Outcome of pediatric germ cell tumor with comparison of carboplatin and cisplatin based regimens: A 10-year analysis.

Carboplatin is being advocated more frequently for treatment of childhood germ cell tumors (GCT), due to less long-term toxicity, and demonstrable equivalence in outcome as compared to cisplatin. This analysis presents the survival of GCT in a low middle-income country and compares two different chemotherapeutic regimens. A retrospective analysis of patient case records was carried out over 10-years (January 2007-December 2016). Chemotherapy regimen used was bleomycin, etoposide, and cisplatin (PEb) for initial 6-½ years and carboplatin, etoposide, and bleomycin (CEb) subsequently. Ninety patients with GCT were treated over 10-years. Malignant GCT was diagnosed in 69 (77%) patients, with 21(23%) having teratoma. The chemotherapy protocol was PEb in 38 (42%), CEb in 28 (31%) patients, while 24 patients were treated with surgery only. Stage 4 tumor was observed in 19 (21%) patients. Relapse or disease progression was seen in 11(12%). Overall and event-free survival at 5-years for the entire cohort was 77% and 73%, being similar with PEb (OS:77%; EFS:72.5%) vs. CEb (OS:69%; EFS: 69%). Significantly better overall survival was noted for patients with gonadal GCT) and non-stage 4 disease, while event-free survival was significantly better in patients with non-stage 4 disease. The chemotherapeutic regimen (PEb vs. CEb), very high AFP (value ≥10,000 IU/L), and risk stratification (low, intermediate, or high-risk disease) did not affect survival significantly. Carboplatin-based strategy was equivalent in our cohort to cisplatin-based strategy, and could be used safely in the LMIC set-up. The overall survival is suboptimal, with delayed presentation, abandonment, and relapse being barriers to survival.

Juvenile granulosa cell tumor of the ovary: A comprehensive clinicopathologic analysis of 15 cases.

OBJECTIVE: Juvenile granulosa cell tumor(JGCT) is an uncommon ovarian sex-cord stromal tumor, with diverse clinical, radiological and histopathologic features. The present study describes the clinicopathological and histomorphological spectrum of JGCTs, and highlights the key differentiating features from its mimics. METHODS: A retrospective analysis of all cases reported as JGCTs during 2011-19 (8 years) was performed with detailed evaluation of clinical, histopathologic data and follow-up details. RESULTS: Of a total 115 GCTs reported during the study period, 15(13%) were reported as JGCTs. The mean age at presentation was 17 years. Abdominal pain and distension were the most common clinical presentations. Five patients were pre-menarchal with 3 exhibiting precocious puberty. Majority of tumors were unilateral(left>right), solid-cystic, ranging in size from 4 to 20 cm. Microscopically, macrofollicular architecture was most frequent (n = 12;80%). The tumor cells depicted variable nuclear pleomorphism, small distinct nucleoli and moderate-abundant pale eosinophilic-clear/vacuolated cytoplasm. Mitotic activity ranged from 1 to 10/10HPFs. Uncommon histopathologic features included microcystic and tubulo-cystic architecture, myxoid degeneration, bizarre tumor giant cells, hob-nailing of the tumor cells, intracytoplasmic hyaline globules, multifocal calcification and thick hyalinized blood vessels. Majority(n = 12;80%) presented in stage I. Surgical treatment included unilateral salpingo-oophorectomy without any adjuvant chemotherapy, bilateral salpingo-oophorectomy (BSO) and total abdominal hysterectomy with BSO with adjuvant BEP chemotherapy (Bleomycin, etoposide, cisplatin). CONCLUSIONS: JGCT is a rare ovarian tumor affecting young women and children with diverse histopathologic features. Despite an aggressive histopathology, these tumors have a good outcome, when diagnosed at an early stage.

Survival in patients with high-risk neuroblastoma treated without autologous stem cell transplant or dinutuximab beta.

The majority of patients with high-risk neuroblastoma (HR-NB) in low- and middle-income countries (LMIC) do not have access to autologous stem cell transplant (ASCT) and dinutuximab. Consolidation with nonmyeloablative chemotherapy is not well-defined, and the outcomes are variable. We report a single-center outcome of patients with HR-NB, treated with nonmyeloablative consolidation. A tabulated compilation of similar reports is included. A retrospective chart review of patients with HR-NB was performed from January 2009 till June 2016. Patients were treated on the backbone of HR-NBL1/SIOPEN protocol. Treatment included induction with rapid-COJEC, surgery, followed by consolidation. Consolidation involved 4 cycles of topotecan, vincristine, and doxorubicin (TVD) instead of ASCT. Infusion of vincristine and doxorubicin were modified for ease and to enable administration in the clinic. Subsequent treatment included radiotherapy to the primary tumor and differentiation therapy with isotretinoin. Over 7½ years, 28 patients with HR-NB were treated. Two (7%) patients had therapy-related mortality. A relapse or disease progression occurred in 11 (39%) patients at a median duration of 17 months (IQR: 5, 18). Treatment abandonment was observed in 4 (14%) patients. The median follow-up of disease-free patients was 49 months (IQR: 45, 79). Patients with relapse were not treated further. A 4-year EFS of 29.3% was observed when 4-cycles of TVD were administered instead of ASCT in patients with HR-NB. The study and the review will aid decision-making for care of patients in LMIC while considering the options of treatment for HR-NB if access to ACST and dinutuximab is lacking.

Colonic mucosa-associated candida assessed by biopsy culture is associated with disease severity in ulcerative colitis: A prospective study.

OBJECTIVE: To evaluate the relationship of mucosa-associated candida (MAC) and disease severity in patients with ulcerative colitis (UC). METHODS: We prospectively investigated the presence, nature, and quantification of MAC in patients with UC and its relationship with disease severity. Consecutive patients with UC were assessed for clinical, endoscopic, histological features and serum markers of disease severity. All patients underwent mucosal brushing cytology, brushing culture, and biopsy culture for candida growth. MAC was considered present if mucosal biopsy culture grew candida. Candida spp. identification was performed by matrix-assisted laser desorption/ionization. Serum ß-D-glucan was measured with a Fungitell assay. Patients with irritable bowel syndrome who had undergone similar investigations were included as controls. RESULTS: Ninety-six patients with UC showed evidence of MAC more often than the controls (n = 20) based on biopsy culture (33.3% vs 5.0%, P = 0.011), brush cytology (30.2% vs 5.0%, P = 0.019), and brush culture (36.5% vs 10.0%, P = 0.021). Patients with UC had higher candida colony counts (≥103 CFU/mL) than controls (34.4% vs 5.0%, P = 0.007). Median ß-D-glucan values were higher in patients with UC than in controls (103.26 pg/mL vs 66.51 pg/mL, P = 0.011). The UC group with MAC had a higher median total Mayo score, C-reactive protein, fecal calprotectin, ß-D-glucan, and histological activity than those without MAC. CONCLUSIONS: Patients with UC more often show evidence of MAC and a higher candida colony count than controls. The presence of MAC is associated with high disease severity in patients with UC.

Role of perfusion CT in the evaluation of adnexal masses.

The objective of this study was to evaluate the role of perfusion computed tomography (PCT) in differentiating benign from malignant adnexal masses. Twenty patients, each of pathologically proven malignant and benign adnexal masses who had undergone PCT on 64-slice CT scanner, were included in the study. The PCT parameters, viz. blood volume (BV), blood flow (BF), permeability surface index area (PS) and time to maximum of the tissue residue function (Tmax) of the adnexal masses were calculated. Statistical analysis to study the association between PCT parameters and histopathological diagnosis was done. In the malignant group, the mean PS, BV and BF values were elevated. The mean Tmax of the benign lesions was higher compared to that of the malignant lesions. There was a significant statistical difference in the PCT parameters between the malignant and benign groups (p value = .001). PCT can be a useful tool for differentiating benign and malignant adnexal masses. Impact statement What is already known on this subject? It is not always possible to distinguish benign from malignant adnexal lesions despite the application of various imaging techniques. Perfusion CT (PCT) is an imaging technique with which we can obtain both the morphological and functional information of tumours. Perfusion-based imaging enables us to objectively evaluate the neovascularity in a lesion. This helps in differentiating the benign lesions from aggressive malignant lesions. What do the results of this study add? The PCT parameters, viz. blood volume (BV), blood flow (BF), permeability surface index area (PS) and time to maximum of the tissue residue function (Tmax) were calculated from adnexal masses on a 64-multi-slice CT scanner and correlated with their histopathological diagnoses. The values of the mean PS, BV and BF values were significantly higher in the malignant adnexal masses. The mean Tmax in the benign masses was more compared to that of the malignant lesions. Significant statistical difference was seen in PCT parameters between malignant and benign groups. What are the implications of these findings for clinical practice and/or further research? PCT can be a useful tool for differentiating benign from malignant adnexal masses. However, more collaborative research and robust validation are imperative to further evaluate this innovative evolving technique.

Spectrum of fungal and parasitic infections on fine needle aspiration cytology.

BACKGROUND: The incidence many fungal and parasitic lesions are on the rise over the decades. In this study, we have analyzed the spectrum of fungal and parasitic lesions diagnosed on fine needle aspiration cytology (FNAC) in a tertiary health care center. METHODS: This is a retrospective study conducted in the period three years and included all cases of fungal and parasitic lesions in the body (superficial and deep) identified on FNAC. RESULTS: There were total of 125 cases comprising of 59 parasitic cases and 66 fungal infections over this period. The various organisms were confirmed by special stains whenever required. In the parasitic group a cysticercosis (43), hydatid (8), filariasis (5), toxoplasmosis (1), leishmaniasis (1), and amoebiasis (1) were identified. The fungal infections included aspergillosis (36), mucormycosis (6), histoplasmosis (3), cryptococcus (4), and candidiasis (2). About a total of 15 cases were broadly classified as fungal infection only. CONCLUSIONS: FNAC is an easy, reliable, and minimally invasive method to diagnose and categorize the various fungal and parasitic lesions in the body for early and definitive treatment.

Role of fine needle aspiration cytology of spleen.

To evaluate the role of fine needle aspiration cytology (FNAC) of spleen in a tertiary care referral centre. FNAC of spleen was done in a total of 130 cases under ultrasonological guidance over a period of 5 years in a tertiary care centre. There were 76 male and 54 female including nine paediatric patients and the age range of the patients was from 2 to 70 years. All patients were evaluated for HIV, Hepatitis B antigen and coagulation profile before the procedure. Of 130 FNAC cases, 26 were inadequate, while 16 were normal splenic aspirate. A definite diagnostic opinion was possible in 88 cases. In this study, there were 13 cases of tuberculosis, 25 cases of granulomatous inflammation, 10 cases of acute suppurative inflammation, and one case each of leishmaniasis, aspergillosis and extramedullary hematopoiesis. In the neoplastic group, we had 26 cases of non-Hodgkins lymphoma, one case of Hodgkin lymphoma and 10 cases of metastatic malignancies. No complications were encountered during FNAC in any of the cases. With proper patient evaluation and emergency backup, USG guided fine needle aspiration cytology of spleen is a safe, easy and rapid procedure for definite diagnosis of neoplastic and non-neoplastic splenic pathology.

Aditya Jyot-Diabetic Retinopathy in Urban Mumbai Slums Study (AJ-DRUMSS): study design and methodology - report 1.

PURPOSE: To describe the methodology of Aditya Jyot-Diabetic Retinopathy in Urban Mumbai Slums Study (AJ-DRUMSS), which was designed (i) to estimate the prevalence of diabetic retinopathy (DR) in a general population, (ii) to study the risk factors associated with DR in those with type 2 diabetes mellitus (DM), and (iii) to create awareness for early detection and develop timely interventional management for DR. METHODS: AJ-DRUMSS is an ongoing population-based cross sectional study conducted in seven wards of slums in Mumbai, India, wherein eligible subjects from the general population were screened for DR and profiled for their demographic, social and biochemical parameters to study the associations of these factors. RESULTS: To date, nearly 54,000 households have been enumerated for both awareness and DR prevalence in five study areas (out of seven) during 17 awareness campaigns and 78 DR screening camps. Of these, 4295 households were included in AJ-DRUMSS. Nearly 15,000 camp subjects (including subjects from awareness-focused areas who also turned up for the screening camps) were screened from the total enumerated households, of which 16.1% were diagnosed with type 2 DM. A total of 14.5% of these had evidence of DR and 3.5% had sight-threatening DR. CONCLUSIONS: A detailed study design of AJ-DRUMSS is described. In the screening camps nearly 3.5% of the diabetic population had sight-threatening DR, which needed an active interventional strategy. This study will help in formulating efficient eye care policies, making optimum use of available resources, reorienting healthcare providers and the ignorant within the population regarding the need for periodic ophthalmic surveillance and timely intervention.

Fine-needle aspiration cytology of orbital meningiomas.

Meningiomas are benign tumors derived from arachnoid cells. Most commonly they arise within the cranial cavity, but they may arise extracranially in various anatomic sites. We present four cases of orbital meningiomas diagnosed on fine-needle aspiration cytology (FNAC) and confirmed on histopathology. All the cases are presented with orbital mass. FNAC smears showed classical whorling and syncytial pattern of cells, with round to oval nucleus, inconspicuous nucleoli and one each case showed intranuclear inclusion and psammoma bodies. FNAC diagnosis of such lesions is difficult, because cytological features may mimic other soft tissue lesions located in orbital region. Awareness of this entity and its cytological appearance is important to allow correct diagnosis.

Cervical cytology in patients with postmenopausal bleeding.

In this study, the role of cervical cytology in the diagnosis of post or perimenopausal (PM) bleeding was explored. A total of 135 patients with PM bleeding were selected. In all these cases both conventional cervical cytology and histopathology follow up were available. The commonest causes of postmenopausal (PM) bleeding with abnormal histopathology were squamous cell carcinoma of cervix (14), endocervical polyp (13), endometrial adenocarcinomas (13) and simple hyperplasia without atypia (13). There were a total 13 cases of endometrial adenocarcinoma and cervical smears of these cases were reported as high grade squamous intra epithelial lesion (1), presence of endometrial cells (4), unsatisfactory due to low cellularity (2), and within normal limit (6). In brief, endometrial carcinoma and hyperplasia are the predominant causes of PM bleeding due to endometrial pathology. The presence of benign looking endometrial cells with PM bleeding always indicates a careful work upto exclude endometrial pathology.

Adverse impact of pretransplant polyoma virus infection on renal allograft function.

BACKGROUND: BK polyoma virus (BKV) has emerged as an important cause of acute and chronic allograft injury in renal transplant recipients. Reactivation of latent infection requires reduction in cell-mediated immunity. We hypothesized that BKV could get reactivated in the urinary tract of patients with end-stage renal disease (ESRD) and impact the allograft function after these individuals undergo transplantation. METHODS: We prospectively examined the urine specimens of 68 ESRD patients and their donors for BKV inclusion containing decoy cells with Papanicoulau staining and immunohistochemistry. Polymerase chain reaction was carried out to confirm the presence of viral DNA. Urine examination was repeated 3-9 months after transplantation and during episodes of graft dysfunction. All graft dysfunction episodes were investigated by biopsy. BKV-associated nephropathy was confirmed by immunoperoxidase staining. Graft loss and doubling of serum creatinine were the study end-points. RESULTS: Decoy cells were detected in 22 ESRD patients and four donors (P < 0.0001). All 22 continued decoy cell excretion after transplantation and two fresh excreters were noted. Patients exhibiting decoy cells had more frequent graft dysfunction episodes (67% vs 30%, P = 0.003) and higher serum creatinine value (P < 0.001). About 33% patients achieved the combined end-points in the BK viruria group, compared with 11% in the non-decoy cell excreters (P = 0.03). Histologically proved BKV nephropathy was noted in 7% cases; all decoy cell excreters. CONCLUSION: We conclude that reactivation of latent BKV infection can occur in ESRD and confers an increased risk of graft dysfunction after transplantation. The mechanism of graft dysfunction in decoy cell excreters who do not develop overt nephropathy needs more studies.

Outcome of adult acute lymphoblastic leukemia with BFM protocol in a resource-constrained setting.

Cure rates for adult acute lymphoblastic leukemia (ALL) in developing countries are significantly lower because of problems unique to these countries. We assessed some of the problems in adult ALL patients (>12 years of age) in a tertiary care hospital of northwest India with modified BFM regimen. The diagnosis of ALL was made according to FAB criteria. The protocol consisted of Phase I & II induction, consolidation, reinduction and maintenance phases. CNS prophylaxis was administered with 24 Gy radiation and intrathecal methotrexate. One hundred and eighteen patients (72.9% males), aged 12-68 years (median 23 years) were treated from January 1997 till December 2003. Follow-up of patients was done till December 2005. Complete remission (CR) was achieved in 85.6% patients after induction therapy and 40% patient relapsed. Most patients (23.7%) relapsed during the maintenance phase or after completion of chemotherapy. At least 15% of patients (15/101) after successful induction abandoned the treatment because of financial constraints, prolonged travel time to treatment facility and switching over to alternative medicines. Fatal infectious complications occurred in 19.5% of patients. The 3-year and 5-year event free survival rates were 29.8% and 21.6% respectively. In conclusion, modified BFM regimen resulted in high induction rates but relatively poor 5-year event free survival. Infections related death and post induction abandonment of treatment were the main reasons for poor overall results.

Cobalt complexes of terpyridine ligand: crystal structure and photocleavage of DNA.

Two new cobalt complexes, [Co(pytpy)(2)](ClO(4))(2), 1, and [Co(pytpy)(2)](ClO(4))(3), 2 where pytpy=pyridine terpyridine, have been synthesized and characterized. Single-crystal X-ray structure of both the complexes has been resolved. The structure shows the complexes to be a monomeric cobalt(II) and cobalt(III) species with two pytpy ligands coordinated to the metal ion to give a six coordinate complex. Both cobalt(II) and cobalt(III) complexes crystallize in meridional configuration. The interaction of these complexes with calf thymus DNA has been explored by using absorption, emission spectral, electrochemical studies and viscosity measurements. From the experimental results the DNA binding constants of 1 and 2 are found to be (1.97+/-0.15)x10(4)M(-1) and (2.7+/-0.20)x10(4)M(-1) respectively. The ratio of DNA binding constants of 1 and 2 have been estimated to be 0.82 from electrochemical studies, which is in close agreement with the value of 0.73 obtained from spectral studies. The observed changes in viscosity of DNA in the presence of increasing amount of complexes 1 and 2 suggest intercalating binding of these complexes to DNA. Results of DNA cleaving experiments reveal that complex 2 efficiently cleaves DNA under photolytic conditions while complex 1 does not cleave DNA under similar conditions.

Cytopathology of uncommon malignant renal neoplasms in the pediatric age group.

Malignant renal neoplasms are common solid tumors in pediatric oncology practice. These include the common Wilms' tumor/nephroblastoma and the uncommon neoplasms such as clear-cell sarcoma of the kidney (CCSK), rhabdoid tumor, renal-cell carcinoma, and others. The aim of this study was to describe in detail the cytopathological features of the histopathologically proven uncommon pediatric renal tumors. Aspirates from Wilms' tumor, which are mesenchyme predominant, show clusters of spindle cells associated with the matrix material. Evidence of rhabdomyoblastic differentiation may be present. CCSK, classic subtype, is characterized by round to oval cells arranged perivascularly and also in sheets and clusters intimately associated with a metachromatic matrix mucopolysaccharide material better appreciated in May-Grunwald-Giemsa (MGG)-stained smears. The cells also have more abundant cytoplasm and may show nuclear grooves. Spindle-cell pattern of CCSK is difficult to diagnose on aspiration cytology. Renal-cell carcinoma of childhood shows similar cytological features as its adult counterpart. Rhabdoid tumor of the kidney is characterized by a monomorphic population of cells with abundant cytoplasm, eccentric nuclei with prominent nucleoli. Intrarenal yolk sac tumor is a rare neoplasm and shows severely pleomorphic cells on aspiration. Awareness of these entities is important for the practicing cytopathologist. Further, non-Wilms' renal malignant neoplasms must be distinguished from the common Wilms' tumor so that appropriate chemotherapy protocols may be instituted in cases where the tumor is in an advanced stage of malignancy.

Morphometric image analysis of follicular lesions of the thyroid.

OBJECTIVE: To determine the role of image morphometry in distinguishing various follicular lesions of the thyroid in cytologic smears. STUDY DESIGN: Archival fine needle aspiration smears of 10 cases each of follicular hyperplasia, follicular adenoma, follicular carcinoma and follicular variant of papillary carcinoma were used for the study. All cases were histopathologically proven. At least 100 random nuclei from each case were subjected to analysis with an image cytometer. Area, convex area, length, width, perimeter, convex perimeter and roundness of nuclei were measured using a 40 x objective (1 pixel = 0.446 micron). RESULTS: ANOVA showed that all the nuclear variables studied were significantly different (P < .05) in follicular hyperplasia as compared to follicular carcinoma and papillary carcinoma. All nuclear variables except roundness were also significantly different (P < .05) between follicular hyperplasia and follicular adenoma. However, between follicular adenoma, follicular carcinoma and papillary carcinoma there was considerable overlap of nuclear morphometric parameters. CONCLUSION: Image morphometry may help to distinguish nonneoplastic follicular lesions (hyperplasia) from neoplastic lesions (adenomas and carcinomas). However, to distinguish benign from malignant follicular lesions, image morphometry might not improve the accuracy of standard cytologic examination.

The natural course of nonsuppurative Calmette-Guérin bacillus lymphadenitis.

In a tertiary level hospital in North India, we studied the outcome of infants with nonsuppurative Calmette-Guérin bacillus (BCG) lymphadenitis managed conservatively. Twenty-three infants with nonsuppurative BCG lymphadenitis diagnosed on the basis of clinical presentation, evidence of granulomatous inflammation and demonstration of acid fast bacilli in the aspirated material were followed prospectively without being offered specific antitubercular drug therapy. Twenty patients were available for final analysis; three were lost to follow-up. Seventeen (85%) had spontaneous regression of BCG lymphadenitis without progression and drainage. The mean time to resolution was 9.1 months. Three (15%) patients developed suppuration and drainage, but even these children had uneventful healing on conservative management only. Nonsuppurative BCG lymphadenitis follows a benign course in most individuals. Most of the cases regress spontaneously with conservative management.