The immunomodulatory role of IDO1-Kynurenine-NAD+ pathway in switching cold tumor microenvironment in PDAC.

Pancreatic ductal adenocarcinoma (PDAC) is the most common exocrine tumor of the pancreas characterized by late diagnosis, adverse overall 5-year survival, a higher propensity for metastatic disease, and lack of efficacy of systemic therapy options. These adverse outcomes can be partly attributed to complex tumor microenvironment (TME). Over the past decade, immunotherapy has revolutionized the management of certain cancers; thus far, the immunologically 'non-inflamed' tumor microenvironment in PDACs has proven to be challenging. Indolamine 2,3-dioxygenase 1 (IDO1) is the rate-limiting enzyme in the catabolic pathway of L-Tryptophan, an essential amino acid, that gives rise to the immunosuppressive metabolite Kynurenine. IDO1, Indolamine 2,3-dioxygenase 2 (IDO2), and Tryptophan 2,3-dioxygenase (TDO) are the key enzymes in the tryptophan catabolic pathway but we focus on the role of the predominant enzyme form IDO1 in this review. Nicotinamide phosphoribosyl transferase (iNAMPT) regulates the intracellular concentration of NAD and is upregulated in the tumor. In light of the potential role of IDO1 as a driver of hostile TME in PDAC and NAD+ as a key coenzyme in anti-tumor immune response, this review urges focus on extensive research and initiation of clinical trials using IDO1 and NAMPT inhibitors in pancreatic cancer in the future.

Retrospective analysis of resected primary colorectal cancer revealed no correlation between node harvest and node involvement.

OBJECTIVE: To analyze the correlation between lymph nodes harvest (LNH) and lymph nodes involvement (LNI). METHODS: A retrospective analysis was done from January 2002 - August 2008 (6.5 years). The data was obtained from medical records, pathology and radiology. The patients with primary colorectal carcinoma (CRC) including synchronous or metachronous cancer, were included. These patients were treated with curative or palliative intent. Exclusion criteria was recurrent colorectal cancer, cancer not operated, cancer not resected (stoma-only, open-close) and endomucosal resection. LNH and LNI were obtained. The data was analyzed and also compared with the literature and the national audit. RESULTS: There were 177 resections (mean=28 +/- 3 per annum). Male to female ratio was 0.9:1 and median age was 71 years. There were 112 (63.3%) colonic and 65 (36.7%) rectal cancers. There were 14 Anterio-posterior resections (APRs) (21.5% of all rectal resections). Eighty four percent of resections were elective (OR=2.2 p=0.003 compared to the national audit). Metastasis was found in 14.6% at presentation. Adenocarcinoma (not otherwise specified) NOS constituted 94% of all histology results. Median lymph node harvest was 12 (mean=13.4 p=0.08). There was no significant LNH-LNI correlation (r=0.17 p=0.02). Survival figures for stages I-III CRC revealed 3-year disease-free survival of 82% (all-stage=69%). CONCLUSION: LNI as a function of tumour and host behaviour is of prognostic significance whereas LNH may be a quality assurance (QA) tool.

Identification of internal carotid artery dissection in patients with migraine--case report and literature review.

Although patho-physiology of spontaneous internal carotid artery dissection (sICAD) is largely unknown, an association with migraine has been suggested but not proven. Migraine is a condition which is worth considering while one is hunting a possible cause for internal carotid artery dissection (ICAD) and it may be found more often than expected. To date it remains a diagnosis of exclusion in patients with migraine. As opposed to migraine with aura, migraine without aura is significantly more frequent among patients with SICAD. It has been suggested that ICAD produces stroke in 36-68% of patients as a result of occlusion of the artery at or near the site of the dissection, or embolization occurring distally from a dislodged fragment of thrombus. We report a 31-year-old woman with headache and ptosis as initial symptoms. Magnetic resonance imaging (MRI) confirmed the diagnosis. Prompt treatment was instituted with anti-platelet agents and the patient had complete resolution of symptoms. Our case report highlights the importance of identifying the patients with ICD with history of migraine, in the absence of other risk factors and adds to the sparse literature currently available on the subject.