Alcohol and Smoking Mediated Modulations in Adaptive Immunity in Pancreatitis

Pancreatitis is a condition of pancreatic inflammation driven by injury to the pancreatic parenchyma. The extent of acinar insult, intensity, and type of immune response determines the severity of the disease. Smoking, alcohol and autoimmune pancreatitis are some of the predominant risk factors that increase the risk of pancreatitis by differentially influencing the adaptive immune system. The overall decrease in peripheral lymphocyte (T-, B- and (natural killer T-) NKT-cell) count and increased infiltration into the damaged pancreatic tissue highlight the contribution of adaptive immunity in the disease pathology. Smoking and alcohol modulate the responsiveness and apoptosis of T- and B-cells during pancreatic insult. Acute pancreatitis worsens with smoking and alcohol, leading to the development of systemic inflammatory response syndrome and compensatory anti-inflammatory response syndrome, suggesting the critical role of adaptive immunity in fatal outcomes such as multiple organ dysfunction. The presence of CD4+ and CD8+ T-lymphocytes and perforin-expressing cells in the fibrotic tissue in chronic pancreatitis modulate the severity of the disease. Due to their important role in altering the severity of the disease, attempts to target adaptive immune mediators will be critical for the development of novel therapeutic interventions

Potentials of Plasma NGAL and MIC-1 as Biomarker(s) in the Diagnosis of Lethal Pancreatic Cancer

Pancreatic cancer (PC) is lethal malignancy with very high mortality rate. Absence of sensitive and specific marker(s) is one of the major factors for poor prognosis of PC patients. In pilot studies using small set of patients, secreted acute phase proteins neutrophil gelatinase associated lipocalin (NGAL) and TGF-β family member macrophage inhibitory cytokine-1 (MIC-1) are proposed as most potential biomarkers specifically elevated in the blood of PC patients. However, their performance as diagnostic markers for PC, particularly in pre-treatment patients, remains unknown. In order to evaluate the diagnostic efficacy of NGAL and MIC-1, their levels were measured in plasma samples from patients with pre-treatment PC patients (n = 91) and compared it with those in healthy control (HC) individuals (n = 24) and patients with chronic pancreatitis (CP, n = 23). The diagnostic performance of these two proteins was further compared with that of CA19-9, a tumor marker commonly used to follow PC progression. The levels of all three biomarkers were significantly higher in PC compared to HCs. The mean (± standard deviation, SD) plasma NGAL, CA19-9 and MIC-1 levels in PC patients was 111.1 ng/mL (2.2), 219.2 U/mL (7.8) and 4.5 ng/mL (4.1), respectively. In comparing resectable PC to healthy patients, all three biomarkers were found to have comparable sensitivities (between 64%-81%) but CA19-9 and NGAL had a higher specificity (92% and 88%, respectively). For distinguishing resectable PC from CP patients, CA19-9 and MIC-1 were most specific (74% and 78% respectively). CA19-9 at an optimal cut-off of 54.1 U/ml is highly specific in differentiating resectable (stage 1/2) pancreatic cancer patients from controls in comparison to its clinical cut-off (37.1 U/ml). Notably, the addition of MIC-1 to CA19-9 significantly improved the ability to distinguish resectable PC cases from CP (p = 0.029). Overall, MIC-1 in combination with CA19-9 improved the diagnostic accuracy of differentiating PC from CP and HCs

A clinical study to assess the efficacy of Triyushnadi Anjana in Kaphaja Abhishyanda with special reference to vernal keratoconjunctivitis

Vernal keratoconjunctivitis / spring catarrh is a variety of exogenous allergic conjunctivitis, which is a very troublesome ocular disease of childhood and in the adolescent age group. The child suffers from intense itching, grittiness, discharge, redness, lacrimation, photophobia, and so on, thereby, decreasing his learning hours. The troublesome features are aggravated in the spring season / hot climate that lasts for years together and rarely persists after adolescence. Mast cell stabilizers, topical Nonsteroidal anti-inflammatory drugs (NSAIDs), and steroids are the available treatment options that too with symptomatic relief and potential side effects, which limits the long-term use of these medicines. The clinical picture of vernal keratoconjunctivitis / spring catarrh is very similar to Kaphaja Abhishyanda, and Triyushnadi Anjana Bhaishajya Ratnavali (B.R.), and its treatment was clinically tried on the patients attending the Netra Roga OPD of the R.G. Government P.G. Ayurveda College Hospital at Paprola (H.P.). A proper protocol and performa was adopted with strict inclusion and exclusion criteria. In the first phase, a pilot study was conducted on 38 clinically diagnosed patients with vernal keratoconjunctivitis, and it gave 100% relief in photophobia, foreign body (FB) sensation, and lacrimation, with marked relief in other features. Encouraged by this pilot work, Triyushnadi Anjana (TA) and 2% sodium cromoglycate (mast cell stabilizer) eye drops in the second-phase clinical trial on 32 patients were tried clinically to evaluate the comparative efficacy. In the second clinical trial, the patients were randomly divided into two groups and Group I was given sodium cromoglycate 2% eye drops and Group II was given TA. The outcome of this study verified the results of the first phase pilot study, and on comparison of the results of the two groups in the second clinical study it was observed that the TA-treated group showed better results. Transient irritation in the eyes was reported by all patients after application of TA, which was relieved by keeping the eyes closed for a few minutes. None of the patients reported any adverse action of the trial drug. Thus, it can be concluded that TA is a safe, cost-effective, and potent Ayurvedic alternative in the treatment of vernal keratoconjunctivitis / spring catarrh

Use of Endoscopic Ultrasound in a Diagnostic Dilemma: Metastatic Breast Cancer to the Stomach

A 55-year-old woman presented with persistent nausea, vomiting, and weight loss previously attributed to Ménétrier’s disease. On further workup, she was found to have metastatic lobular breast carcinoma causing gastric outlet obstruction, diagnosed by endoscopic ultrasound with fine needle aspiration after previous gastric mucosal biopsies were unremarkable. In most reported cases of gastric metastasis from breast cancer, a diagnosis was established by mucosal biopsy. This case is an important reminder that mucosal biopsies can be negative in about 20% of patients with gastric metastasis, which may lead to a delay in diagnosis and treatment. Gastroenterologists should be diligent in taking deeper biopsies if there is a suspicion for gastric metastasis

Needle-Knife Fistulotomy for the Rescue: An Unusual Cause of Iatrogenic Extrahepatic Biliary Obstruction

A 71-year-old male presented to our institution with cholestatic hepatitis after having recently undergone upper endoscopy for treatment of gastrointestinal bleeding. Further investigation with endoscopic retrograde cholangiopancreatography revealed a hemostatic clip on the ampulla of Vater. After initial attempts at cannulation of the common bile duct were unsuccessful, biliary decompression was achieved by use of needle-knife fistulotomy. A common bile duct stent was placed and the liver function tests improved prior to discharge

Reciever Operating Chacteristic curves comparing NGAL, MIC-1, CA19-9 for differentiating PC from HC (panel A) and CP (panel B) and combination of CA19-9 and MIC-1 in differentiating treatment naïve resectable PC from CP.

<p>The combined use of MIC-1 with CA 19-9 significantly improved the sensitivity and accuracy in differentiating resectable PC from CP (AUC = 0.85 Vs 0.74, p = 0.029, C.I. 0.76–0.94) in comparison to CA19-9 alone.</p

Comparison of Area under the ROC curve for NGAL, MIC-1 and CA19-9 in the diagnosis of pancreatic cancer^≠.

<p>PC (pancreatic cancer), CP (chronic pancreatitis), AUC (area under the curve), SE (standard error).^aP-value against CA19-9 alone.*Marker inclusion in combination tests was based on statistical significance of differentiation of individual biomarkers levels by multivariate analysis). ^≠PC patient samples were limited to treatment naïve samples only for this analysis.</p

Determining optimum cut-off of CA19-9, NGAL and MIC-1 for diagnosis of pancreatic cancer^≠.

<p>HC: Healthy Controls; CP: Chronic Pancreatitis; PC: Pancreatic Cancer; ln: natural log; ND: Not Determined.^≠PC patient samples were limited to treatment naïve samples only for this analysis.</p

Diagnostic potential^≠ of NGAL, MIC-1 and CA19-9 at pre-defined cut-off.

≠<p>PC patient samples were limited to treatment naïve samples only for this analysis.</p