mechanisms involved and the influence of CT on the biological behaviour of ovarian tumour cells are discussed.

Animals↗
PubMed1998

Variations in the management and survival of women with endometrial cancer in south east England.

OBJECTIVES: To compare the management of women with endometrial cancer to locally developed clinical guidelines, and to examine the factors influencing their survival. STUDY DESIGN: Observational study in seven districts of the South East Thames Regional Health Authority. RESULTS: 133 women were diagnosed with endometrial cancer. 40 (30%) women had all appropriate staging investigations, stage was stated in the notes for 38 (29%) women, and 42 (32%) women were treated appropriately. Forty-three (32%) women died during the study period. Histology of adenocarcinoma, stage I disease, appropriate surgery/radiotherapy, good differentiation of tumour and depth of myometrial invasion less than two-thirds were significantly associated with increased survival. CONCLUSIONS: In addition to the usual clinical variables, appropriate treatment was associated with increased survival. Adherence to the guidelines for both treatment and staging was low, so ways of improving compliance with guidelines need to be found.

Adenocarcinoma↗
PubMed1997

Tumor lymphocytes in patients with advanced ovarian cancer: changes during in vitro culture and implications for immunotherapy.

Tumor specimens and ascites of patients with advanced ovarian cancer were utilized to obtain both primary ovarian carcinoma cell cultures and lymphocytes: tumor-infiltrating lymphocytes (TILs) from solid tumor tissue and tumor-associated lymphocytes (TALs) from peritoneal fluid. Tumor lymphocytes were grown in coculture with autologous tumor cells and recombinant human IL-2 (rhIL-2) for up to 4 weeks and at weekly intervals these were examined with respect to phenotype and cytotoxicity. The phenotype was studied using flow cytometry for a variety of human immunocompetent cell surface markers (CD3, CD4 CD8, CD16, CD56, TCR alphabeta, TCRgammadelta). Cytotoxicity was investigated using 4-hr 51Cr-release assays with the primary ovarian carcinoma cell cultures and the K562 cell line as target cells. The tumor lymphocytes did not demonstrate any obvious trend in phenotype changes during culture, although for different cultures a large range was noted for the various lymphocyte populations studied. Cytotoxicity against both autologous and allogeneic targets declined with culture length for the majority (6/7) of the lymphocyte cell lines tested (greatest at 1 week and least at 3 weeks). These initial results indicate that an in vitro non-MHC-restricted cytotoxic function of peritoneal lymphocytes can be effectively activated with IL-2 and autologous tumor cells. However, if activated lymphocytes are to be employed as a form of immunotherapy, they should be given within the first week of culture for maximum cytotoxic effect.

Cytotoxicity, Immunologic↗
PubMed1997

Management and survival of ovarian cancer patients in south east England.

The aim of this study was to audit the effect of adherence to regionally developed guidelines on survival in women with ovarian cancer. A prospective audit of 118 newly diagnosed cases of ovarian cancer in seven district health authorities of South East Thames, U.K. was undertaken. Appropriateness of clinical investigation and management and survival by type of hospital were examined: 118 incident cases were registered in 1991 for the audit. The mean age of the women was 61.29 years (S.D. 14.24) (range 27-92). 25 (21%) were stage I, 15 (13%) stage II, 77 (66%) stage III/IV. 62 (53%) women had the appropriate pre-operative investigations and 75 (64%) were staged in the notes. Management took place in hospitals treating as few as 1 case a year. Overall, 47 (43%) women were appropriately managed which was influenced by type of hospital of surgery (19 (66%) teaching, 20 (45%) non-teaching with oncology support, 8 (28%) non-teaching (P = 0.02). 64 women (54% died by 1 June 1994) (mean follow-up 2.1 years) (minimum 2.41 years, maximum 3.41 years). In multiple regression analysis, death was significantly more likely in women who had been inappropriately managed, those with more advanced disease and those with postoperative complications. This audit indicates that despite the development of guidelines, investigation and management of ovarian cancer varied considerably between hospitals. Management of this cancer of intermediate incidence occurs in hospitals managing as few as 1 case per year. Pre-operative and operative management was inappropriate for the majority of women and this significantly influenced survival. These data have implications for the purchasing of cancer services for this disease.

Adult↗
PubMed1997

Detection of human papillomavirus type 16 early-gene transcription by reverse transcription-PCR is associated with abnormal cervical cytology.

Human papillomavirus type 16 (HPV-16) is associated with abnormal Papanicolou smears, indicative of cervical intraepithelial neoplasia. HPV-16 is the most common genital HPV and is found in up to 40% of young women with normal cervical cytology. In order to investigate whether transcriptionally active HPV-16 infection is associated with abnormal cervical smears, a reverse transcription-nested PCR assay with primers from the E5 open reading frame was developed to detect all HPV-16 early-region mRNA (E-mRNA) transcripts. It was used to study HPV-16-infected women with normal and abnormal cervical cytologies to obtain evidence of active infection. Among HPV-16 DNA-positive women, HPV-16 E-mRNA was detected in 15 of 37 (40.5%) women with abnormal cervical cytology but in only 4 of 35 (11.4%) women with normal cytology (P = 0.007). Thus, HPV-16 E-mRNA transcription is associated with abnormal cervical smears and may have value as a prognostic marker of progressive disease.

Adult↗
PubMed1997

Heat-shock protein 27 (HSP27) and its role in female reproductive organs.

Heat shock, other environmental and pathophysiological stress stimulate synthesis of heat shock proteins (HSP) family. These proteins enable the cell to survive and recover from stressful conditions but as yet incompletely understood mechanisms. Beside its role in thermotolerance, it plays a role in cell proliferation and drug resistance which makes this protein of special clinical interest. Published data suggest that HSP27 is related to estrogen in breast and to estrogen and progesterone in the endometrium. It has been shown that some but not all estrogen positive breast cancers express HSP27, and overexpression has been associated with the degree of tumor differentiation, and response to hormonal therapy (Tamoxifen). In endometrial carcinomas, the presence of HSP27 is correlated with the degree of tumor differentiation as well as with the presence of oestrogen and progesterone receptors. Studies suggest that detection of HSP27 in endometrial carcinoma, should not be considered as a method for identifying hormone-responsive tumors or indicator or presence of estradiol receptors. In the cervix HSP27 is a marker of cell differentiation, and is highly expressed during the process of squamous metaplasia. Expression in the ovary is still controversial and requires further confirmation of recent observations.

Breast↗
PubMed1997

Relationship between human papillomavirus infection and overexpression of p53 protein in cervical carcinomas and lymph node metastases.

Overexpression of p53 protein is common in cervical carcinoma. We investigated archival biopsies from 26 cervical cancer patients (24 with available lymph nodes) to determine the relationship between p53 overexpression and HPV infection at the cervix and lymph nodes. Twelve cervical carcinoma patients had p53 protein in cervical biopsies detectable by immunohistochemistry using monoclonal antibody DO-1, and 22 were positive for HPV DNA in polymerase chain reaction assays (16, contained HPV-16; 3, HPV-18; and, 3 HPV-X). Seven cervical cancer patients had one or more lymph nodes positive for p53 protein, and all but one of these were concordantly p53 positive at the cervix. However, detection of p53 protein in cervical biopsies was predictive neither of the expression of p53 at draining lymph nodes (P > 0.1) nor of the occurrence of metastases (P > 0.1). Fourteen patients were positive at one or more lymph nodes for HPV DNA. Cervical positivity for HPV DNA was associated significantly with concordant HPV positivity at the lymph nodes (P = 0.039) and was predictive of metastases (P = 0.019). There was no association between positivity for p53 and for HPV DNA at primary cervical carcinomas or at the lymph nodes (all P > 0.1). We conclude that, although detectable p53 protein is a common feature of cervical carcinomas, it is not predictive of metastases and is independent of HPV infection.

Adolescent↗
PubMed1997

Effect of combined nitrogen on the expression of nitrate reductase and nitrite reductase in Azorhizobium caulinodans.

In aerobically grown Azorhizobium caulinodans strain IRBG 46, in vivo expression of nitrate reductase (NR) and nitrite reductase (NiR) requires the presence of either nitrate or nitrite. On the contrary mere microaerobic conditions are sufficient for the expression of NR and NiR, however, addition of nitrate to the growth medium enhanced the activities of the enzymes. Optimum concentration of nitrate for maximum expression of NR and NiR activities was different in aerobic and microaerobic conditions. Nitrite was released into the medium both in aerobic and microaerobic conditions beyond a particular concentration of nitrate in the medium. Dissimilatory nitrate reduction was affected to a lesser extent by ammonium compared to assimilatory nitrate reduction.

Nitrate Reductase↗