Surgery and Staging of Pancreatic Neuroendocrine Tumors: A 14-Year Experience

Background  

The aims of this study were to evaluate contemporary outcomes associated with the surgical management of pancreatic neuroendocrine tumors (PNETs) and to assess the prognostic value of the World Health Organization (WHO) classification and TNM staging for PNETs.     

Hepatitis B Virus Infection Predicts Extrahepatic Metastasis After Hepatic Resection in Patients With Large Hepatocellular Carcinoma

Background Although extrahepatic metastasis occurs rarely after hepatic resection for hepatocellular carcinoma (HCC), the prognosis of these patients is extremely poor. Predictors of extrahepatic metastasis have not been fully investigated. Methods To identify predictors of extrahepatic metastasis after resection, we retrospectively investigated 77 patients with HCC tumors >50 mm in diameter who underwent hepatic resection. We investigated correlations between postoperative extrahepatic metastasis and clinicopathologic factors as well as extrahepatic metastasis-free survival rate by log rank test and predictors of extrahepatic metastasis by univariate and multivariate logistic regression models. Results Hepatitis B surface antigen (HBs-Ag) was found in 25 (32.5%) of 77 patients, and extrahepatic metastasis occurred in 26 (33.8%). Patients with extrahepatic metastasis showed better liver function and a high occurrence of HBs-Ag positivity than those without. The 5-year extrahepatic metastasis-free survival rate was worse in patients with HBs-Ag positivity, larger tumors (≥70 mm), higher alfa-fetoprotein level (≥300 ng/mL), and lower indocyanine green retention rate at 15 minutes (ICGR₁₅) (<15%) than in those without. By univariate logistic regression analysis, HBs-Ag positivity, larger HCC tumor (≥70 mm), lower ICGR₁₅ (<15%), and lower preoperative lymphocyte count (<1000/mm³) were predictors of extrahepatic metastasis (P < .1). By multivariate analysis, HBs-Ag positivity was an independent predictor of postoperative extrahepatic metastasis (P = .04). Conclusions In patients positive for HBs-Ag, radiologic examination of extrahepatic organs should be performed as a part of the postoperative surveillance. Hepatitis B virus infection may promote establishment of extrahepatic metastasis.     

Antioxidant,cytotoxic, and anti-venom activity of Alstonia parvifolia Merr. Bark

Objective: To evaluate antioxidant, cytotoxic, and anti-venom capacity of crude bark extracts of Alstonia parvifolia Merr. Methods: Gas chromatography-mass spec...     

Novel Linker Variants of Antileishmanial/Antitubercular 7-Substituted 2-Nitroimidazooxazines Offer Enhanced Solubility

Antitubercular 7-substituted 2-nitroimidazo[2,1-b][1,3]oxazines were previously shown to exhibit potent antileishmanial and antitrypanosomal activities, culminating in a new clinical investigational drug for visceral leishmaniasis (DNDI-0690). To offset development risks, we continued to seek further leads with divergent candidate profiles, especially analogues possessing greater aqueous solubility. Starting from an efficacious monoaryl derivative, replacement of the side chain ether linkage by novel amine, amide, and urea functionality was first explored; the former substitution was well-tolerated in vitro and in vivo but elicited marginal alterations to solubility (except through a less stable benzylamine), whereas the latter groups resulted in significant solubility improvements (up to 53-fold) but an antileishmanial potency reduction of at least 10-fold. Ultimately, we discovered that O-carbamate 66 offered a more optimal balance of increased solubility, suitable metabolic stability, excellent oral bioavailability (100%), and strong in vivo efficacy in a visceral leishmaniasis mouse model (97% parasite load reduction at 25 mg/kg).     

Caregiver-Care Recipient Relationship Closeness is Associated With Neuropsychiatric Symptoms in Dementia

Objective

Closer caregiver-care recipient (CG-CR) relationships are associated with better cognitive and functional abilities, activities of daily living (in persons with dementia), and lower informal care costs.

Therapeutic approaches for neuronopathic lysosomal storage disorders

Therapy of the central nervous system (CNS) manifestations of lysosomal storage diseases (LSDs) has remained a major challenge because of its inability to deliver therapeutic agents efficiently across the intact blood–brain barrier. Non-specific therapies such as hematopoietic stem cell transplantation have been useful in globoid cell leukodystrophy (Krabbe disease) and in some mucopolysaccharidoses. Anti-inflammatory agents also show promise as adjuvant therapy. High doses of replacement therapy with native or modified enzyme show renewed promise for correction of CNS cells. Alternatively, small molecules can enter the brain relatively easily and promote reduction of accumulated substrate or function as pharmacological chaperones to enhance the level of the deficient enzyme. Gene therapy is still being developed and tested in patients. It is therefore likely that, thanks to a better understanding of disease mechanism, a variety of therapeutic approaches, used alone or in combination, will be useful to treat the devastating neurological complications of LSDs.     

Safety and learning curve in robotic colorectal surgery

Robotic surgery has recently started to be used for minimally invasive colorectal surgery. Because of limited access and high cost, very few colorectal units are available in the US. We describe our experience with benign and malignant disease since September 2008 in a dedicated colorectal practice. A prospective collected robotic database was queried for colon and rectal procedures. Anonymized demographic, intraoperative, and postoperative data, and pathology information, were collected and analyzed. A total of 48 robotic procedures for colorectal maladies were performed in the study period. There were 35 females and 13 males. The average age was 57 years. Twenty-two cases were performed for diverticulitis, 13 for malignancy (10 distal rectum (<8 cm anal verge), two rectosigmoid, and one ascending colon cancer), 10 for rectal prolapse, two for rectovaginal fistula, and one for incidental appendiceal mucocele found during a gynecologic resection. The average operating room time (OR) was 162 min and there were no conversions to open procedures. Blood loss averaged 104 mL. Mean length of hospital stay (LOS) was 5.4 days. Patient readmission occurred in 27.3% of cases. The anastamotic leak rate was 2.1% (one patient). No mortalities were reported. When the analysis was performed for colorectal malignancies (13 procedures), there were nine females and four males. Average age was 59 years. The mean OR time was 191.1 min. Mean intraoperative blood loss was 123 mL and there were no conversions to open surgery. Average LOS was 7.0 days. There was one anastamotic leak (7.7%). The length of stay was increased for the patient with anastamotic leak (18 days) and for a patient with high stoma output and postoperative ileus (17 days). Readmission rate was 30.1%. The total number of lymph nodes retrieved averaged 19.5, with a mean distal margin of 3.0 cm and in all cases negative radial margins. Robotic colorectal surgery for benign and malignant disease is safe, and short-term outcomes are comparable with those of traditional and laparoscopic surgery. Oncologic resections were adequate with excellent lymph node sampling and radial and distal margins.     

Rebuilding the Heart in Darwin's Year: Stem Cell Therapies in a Darwinian Context

The present paper tries to honour Charles Darwin's memory in the year in which the world celebrates the 200 anniversary of his birth and the 150 of the publication of The Origin of Species. After pointing out that the basis of his theory of evolution, “improvement of species”, is a time-dependent concept, commenting on the role that atrophied organs played in Darwin's work and relating this with Darwinian medicine, it is suggested that stem cell and cardiovascular therapies could be perhaps connected with some of the ideas and possibilities already envisaged by Darwin and mentioned in one of his books, The Variation of Animals and Plants under Domestication (1868).