Sanjay Thulkar

Best Supportive Care Compared With Chemotherapy for Unresectable Gall Bladder Cancer: A Randomized Controlled Study

PURPOSE We designed this study to evaluate efficacy of modified gemcitabine and oxaliplatin (mGEMOX) over best supportive care (BSC) or fluorouracil (FU) and folinic acid (FA) in unresectable gall bladder cancer (GBC). PATIENTS AND METHODS Patients with unresectable GBC were enrolled for single center randomized study. Arm A, BSC; arm B, FU 425 mg/m(2) and FA 20 mg/m(2) intravenous (IV) bolus weekly for 30 weeks (FUFA); arm C, gemcitabine 900 mg/m(2) and oxaliplatin 80 mg/m(2) IV infusion on days 1 and 8 every 3 weeks for maximum of six cycles. Eighty-one patients were randomly assigned, arms A (n = 27), B (n = 28), and C (n = 26). RESULTS Complete response plus partial response in the three groups was 0 (0%), four (14.3%), and eight (30.8%) respectively (P < .001). Two patients in the mGEMOX arm and one patient in the FUFA arm underwent curative resection after chemotherapy. One patient in the mGEMOX arm had complete pathologic response. Median overall survival (OS) was 4.5, 4.6, and 9.5 months for the BSC, FUFA, and mGEMOX arms (P = .039), respectively. Progression-free survival (PFS) was 2.8, 3.5, and 8.5 months for the three groups (P < .001). There was no difference in grade 3/4 toxicities in the chemotherapy arms except transaminitis, which was more prevalent in mGEMOX arm (P = .04). Two patients in the FUFA arm and 10 patients in the mGEMOX arm had grade 3 or 4 myelosuppression. Two patients in the mGEMOX group had neutropenic fever that resolved with antibiotics. CONCLUSION This randomized controlled trial confirmed the efficacy of chemotherapy (mGEMOX) compared with BSC and FUFA in improving OS and PFS in unresectable GBC.

Malignant peripheral nerve sheath tumors (MPNST)--clinicopathological study and treatment outcome of twenty-four cases.

BackgroundMalignant peripheral nerve sheath tumor (MPNST) is biologically an aggressive tumor for which the treatment of choice is the surgery. We reviewed the clinical profile, diagnostic methods, treatment patterns, and outcome of twenty-four MPNST patients in this study.Patients and methodsA retrospective analysis of 24 MPNST patients, treated from 1994 to 2002, in the department of Surgical Oncology at All India Institute of Medical Sciences, New Delhi, was done. A combination of gross, histopathological and immunohistochemical findings, and proliferation markers (MIB1) were considered for diagnosis and grade of the MPNST. Survival analysis was done by the Kaplan-Meier method and differences were evaluated with the log-rank test. Multivariate analysis was carried out by using Coxs proportional hazards model by using SPSS (Version 9, Chicago, Illinois) software.ResultsMPNST constituted 12% of all soft tissue sarcomas, where 21% (5/24) of patients had associated Von Recklinghausens disease (VRHD). A higher incidence of male preponderance and multifocal MPNST were noted in the present series. At a mean follow-up of 38 months, 13 (54 %) patients had relapse of disease and 5-year over all and disease free survival were 58% and 35% respectively. In univariate analysis, sex (p = 0.05), tumor depth (p < 0.03), and cellular differentiation (p < 0.002) were shown to be adverse prognostic factors for disease free survival and sex (p = 0.04), cellular differentiation (p < 0.0004), and tumor grade (p = 0.05) for overall survival. However, in multivariate analysis, cellular differentiation (p < 0.005) and tumor grade (p < 0.01) emerged as independent prognostic factors for both disease free and overall survival, respectively. Postoperative radiotherapy (RT) has shown a definite role in both disease free and overall survival in this study.ConclusionMPNSTs constituted a significant proportion (12%) of soft tissue sarcoma in our medical center. Heterogeneous differentiation and multifocality of the tumor were few distinct features of MPNST. Sex and cellular differentiation were noticed as the new adverse prognostic factors and adjuvant radiotherapy has been proved to be a significant treatment tool in the current series.

Early Clinical Outcomes and Toxicity of Intensity Modulated Versus Conventional Pelvic Radiation Therapy for Locally Advanced Cervix Carcinoma: A Prospective Randomized Study

PURPOSE To evaluate the toxicity and clinical outcome in patients with locally advanced cervical cancer (LACC) treated with whole pelvic conventional radiation therapy (WP-CRT) versus intensity modulated radiation therapy (WP-IMRT). METHODS AND MATERIALS Between January 2010 and January 2012, 44 patients with International Federation of Gynecology and Obstetrics (FIGO 2009) stage IIB-IIIB squamous cell carcinoma of the cervix were randomized to receive 50.4 Gy in 28 fractions delivered via either WP-CRT or WP-IMRT with concurrent weekly cisplatin 40 mg/m(2). Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events, version 3.0, and late toxicity was graded according to the Radiation Therapy Oncology Group system. The primary and secondary endpoints were acute gastrointestinal toxicity and disease-free survival, respectively. RESULTS Of 44 patients, 22 patients received WP-CRT and 22 received WP-IMRT. In the WP-CRT arm, 13 patients had stage IIB disease and 9 had stage IIIB disease; in the IMRT arm, 12 patients had stage IIB disease and 10 had stage IIIB disease. The median follow-up time in the WP-CRT arm was 21.7 months (range, 10.7-37.4 months), and in the WP-IMRT arm it was 21.6 months (range, 7.7-34.4 months). At 27 months, disease-free survival was 79.4% in the WP-CRT group versus 60% in the WP-IMRT group (P=.651), and overall survival was 76% in the WP-CRT group versus 85.7% in the WP-IMRT group (P=.645). Patients in the WP-IMRT arm experienced significantly fewer grade ≥2 acute gastrointestinal toxicities (31.8% vs 63.6%, P=.034) and grade ≥3 gastrointestinal toxicities (4.5% vs 27.3%, P=.047) than did patients receiving WP-CRT and had less chronic gastrointestinal toxicity (13.6% vs 50%, P=.011). CONCLUSION WP-IMRT is associated with significantly less toxicity compared with WP-CRT and has a comparable clinical outcome. Further studies with larger sample sizes and longer follow-up times are warranted to justify its use in routine clinical practice.

Potential of magnetic resonance spectroscopic imaging in predicting absence of prostate cancer in men with serum prostate-specific antigen between 4 and 10 ng/ml: a follow-up study.

OBJECTIVES Screening for prostate cancer using serum prostate-specific antigen (PSA) determination has a positive predictive value of only 30% to 42% for a PSA level between 4 and 10 ng/mL. Magnetic resonance spectroscopic imaging (MRSI), which identifies cancer on the basis of changes in cellular metabolite levels, might be able to identify patients with noncancerous PSA elevation and help avoid unnecessary biopsies. We tested this hypothesis by evaluating the incidence of prostate cancer in men with a PSA level of 4 to 10 ng/mL and a negative MRSI study. METHODS A total of 155 men underwent a three-dimensional proton MRSI of the prostate before transrectal ultrasound-guided biopsy for clinical indications. MRSI was performed using an endorectal coil on a 1.5-T magnetic resonance scanner. Patients with no voxels positive for malignancy underwent standard sextant biopsy, and additional MRSI-targeted biopsies were obtained in men with suspicious or malignant voxels. Patients with a biopsy negative for cancer underwent repeat serum PSA estimation every 6 months for a minimum of 18 months. RESULTS Of the 155 men, 36 (mean PSA level of 6.47 ng/mL, range 4.25 to 9.9) had no malignant voxels on MRSI. None of them were positive for cancer on biopsy. Of these 36 men, 26 completed at least 18 months (mean 26.9, range 18 to 44) of follow-up. Four patients required repeat biopsies and one, with a persistently elevated PSA level was diagnosed with prostate cancer 29 months after the initial MRSI. CONCLUSIONS The results of our study have shown that prostate biopsy can be deferred in patients with an increased serum PSA of 4 to 10 ng/mL if their MRSI does not show any malignant voxels.

Transcatheter arterial embolization in the management of hemobilia

BackgroundThis retrospective analysis evaluated the clinical and radiologic results of transcatheter arterial embolization (TAE) in the treatment of significant hemobilia. The imaging findings, embolization technique, complications, and efficacy are described.MethodsThirty-two consecutive patients (21 male, 11 female, age range 8–61 years) who were referred to the radiology department for severe or recurrent hemobilia were treated by TAE. Causes of hemobilia were liver trauma (n = 19; iatrogenic in six and road traffic accident in 13), vasculitis (n = 6), vascular malformations (n = 2), and hepatobiliary tumors (n = 5). Iatrogenic liver trauma was secondary to cholecystectomy in those six patients. Four of five hepatobiliary tumors were inoperable malignant tumors and one was a giant cavernous hemangioma. Arterial embolization was done after placing appropriate catheters as close as possible to the bleeding site. Embolizing materials used were Gelfoam, polyvinyl alcohol particles or steel coils, alone or in combination. Postembolization angiography was performed in all cases to confirm adequacy of embolization. Follow-up color Doppler ultrasound and contrast-enhanced computed tomography was done in all patients.ResultsUltrasonic, computed tomographic, and angiographic appearances of significant hemobilia were assessed. Angiogram showed the cause of bleeding in all cases. Three patients with liver trauma due to accidents required repeat embolization. Eight patients required surgery due to failed embolization (continuous or repeat bleeding in four patients, involvement of the large extrahepatic portion of hepatic artery in two, and coexisting solid organ injuries in two). Severity of hemobilia did not correlate with grade of liver injury. All 13 patients with blunt hepatic trauma showed the cause of hemobilia in the right lobe. No patient with traumatic hemobilia showed an identifiable cause in the left lobe. There were no clinically significant side effects or complications associated with TAE except one gallbladder infarction, which was noted at surgery, and cholecystectomy was performed with excision of the hepatic artery aneurysm.ConclusionTAE is a safe and effective interventional radiologic procedure in the nonoperative management of patients who have significant hemobilia.

Role of (68)Ga-DOTATOC PET-CT in the diagnosis and staging of pancreatic neuroendocrine tumours.

ObjectiveThe objective of the present study was to evaluate the role of 68Ga-DOTA(0)-Phe(1)-Tyr(3)-octreotide (68Ga-DOTATOC) positron emission tomography computed tomography (PET-CT) for detection and staging of pancreatic neuroendocrine tumours (NETs).MethodsTwenty patients with clinically suspected and/or histopathologically proven pancreatic NET underwent 68Ga-DOTATOC PET-CT imaging for staging and /or localisation of primary lesion. They also underwent contrast enhanced CT (CECT) and 8 patients underwent 18F-FDG PET-CT. SUVmax of primary and metastatic lesions were measured. Results were verified with histopathology for primary tumour and with clinical follow up/MRI and /or biopsy for metastatic disease. Results of 68Ga-DOTATOC PET-CT were compared to CECT and 18F-FDG PET-CT.Results68Ga-DOTATOC PET-CT correctly localised primary in all 20, CECT in 15 and 18F-FDG PET-CT in 2 patients. 68Ga-DOTATOC PET-CT demonstrated metastases in 13 patients, CECT in 7 and 18F-FDG PET-CT in 2. 68Ga-DOTATOC PET-CT emerged as the best investigation with 100% sensitivity and PPV for detecting primary tumour and metastatic disease. The detection rate of CECT was lower than 68Ga-DOTATOC PET-CT, both for primary tumour (20vs.15) or metastatic disease (13vs.7). 18F-FDG PET-CT performed poorly for primary and metastasis.ConclusionGa-DOTATOC PET-CT is a very useful imaging investigation for diagnosing and staging pancreatic NET.

Adrenal Involvement in Non-Hodgkin's Lymphoma: Four Cases and Review of Literature

Primary adrenal non-Hodgkins lymphoma is very rare. We have seen 2 such cases among 241 cases of non-Hodgkins lymphoma (0.83%) over the past 4 years. We could detect 2 more cases who had adrenal involvement, in addition to other extra nodal disease sites. Review of English literature revealed 65 cases of primary adrenal non-Hodgkins lymphoma, most being single case reports. Salient features included—median age of 68 years (mean age of 47.25 years in our series), bilateral adrenal involvement in 60%, and predominantly diffuse large cell histology with ‘B’ cell immunophenotype. Adrenal insufficiency was present in two-thirds of the patients at diagnosis. Chemotherapy with or without radiotherapy is the mainstay of treatment. About half the patients respond to treatment, with median survival of 4 months. The high index of suspicion for early diagnosis and prompt treatment may improve outcome.

Sonographic findings in grade III dengue hemorrhagic fever in adults

Sonography has been used to evaluate children with dengue hemorrhagic fever, but to our knowledge no such studies have been conducted with adults. We present the sonographic findings in 40 adults with severe (grade III) dengue hemorrhagic fever (DHF).

Pediatric Nonlymphoblastic Non-Hodgkin Lymphoma: Baseline, Interim, and Posttreatment PET/CT versus Contrast-enhanced CT for Evaluation—A Prospective Study

PURPOSE To prospectively examine the roles of positron emission tomography (PET)/computed tomography (CT) and conventional contrast material-enhanced CT at baseline, after two cycles of chemotherapy, and after completion of chemotherapy in pediatric patients with nonlymphoblastic non-Hodgkin lymphoma (NHL) who were treated with similar standard treatment protocols. MATERIALS AND METHODS The institutional ethics committee approved the study protocol, and all patients were enrolled after written informed consent was obtained. Patients with nonlymphoblastic NHL were prospectively enrolled between January 2008 and March 2010. Patients underwent contrast-enhanced CT and PET/CT for staging and for response assessment after two cycles of chemotherapy (interim) and treatment completion. Complete metabolic response versus no metabolic response at PET/CT and complete response versus no complete response at contrast-enhanced CT was analyzed by using Kaplan-Meier survival analysis. RESULTS The final study included 34 patients with nonlymphoblastic NHL (median age, 10.5 years). Baseline PET/CT and contrast-enhanced CT showed concordance in depiction of 112 disease sites; PET/CT depicted 18 more disease sites and two fewer disease sites than contrast-enhanced CT (P = .0003). Disease in five of 34 patients was upstaged, and disease in no patient was downstaged at PET/CT. There was 100% (four of four) concordance between bone marrow involvement at biopsy and stage at PET/CT. The median length of follow-up was 20.3 months. Response at interim PET/CT and contrast-enhanced CT could not predict progression-free survival (PFS) (P = .083 and .18, respectively) or overall survival (OS) (P = .159 and.08, respectively). Posttreatment PET/CT and contrast-enhanced CT findings could predict PFS (P = .036 and .002, respectively) and posttreatment contrast-enhanced CT findings could predict OS (P = .035); however, posttreatment PET/CT findings could not predict OS (P = .067). CONCLUSION PET/CT depicts additional sites compared with contrast-enhanced CT and results in upstaging of disease. Either PET/CT or contrast-enhanced CT may be used for response assessment and prognostication in stage III or IV nonlymphoblastic pediatric NHL.

Bone scintigraphy in breast cancer: added value of hybrid SPECT-CT and its impact on patient management.

PurposeTo evaluate the incremental value of single-photon emission computed tomography—computed tomography (SPECT-CT) over planar scintigraphy and SPECT alone for equivocal bone scintigraphy lesions in patients with breast cancer and to assess its impact on patient management. MethodsA total of 102 patients with 115 equivocal lesions on planar scintigraphy underwent SPECT and SPECT-CT of selected volume. Images were evaluated in separate sessions to minimize recall bias. A scoring scale of 1–5 was used, where 1 is definitely metastatic, 2 is probably metastatic, 3 is indeterminate, 4 is probably benign, and 5 is definitely benign. With receiver operating characteristic analysis, area under the curves was constructed for each modality. Clinical/imaging follow-up and/or histopathology were taken as the reference standard. ResultsThere were 52 indeterminate lesions on planar scintigraphy, 15 on SPECT, and three on SPECT-CT. Area under the curve for SPECT-CT was significantly larger compared with planar scintigraphy (P<0.001) and SPECT (P=0.033). This improvement was mostly for lytic lesions (P<0.0001). In patients (n=67) in whom the lesions under evaluation were the only lesions and hence whose management was decided, SPECT-CT was superior to SPECT (P=0.045) and planar scintigraphy (P <0.001). ConclusionSPECT-CT is better than planar scintigraphy and SPECT alone for characterizing equivocal bone scintigraphy lesions in patients with breast cancer and can have a significant impact on patient management.