Metastatic atypical renal tumour with metanephric characteristics treated with Sunitinib.

Metanephric Adenoma (MA) is a rare and unclassifiable renal tumour with sparse reported clinical and morphological features. Generally MA's have a benign course without recurrence after nephrectomy, however a few cases received oncological treatment due to malignant progression. We present a 42-year-old woman who years after an initial nephrectomy developed several processes and biopsy confirmed recurrence of MA. Sunitinib was given for only two weeks, as she developed side-effects and currently the patient undergoes control scans with only minimal growth of the processes. This is the first case of MA treated with Tyrosin-Kinase-Inhibitor.

Role of endoscopic ultrasound-guided-fine needle aspiration biopsy in the diagnosis of lymphoma of the pancreas: A clinicopathological study of nine cases.

OBJECTIVE: Endoscopic ultrasound-guided-fine needle aspiration (EUS-FNA) is an established first-line procedure in the management of solid and cystic pancreatic masses. Lymphoma is an uncommon diagnosis in EUS-FNA of the pancreas, and it is more common for such a diagnosis to be because of secondary involvement of the pancreas by a lymphoproliferative disorder than for this to represent isolated primary pancreatic lymphoma (PPL). We present the clinical, EUS and cytological features of these lesions. MATERIAL AND METHODS: After obtaining approval from our Institutional Review Board (IRB), nine cases of lymphoma diagnosed on EUS-FNA at a tertiary care cancer centre over a period of 8 years from 2008 to 2016 were retrieved from our endoscopy and pathology archives. Rapid onsite evaluation (ROSE) was carried out by a trained cytopathologist in all these cases. Cell blocks were available in seven cases, and immunophenotyping was performed on cell blocks using the immunoperoxidase method. Flow cytometry was performed in two cases. RESULTS: The most frequent site of involvement was the head of the pancreas (n=5, 55.6%). Four out of nine cases were diagnosed as PPL (44.4%). Five cases were diagnosed as lymphoma secondarily involving the pancreas (55.6%). The most frequent diagnosis was diffuse large B-cell lymphoma (n=6, 66.7%), followed by Hodgkin's lymphoma (n=2, 22.2%) and peripheral T-cell lymphoma (n=1, 11.1%). CONCLUSION: EUS-FNA in experienced hands is a valuable diagnostic modality, in conjunction with ROSE, immunohistochemistry and flow cytometry, in the diagnosis and sub-typing of both primary and secondary pancreatic lymphoma.

CDX2 as a prognostic marker in gastric cancer.

BACKGROUND: There is considerable evidence in the literature to suggest a role for CDX2 in intestinal metaplasia and development of gastric cancer, but its impact on the prognosis of gastric cancer continues to be a matter of debate. OBJECTIVE: We conducted this study to assess the prognostic -implications of CDX2 in gastric cancer. METHOD: We retrospectively reviewed our database for gastric carcinoma cases diagnosed at our hospital from 2004 to 2008. Histopathology slides of these were subsequently stained with CDX2 immuno-histochemical stain. CDX2 positive and negative groups were then compared for overall survival. RESULTS: A total of 101 patients (mean age 50y ; 60% male) were included in the study. 31/101 (30.7%) cases were CDX2 positive. Of these, 23/31 (74%) patients underwent curative surgical resection. In the CDX2 negative group, only 12/70 (17%) patients underwent curative surgery (p = .0001). Of those who underwent surgical resection, 9% had stage I, 37% had stage II, 43% had stage III, and 11% had stage IV tumours on TNM staging of post-surgical histological specimens. Mean overall survival of CDX2 positive group was 17 months, compared to 6 months in the CDX2 negative group (p = 0.0001). CONCLUSIONS: CDX2 positive gastric carcinomas are more likely to be resectable and patients whose tumours stain positive for CDX2 have significantly better survival.

Clinical outcome of primary non-metastatic breast cancer: A single institution experience.

BACKGROUND: We report on prognostic factors and long-term survival of non-metastatic breast cancer patients treated at Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH and RC) in Pakistan. MATERIALS AND METHODS: This retrospective cohort study is based on a review of 2829 pathologically confirmed non-metastatic breast cancer patients managed from January 1995 to May 2009. Median age was 45 years. Stage at presentation: Stage I (9%), stage II (59%), and stage III (32%). Infiltrating ductal carcinoma (92%) constituted the most prevalent histological subtype. Estrogen (ER), progesterone (PR) and Her2-neu were positive in 49%, 50%, and 26%, respectively. A mastectomy was performed in 67% and conservative surgery in 33% of the patients. Post-operative radiotherapy was delivered in 85% of the cases. Ninety percent of the patients received chemotherapy and mainly consisted of anthracycline-based regimens + taxanes. Hormonal manipulation was done in ER/PR positive patients. RESULTS: The 5- and 10-year overall survival (OS) was 70% (95% confidence interval [CI]: 68.2-71.8%) and 54% (95%CI: 51.2-56.8%), while disease free survival (DFS) was 65% (95% CI: 63-67%) and 52% (95% CI: 49.2-54.8%), respectively. Recurrence following primary treatment was seen in 35% of the patients. On multivariate analysis T stage, number of axillary nodal involvement, tumor grade, ER status and family history, were found to be independent predictors for OS and DFS. CONCLUSIONS: Over 90% of non-metastatic breast cancer patients present with stagesII and III disease and a significant proportion develop distant metastasis accounting for overall long-term outcome inferior to developed countries. Efforts should be directed to raise the level of health awareness and screening programs to improve early detection in Pakistan.

BRAF mutation status in primary and metastatic melanomas in two regions with differing potential ultraviolet radiation exposure.

BACKGROUND: Melanoma is seen as a heterogeneous molecular entity, with solar ultraviolet radiation (UVR) and BRAF mutation status being important determinants. AIM: To study primary and metastatic melanomas from two UVR-distinct regions to elucidate correlations between prognostic predictors, UVR and BRAF mutation status. METHODS: Extended BRAF testing for 9 mutations was obtained for 95 primary melanomas [Lebanon (LB) n = 55, Pakistan (PK) n = 40)] and 65 metastatic melanomas (LB n = 36, PK n = 29). Collected data included patient age and sex, melanoma size and anatomical location, prognostic parameters and solar elastosis grade for primary melanomas. For metastatic melanomas, site of metastasis, magnitude of necrosis and degree of pigmentation were assessed. Cumulative 21-year averages of potential UVR exposure for Lebanon (110 kJ/m(2) /year) and Pakistan (128 kJ/m(2) /year) were derived from the National Center for Atmospheric Research databases. RESULTS: BRAF mutation status was obtained for 146/160 cases (91.3%). Overall mutation rate was 24/88 (27.3%) in primary and 25/58 (43.1%) in metastatic melanoma. V600E was the predominant mutation in 21/24 (87.5%) of primary and 23/25 (92%) of metastatic melanomas. A 60% discordant mutation rate was identified; of three patients, two lost the mutation in the metastasis and one gained it. The relative incidence of BRAF mutation with potential UVR exposure showed a similar trend in primary (low vs. high UVR: 32.1% vs. 20.0%) and metastatic (57.1% vs. 21.7%) melanomas (P < 0.05). Predictors of BRAF mutations were trunk location and epithelioid and mixed cytology for primary and subcutaneous metastasis, low UVR exposure and absence of pigmentation for metastatic melanomas (P < 0.05). BRAF-positive status in primary melanomas was predicted by multivariate binary logistic regression with reasonable accuracy (C-statistic = 0.67, 95% CI 0.530-0.81 with one independent predictor, namely, epithelioid cytology (OR = 5.11, 95% CI 1.38-8.88, P = 0.01). In metastatic melanomas, high UVR (OR = 0.21, 95% CI 0.06-0.07; P < 0.01) was an independent negative predictor of BRAF mutation. CONCLUSIONS: We have documented the rate of different BRAF mutation types in a Lebanese and Pakistani cohort, and assessed correlations with prognostic markers and potential UVR exposure.

BRAF mutational epidemiology in dysplastic nevi: does different solar UV radiation exposure matter?

BACKGROUND: Proto-oncogene B-Raf (BRAF) mutation rates have been reported in nevi and melanomas of homogeneous Caucasian cohorts. OBJECTIVE: To study the demographics of BRAF mutations in dysplastic nevi of populations with differing potential solar UV radiation exposure. METHODS: Extended BRAF testing for 9 mutations in 125 dysplastic nevi from 101 patients, derived from populations with differing potential UV radiation exposure rates (Lebanon and Saudi Arabia), was performed. Clinical and microscopic parameters were recorded. RESULTS: BRAF mutation status was carried out for 101/125 (80.8%) cases with an overall mutation rate of 62.4% (63/101). V600E (c.1799T > A) was the predominant mutation, found in 61/63 (96.8%) cases. BRAF mutation rate differed significantly by potential UV radiation exposure (Lebanon: 53.4%, Saudi Arabia: 74.4%, P < 0.05). A 43.8% discordant mutation rate (7/16 patients) was found in patients with multiple nevi, including 2 patients with different BRAF mutations. Microscopic examination subdivided the dysplasia into mild (n = 24), moderate (n = 60) and severe (n = 41) with trunk predominance (72.8%). Higher rates of pigment in the stratum corneum were identified in Saudi Arabia (P < 0.05). No statistical significant increase in BRAF mutation rate was noted with advanced architectural and cytological atypia. Parameters associated with a negative BRAF mutation status included upper extremity location, regression, cohesiveness and presence of suprabasal melanocytes (P < 0.05). Positive BRAF mutation status was reasonably predicted by multivariate binary logistic regression by 2 independent predictors: Geographic location and compound nevus type. CONCLUSIONS: In our Near Eastern cohort, the BRAF mutation rate varied significantly by geographic location. In patients with multiple dysplastic nevi examined, discordant BRAF mutation status potentially negates an underlying constitutional predilection.

Interaction of N-nitrosodiethylamine/bovine serum albumin complexes with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine monolayers at the air-water interface.

We report the effect of N-nitrosodiethylamine (NDA) on the interaction between bovine serum albumin (BSA) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine monolayers (DPPC) at the air-water interface. We prepared aqueous solutions of NDA/BSA complexes maintaining a constant concentration of BSA of 1.49 x 10(-9) M and using NDA concentrations to obtain 2000, 4000, 6000, 12,500, and 25,000 NDA/BSA molar ratios. The hysteresis area and the compressional modulus of the compression-expansion cycles performed at different times were dependent on the NDA concentration. The cycles performed demonstrate the stability of the new phase of DPPC/BSA and DPPC/NDA/BSA monolayers. This was achieved probably because the BSA concentration used was lower than the one needed for BSA to inhibit the return of DPPC molecules to the interface. Results of the compressional modulus at the onset of the new phase, obtained around 17 mN/m, 15 min and 1, 3, 5, and 12 h after DPPC deposition, indicated that the 3.0 x 10(-6) M NDA concentration produced a more rigid film, probably due to the higher alpha-helix content of BSA. AFM images were obtained for DPPC/BSA and two DPPC/NDA/BSA complexes. Our images show that 12,500 NDA/BSA molecules were mostly adsorbed in the liquid condensed phase. However, BSA molecules were distributed more homogeneously.

Genotoxicity of neutrons in Drosophila melanogaster. Somatic mutation and recombination induced by reactor neutrons.

This paper describes the observation of a direct relationship between the absorbed doses of neutrons and the frequencies of somatic mutation and recombination using the wing somatic mutation and recombination test (SMART) of Drosophila melanogaster. This test was used for evaluating the biological effects induced by neutrons from the Triga Mark III reactor of Mexico. Two different reactor power levels were used, 300 and 1000 kW, and two absorbed doses were tested for each power level: 1.6 and 3.2 Gy for 300 kW and 0.84 and 1.7 Gy for 1000 kW. A linear relationship was observed between the absorbed dose and the somatic mutation and recombination frequencies. Furthermore, these frequencies were dependent on larval age: In 96-h-old larvae, the frequencies were increased considerably but the sizes of the spots were smaller than in 72-h-old larvae. The analysis of the balancer-heterozygous progeny showed a linear absorbed dose- response relationship, although the responses were clearly lower than found in the marker-trans-heterozygous flies. Approximately 65% of the genotoxicity observed is due to recombinational events. The results of the study indicate that thermal and fast neutrons are both mutagenic and recombinagenic in the D. melanogaster wing SMART, and that the frequencies are dependent on neutron dose, reactor power, and the age of the treated larvae.

Lithium carbonate Li 2 CO 3 as a material for thermal neutron fluence measurements.

A possibility to use the electron paramagnetic resonance (EPR) signal of neutron-irradiated lithium carbonate for thermal neutron fluence measurements has been investigated. The following aspects of the system have been studied: peak-to-peak signal amplitude as a function of thermal neutron fluence, signal fading, signal repeatability, sample batch homogeneity, and zero-fluence response of the probes. It has been concluded that lithium carbonate can be used as a material sensitive to thermal neutron fluences.

Determination of neutron absorbed doses in lithium aluminates.

Lithium-based ceramics have been proposed as tritium breeders for fusion reactors. The lithium aluminate (gamma phase) seems to be thermally and structurally stable, the damages produced by neutron irradiation depend on the absorbed dose. A method based on the measurement of neutron activation of foils through neutron capture has been developed to obtain the neutron absorbed dose in lithium aluminates irradiated in the thermal column facility and in the fixed irradiation system of a Triga Mark III Nuclear Reactor.