Role of Bone Scan and MRI in Designing of Customized Prosthesis for Limb Salvage Surgery of Long Bone Tumors: 4 Years of Single Institution Analysis.

The purpose of this study is to evaluate the role of bone scan (BS) and MRI measurement data in designing Custom Made Prosthesis (CMP) in Limb Salvage Surgery (LSS) in orthopedic oncology patients. The study was done on 126 patients, which include 88 males and 38 females. Pre-operative planning including determination of the osteotomy plane and dimension of the prosthesis was performed based on Tc99m MDP bone scan and MR images comparing with the histopathology examination (HPE) values. Descriptive statistics using appropriate measures of central tendency and dispersion were employed to describe the data. Karl-Pearson correlation coefficient was used to establish the association between continuous covariates. Paired t-test was utilized to test the differences in paired values for statistical significance. Bone scan and HPE values are positively correlated; p value is 0.913 (p < 0.001). However, mean difference between the HPE and bone scan is statistically significant (p < 0.001). MRI scan and HPE values are positively correlated 0.920 (p < 0.001) and mean difference is also statistically not significant (0.920; p < 0.001). If we apply ± 20% window, 94/126 patients (75%) bone scan measurements and 94/112 patients (84%) MRI measurements are matching with the HPE measurements. We conclude that bone scan measurements were found to be more or less equal to MR imaging for determining the tumor extent for the fit of the prosthesis and excellent functional results.

Dendritic cells matured with recombinant human sperm associated antigen 9 (rhSPAG9) induce CD4+, CD8+ T cells and activate NK cells: a potential candidate molecule for immunotherapy in cervical cancer.

BACKGROUND: Dendritic cell (DC)-based immunotherapy is capable of activating the immune system and in particular tumor-specific cytotoxic T lymphocytes (CTLs) to eradicate the tumor. However, major limitations are the availability of autologous tumor cells as antigenic source and the selection of antigen that may have potential to activate both CD4+ and CD8+ T cells in immune-specific manner. Recently, we reported the expression of sperm associated antigen 9 (SPAG9) that is associated with various types of malignancies including cervical cancer. We examined the recombinant human SPAG9 (rhSPAG9) as an antigenic source for generating efficient DCs to stimulate CD4+ and CD8+ T cell responses for future DCs-based vaccine trials in cervical cancer patients. METHODS: Human monocytes derived DCs were pulsed with different concentrations (250 ng/ml to 1000 ng/ml) of recombinant human SPAG9 (rhSPAG9) and evaluated for their phenotypic and functional ability. The efficacy of DCs primed with 750 ng/ml of rhSPAG9 (SPDCs) was compared with DCs primed with autologous tumor lysates (TLDCs), to induce CD4+, CD8+ T cells and activating NK cells. In addition, we investigated the effect of the chemotherapeutic drug cisplatin on phenotypic and functional potential of SPDCs. RESULTS: Phenotypic and functional characterization of DCs pulsed with 750 ng/ml rhSPAG9 was found to be optimal and effective for priming DCs. SPDCs were also capable of stimulating allogeneic T cells similar to TLDCs. SPDCs showed a statistically insignificant increase in the expression of maturation marker CD83 and migration towards CCL19 and CCL21 compared with TLDCs (CD83; P = 0.4; migration; P = 0.2). In contrast, although TLDCs showed better proliferation and secretion of Th1 cytokines (IL12p40, IL12p70 and IFNγ) compared to SPDCs, this difference was not statistically significant (IL12p40, P = 0.06). Further we also observed that clinical dose of cisplatin (200 µM) treated SPDCs were able to stimulate the proliferation of cytotoxic T lymphocytes without increasing the FOXP3+ Tregs in autologous co-cultures. CONCLUSIONS: In summary, in order to overcome the limitation of the availability of autologous tumor cells as antigenic sources, our present strategy provides an insight to consider rhSPAG9 as a strong immunogen for DC-based immunotherapy for cervical cancer trials and warrants further studies. This is the first report to suggest that rhSPAG9 is an effective antigen for pulsing DCs that are capable of eliciting a potent Th1 response which, in turn, may help in decreasing the tumor burden when used along with a cisplatin based combinatorial regimen for therapeutic intervention.

Autologous cervical tumor lysate pulsed dendritic cell stimulation followed by cisplatin treatment abrogates FOXP3+ cells in vitro.

OBJECTIVE: Dendritic cells (DCs) are administered as immunotherapeutic adjuvants after the completion of standard treatment in most settings. However, our Phase I trial indicated that one patient out of four, who received autologous tumor lysate-pulsed dendritic cell (TLDC) also received cisplatin chemotherapy and experienced complete regression of her lung lesion, continuing to be disease free till date. Hence, the objective of our current study is to evaluate the sustenance or augmentation of immune responses when autologous human papillomavirus positive cervical tumor lysate pulsed DC- are combined with cisplatin, using co-culture assays in vitro. METHODS: Before treatment, peripheral blood and punch biopsy samples were collected from 23 cervical cancer patients after obtaining an informed consent. DC functionality was confirmed through phenotypic and functional assays using autologous peripheral blood mononuclear cells as responders. For cisplatin experiments, the drug was added at 150, 200 (clinical dose equivalent), and 400 µM concentrations to DCs alone or DC-T cell co-cultures. Phenotypic assessment and functional characterization of DCs was done using flow cytometry. Cytokine enzyme-linked immunosorbent assay and interferon (IFN)-γ enzyme-linked immune absorbent spot assays were also performed. RESULTS: The functionality of TLDCs was not compromised upon cisplatin treatment in vitro even at the highest (400 µM) concentration. Even though cisplatin treatment reduced the secretion of IFN-γ and interleukin (IL)-12p40 in co-cultures stimulated with TLDCs, this effect was not significant (p>0.05). A doubling of IFN-γ secretion following cisplatin treatment was observed in at least one of three independent experiments. Additional experiments showed a reduction in both FOXP3+ regulatory T cells and IL-10 levels. CONCLUSION: Our results provide evidence that cisplatin treatment may be given after autologous TLDC administration to maintain or improve a productive anti-tumor response in vaccinated patients.

Adult acute lymphoblastic leukemia mimicking renal cell carcinoma with wide spread bone metastasis.

A few cases with bilateral renal enlargement in acute lymphoblastic leukemia (ALL) are reported in literature. In this article, we report an unusual case of ALL in an adult presenting as multiple lesions in both kidneys and multiple bone lesions.

XPD Lys751Gln increases the risk of breast cancer.

Breast cancer incidence has been on the increase in south Indian women. Polymorphisms in DNA repair genes modify an individual's risk to cancer. XPD (Xeroderma pigmentosum D), a DNA helicase gene involved in nucleotide excision repair and transcription coupled repair, may affect an individual's DNA repair capacity, particularly that of bulky adducts. This case-control study (250 breast cancer cases and 500 healthy controls) aimed to investigate the role of the XPD Lys751Gln polymorphism as a risk factor in the development of breast cancer. Genotyping was performed using the Taq Man allelic discrimination assay. Immunohisto-chemistry was used to quantitate the level of polycyclic aromatic hydrocarbon (PAH) adducts in biopsy samples obtained from the breast cancer patients. Results showed that the XPD Gln/Gln genotype was significantly associated with an increased risk of breast cancer (OR, 1.75; 95% CI 1.02-2.80), particularly in premenopausal female patients (OR, 2.6; 95% CI 1.33-4.79). PAH adduct levels were significantly higher in the cases with breast cancer as compared to the normal breast tissue. This study reveals that XPD may play a role in increasing breast cancer risk particularly in premenopausal females.

Large-cell neuroendocrine carcinoma of the kidney: Clinicopathologic features.

Neuroendocrine tumors are rare entities which can arise in various sites of the body. The presence of both neural and endocrine elements in conjunction characterises these tumors pathologically. Most of these tumors are non secretory in nature, and arise in organs where there may not be any neuroendocrine elements. Carcinoid tumors are the most common entities reported in the kidney. There have been only a couple of case series of non-carcinoid neuroendocrine tumors of the kidney reported in literature. Surgical resection appears to be the best available treatment modality. Chemotherapy has been attempted with dismal results. The biological behaviour is determined by the occurrence of metastases to the liver or lung. We report a patient with a large cell neuroendocrine carcinoma of the kidney, who underwent radical resection and is doing well on follow-up. The diagnosis was confirmed by immune-histochemistry.

Sarcomatoid carcinoma of the penis: Clinicopathologic features.

Sarcomatoid carcinomas are biphasic tumors, which can occur at any site in the human body. Very few cases have been reported in the literature as arising from the penis. A few studies consider these tumors as a variant of squamous cell carcinoma or a metaplastic differentiation of the mesenchyme. Their clinical behavior is aggressive with both blood borne and lymphatic metastases. Treatment is by surgical excision, and dissected lymph nodes have shown both epithelial and sarcomatous components. We report a 50-year-old gentleman, with a sarcomatoid carcinoma of the penis, which was confirmed immunopathologically. The rarity of this entity makes it a clinicopathologic curiosity.

Syringomatous adenoma of the nipple: report of a case.

Syringomatous adenoma of the nipple is a rarely encountered neoplasm of the breast with histological features similar to eccrine syringoma of the skin. This tumour which is locally invasive with high potential for recurrence if incompletely excised is considered benign and a complete excision is sufficient. Hence it deserves recognition by pathologists and surgeons for appropriate management. We report a case of syringomatous adenoma of the nipple in a postmenopausal diabetic woman who was incidentally found to have a subareolar mass in her right breast. Clinical examination and mammographic findings indicated malignancy. Histopathological examination showed features of syringomatous adenoma of the nipple. A clinicopathological study and histological differential diagnosis of this unusual tumour is described.

Primary fibrosarcoma of the ovary--report of two cases.

The authors describe two cases of primary fibrosarcoma of the ovary in 48 years and 66 years old women. Patients presented with abdominal masses associated with pain in the first case. USG and CT scan of the abdomen revealed ovarian tumours involving the left side in both cases . Both underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. Histological examination showed features of fibrosarcoma grade I and grade III respectively. A clinicopathological study and brief review of literature is presented.