Dual malignancy: a rare presentation of synchronous periampullary carcinoma with renal cell carcinoma

The occurrence of synchronous pancreatic cancer and other primary cancer is not frequent and reaches about 5.6% as reported in autoptic studies. Double resections of the pancreas with another organ due to synchronous malignancies have been published only in quite sporadic sets of cases or individual case reports. We present a case report of a 40 years lady who presented with intermittent pain, fever and jaundice for 15 days. Examination revealed a palpable gall bladder, firm in consistency and tender to touch. She was admitted with a provisional diagnosis of cholangitis and started on intravenous antibiotics. Patient’s clinical condition improved and she was planned for a CECT and MRCP which revealed an heterogenously enhancing mass lesion in upper pole of left kidney, s/o of renal cell carcinoma (RCC) and an enhancing lesion in periampullary region s/o periampullary carcinoma with no evidence of free fluid or metastasis. ERCP guided biopsy revealed moderately differentiated adenocarcinoma and USG guided renal biopsy revealed clear cell carcinoma. Whipple’s procedure with left nephrectomy was performed. Intra operative findings revealed post-operative course and hospital stay was uneventful. Biopsy revealed poorly differentiated pancreaticobiliary adenocarcinoma with no lympho vascular or lymph nodal invasion (pT3aN0) and left sided clear cell renal carcinoma with no lympho vascular invasion (pT1N0). Synchronous malignancy of pancreas and kidney is a very rare presentation. Literature describes presence of RCC with periampullary metastasis and patients presenting with RCC post whipple’s procedure but only a handful of case reports describe presence of dual malignancy as reported above.

A multicenter study to confirm further diagnostic value of strain ratio method giving to 5-point scoring by elastography for differentiation of breast lesions / 中华超声影像学杂志

Objective To confirm whether strain ratio should be added after evaluation of lesions with 5-point elasticity scoring for differentiating breast lesions on ultrasonic elastography(UE).Methods Eight hundred and forty-six consecutive female patients with 1 071 breast lesions were recruited into a multicenter retrospective study,which involved 8 centers across China.All the patients underwent the UE procedure and the strain ratios were calculated.The sensitivity,specificity,accuracy,PPV and NPV were calculated for each of the two evaluation systems and the areas under the ROC curve were compared.Results The strain ratios of 559 benign lesions(2.7±1.4)and 512 malignant lesions(8.1±5.9)were significantly different (P<0.001).When the cutoff point was 3.03,strain ratio method had 81.6% sensitivity,89.7% specificity,81.7% accuracy,80.2% PPV and 84.2% NPV.The areas under the ROC curve with the strain ratio method and 5-point scoring method were 0.865 and 0.862,respectively(P =0.622).For the lesions with elasticity score 3 and 4,the areas under the ROC curve of the two Methods were 0.71 1 and 0.629, respectively(P = 0.020).Conclusions Although the two UE Methods have similar diagnostic performance,separate calculation of the strain ratios seems compulsory,especially for the lesions with elasticity score 3 and 4.

Prevalence of human papillomavirus infection & cervical abnormalities in HIV-positive women in eastern India.

Background & objectives: India has the third highest burden of HIV and highest number of cervical cancer in the world. A cross-sectional study was performed to determine the prevalence and types of human papillomavirus (HPV) infection, and the factors associated with HPV infection and abnormal cervical cytology in HIV-positive women attending the Antiretroviral Therapy (ART) Centre in a tertiary care hospital in eastern India. Methods: We screened 216 HIV- positive women with Papanicolau smear cytology and HPV testing. HPV DNA was detected by using consensus primers followed by sequencing. Results: Of the 216 HIV-positive women screened, 58 (26.85%) were HPV-positive; 56 (25.9%) were of high-risk (HR) HPV type. The most prevalent HPV type was HPV-16 (7.9%); non 16 and 18 HPV types were present in 17.6 per cent patients. Age ≤ 35 yr [(OR), 2.56 (1.26-5.19)], illiteracy [OR, 2.30 (1.19-4.46)], rural residence [OR, 3.99 (1.27-12.56)] and CD4 ≤350/μl [OR, 2.46 (1.26-4.83)] were associated with increased risk of acquisition of HPV. One hundred thirty nine (74.33%) patients had normal/ negative for intraepithelial lesions (NILM) cytology, three (1.60%) had atypical squamous cells of undetermined significance (ASCUS), 32 (17.11%) had low-grade squamous intraepithelial lesions (LSIL), 10 (5.35%) had high-grade squamous intraepithelial lesions (HSIL) and three (1.60%) had carcinoma cervix. WHO clinical Stage III and IV [OR, 2.83 (1.07-7.49)] and CD4 ≤350/μl [OR, 2.84 (1.30-6.20)] were risk factors for abnormal cytology. Interpretation &conclusions: Our study showed 26.85 per cent HPV positivity in HIV infected women in this region, with HPV-16 as the commonest genotype. Abnormal cervical cytology was seen in about 25 per cent women. Regular Pap smear screening as recommended by the National AIDS Control Organization will help in early detection of cervical abnormalities in HIV- positive women.

Determinants of survival in adult HIV patients on antiretroviral therapy in Eastern Uttar Pradesh: A prospective study.

Background & objectives: The National AIDS Control Organization (NACO) of India has been providing free ARV (antiretroviral) drugs since 2004. by 2012, 486,173 patients had received treatment through the antiretroviral therapy (ART) centres. The objective of this observational study was to assess the factors determining survival of patients on ART under routine programme conditions in an ART centre in north India five years after its inception. Methods: Treatment naive HIV positive patients who were enrolled in the ART centre between May 2009 and May 2010 and started on ART as per the Revised NACO guidelines 2009, were included in the study and outcome was assessed after two years of follow up. Results: A total of 1689 patients were included in the analysis, of whom 272 (16.10%) expired, 205 (12.13%) were lost to follow up (LFU), 526 (31.14%) were transferred out to other facilities and 686 (40.63%) were alive at the end of two years. Majority (92%) of the deaths occurred in the first six months of therapy. Age >30 yr, male gender, poor functional status, haemoglobin level <11 g/dl, body weight <45 kg and CD4 count <100/μl at baseline had significantly higher relative hazard of death. Most LFU also occurred in the first six months and these patients had significantly low CD4 count, weight, haemoglobin level and higher number of patients in Stages III and IV as compared to those who survived. Interpretation & conclusions: The study findings revealed poor survival in the first six months of therapy especially in those with severe immunosuppression. This emphasizes the need for early enrolment into the programme. The high LFU occurring early after initiation of therapy suggests the urgent need to build an efficient patient retrieval system in the programme.

Clinical profile, risk factors and aetiology of young stroke: a tertiary care hospital based study from the Sub-Himalayan region in North India.

Background: Rapid urbanisation of rural areas is predicted to increase the incidence of risk factors for vascular events like stroke. There is scarcity of literature addressing issue of stroke from Sub-Himalayan region in North India. Methods: The study was conducted in the department of medicine, R. P. govt. medical college, Kangra, Himachal Pradesh. Consecutive patients between the age of 15-45 years presenting with signs and symptoms of stroke in a duration of one year were included in the study. CT scan-head and lipid profile was done in all patients. Other relevant investigations to rule out aetiology were undertaken. Results: Thirty two patients with the mean age of 41.1 ± 5.41 years were recruited. The incidence of stroke in young forming 8.55% of the total stroke patients (374). There were larger proportion of male patients with a ratio of 3:1.16 patients (50%) presented between 6 am and 12 pm in the morning hours of day. Maximum patients presented in winter months from November to January. Average delay of presentation to hospital was 30.8 hours. 19 patients (59.3%) presented with infarct. Most common symptom reported was weakness in 18 (56.2%). Predominant traditional risk factors observed was hypertension in 18 (53.1%). Hyperhomocysteinemia was seen in 4 patients (12.5%). Primary antiphospholipid antibody syndrome was seen in 2 (6.25%). Conclusion: This study demonstrated predominant presence of conventional risk factors in young strokes. There was substantial time delay of presentation. Majority of patients presented in winter months. Prevention of vascular risk factors as well as issue of factors leading to delay in presentation needs to be addressed.

Ethical research is grounded in quality data: a clinical data management workshop in Varanasi.

Research ethics is closely related to scientific and methodological standards. A research project involving human participants is never ethical if it is not scientifically and methodologically sound in the first place. Clinical data management, despite often being perceived as “just” a technical methodological service, plays in fact a key role in ensuring that data collected within a medical research are true, accurate and reliable; that subjects’ privacy and confidentiality are duly ensured, and that the study findings will serve the interests of individual and public health.

Recent advances in the diagnosis and treatment of kala-azar.

In India, about 100 000 cases of visceral leishmaniasis (VL) or kala-azar are estimated to occur annually, 90% of which occur in the state of Bihar. Currently, antibody-based tests such as the rK39-based immunochromatographic strip test and the direct agglutination test (DAT) are widely used for the diagnosis of VL. However, their major drawback is continued positivity both long after cure and in a high proportion of individuals living in endemic areas. Thus, antibody-based tests must always be used in combination with a standardized clinical case definition for VL. There have been many breakthroughs in the past decade in the treatment of kala-azar in India, such as approval of oral miltefosine and paromomycin, single-dose treatment with liposomal amphotericin B and multidrug treatment. Encouraged by these advances, an ambitious VL elimination programme was launched with the aim to eliminate VL as a public health problem in India, Nepal and Bangladesh by 2015. Early diagnosis, complete treatment of cases, integrated vector management, effective disease surveillance, and clinical and operational research should be the five key components of the strategy to achieve this goal.

How do health care providers deal with kala-azar in the Indian subcontinent.

Background & objectives: Three countries, Bangladesh, India and Nepal, set out to eliminate kala-azar by 2015. This study was aimed to document the knowledge and practices in kala-azar case management of public and private health providers in these three countries. Methods: A health care provider survey was conducted in 2007 at 4 study sites, viz., Muzaffarpur and Vaishali districts in India, Mahottari district in Nepal, and Rajshahi district in Bangladesh. Interviews were conducted with formal and informal health care providers at their home or practice. Results: About half of the providers in India and Nepal knew the rapid diagnostic test rK39 recommended by the elimination initiative, but this was not in Bangladesh. Knowledge of the recommended first-line drug, miltefosine, was good in India and Nepal but less so in Bangladesh. Interpretation & conclusions: Innovative tools for VL care have not yet been fully taken up by private for profit care providers in the three countries that launched a VL elimination initiative. The elimination initiative needs to address these gaps in private providers’ knowledge, given their substantial share in the care of VL patients.

High incidence of zidovudine induced anaemia in HIV infected patients in eastern India.

Background & objectives: Zidovudine (ZDV) is the preferred nucleoside reverse transcriptase inhibitor in the first line antiretroviral regimen in India. It is known to be associated with life threatening toxicity like anaemia. This study was aimed at determining the prevalence of ZDV induced anaemia in HIV infected patients initiated on ZDV containing antiretroviral therapy regimen and also to find out the correlates, if any, for causing ZDV induced anaemia. Methods: This retrospective study was carried in ART Centre, Sir Sunderlal Hospital, Banaras Hindu University, Varanasi between March 2005 to December 2007. HIV infected patients registered at ART Centre were treated according to guidelines of National AIDS Control Organization (NACO). Patients (n=1256) with haemoglobin (Hb) >8 g/dl were prescribed ZDV based antiretroviral therapy regimens. Patients developing anaemia (<8 g/dl) with other causes of anaemia excluded were recorded. Correlation of baseline characteristics (age, gender, haemoglobin levels, weight, CD4 counts and WHO clinical stage) with risk of developing anaemia was also calculated. Results: Two hundred three (16.2%) patients on ZDV regimen developed anaemia (<8 g%); 7.9 per cent (n=100) of these developed severe anaemia (<6.5 g%). Females were more prone to develop anaemia (P=0.026). Age, weight, WHO clinical stage and CD4 counts had no relation to development of anaemia. Interpretation & conclusion: High incidence of ZDV induced anaemia seen in this study indicates regular monitoring of patients, particularly women on ZDV based antiretroviral regimens.

Ultrasonography for diagnosis of abdominal tuberculosis in HIV infected people.

Background & objectives: There is an increasing incidence of abdominal tuberculosis with the advent of HIV infection. This study was aimed at determining the pattern of presentation of abdominal tuberculosis on ultrasonography (USG) in HIV positive patients. Methods: This retrospective study was carried at the ART Centre, Sir Sunderlal Hospital, Banaras Hindu University, Varanasi, between March 2005 to July 2007. HIV positive patients (n=2453) with prolonged fever, abdominal pain/distension, altered bowel habits and diarrhoea underwent ultrasonography for tuberculosis of abdomen. The different ultrasonological findings in abdominal tuberculosis were noted. CD4 counts of these patients were also recorded. Results: Of the total 2453 patients, 244 showed findings suggestive of abdominal tuberculosis. Lymphadenopathy with predominantly hypoechoic/necrotic echotexture was seen in 158/244 (64.8%) patients. Splenomegaly was seen in 68 patients with 61 of them (89.7%) showing multiple hypoechoic lesions in the parenchyma. 53 of 244 (21.7%) showed extensive abdominal involvement. Liver enlargement was seen as a part of extensive abdominal involvement. A total of 203 patients completed antitubercular treatment, of which 198 (97.5%) showed resolution of lesions in USG. CD4 counts in patients with extensive abdominal involvement were lowest compared to CD4 count in patients with others USG findings. Interpretation & conclusion: Ultrasonological findings like lymphadenopathy (≥1.5 cm) with hypoechoeic/necrotic echotexture, hypoechoic splenic lesions and extensive abdominal involvement in HIV infected patients may be suggestive of abdominal tuberculosis.

Effect of untreated bed nets on blood-fed Phlebotomus argentipes in kala-azar endemic foci in Nepal and India

Observational studies in the Indian subcontinent have shown that untreated nets may be protective against visceral leishmaniasis (VL). In this study, we evaluated the effect of untreated nets on the blood feeding rates of Phlebotomus argentipes as well as the human blood index (HBI) in VL endemic villages in India and Nepal. The study had a "before and after intervention" design in 58 households in six clusters. The use of untreated nets reduced the blood feeding rate by 85 percent (95 percent CI 76.5-91.1 percent) and the HBI by 42.2 percent (95 percent CI 11.1-62.5 percent). These results provide circumstantial evidence that untreated nets may provide some degree of personal protection against sand fly bites.

Functionality of drug efflux pumps in antimonial resistant Leishmania donovani field isolates.

The recent upsurge of antimony (Sb) resistance is a major impediment to successful chemotherapy of visceral leishmaniasis (VL). Mechanisms involved in antimony resistance have demonstrated an upregulation of drug efflux pumps; however, the biological role drug efflux pumps in clinical isolates remains to be substantiated. Thus, in this study, the functionality of drug efflux pumps was measured in promastigotes and axenic amastigotes isolated from VL patients, who were either Sb-sensitive (AG83, 2001 and MC9) or resistant (NS2, 41 and GE1) using rhodamine123 as a substrate for multidrug resistant (MDR) pumps and calcein as a substrate for multidrug resistance-associated proteins (MRP) respectively; their specificity was confirmed using established blockers. Sb-resistant (Sb-R) isolates accumulated higher amounts of R123, as compared to Sb-sensitive (Sb-S) isolates. Verapamil, a MDR inhibitor failed to alter R123 accumulation, suggesting absence of classical MDR activity. In Sb-R isolates, both promastigotes and axenic amastigotes accumulated significantly lower amounts of calcein than Sb-S isolates and probenecid, an established pan MRP blocker, marginally increased calcein accumulation. Depletion of ATP dramatically increased calcein accumulation primarily in Sb-R isolates, indicating existence of a MRP-like pump, which was more active in Sb-R isolates. In conclusion, our data suggested that overfunctioning of a MRP-like pump contributed towards generation of Sb-R phenotype in L. donovani field isolates.

Visceral leishmaniasis - current therapeutic modalities.

Major therapeutic obstacles in the treatment of visceral leishmaniasis (VL) include the alarming increase in antimonial unresponsiveness especially in Bihar, India and relapses in HIV-Leishmania co-infected patients. The therapeutic armamentarium for VL is currently plagued with several limitations as the available drugs are toxic, majority are effective only parenterally and need to be administered for extended periods. The first orally effective drug, miltefosine has been approved for treating VL. In antimony refractory zones, pentavalent antimony has been largely replaced by amphotericin B deoxycholate, but prolonged hospitalization, toxic effects, and requirement for monitoring greatly hamper its widespread application in endemic regions. Lipid formulations of amphotericin B, a remarkable advance in amphotericin B therapy, have greatly reduced toxicity enabling large doses to be delivered over a short period. Even a single dose treatment with liposomal amphotericin B cures > 90 per cent patients; however, the stumbling block is its prohibitive cost that precludes its widespread accessibility in endemic countries. Studies using paromomycin in VL are encouraging, and judging by the preliminary results of a recently concluded phase III trial, it could be an extremely useful and affordable antileishmanial drug. Other orally effective drugs include the azoles and allopurinol but these have met with limited success owing to either poor efficacy or unacceptable toxicity. Sitamaquine has undergone limited evaluation, and the data suggest effective antileishmanial activity; its role has to be delineated for which additional developmental studies are proposed. This review highlights the progress made in the treatment of VL, including the multiple mechanisms of action of antileishmanial drugs with a view to enable the researcher to undertake the challenge of providing affordable and effective chemotherapy.