Change in neoadjuvant chemotherapy could alter the prognosis of patients with pancreatic adenocarcinoma: A case report

BACKGROUNDNeoadjuvant treatment has become a standard of care for borderline or locally advanced pancreatic cancer and is increasingly considered even for up-front resectable disease. The aim of this article is to present the case of a 62-year-old patient with locally advanced pancreatic adenocarcinoma who was successfully treated with gemcitabine plus nab-paclitaxel after the failure of the first line treatment.CASE SUMMARYComputerized tomography scan and magnetic resonance imaging demonstrated a nodular lesion of ill-defined limits in the body of the pancreas, measuring approximately 4.2 cm × 2.7 cm, with an infiltrative aspect. The tumor had contact with the superior mesenteric vein, splenomesenteric junction and the proximal segment of the splenic artery, causing focal reduction of its lumens. Due to vascular involvement, neoadjuvant chemotherapy treatment with eight cycles of “folinic acid, 5-fluorouracil, irinotecan and oxaliplatine” (FOLFIRINOX) were performed. At the end of the cycles, surgery was performed, but the procedure was interrupted due to finding of lesions suspected of metastasis. Gemcitabine plus nab-paclitaxel was then successfully used for neoadjuvant treatment with subsequent R0 surgical resection.CONCLUSIONGemcitabine plus nab-paclitaxel may be effective as an alternative regimen when FOLFIRINOX fails as the first line of treatment, suggesting the need for further studies to identify which patients would benefit from each type of therapeutic approach.     

EFFECT OF EXERCISE ON GLUTAMINE SYNTHESIS AND TRANSPORT IN SKELETAL MUSCLE FROM RATS

• 1 Reductions in plasma glutamine are observed after prolonged exercise. Three hypotheses can explain such a decrease: (i) high demand by the liver and kidney; (ii) impaired release from muscles; and (iii) decreased synthesis in skeletal muscle. The present study investigated the effects of exercise on glutamine synthesis and transport in rat skeletal muscle.
• 2 Rats were divided into three groups: (i) sedentary (SED; n = 12); (ii) rats killed 1 h after the last exercise bout (EX‐1; n = 15); and (iii) rats killed 24 h after the last exercise bout (EX‐24; n = 15). Rats in the trained groups swam 1 h/day, 5 days/week for 6 weeks with a load equivalent to 5.5% of their bodyweight.
• 3 Plasma glutamine and insulin were lower and corticosterone was higher in EX‐1 compared with SED rats (P < 0.05 and P < 0.01, respectively). Twenty‐four hours after exercise (EX‐24), plasma glutamine was restored to levels seen in SED rats, whereas insulin levels were higher (P < 0.001) and costicosterone levels were lower (P < 0.01) than in EX‐1. In the soleus, ammonia levels were lower in EX‐1 than in SED rats (P < 0.001). After 24 h, glutamine, glutamate and ammonia levels were lower in EX‐24 than in SED and EX‐1 rats (P < 0.001). Soleus glutamine synthetase (GS) activity was increased in EX‐1 and was decreased in EX‐24 compared with SED rats (both P < 0.001).
• 4 The decrease in plasma glutamine concentration in EX‐1 is not mediated by GS or glutamine transport in skeletal muscle. However, 24 h after exercise, lower GS may contribute to the decrease in glutamine concentration in muscle.

     

Aortic valve hemodynamics in atrial fibrillation: Should the highest Doppler signal be used to estimate severity of aortic stenosis?

Grading severity of AS in AF is complicated by varying stroke volumes associated with fluctuating maximum velocities and pressure gradients across the aortic valve. Current guidelines recommend averaging five continuous‐wave peak velocity and mean gradient (MG) Doppler signals across the aortic valve when estimating severity of AS in AF. However, it is unknown when grading severity of AS how the average of multiple Doppler signals vs the highest Doppler signal in AF compares to the Doppler signals when the patient is in normal sinus rhythm. We present a series of patients with AS who had two echocardiograms performed within 2‐4 months of each other, one when in normal sinus rhythm and one when in AF, and compare the aortic valve hemodynamics associated with the two rhythms.     

Cytogenetic studies in patients with secondary leukemia/dysmyelopoietic syndrome after different treatment modalities

Cytogenetic studies of 68 patients who developed secondary leukemia (SL)/dysmyelopoietic syndrome (DMS) after extensive chemotherapy and/or radiation therapy as well as patients who developed SL/DMS without such treatment showed that those patients who received radiation alone or with chemotherapy had more extensive numerical and structural abnormalities than those who received only chemotherapy. In terms of the specific chromosomal abnormalities, there are no differences between the various treatment groups. Hypodiploidy is the most common form of aneuploidy in these patients, with the most common numerical abnormality being the loss of chromosome 7. The most common structural abnormalities involved chromosomes 3 and 5. When compared with patients with de novo leukemia and DMS, the chromosomal abnormalities in these patients are more complex and extensive. Serial studies revealed that cytogenetic abnormalities do not precede the development of hematologic changes by significant time periods.     

Correction of the platelet adhesion defect in delta-storage pool deficiency at elevated hematocrit--possible role of adenosine diphosphate

Previous studies on patients with storage pool deficiency (SPD) who are specifically deficient in platelet dense granules (delta-SPD) have suggested a role for dense granule substances, in all likelihood adenosine diphosphate (ADP), in mediating thrombus formation on subendothelium at high shear rates. The role of dense granule substances in mediating platelet adhesion appears to be more complicated Previous studies in delta-SPD suggested an adhesion defect that was strongly influenced by the patient's hematocrit (Hct) value. To explore further the possibility that red blood cells (RBCs) may influence the role that platelet storage granules play in mediating adhesion at high shear rates, we have measured adhesion (and thrombus formation) throughout a preselected range of Hct values (30% to 60%) in normal subjects and in patients with delta-SPD. The present studies confirm the defect in platelet adhesion in patients with delta-SPD, most significantly at Hct values of 30% to 40%. This defect (but not that of thrombus formation) can be completely corrected by the addition of RBCs. The correction of the platelet adhesion defect by RBCs was specific for delta-SPD; it was not observed in either von Willebrand's disease or thrombasthenia. Studies performed on normal blood under conditions that could be expected to block any effect of ADP on adhesion and an analysis of the type of adhesion defect in delta-SPD suggest that ADP may be involved in the process required for platelet spreading on the subendothelium. The corrective effect of RBCs on platelet adhesion in delta-SPD appears to be chemical rather than physical in nature, possibly due to shear-induced release of RBC ADP or to other recently described properties of RBCs that enhance collagen- induced platelet interactions.     

Indications for surgery for aortic regurgitation

Aortic valve replacement for isolated aortic regurgitation (AR) is usually not indicated unless the regurgitation is severe. However, not all patients with severe AR require aortic valve replacement. This review focuses on the causes of AR and the pathophysiology of acute versus chronic AR, and the attendant adaptive mechanisms of the left ventricle that ultimately determine their different natural histories. Aortic valve surgery must be performed in a timely manner to prevent cardiac death, ameliorate symptoms, and limit late postoperative excess mortality.     

The Natural Abundance Of L-Canavanine,An Active Anticancer Agent,in Alfalfa,Medicago Sativa (L.)

L-Canavanine, a potentially toxic antimetabolite of L-arginine that is stored by many leguminous plants, has demonstrative antineoplastic activity against a number of animal-bearing carcinomas and cancer cell lines. This investigation evaluated the natural abundance of this anti-cancer compound in commercially available sprouts, and in ten varieties of the seed of alfalfa, Medicago Sativa (L.). Canavanine abundance in commercially grown sprouts varied according to the source; the young plant stored appreciable canavanine that ranged from 1.3 to 2.4% of the dry matter. Alfalfa seeds were also rich in this nonprotein amino acid as the canavanine content varied from 1.4 to 1.8% of the dry matter. On average, the tested seeds contained 1.54 ± 0.03% canavanine. Alfalfa seed canavanine content was comparable to the levels found in the seeds of representative members of the genus Canavalia , which are amongst the more abundance sources of this antimetabolite.