Pathological Margin Clearance and Survival After Pancreaticoduodenectomy in a US and European Pancreatic Center.

BACKGROUND: The optimal definition of a margin-negative resection and its exact prognostic significance on survival in resected pancreatic adenocarcinoma remains unknown. This study was designed to assess the relationship between pathological margin clearance, margin type, and survival. METHODS: Patients who underwent pancreaticoduodenectomy with curative intent at two academic institutions, in Amsterdam, the Netherlands, and Boston, Massachusetts, between 2000 and 2014 were retrospectively evaluated. Overall survival, recurrence rates, and progression-free survival (PFS) were assessed by Kaplan-Meier estimates and multivariate Cox proportional hazards analysis, according to pathological margin clearance and type of margin involved. RESULTS: Of 531 patients identified, the median PFS was 12.9, 15.4, and 24.1 months, and the median overall survival was 17.4, 22.9, and 27.7 months for margin clearances of 0, < 1, and ≥1 mm, respectively (all log-rank p < 0.001). On multivariate analysis, patients with a margin clearance of ≥1 mm demonstrated a survival advantage relative to those with 0 mm clearance [hazard ratio (HR) 0.71, p < 0.01], whereas survival was comparable for patients with a margin clearance of < 1 mm versus 0 mm (HR: 0.93, p = 0.60). Patients with involvement (0 or < 1 mm margin clearance) of the SMV/PV margin demonstrated prolonged median overall survival (25.7 months) relative to those with SMA involvement (17.5 months). CONCLUSIONS: In patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma, a margin clearance of ≥1 mm correlates with improved survival relative to < 1 mm clearance and may be a more accurate predictor of a complete margin-negative resection in pancreatic cancer. The type of margin involved also appears to impact survival.

Unique predictors and economic burden of superficial and deep/organ space surgical site infections following pancreatectomy.

BACKGROUND: Surgical site infections (SSIs) are common following pancreatectomy and associated with significant morbidity and economic burden. We sought to identify distinct predictors for superficial versus deep/organ space SSIs and their effects on surgical outcomes. METHODS: ACS-NSQIP targeted pancreatectomy 2014 and 2015 databases were queried. Univariate and multivariate models were developed for both types of SSI, length of stay (LOS), and readmission. Costs were estimated based on Centers for Medicare & Medicaid Services (CMS) recommendations. RESULTS: Of 8093 patients, there were 422 (5.2%) superficial and 1005 (12.4%) deep/organ space SSIs. On multivariate analyses, preoperative biliary stenting was predictive only for superficial SSI (OR: 2.21), while BMI of 25-29.9 (OR: 1.25) and BMI ≥30 kg/m2 (OR: 1.53), pancreatic duct size <3 mm (OR: 1.30), and intermediate (OR: 1.67) versus hard gland texture were predictors of deep/organ-space SSI. Superficial and deep/organ space SSIs were independent predictors of prolonged LOS (OR: 1.74 vs 1.80) and readmission (OR: 2.59 vs 6.57). Additional readmission costs per patient secondary to superficial SSI and deep/organ space SSI were $7661.37 and $18,409.42, respectively. CONCLUSION: Deep/organ space SSI contributes more profoundly to prolonged hospital stay, readmission, and additional costs, suggesting that strategies should focus on preferential prevention of deep/organ space infections.

Surgical Management of Gallbladder Cancer: Simple Versus Extended Cholecystectomy and the Role of Adjuvant Therapy.

OBJECTIVE: To assess if simple cholecystectomy with adjuvant therapy could provide outcomes comparable to extended cholecystectomy. BACKGROUND: Current guidelines recommend extended/radical cholecystectomy for T2/T3 gallbladder cancer; however, many tumors are discovered incidentally at laparoscopic cholecystectomy. METHODS: The national Cancer Data Base 2004 to 2014 was queried for patients with pT2/T3 gallbladder adenocarcinoma who underwent resection. Adjuvant therapy was defined as chemotherapy, with or without radiotherapy, within 90 days of surgery. Baseline characteristics and overall survival were compared by χ and Kaplan-Meier method, respectively. One-to-one propensity score matching for receipt of adjuvant therapy was used to account for potential selection bias. RESULTS: A total of 6825 patients were identified. Diagnosis was made predominantly (78.9%) at the time of surgery or on pathology; 31.8% (2168) received adjuvant therapy. The majority, 88.8% (6060), had a simple cholecystectomy. Patients who received adjuvant therapy versus surgery alone were more likely to: be younger, privately insured, have no comorbidities, pT3 disease, positive lymph nodes, positive resection margins, and extended cholecystectomy. After matching, median survival was significantly longer for extended cholecystectomy with adjuvant therapy (23.3 months) than cholecystectomy with adjuvant therapy (16.4 months), which was significantly longer than either simple (12.4 months) or extended (10.7 months) cholecystectomy alone (all log-rank P<0.001). CONCLUSIONS: Adjuvant therapy prolongs survival after resection of T2/T3 tumors. Simple cholecystectomy with adjuvant therapy appears to be superior to extended resection alone in the short term and may serve as a potential alternative to re-resection in select high-risk individuals.

Upper extremity deep venous thrombosis after port insertion: What are the risk factors?

BACKGROUND: Totally implantable venous access devices (ports) are widely used, especially for cancer chemotherapy. Although their use has been associated with upper extremity deep venous thrombosis, the risk factors of upper extremity deep venous thrombosis in patients with a port are not studied adequately. METHODS: The Healthcare Cost and Utilization Project's Florida State Ambulatory Surgery and Services Database was queried between 2007 and 2011 for patients who underwent outpatient port insertion, identified by Current Procedural Terminology code. Patients were followed in the State Ambulatory Surgery and Services Database, State Inpatient Database, and State Emergency Department Database for upper extremity deep venous thrombosis occurrence. The cohort was divided into a test cohort and a validation cohort based on the year of port placement. A multivariable logistic regression model was developed to identify risk factors for upper extremity deep venous thrombosis in patients with a port. The model then was tested on the validation cohort. RESULTS: Of the 51,049 patients in the derivation cohort, 926 (1.81%) developed an upper extremity deep venous thrombosis. On multivariate analysis, independently significant predictors of upper extremity deep venous thrombosis included age <65 years (odds ratio = 1.22), Elixhauser score of 1 to 2 compared with zero (odds ratio = 1.17), end-stage renal disease (versus no kidney disease; odds ratio = 2.63), history of any deep venous thrombosis (odds ratio = 1.77), all-cause 30-day revisit (odds ratio = 2.36), African American race (versus white; odds ratio = 1.86), and other nonwhite races (odds ratio = 1.35). Additionally, compared with genitourinary malignancies, patients with gastrointestinal (odds ratio = 1.55), metastatic (odds ratio = 1.76), and lung cancers (odds ratio = 1.68) had greater risks of developing an upper extremity deep venous thrombosis. CONCLUSION: This study identified major risk factors of upper extremity deep venous thrombosis. Further studies are needed to evaluate the appropriateness of thromboprophylaxis in patients at greater risk of upper extremity deep venous thrombosis.

Regional variation in the treatment of pancreatic adenocarcinoma: Decreasing disparities with multimodality therapy.

BACKGROUND: Survival in pancreatic cancer remains poor with curative potential dependent on operative resection. We reviewed national adherence to practice guidelines to evaluate regional variation in the treatment and survival of patients with pancreatic cancer. METHODS: Retrospective cohort review of adults with pancreatic adenocarcinoma using the National Cancer Data Base from 2006 to 2013. Overall survival was compared by the Kaplan-Meier method and Cox proportional hazards models. Sequential multivariate logistic regression models were generated for odds of: a) diagnosis in stage I/II, b) resection, and c) receipt of multimodality therapy, defined as operative resection plus chemotherapy with or without radiation. Five geographic regions of the United States were used for analyses. RESULTS: A total of 115,952 patients were identified. At least 22% of patients in all stages received no treatment, with only 38.4% and 32.3% of stage I and II patients receiving multimodality therapy. On unadjusted analysis, the Northeast had the greatest survival for all stages of disease, most pronounced for stage I where patients lived 2 to 3 more months (log-rank P < .0001). While adjusted odds of early diagnosis and resection were comparable or greater across regions relative to the Northeast, patients who underwent resection in the Northeast were significantly more likely to receive multimodality therapy. Multivariate Cox modeling for patients receiving multimodality therapy accounted for differences in 3 of 4 remaining regions. CONCLUSION: Regional variations exist in pancreatic cancer treatment and survival. While providing multimodality cancer-directed therapy can help mitigate these differences, survival with pancreatic cancer needs to be interpreted in the context of overall health, underlying risk factors, and life expectancy.

Totally Implantable Venous Access Devices: A Review of Complications and Management Strategies.

OBJECTIVE: Totally implantable venous access devices (portacaths, or "ports"), are widely used for intermittent central venous access especially for cancer patients. Although ports have a superior safety margin compared with other long-term venous access devices, there are a number of complications associated with their use. METHODS: This is a narrative review. We searched PubMed and Google Scholar for articles about complications related to the use of portacaths. "Similar articles" feature of PubMed and reference list of the existing literature were also reviewed for additional relevant studies. RESULTS: In this review, we provide the latest evidence regarding the most common ones of these adverse events and how to diagnose and treat them. Immediate complications including pneumothorax, hemothorax, arterial puncture, and air embolism as well as late complications such as port infection, malfunction, and thrombosis are covered in detail. CONCLUSIONS: Physicians should be familiar with port complications and their diagnosis and management.

National Rise of Primary Pancreatic Carcinoid Tumors: Comparison to Functional and Nonfunctional Pancreatic Neuroendocrine Tumors.

BACKGROUND: New guidelines recommend differentiating between carcinoid and pancreatic neuroendocrine tumors (PNETs) during clinical trials. However, little is known about the behavior and incidence of primary pancreatic carcinoid tumors. STUDY DESIGN: We performed a retrospective cohort study using the National Cancer Data Base (NCDB) to identify adults with primary PNETs diagnosed between 2004 and 2013. The Kaplan-Meier method was used to evaluate overall survival, and multivariate Cox proportional hazards model was used to assess the hazard of death in resected patients. RESULTS: Of 10,752 patients, 12.7% were diagnosed with carcinoid tumors, 84.7% with nonfunctional and 2.6% with functional PNETs. Although the number of functional PNETs has remained relatively constant over time, rates of nonfunctional and carcinoid tumors have risen dramatically. Only 36 (5.7%) carcinoid tumors were diagnosed in 2004; this increased to 497 (27.7%) in 2013. Overall survival was significantly longer for carcinoid compared with functional and nonfunctional tumors (log-rank p < 0.0001), with 5-year survival rates of 63.1%, 58.3%, and 52.6%, respectively. For patients having resection, overall survival further improved for carcinoid tumors relative to functional (log-rank p = 0.0011) and nonfunctional (log-rank p < 0.0001) tumors, but the survival difference between functional and nonfunctional tumors disappeared (log-rank p = 0.4579); 5-year survival rates were 89.2%, 76.6%, and 78.7%, respectively. On multivariate Cox regression of the resected cohort, mortality was significantly higher for patients with functional (hazard ratio [HR] 1.81) and nonfunctional (HR 1.40) PNETs compared with carcinoid tumors. CONCLUSIONS: Primary pancreatic carcinoid tumors are increasingly being diagnosed. Differentiating PNET subtypes plays an important role in prognostication. Resection remains a critical component of care.

Biological Drugs in Guillain-Barré Syndrome: An Update.

BACKGROUND: Guillain-Barré Syndrome (GBS) is currently considered the most common global cause of acute flaccid paralysis. Currently, standard therapy for Guillain-Barré Syndrome includes intravenous immunoglobulin or plasma exchange. Despite medical advances regarding these treatments, many treated patients do not reach full recovery. Therefore several biological agents have attracted the attentions from researchers during the last decades, and various studies have investigated their role in Guillain-Barré Syndrome. OBJECTIVE: The present study aims to address emerging biological approaches to GBS while considering their efficiency and safety in treating the disease. MATERIALS AND METHODS: An extensive electronic literature search was conducted by two researchers from April 2016 to July 2016. Original articles, clinical trials, systematic reviews (with or without meta-analysis) and case reports were selected. Titles and abstracts of papers were screened by reviewers to determine whether they met the eligibility criteria, and full texts of the selected articles were retrieved. RESULTS: Herein authors focused on the literature data concerning emerging biological therapeutic agents, namely anti-C5 monoclonal antibody (Eculizumab), anti-C1q monoclonal antibody, anti-T cell monoclonal antibody, anti-CD2 monoclonal antibody, anti L-selectin monoclonal antibody, anti- CD20 monoclonal antibody (Rituximab), anti-CD52 monoclonal antibody (Alemtuzumab) and cytokine targets. By far, none of these agents have been approved for the treatment of GBS by FDA. CONCLUSION: Literature findings represented in current review herald promising results for using these biological targets. Current review represents a summary of what is already in regards and what progress is required to improve the immunotherapeutic approach of treating GBS via future studies.

Therapeutic approaches to pediatric pseudotumor cerebri: New insights from literature data.

The pseudotumor cerebri syndrome (PTCS), also known as idiopathic intracranial hypertension (IIH), is characterized by signs and symptoms of increased intracranial pressure such as headache and cranial nerve palsies, in the absence of any space-occupying mass. This condition commonly affects overweight women of childbearing age, even if it is also frequent in men and children. Children with PTCS may present with atypical signs and symptoms, with a different prognosis compared to adults. However, the treatment is the same for both children and adults, even if there are no strict treatment guidelines in regards. All treatment strategies in children are based on retrospective studies and none has been evaluated in prospective or randomized controlled trial studies. This review focuses on literature data on PTCS treatment in children.

Leukocytosis and neutrophilia after laparoscopic gastric plication.

BACKGROUND: Laparoscopic gastric plication (LGP) is a relatively novel bariatric surgery technique. We have encountered a noticeable proportion of our LGP patients with findings such as leukocytosis and neutrophilia and hypothesized that they are part of normal body response to the operation. OBJECTIVE: To evaluate the prevalence and clinical importance of leukocytosis, neutrophilia and abnormal vital signs in patients undergoing LGP during postoperative period. METHODS: Forty-four consecutive LGP patients were prospectively followed for 3 months. Records of 44 laparoscopic cholecystectomy patients were also reviewed for comparison. Preoperative and postoperative laboratory test were performed. Minor and major complications were recorded during the study period. RESULTS: Mean body mass index (BMI) and age were 37and 42.5, respectively. Mean hospital stay was 3.6 days (range: 3-8 days). Leukocytosis and neutrophilia were detected in 63% and 72% of the LGP patients, respectively, 48 h after the procedure. Whereas, after cholecystectomy only 38.5% and 18% of patients had leukocytosis and neutrophilia, respectively. 25% of the patients suffered from at least one minor complication after LGP. There was no mortality. CONCLUSIONS: Leukocytosis and neutrophilia are very common after LGP in both the complicated and uncomplicated cases, and may be a part of normal response to surgery.

Percutaneous versus Cut-Down Technique for Indwelling Port Placement.

The superiority of surgical cut-down of the cephalic vein versus percutaneous catheterization of the subclavian vein for the insertion of totally implantable venous access devices (TIVADs) is debated. To compare the safety and efficacy of surgical cut-down versus percutaneous placement of TIVADs. This is a single-institution retrospective cohort study of oncologic patients who had TIVADs implanted by 14 surgeons. Primary outcomes were inability to place TIVAD by the primary approach and postoperative complications within 30 days. Multivariate analysis was performed by logistic regression. Secondary outcomes included operative time. Two hundred and forty-seven (55.9%) percutaneous and 195 (44.1%) cephalic cut-down patients were identified. The 30-day complication rate was 5.2 per cent: 14 patients (5.7%) in the percutaneous and nine (4.6%) in the cut-down group. The technique was not a significant predictor of having a 30-day complication (odds ratio = 0.820; 95% confidence interval 0.342-1.879). Implantation failure was observed in 16 percutaneous patients (6.5%) and 28 cut-down patients (14.4%) (adjusted odds ratio for cephalic vs cut-down = 2.387; 95% confidence interval 1.275-4.606). The median operative time for percutaneous patients was 46 minutes (interquartile range = 35, 59) versus 37.5 minutes (interquartile range = 30, 49) for cut-down patients(P < 0.0001). Both the percutaneous and cut-down technique are safe and effective for TIVAD implantation. Operative times were shorter and the odds of implantation failure higher for cephalic cut-down. As implantation failure is common, surgeons should familiarize themselves with both techniques.

Nervous system involvement in clinical peripheral inflammation: A description of three pediatric cases.

Latest research data have emphasized the interaction between the nervous and the immune systems. In this regard, it has been demonstrated that the disruption of the blood-brain barrier (BBB) secondary to peripheral inflammation may play a key role in this relationship. This assumption is linked to recent findings according to which units that constitute the BBB are not only simply neurologic but have also been reconsidered as "neurovascular" elements, through which immune system molecules are vehiculated within the central nervous system (CNS). Herein, we report two cases of food allergy (FA) and one case of infective gastroenteritis, associated with a spectrum of neurologic disorders involving both the CNS and the peripheral nervous system (PNS), postulating some etiopathogenic hypotheses to explain the link between peripheral inflammation and diseases of the nervous system (NS). Three pediatric cases of secondary NS involvement after gastrointestinal (GI) inflammation of different nature have been reported. The first case highlights the link between FA and CNS; the second one is based on a description of a link between GI infection and CNS involvement while the third one describes the relationship between FA and PNS. The importance of these reports relies on the clinical demonstration of a link between the immune system and the NS. The relationship between immune system and NS seems to have pleiotropic aspects, involving different areas of the NS, such as CNS and PNS, which also seem to be in some way interconnected.

Changes in the body composition after laparoscopic gastric plication: a short-term prospective case series.

BACKGROUND: While laparoscopic gastric plication (LGP) results in a rapid weight loss in the first postoperative months, changes in body composition after LGP have not been studied previously. OBJECTIVE: To evaluate the body composition after LGP. SETTING: A tertiary referral hospital. METHOD: This is a consecutive case series. Body composition was measured using bioimpedance analysis with a Tanita BC-418 by 1 nutritionist. Weight, fat mass (FM), fat-free mass (FFM), and total body water (TBW) were measured at baseline and at 1, 3, and 6 months postoperative. RESULTS: Sixteen consecutive patients underwent LGP. No intraoperative or major postoperative complications occurred during the follow-up period. No patient was lost to follow-up at any point during the study period. Mean postoperative total weight loss was 31 kg after 6 months, of which 25.5 kg (83%) was due to FM reduction. %FM was decreased by 15% after 6 months, whereas %TBW increased by 11%. CONCLUSIONS: Most of the weight loss caused by LGP is attributable to FM loss, and FFM loss is minimal after LGP. Therefore, LGP shifts body composition toward normal.

Natalizumab in multiple sclerosis: discontinuation, progressive multifocal leukoencephalopathy and possible use in children.

In the early 1990s, attention was drawn to the migration of immune cells into the central nervous system via the blood-brain barrier. The literature showed that lymphocytes binding to the endothelium were successfully inhibited by an antibody against α4ß1 integrin. These biological findings resulted in the development of a humanized antibody to α4 integrin - natalizumab (NTZ) - to treat multiple sclerosis (MS). Here, we provide a systematic review and meta-analysis on the efficacy and safety of natalizumab, trying to answer the question whether its use may be recommended both in adult and in pediatric age groups as standard MS treatment. Our results highlight the improvement of clinical and radiological findings in treated patients (p < 0.005), confirming NTZ efficacy. Nevertheless, if NTZ is shown to be efficient, further studies should be performed to evaluate its safety and to target the MS profile that could benefit from this treatment.

The usefulness of immunotherapy in pediatric neurodegenerative disorders: A systematic review of literature data.

Immunotherapeutic strategies to treat neurodegenerative disorders have inspired the scientific community. The aim of our review is to address the translational aspects of neuroimmunology to describe the efficacy of immunotherapy in the treatment of pediatric neurodegenerative disorders. In the studies we analyzed IVIG were found to be efficient in the treatment of post-streptococcal neurodegenerative disorders, even if in PANDAS, plasma-exchange (PE) showed a higher efficiency. IVIG were also successfully used in ADEM and Guillan-Barré syndrome. In Sydenham Chorea the use of methylprednisolone was found in most cases as efficient as IVIG, while in Tourette's Syndrome, Colecoxib was successfully used in one patient. Pediatric Multiple Sclerosis seems to respond better to immunosuppressant agents (Mitoxantrone, Cyclophosphamide, Natalizumab), as well as Neuromyelitis optica (Rituximab, Mycofenolate). The importance of this review relies in the attempt to draw standardized guidelines for immunotherapy in pediatric neurodegeneratve disorders.

Epilepsy and innate immune system: A possible immunogenic predisposition and related therapeutic implications.

Recent experimental studies and pathological analyses of patient brain tissue samples with refractory epilepsy suggest that inflammatory processes and neuroinflammation plays a key-role in the etiopathology of epilepsy and convulsive disorders. These inflammatory processes lead to the secretion of pro-inflammatory cytokines responsible for blood-brain-barrier disruption and involvement of resident immune cells in the inflammation pathway, occurring within the Central Nervous System (CNS). These elements are produced through activation of Toll-Like Receptors (TLRs) by exogenous and endogenous ligands thereby increasing expression of cytokines and co-stimulatory molecules through the activation of TLRs 2, 3, 4, and 9 as reported in murine studies.It has been demonstrated that IL-1ß intracellular signaling and cascade is able to alter the neuronal excitability without cell loss. The activation of the IL-1ß/ IL-1ß R axis is strictly linked to the secretion of the intracellular protein MyD88, which interacts with other cell surface receptors, such as TLR4 during pathogenic recognition. Furthermore, TLR-signaling pathways are able to recognize molecules released from damaged tissues, such as damage-associated molecular patterns/proteins (DAMPs). Among these molecules, High-mobility group box-1 (HMGB1) is a component of chromatin that is passively released from necrotic cells and actively released by cells that are subject to profound stress. Moreover, recent studies have described models of epilepsy induced by the administration of bicuculline and kainic acid that highlight the nature of HMGB1-TLR4 interactions, their intracellular signaling pathway as well as their role in ictiogenesis and epileptic recurrence.The aim of our review is to focus on different branches of innate immunity and their role in epilepsy, emphasizing the role of immune related molecules in epileptogenesis and highlighting the research implications for novel therapeutic strategies.

Therapeutic targeting of Toll-like receptors in cutaneous disorders.

INTRODUCTION: The role of skin, as a part of the immune system has long been elucidated. Toll-like receptors (TLRs), a group of pattern recognition receptors, are involved in the recognition of invading pathogens, initiation of immune responses and regulation of both innate and adaptive immune systems. There is a growing body of evidence supporting the role of TLRs in the pathophysiology of several skin conditions, which mandates the development and study of therapeutic strategies that target TLRs. AREAS COVERED: With regards to the role of TLRs in pathogenesis of diverse cutaneous conditions, recent advances, as well as the future prospects of therapeutic implications of TLRs in cutaneous disorders is reviewed in this article. EXPERT OPINION: Although non-specific therapeutic strategies seem to reduce the symptoms in majority of patients, a considerable proportion remain untreated or have to deal with inevitable adverse effects of such therapies. Since TLRs regulate many patholophysiological processes, they could be good candidates for more specific therapeutic approaches. TLR targeting as the first recipient of invading pathogens is a growing concept in this field.

Clinical performance of seven prescreening tools for osteoporosis in Iranian postmenopausal women.

This study was designed to evaluate seven prescreening osteoporosis models in postmenopausal Iranian women. This study was performed on 8644 postmenopausal women who have been referred for bone mineral densitometry (BMD) in BMD center of Shariati hospital in Tehran between 2001 and 2011. Diagnostic properties of seven prescreening instruments were evaluated. With regard to area under curve (AUC), these models have low accuracy (AUC ≤ 0.65). Considering only femoral neck or total femur area, these models had low accuracy but were more sensitive. Except for three models with sensitivities of ≤65 % in both osteoporosis and fracture threshold, other models were around 70 % sensitive. However, these models were not considered clinically useful regarding their positive predictive values (PPV) especially in BMDs ≤02.5. With regard to different measures of diagnostic property, none of these models were good screening tools for osteoporosis or fracture threshold. Although some of them are sensitive, considering other measures such as PPV indicates that they are not completely useful for clinical use. Attempts should be made for developing newer prescreening methods and calibration of the existing models with regard to the studied population.