Heller myotomy versus Heller myotomy with fundoplication in patients with achalasia: a systematic review and meta-analysis.

INTRODUCTION: Heller myotomy (HM) remains the gold standard procedure for achalasia. The addition of different types of fundoplication to HM has been debated in several studies. Given the contradictory reports, this meta-analysis was undertaken to compare different outcomes after HM and HM with fundoplication (HMF). METHODS: An electronic search was performed among five major databases (PubMed, Ovid, Scopus, Cochrane Library, Google Scholar) from inception to October 2019, identifying all randomised and non-randomised studies comparing HM with HMF. Two authors searched electronic databases using the keywords 'achalasia' AND 'dysphagia' AND 'gastroesophageal reflux' and all data were pooled for random-effects meta-analysis. The primary and secondary outcomes were gastroesophageal reflux and dysphagia, respectively. RESULTS: A total of six studies were included and involved 576 patients comparing HM and HMF. There was no statistically significant difference between gastroesophageal reflux in the HM vs HMF group (21.3% vs 22.9%, RR 1.32, 95% CI 0.60-2.88, p = 0.49). There was a slightly higher incidence of dysphagia observed in HM vs HMF (14.8% vs 10.8%, RR 1.54, 95% CI 0.98-2.41, p = 0.06). CONCLUSIONS: There was no statistically significant difference in long-term outcomes between a group of patients undergoing HM and a group who underwent HM with fundoplication.

Tagraxofusp, a novel CD123-directed cytotoxin to treat blastic plasmacytoid dendritic cell neoplasm.

Tagraxofusp is a toxin-cytokine fusion protein consisting of engineered diphtheria toxin (DT) and interleukin-3 (IL-3). The IL-3 domain binds to the cluster of differentiation 123 (CD123) and translocates DT into the cytosol, which leads to cell death. Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy with a strong expression of CD123. Historical data show that the prognosis of BPDCN is poor, with a median overall survival of 9 to 13 months. On December 21, 2018, the United States Food and Drug Administration (FDA) approved tagraxofusp for the treatment of adults and children with newly diagnosed or relapsed/refractory BPDCN, becoming the first FDA-approved drug for this disease. In this review, we examine the preclinical studies and phase I/II clinical studies that led to FDA approval of tagraxofusp, focusing on its molecular pharmacology, pharmacokinetics, efficacy and safety profile. We also discuss future directions regarding BPDCN management.

Large cystic lympangioma of the pancreas: a case reportum.

Lymphangioma of the pancreas is rare and presents as a large cystic mass in the retroperitoneum. The pancreatic origin can be confirmed by careful evaluation of cross sectional imaging. Preoperative differentiation from other pancreatic cystic neoplasms is difficult but possible. Large symptomatic lesions warrant surgery. The diagnosis is confirmed by typical features on histopathology and immunohistochemistry. Presented here is a case report of a pancreatic lymphangioma, discussed in the context of available literature.

Safety and effectiveness of antireflux surgery in obese patients.

Introduction The incidence of gastro-oesophageal reflux disease and obesity has increased significantly in recent years. The number of antireflux procedures being carried out on people with a higher body mass index (BMI) has been rising. Evidence is conflicting for outcomes of antireflux surgery in obese patients in terms of its safety and efficacy. Given the contradictory reports, this meta-analysis was undertaken to establish the outcomes of antireflux surgery (ARS) in obese patients and its associated safety. Methods A systematic electronic search was conducted using the PubMed, MEDLINE®, Ovid®, Cochrane Library and Google Scholar™ databases to identify studies that analysed the effect of BMI on the outcomes of ARS. A meta-analysis was performed using the random effects model. The intraoperative and postoperative outcomes that were examined included operative time, conversion to an open procedure, mean length of hospital stay, recurrence of acid reflux requiring reoperation and wrap migration. Results A total of 3,772 patients were included in 13 studies. There was no significant difference in procedure conversion rate, recurrence of reflux requiring reoperation or wrap migration between obese and non-obese patients. However, both the mean operative time and mean length of stay were longer for obese patients. Conclusions ARS in obese patients with gastro-oesophageal reflux disease is safe and outcomes are comparable with those in patients with a BMI in the normal range. A high BMI should therefore not be a deterrent to considering ARS for appropriate patients.

Laparoscopy-assisted gastrectomy in the elderly: experience from a UK centre.

BACKGROUND Gastric cancer has a high incidence in the elderly in the UK, with a significant number of patients aged 75 years or more. While surgery forms the mainstay of treatment, evidence pertaining to the management of gastric cancer in the Western population in this age group is scarce. METHODS We retrospectively reviewed the outcomes of laparoscopy-assisted total and distal gastrectomies at our centre from 2005 to 2015. Patients aged 70 years or above were included in the elderly group. RESULTS A total of 60 patients underwent laparoscopy-assisted gastrectomy over a 10-year period, with a predominance of male patients. There was no significant difference in the rate of overall surgical and non-surgical complications, in-hospital mortality, operation time and length of hospital stay, between the elderly and non-elderly groups. Univariate analysis, performed for risk factors relating to anastomotic leak and surgical complications, showed that age over 70 years and higher American Association of Anesthesiologists grades are associated with a higher, though not statistically significant, number of anastomotic leaks (P = 1.000 and P = 0.442, respectively) and surgical complications (P = 0.469 and P = 0.162, respectively). The recurrence rate within the first 3 years of surgery was significantly higher in the non-elderly group compared with the elderly group (Log Rank test, P = 0.002). There was no significant difference in survival between the two groups (Log Rank test, P = 0.619). CONCLUSIONS Laparoscopy-assisted gastrectomy is safe and feasible in an elderly population. There is a need for well-designed, prospective, randomised studies with quality of life data to inform our practice in future.

Parietex™ Composite mesh versus DynaMesh®-IPOM for laparoscopic incisional and ventral hernia repair: a retrospective cohort study.

INTRODUCTION Laparoscopic incisional and ventral hernia repair (LIVHR) is widely accepted and safe but the type of mesh used is still debated. We retrospectively compared postoperative outcomes with two different meshes commonly used in LIVHR. METHODS This is a retrospective study of patients who underwent incisional hernia repair between January 2008 and December 2010. Two meshes were used: Parietex™ Composite (Covidien, New Haven, CT, USA) and the DynaMesh®-IPOM (FEG Textiltechnik mbH, Aachen, Germany). The two groups were compared with respect to recurrence rates, incidence of seroma and intestinal obstruction. RESULTS Among the 88 patients who underwent LIVHR, 75 patients (85.2%) presented with primary incisional hernia, 10 (11.4%) presented with a first recurrence and 3 (3.4%) presented with a second recurrence. Median follow-up was 53.6 months (range 40-61 months). 12.9% of patients had recurrence in the Parietex™ Composite mesh group (n=62) in comparison to 3.8% in the DynaMesh®-IPOM mesh group (n=26; P=0.20). DynaMesh®-IPOM was associated with a significantly higher incidence of intestinal obstruction secondary to adhesions (11.5% vs. 0%, P=0.006) and lower incidence of seroma and haematoma formation compared to Parietex™ composite mesh group (0% vs. 6.4% of patients; P=0.185). CONCLUSIONS LIVHR is a safe and feasible technique. Dynamesh®-IPOM is associated with a significantly higher incidence of adhesion related bowel obstruction, albeit with a lower incidence of recurrence, seroma and haematoma formation compared with Parietex™ Composite mesh. However, there is a need for further well-designed, multicentre randomised controlled studies to investigate the use of these meshes.

Meta-analysis of closure of the fascial defect during laparoscopic incisional and ventral hernia repair.

BACKGROUND: Laparoscopic incisional and ventral hernia repair (LIVHR) is being used increasingly, with reported outcomes equivalent to those of open hernia repair. Closure of the fascial defect (CFD) is a technique that may reduce seroma formation and bulging after LIVHR. Non-closure of the fascial defect makes the repair of larger defects easier and reduces postoperative pain. The aim of this systematic review was to determine whether CFD affects the rate of adverse outcomes, such as recurrence, pseudo-recurrence, mesh eventration or bulging, and the rate of seroma formation. METHODS: A systematic search was performed of PubMed, Ovid, the Cochrane Library, Google Scholar and Scopus to identify RCTs that analysed CFD with regard to rates of adverse outcomes. A meta-analysis was done using fixed-effect methods. The primary outcome of interest was adverse events. Secondary outcomes were seroma, postoperative pain, mean hospital stay, mean duration of operation and surgical techniques employed. RESULTS: A total of 16 studies were identified involving 3638 patients, 2963 in the CFD group and 675 in the non-closure of facial defect group. Significantly fewer adverse events were noted following CFD than non-closure (4·9 per cent (79 of 1613) versus 22·3 per cent (114 of 511)), with a combined risk ratio (RR) of 0·25 (95 per cent c.i. 0·18 to 0·33; P < 0·001). CFD resulted in a significantly lower rate of seroma (2·5 per cent (39 of 1546) versus 12·2 per cent (47 of 385)), with a combined RR of 0·37 (0·23 to 0·57; P < 0·001), and shorter duration of hospital stay. No significant difference was noted in postoperative pain. CONCLUSION: CFD during LIVHR reduces the rate of seroma formation and adverse hernia-site events.

A systematic review of image segmentation methodology, used in the additive manufacture of patient-specific 3D printed models of the cardiovascular system.

BACKGROUND: Shortcomings in existing methods of image segmentation preclude the widespread adoption of patient-specific 3D printing as a routine decision-making tool in the care of those with congenital heart disease. We sought to determine the range of cardiovascular segmentation methods and how long each of these methods takes. METHODS: A systematic review of literature was undertaken. Medical imaging modality, segmentation methods, segmentation time, segmentation descriptive quality (SDQ) and segmentation software were recorded. RESULTS: Totally 136 studies met the inclusion criteria (1 clinical trial; 80 journal articles; 55 conference, technical and case reports). The most frequently used image segmentation methods were brightness thresholding, region growing and manual editing, as supported by the most popular piece of proprietary software: Mimics (Materialise NV, Leuven, Belgium, 1992-2015). The use of bespoke software developed by individual authors was not uncommon. SDQ indicated that reporting of image segmentation methods was generally poor with only one in three accounts providing sufficient detail for their procedure to be reproduced. CONCLUSIONS AND IMPLICATION OF KEY FINDINGS: Predominantly anecdotal and case reporting precluded rigorous assessment of risk of bias and strength of evidence. This review finds a reliance on manual and semi-automated segmentation methods which demand a high level of expertise and a significant time commitment on the part of the operator. In light of the findings, we have made recommendations regarding reporting of 3D printing studies. We anticipate that these findings will encourage the development of advanced image segmentation methods.

Day case laparoscopic cholecystectomy in patients with high BMI: Experience from a UK centre.

INTRODUCTION: Symptomatic gall stones may require laparoscopic cholecystectomy (LC), which is one of the most commonly performed general surgical operations in the western world. Patients with a high body mass index (BMI) are at increased risk of having gall stones, and are often considered at high risk of surgical complications due to their increased BMI. We believe that day case surgery could nevertheless have significant benefits in terms of potential cost savings and patient satisfaction in this population. We therefore compared the outcomes of day case patients undergoing LC stratified by BMI, with a specific focus on the safety and success of the procedure in obese and morbidly obese groups. METHODS: We reviewed a database of day case procedures performed between January 2004 and December 2012, including all patients with symptomatic gall stone disease who underwent LC. The patients were divided in four BMI groups: less than 25 kg/m(2), 25-29 kg/m(2), 30-39 kg/m(2) and 40 kg/m(2) or above. RESULTS: The overall success rate for day case surgery was 78%. There were no significant differences in rates of intra-abdominal collection or readmission with increasing BMI. However, increasing BMI was associated with a significant increase in the rate of wound infection. CONCLUSIONS: LC in patients with a high BMI is safe and can be performed effectively as a day case procedure.

Characterising benign fibrous soft-tissue tumours in adults: why is it so difficult and what do we need to know?

Fibrous, myofibroblastic, and fibrohistiocytic soft-tissue tumours are amongst the most common benign soft-tissue lesions encountered in clinical practice. They demonstrate varied biological behaviour and imaging characteristics. Benign fibroblastic lesions, such as nodular fasciitis, are small, have a self-limited course, and rarely recur after excision, whereas deep fibromatosis and plexiform fibrohistiocytic tumours tend to exhibit more aggressive features and often have high recurrence rates. MRI with its superior tissue contrast, multiplanar imaging capability, and lack of ionising radiation is regarded as the preferred method of tumour evaluation, tissue characterisation, and assessment of treatment response. Histopathological features are depicted at MRI, reflecting the amount and distribution of the cellular and fibrous matrix. Cellular tumours tend to show higher T2 signal intensity and post-contrast enhancement as compared to tumours with greater collagenous content, which appear dark and show less enhancement. Awareness of MR characteristics, pathological behaviour, and common sites of occurrence of fibrous soft-tissue tumours will help radiologists to determine the appropriate differential diagnosis and guide patient management.

MRI features of soft-tissue lumps and bumps.

Superficial soft-tissue lesions are frequently encountered by radiologists in everyday practice. Characterization of these soft-tissue lesions remains problematic, despite advances in imaging. By systematically using clinical history, anatomical location, and signal intensity characteristics on MRI images, one can determine the diagnosis for the subset of determinate lesions that have characteristic clinical and imaging features as well as narrow the differential diagnoses for lesions with non-specific or indeterminate characteristics. In this review, a spectrum of histologically proven benign and malignant superficial soft-tissue lesions from a single institution will be presented. In addition, a few tumour-like conditions will be included as they can be encountered during imaging of soft-tissue masses.

Decorin biology, expression, function and therapy in the cornea.

Decorin is a small leucine-rich proteoglycan (SLRP) that plays a vital role in many important cellular processes in several tissues including the cornea. A normal constituent of the corneal stroma, decorin is also found in the majority of connective tissues and is related structurally to other small proteoglycans. It interacts with various growth factors such as epidermal growth factor (EGF) and transforming growth factor beta (TGFß) to regulate processes like collagen fibrillogenesis, extracellular matrix (ECM) compilation, and cell-cycle progression. Studies have linked decorin dysregulation to delayed tissue healing in patients with various diseases including cancer. In the cornea, decorin is involved in the regulation of transparency, a key function for normal vision. It has been reported that mutations in the decorin gene are associated with congenital stromal dystrophy, a disease that leads to corneal opacity and visual abnormalities. Decorin also antagonizes TGFß in the cornea, a central regulatory cytokine in corneal wound healing. Following corneal injury, increased TGFß levels induce keratocyte transdifferentiation to myofibroblasts and, subsequently, fibrosis (scarring) in the cornea. We recently reported that decorin overexpression in corneal fibroblasts blocks TGFß-driven myofibroblast transformation and fibrosis development in the cornea in vitro suggesting that decorin gene therapy can be used for the treatment of corneal scarring in vivo.

Mature ovarian dermoid cyst invading the urinary bladder.

Mature ovarian dermoid cysts are common lesions, accounting for up to 10-25% of all ovarian neoplasms. Uncomplicated dermoid cysts are often asymptomatic and are relatively easy to diagnose on imaging and to treat. Symptoms develop once complications set in and these may cause diagnostic dilemmas. Torsion (16%) is the most common complication, while rupture, suppuration and malignant transformation are relatively uncommon. Of all these complications, spontaneous rupture into the urinary bladder is least common. The diagnosis of this condition has been through the use of cystoscopy or laparotomy in all cases reported so far. We report a case of a 30-year-old patient with pyuria and dysuria, where ultrasound examination clearly demonstrated an ovarian dermoid cyst invading the urinary bladder. A clear-cut imaging diagnosis helped to allow planning of surgery in advance and a mucosa-sparing partial bladder resection could be performed.

Clinical and immunohistochemical prognostic factors in adult glioblastoma patients.

OBJECTIVE: Glioblastomas are the commonest and the most malignant of all adult brain tumors, characterized by genetic instability, intratumoral histopathological variability, and unpredictable clinical behavior. The utility of tumor markers that reflect their underlying biology is becoming increasingly important with respect to patient prognostication and their potential role as molecular targets of therapy is being recognized. In this study, we aimed to identify the clinical factors and some immunohistochemical markers that could have an effect on patient survival in supratentorial glioblastomas. MATERIALS AND METHODS: We evaluated 54 cases of adult supratentorial glioblastomas operated over a span of 1 year, with respect to clinical features such as age, Karnofsky performance score (KPS), extent of resection, adjuvant therapy, and immunohistochemical expression of p53, EGFR (Epidermal Growth Factor Receptor) and PTEN (Phosphatase and Tensin homolog). RESULTS: Radiotherapy and KPS at presentation were significant predictors of outcome in both univariate and multivariate analyses. Among immunohistochemical variables; loss of PTEN expression in association with over-expression of EGFR showed a trend towards poorer survival, in univariate analysis. Over-expression of EGFR and/or p53 emerged as significant predictors of poor outcome on multivariate analysis, despite failing to prognosticate on univariate analysis. CONCLUSIONS: Our study shows that EGFR and p53 overexpression along with loss of PTEN expression are important adjuncts to clinical variables in prognosticating glioblastoma patients.

Spontaneous transmural migration of retained surgical textile into both small and large bowel: a rare cause of intestinal obstruction.

Retained surgical textile is an infrequent but serious complication of abdominal surgery. Diagnosis is often delayed owing to non-specific clinical symptoms and inconclusive imaging features. Medicolegal implications further complicate the issue. We report a case of a 30-year-old woman who had previously undergone caesarean section and who presented with pain and features of intestinal obstruction. Contrast-enhanced CT revealed a heterogeneous ill-defined mass with mottled air densities lying within both the large and the small bowel. Barium study beautifully demonstrated the intraluminal mass in the transverse colon extending into the jejunum, with a fistulous communication between the two loops. To the best of our knowledge, this is the first reported case in which the gauze migrated simultaneously into the large and small bowel, and where the exact site of migration was clearly mapped out on pre-operative imaging studies.

Primary central nervous system lymphomas: Indian experience, and review of literature.

UNLABELLED: Primary central nervous system lymphomas (PCNSLs) are a rare form of non-Hodgkin's lymphoma which arise within and remain confined primarily to the central nervous system (CNS). They generally account for 1-2% of all primary brain tumors and are reported to be on the rise due to the Acquired Immune Deficiency Syndrome (AIDS) epidemic. AIMS AND OBJECTIVES: To study the clinicopathological and immunophenotypic characteristics of PCNSLs and look for any differences in PCNSLs reported in India from those in other countries. MATERIALS AND METHODS: All cases of PCNSLs between January 1998 and December 2006 were reviewed. Presence of lymphadenopathy, organomegaly and bone marrow study was done to exclude the possibility of secondary involvement by lymphoma. The diagnosis was confirmed by histopathology with Hematoxylin and Eosin and reticulin stains. Immunohistochemistry (IHC) with leucocyte common antigen (LCA), CD 20 and CD 3 was performed on available blocks. The immune status was evaluated by clinical examination and human immunodeficiency virus (HIV) serology (since 1996). RESULTS: In a 19-year study period, there were 56 patients of PCNSLs, accounting for 1.07% of all intracranial neoplasms. The patients ranged from 10-75 years of age with a median age of 42 years. Barring one patient who was HIV positive, all the others were immunocompetent. All cases were diffuse large cell lymphomas on histopathology. IHC with LCA and CD 20 revealed positivity in 100% and 86.4% cases respectively. There was a single case of CD 3 positive T-cell lymphoma. In the present study, PCNSLs occurred in young immunocompetent patients and majority were diffuse large B cell lymphomas.

Bacillus circulans endophthalmitis.

An 80-year-old woman presented with right endophthalmitis, characterized by chalky white deposits covering her posterior capsule. This occurred 17 months after uncomplicated right cataract surgery. A three-port pars plana vitrectomy and partial posterior capsulectomy isolated Bacillus circulans, and the patient made a rapid and full recovery on topical cephalothin and prednisolone acetate 1%. The case demonstrates that, unlike endophthalmitis due to other Bacillus spp., B. circulans endophthalmitis does not necessarily follow a fulminant course. It is the first report describing a subacute presentation, and response to posterior capsulectomy and simple antibiotic therapy It is also the first description of B. circulans causing white plaques in the posterior capsule, a finding characteristic of chronic endophthalmitis and previously considered pathognomonic of Proprionibacterium acnes endophthalmitis.

Mutation of the conserved N-terminal cysteine (Cys92) of human presenilin 1 causes increased A beta42 secretion in mammalian cells but impaired Notch/lin-12 signalling in C. elegans.

The presenilin proteins are involved in the proteolytic processing of transmembrane proteins such as Notch/lin-12 and the beta-amyloid precursor protein (betaAPP). Mutation of a conserved cysteine (Cys60Ser) in the C. elegans presenilin sel-12 has a loss-of-function effect on Notch/lin-12 processing similar to that of null mutations in sel-12. In contrast, in mammalian cells, most missense mutations increase gamma-secretase cleavage of betaAPP. We report here that mutation of this conserved cysteine (Cys92Ser) in human presenilin 1 confers a loss-of-function effect in C. elegans, but causes increased A beta42 secretion in mammalian cells. These data suggest that the role of presenilins in Notch/lin-12 signalling and betaAPP processing are either separately regulated activities or independent activities of the presenilins.

Serum TNF-alpha and free radical scavengers in neonatal septicemia.

Tumor necrosis factor-alpha (TNF-alpha) and free radicals have been implicated in the pathogenesis of neonatal septicemia and its complications. This case control study was conducted between November 1996 to July 1997 to determine the levels of TNF-alpha and free radical scavengers viz. superoxide dismutase (SOD) and glutathione peroxidase (GPX) in the serum of 30 septic neonates and 20 healthy controls. Patients with neonatal sepsis registered significantly higher levels of TNF-alpha, SOD and GPX in comparison to controls (p < 0.05). The neonates with septic shock had five fold increase in TNF-alpha levels (2262 +/- 605.8 pg/ml) as compared to those without shock (738.8 +/- 728.8 pg/ml). There was no statistically significant difference in levels of antioxidant enzymes between neonates with shock and without shock. The levels of TNF-alpha and antioxidant enzymes were not affected by the type of organism isolated in blood culture.

Mutations in GDI1 are responsible for X-linked non-specific mental retardation.

Rab GDP-dissociation inhibitors (GDI) are evolutionarily conserved proteins that play an essential role in the recycling of Rab GTPases required for vesicular transport through the secretory pathway. We have found mutations in the GDI1 gene (which encodes uGDI) in two families affected with X-linked non-specific mental retardation. One of the mutations caused a non-conservative substitution (L92P) which reduced binding and recycling of RAB3A, the second was a null mutation. Our results show that both functional and developmental alterations in the neuron may account for the severe impairment of learning abilities as a consequence of mutations in GDI1, emphasizing its critical role in development of human intellectual and learning abilities.