Role of NF-KB in Loss of Skeletal Muscle Mass in Cancer Cachexia and its Therapeutic Targets

Cancer cachexia is a type of cancer metabolic syndrome characterized by wasting of energy storage tissue of the body such as loss of skeletal muscle or fat body mass. It is one of the most common forms of cachexia. Researchers have shown that around 50%–80% cancer patients are cachectic and about 22% cancer related deaths are due to cachexia.Recent evidences confirm that skeletal muscle loss is induced by different mediator based mechanisms such as cytokines, tumor-derived factors, TNF-alpha receptors, androgen receptors, negative modulator of growth factors, and ubiquitin-proteasome pathways. These mediators interact with their unique receptors on skeletal muscles and activate nuclear factor-kappa-B (NF-κB) which is a transcription factor essential for atrophy based muscle protein degradation. Inhibition of NF-κB ameliorates cancer-induced muscle loss are suggestive of a new set of drug targets for clinical intervention in cancer cachexia. Here we summarize the recent advances concerning involvement of NF-κB in loss of skeletal muscle mass in cancer cachexia and its therapeutic targets. Future experimental efforts may focus on discovering of new drugs that act as potential therapeutic targets in cancer cachexia against the myriad of signaling pathways to precisely understand the mechanisms of loss of skeletal muscle mass and adipose tissue which could demonstrates significant improvement in treatment outcome, functional status and quality of life of the patients

Lipoma of Guyon’s canal causing ulnar neuropathy

Lipoma is a benign soft tissue tumor which rarely causes neuropathy. In closed compartments such as Guyon’s canal, even small volume loss can lead to compression of nerve. Hence in such areas, even innocuous tumors such as lipomas can cause neuropathy and warrant surgery. We present one such case of ulnar neuropathy caused by lipoma of Guyon’s canal

Meniscal ossicle

Meniscal ossicle, or bone within the substance of meniscus, is a rare entity and commonly confused with a loose body both clinically and radiologically. MRI is the modality that can definitely diagnose meniscal ossicle and avoid unnecessary diagnostic arthroscopy. Here we report one such case diagnosed using MRI; this patient is doing well without surgery one year after diagnosis

Macrodystrophia lipomatosa involving multiple nerves

Macrodystrophia lipomatosa (MDL), a rare congenital disorder, is considered by some to be a localized form of Proteus syndrome. The implication of the PTEN (phosphatase and tensin homolog deleted on chromosome 10) gene in both strengthens this belief. We present a case who had MDL in multiple nerve territories—all on the same side of the body—with hypertrophy of mainly fibroadipose tissue throughout their distribution, thus pointing to a form of localized hemihypertrophy; both hemihypertrophy and lipomatous tumors are components of Proteus syndrome

Thirteen Years’ Experience of Diaphragmatic Injury in Children from the Post Graduate Institute of Medical Sciences (PGIMS), Rohtak, India

Background: Diaphragmatic hernia is migration of abdominal viscera into the thoracic cavity through a defect in the diaphragm. In children, it is mostly congenital; traumatic diaphragmatic hernia being less common. This study aimed to review our experience with traumatic diaphragmatic rupture (TDR) and to identify the clinical findings and diagnostic modality that may help in early diagnosis and prompt therapy. Methods: The study involved 11 children (1-18 years old) with TDR who were hospitalised between 1993 and 2005. In addition to clinical examination, a plain X-ray of the chest and abdomen, an ultrasound, barium studies, and a computerised tomography (CT) scan were used to evaluate the patients. Results: All of the diaphragmatic ruptures occurred on the left side, with 10 occurring in the posterolateral part and 1 near the oesophageal hiatus. Two of our patients presented 7 and 10 days after the injury, and 1 patient presented 1 year after the trauma. Conclusion: TDR should remain a diagnostic possibility in children. These patients are best assessed using a CT scan. New research on stem cells and tissue-engineered bioprosthetics may pave the path for better future therapies in these cases

rCBV- and ADC-based Grading of Meningiomas With Glimpse Into Emerging Molecular Diagnostics

Introduction: This study was conducted to grade meningiomas based on relative Cerebral Blood Volume (rCBV) and Apparent Diffusion Coefficient (ADC) to help surgeons plan the approach and extent of operation as well as decide on the need of any adjuvant radio/chemo therapy. The current and evolving genomic, proteomic, and spectroscopic technologies are also discussed which can supplement the current radiologic methods and procedures in grading meningiomas. Methods: A total of 35 patients with meningioma prospectively underwent basic MR sequences (T1W, T2W, T2W/FLAIR) in axial, sagittal and coronal planes followed by Diffusion Weighted (DW) imaging having b value of 1000 (minimum ADC values used for analysis). Then, gadobenate dimeglumine/meglumine gadoterate was administered (0.1 mmol/kg at a rate of 4 mL/s) followed by saline flush (20 mL at a rate of 4 mL/s). Next, T2*W/FFE dynamic images were acquired; dynamics showing maximum fall in intensity was used for creating rCBV and relative Cerebral Blood Flow (rCBF) maps and calculating rCBV. Results: Both maximum rCBV and minimum ADC within the tumor were not significant for differentiating benign from malignant meningiomas. A cut-off maximum rCBV of 2.5 mL/100 g in peritumoral edema was 75% sensitive, 84.6% specific, and 83.3% accurate in differentiating benign from malignant meningiomas.  Conclusion: Benign and malignant meningiomas can be differentiated based on maximum rCBV in peritumoral edema but ADC values within the tumor are insignificant in differentiating benign and malignant tumors. rCBV values within tumor, however, may be helpful in subtyping meningiomas, especially transitional and meningothelial meningiomas

rCBV and ADC based grading of gliomas with glimpse into radiogenomics

Purpose. The present study was carried out to study the role of relative cerebral blood volume (rCBV), apparent diffusion coefficient (ADC) and MR spectroscopy in grading gliomas to help the surgeon plan the approach and extent of surgery as well as judge the need for any adjuvant radio/chemotherapy. Methods. 65 patients with glioma were prospectively studied with MRI. Basic MR sequences (T1W, T2W, T2W/FLAIR) were followed by diffusion-weighted (DW) imaging with b value of 1000 (minimum ADC values used for analysis). Then the patients were administered Gadobenate Dimeglumine/ Meglumine Gadoterate in a dose of 0.1mmol/kg at a rate of 4ml/sec after which 20ml of saline was flushed at a rate of 4ml/sec and  T2*W/FFE dynamic images were acquired; dynamics showing maximum fall in the intensity were used for creating rCBV and rCBF maps and calculating rCBV. Single voxel spectroscopy (SVC) was done using the PRESS sequence with intermediate TE of 144ms. NAA/Cr, Cho/Cr, Cho/NAA, Cho+Cr/NAA and NAA/Crn ratios (NAA from the tumour, Crn from the normal side) were calculated. Results. Grade I gliomas showed minimum ADC>0.84x10-3mm2/s and maximum rCBV<1.9ml/100gm, grade II gliomas showed min ADC 0.75-0.84x10-3mm2/s and max rCBV of 1.9-2.6ml/100gm, grade III had min ADC of 0.70-0.75x10-3mm2/s and max rCBV of 2.7-3.0ml/100gm, while grade IV tumors showed min ADC<0.70x10-3mm2/s and max rCBV>3.0ml/100gm. rCBV values were better than ADC values in differentiating grade I from II and grade II from III. The ADC values were better than rCBV values in differentiating grade III from grade IV. Conclusions. Both minimum ADC and maximum rCBV within the tumour were significant but these parameters within peritumoral oedema were not significant in grading gliomas. Though lipid and lactate (especially lipid) peaks were found more frequently in higher-grade tumours, various spectroscopy parameters were not significant in grading gliomas. Preoperative grading of gliomas with the help of advanced MR parameters like ADC and rCBV can help the surgeon plan the approach and extent of surgery as well as judge the need for any adjuvant radio/chemotherapy. Advancing radio-genomic and radiomic technologies can supplement the current radiologic methods of diagnosis and prognosis. &nbsp