CA19-9 Normalization During Pre-operative Treatment Predicts Longer Survival for Patients with Locally Progressed Pancreatic Cancer

Background

Compared to the widely adopted 2–4 months of pre-operative therapy for patients with borderline resectable (BR) or locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC), our institution tends to administer a longer duration before considering surgical resection. Using this unique approach, the aim of this study was to determine pre-operative variables associated with survival.

Methods

Records from patients with BR/LA PDAC who underwent attempt at surgical resection from 1992–2014 were reviewed.

Results

After a median duration of 6 months of pre-operative treatment, 109 patients with BR/LA PDAC (BR 63, LA 46) were explored; 93 (85.3 %) underwent pancreatectomy. Those who received at least 6 months of pre-operative treatment had longer median overall survival (OS) than those who received less (52.8 vs. 32.1 months, P?=?0.044). On multivariate analysis, pre-operative treatment duration was the strongest predictor of survival (hazard ratio (HR) 4.79, P?=?0.043). However, OS was similar in those whose CA19-9 normalized regardless of whether they received more or less than 6 months of chemotherapy (71.4 vs. 101.8 months, P?=?0.930).

Conclusions

Pre-operative CA19-9 decline can guide treatment duration in patients with BR/LA PDAC. We endorse 6 months of therapy except in those patients whose values normalize, where surgery can be considered after a shorter course.

     

An increasing proportion of perinephric to subcutaneous fat is associated with adverse perioperative outcomes of robotic partial nephrectomy

To investigate the association of perinephric fat (PF) thickness and the ratio of perinephric to subcutaneous fat (PF:SF) thickness on perioperative outcomes following robotic partial nephrectomy (RPN), 240 patients undergoing RPN with preoperative computed tomography (CT) axial imaging were included. Perinephric and subcutaneous fat thickness was measured at the level of the renal vein and umbilicus, respectively. The association between PF thickness and PF:SF ratio and perioperative outcomes was determined by Spearman correlation and logistic regression. 121 men and 119 women with a median age of 55 years, BMI of 32, tumor size of 2.6 cm, and RENAL nephrometry score of 6 were included. On preoperative imaging, median PF thickness was 2.2 cm, SF thickness was 3.1 cm, and PF:SF ratio was 0.63. There were statistically significant positive correlations between PF thickness (Spearman correlation coefficient = 0.26, p = 0.001) and PF:SF ratio (Spearman correlation coefficient = 0.33, p < 0.0001) with longer operative duration of RPN. In addition, an increasing PF:SF ratio was associated with a greater risk of perioperative complications (OR = 1.82, 95 % CI 1.1–3.0, p = 0.02). No association was observed with respect to ischemia time, blood loss, length of stay, or margin status. PF thickness is associated with longer OR duration, and a greater PF:SF ratio correlated with increased OR duration and complications following RPN. These easily measured indices of fat distribution are likely more accurate in predicting perioperative outcomes after RPN than BMI alone.     

The influence of liver dysfunction on cyclosporine pharmacokinetics —A comparison between 70 per cent hepatectomy and complete bile duct ligation in dogs—

The influence of experimentally induced hepatic dysfunction on the pharmacokinetics of Cyclosporine A (CsA) was determined in dogs. The pharmacokinetics of oral (PO) and intravenous (IV) CsA were studied before and after 70 per cent hepatectomy or complete bile duct ligation (CBDL). Changes in liver function were monitored by serial measurements of serum bilirubin, and by the maximum removal rate (Rmax) and plasma disappearance rate (ICG-K) of indocyanine green (ICG). Concentrations of CsA in whole blood were measured by HPLC. Seventy per cent hepatectomy caused significant liver dysfunction: the ICG-Rmax decreased by 47.7±7.1 per cent (mean±SD) and the ICG-K decreased by 61.3±9.7 per cent during the first week after hepatectomy. At the same time, the systemic clearance (CLs) of IV-CsA decreased by 43.9±8.2 per cent, the area under the concentration curve (AUC) of IV-CsA increased by 35.4±20.8 per cent and the bioavailability of CsA decreased by 26.4±14.8 per cent. CBDL also induced significant liver dysfunction: the ICG-Rmax decreased by 39.1±12.8 per cent and the ICG-K decreased by 65.6±3.6 per cent in the second week after the operation. During the same period, the AUC of PO-CsA decreased by 69.9±10.7 per cent and the bioavailability of CsA also decreased markedly by 73.9±15.6 per cent. These data indicate that hepatic impairment significantly influences the pharmacokinetics of CsA, not only by the changes in intestinal absorption, but also by those in hepatic, metabolism. Dose adjustment is therefore necessary in the presence of hepatic dysfunction in order to maintain an adequate blood concentration of CsA without causing side effects. This research was performed in the Department of Surgery, University of Pittsburgh Health Center, University of Pittsburgh, USA     

Patterns of Use of Induction Therapy for T2N0 Esophageal Cancer

1. Download : Download high-res image (251KB)
2. Download : Download full-size image

     

The interplay between metabolic alterations,diastolic strain rate and exercise capacity in mild heart failure with preserved ejection fraction: a cardiovascular magnetic resonance study

Background

Heart failure (HF) is characterized by altered myocardial substrate metabolism which can lead to myocardial triglyceride accumulation (steatosis) and lipotoxicity. However its role in mild HF with preserved ejection fraction (HFpEF) is uncertain. We measured myocardial triglyceride content (MTG) in HFpEF and assessed its relationships with diastolic function and exercise capacity.

Methods

Twenty seven HFpEF (clinical features of HF, left ventricular EF >50%, evidence of mild diastolic dysfunction and evidence of exercise limitation as assessed by cardiopulmonary exercise test) and 14 controls underwent ¹H-cardiovascular magnetic resonance spectroscopy (¹H-CMRS) to measure MTG (lipid/water, %), ³¹P-CMRS to measure myocardial energetics (phosphocreatine-to-adenosine triphosphate - PCr/ATP) and feature-tracking cardiovascular magnetic resonance (CMR) imaging for diastolic strain rate.

Results

When compared to controls, HFpEF had 2.3 fold higher in MTG (1.45?±?0.25% vs. 0.64?±?0.16%, p?=?0.009) and reduced PCr/ATP (1.60?±?0.09 vs. 2.00?±?0.10, p?=?0.005). HFpEF had significantly reduced diastolic strain rate and maximal oxygen consumption (VO₂ max), which both correlated significantly with elevated MTG and reduced PCr/ATP. On multivariate analyses, MTG was independently associated with diastolic strain rate while diastolic strain rate was independently associated with VO₂ max.

Conclusions

Myocardial steatosis is pronounced in mild HFpEF, and is independently associated with impaired diastolic strain rate which is itself related to exercise capacity. Steatosis may adversely affect exercise capacity by indirect effect occurring via impairment in diastolic function. As such, myocardial triglyceride may become a potential therapeutic target to treat the increasing number of patients with HFpEF.

     

Idiopathic hyperzincemia with associated copper deficiency anemia: a diagnostic dilemma

Prompt serum copper and zinc in addition to vitamin B12 levels should be measured in patients suffering from refractory anemia with neurological symptoms. A timely copper supplementation can help revert the hematological and possibly the neurological manifestations.     

Emergence of <Emphasis Type="Italic">Moraxella bovoculi</Emphasis> Associated with Keratoconjunctivitis in an Organized Dairy Farm of India

An investigation was carried out in an organized dairy farm of Tamil Nadu State, India where cattle were reported to have eye infection. Preliminary clinical intervention revealed that the animals had infectious bovine keratoconjunctivitis (IBK). Isolation and identification of pathogen from eye swab revealed the presence of Moraxella spp. On further molecular characterization by Polymerase chain reaction (PCR) suggested that the isolate as Moraxella bovoculi. PCR followed by sequencing was carried and the results showed that the isolate was M. bovoculi and the sequence was submitted in the GenBank with the sequence id. KX121047. Animals were treated with antibiotics as per the results from antibiotic sensitivity test and treatment yielded good results as the animals responded to treatment. This report is the first of its kind from India as there was no previous report regarding M. bovoculi from the country. Further insights into the bacterial genome can aid in identification of the genes or regions involved in pathogenesis of IBK and also to carve out the prevention and control strategies of IBK.