Elimination of Microglia Improves Functional Outcomes Following Extensive Neuronal Loss in the Hippocampus.

With severe injury or disease, microglia become chronically activated and damage the local brain environment, likely contributing to cognitive decline. We previously discovered that microglia are dependent on colony-stimulating factor 1 receptor (CSF1R) signaling for survival in the healthy adult brain, and we have exploited this dependence to determine whether such activated microglia contribute deleteriously to functional recovery following a neuronal lesion. Here, we induced a hippocampal lesion in mice for 25 d via neuronal expression of diphtheria toxin A-chain, producing both a neuroinflammatory reaction and behavioral alterations. Following the 25 d lesion, we administered PLX3397, a CSF1R inhibitor, for 30 d to eliminate microglia. This post-lesion treatment paradigm improved functional recovery on elevated plus maze and Morris water maze, concomitant with reductions in elevated proinflammatory molecules, as well as normalization of lesion-induced alterations in synaptophysin and PSD-95. Further exploration of the effects of microglia on synapses in a second cohort of mice revealed that dendritic spine densities are increased with long-term microglial elimination, providing evidence that microglia shape the synaptic landscape in the adult mouse brain. Furthermore, in these same animals, we determined that microglia play a protective role during lesioning, whereby neuronal loss was potentiated in the absence of these cells. Collectively, we demonstrate that microglia exert beneficial effects during a diphtheria toxin-induced neuronal lesion, but impede recovery following insult. SIGNIFICANCE STATEMENT: It remains unknown to what degree, and by what mechanisms, chronically activated microglia contribute to cognitive deficits associated with brain insults. We induced a genetic neuronal lesion in mice for 25 d and found activated microglia to increase inflammation, alter synaptic surrogates, and impede behavioral recovery. These lesion-associated deficits were ameliorated with subsequent microglial elimination, underscoring the importance of developing therapeutics aimed at eliminating/modulating chronic microglial activation. Additionally, we found long-term microglial depletion globally increases dendritic spines by ∼35% in the adult brain, indicating that microglia continue to sculpt the synaptic landscape in the postdevelopmental brain under homeostatic conditions. Microglial manipulation can therefore be used to investigate the utility of increasing dendritic spine numbers in postnatal conditions displaying synaptic aberrations.

Role of endoscopic stents and selective minimal access drainage in oesophageal leaks: feasibility and outcome.

BACKGROUND: Leaks following oesophageal surgery are considered to be amongst the most dreaded complications and contributory to postoperative mortality. Controversies still exist regarding the best option for the management of oesophageal leaks due to lack of standardized treatment protocols. This study was designed to analyse the feasibility outcome and complications associated with placement of removable, fully covered, self-expanding metallic stents for oesophageal leaks with concomitant minimally invasive drainage when appropriate. METHODS: The study group included 32 patients from a prospectively maintained database of oesophageal leaks, with the majority being anastomotic leaks after minimally invasive oesophagectomy (n = 28), followed by laparoscopic cardiomyotomy (n = 3) and extended total gastrectomy (n = 1). The procedures took place between March 2007 and April 2013. RESULTS: Most patients had an intrathoracic leak (n = 22), with a mean time to detection of the leak following surgery of 7.50 days (SD = 2.23). Subsequent to endoscopic stenting, enteral feeding via a nasojejunal tube was started on the second day and oral feeding was delayed until the 14th day (n = 31). Six patients underwent thoracoscopic (n = 5) or laparoscopic drainage (n = 1) along with stenting for significant mediastinal and intra-abdominal contamination. The stent migration rate of our study was 8.54%. The overall success in terms of preventing mortality was 96%. CONCLUSION: Endoscopic stenting should be considered a primary option for managing oesophageal leaks. Delayed oral intake may reduce the incidence of stent migration. Larger stents (bariatric or colorectal stents) serve as a useful option in case of migrated stents. Combined minimally invasive procedures can be safely adapted in appropriate clinical circumstances and may contribute to better outcomes.

Longitudinal in vivo imaging to assess blood flow and oxygenation in implantable engineered tissues.

The functionality of vascular networks within implanted prevascularized tissues is difficult to assess using traditional analysis techniques, such as histology. This is largely due to the inability to visualize hemodynamics in vivo longitudinally. Therefore, we have developed dynamic imaging methods to measure blood flow and hemoglobin oxygen saturation in implanted prevascularized tissues noninvasively and longitudinally. Using laser speckle imaging, multispectral imaging, and intravital microscopy, we demonstrate that fibrin-based tissue implants anastomose with the host (severe combined immunodeficient mice) in as short as 20 h. Anastomosis results in initial perfusion with highly oxygenated blood, and an increase in average hemoglobin oxygenation of 53%. However, shear rates in the preformed vessels were low (20.8±12.8 s(-1)), and flow did not persist in the vast majority of preformed vessels due to thrombus formation. These findings suggest that designing an appropriate vascular network structure in prevascularized tissues to maintain shear rates above the threshold for thrombosis may be necessary to maintain flow following implantation. We conclude that wide-field and microscopic functional imaging can dynamically assess blood flow and oxygenation in vivo in prevascularized tissues, and can be used to rapidly evaluate and improve prevascularization strategies.

Concomitant laparoscopic ventral hernia mesh repair and bariatric surgery: a retrospective study from a tertiary care center.

OBJECTIVE: To analyze the safety in combing laparoscopic ventral hernia repair with a mesh and bariatric surgery. BACKGROUND: Obesity is one of the important precipitating factors for primary and recurrent ventral hernias (incisional and umbilical) and it is not uncommon to find these hernias in patients opting for obesity surgery. But, with no consensus or recommendation and concern of mesh infection, surgeons fear in combining these procedures, especially Roux en Y gastric bypass and sleeve gastrectomy. METHODS: In this study, we have retrospectively analyzed all patients who underwent concomitant bariatric procedure and mesh repair for ventral hernia at our institute. RESULTS: A total of 36 out of 765 patients operated at our institute between 2003 and 2011 had concomitant procedures. Eleven patients had Roux en Y gastric bypass (group I) and remaining 25 had sleeve gastrectomy (group II) performed on them. The operating times were 149 min(120-210 min) in group I and 122 min (90-220min) in group II. No immediate complications or any incidence of mesh infection or recurrence in either of the groups. CONCLUSION: Concomitant mesh repair for ventral hernias can be safely combined with bariatric procedures like Roux en Y gastric bypass and sleeve gastrectomy. But, for beginners, these should be done only in selected cases after fully informed consent from the patients.

Quantifying the Erlenmeyer flask deformity.

OBJECTIVE: Erlenmeyer flask deformity is a common radiological finding in patients with Gaucher's disease; however, no definition of this deformity exists and the reported prevalence of the deformity varies widely. To devise an easily applied definition of this deformity, we investigated a cohort of knee radiographs in which there was consensus between three experienced radiologists as to the presence or absence of Erlenmeyer flask morphology. METHODS: Using the presence or absence of Erlenmeyer flask morphology as a benchmark, we measured the diameter of the femur at the level of the physeal scar and serially at defined intervals along the metadiaphysis. RESULTS: A measured ratio in excess of 0.57 between the diameter of the femoral shaft 4 cm from the physis to the diameter of the physeal baseline itself on a frontal radiograph of the knee predicted the Erlenmeyer flask deformity with 95.6% sensitivity and 100% specificity in our series of 43 independently diagnosed adults with Gaucher's disease. Application of this method to the distal femur detected the Erlenmeyer flask deformity reproducibly and was simple to carry out. CONCLUSION: Unlike diagnostic assignments based on subjective review, our simple procedure for identifying the modelling deformity is based on robust quantitative measurement: it should facilitate comparative studies between different groups of patients, and may allow more rigorous exploration of the pathogenesis of the complex osseous manifestations of Gaucher's disease to be undertaken.

Minimally invasive oesophagectomy for carcinoma oesophagus--approaches and options in a high volume tertiary centre.

Minimally invasive oesophagectomy is being increasingly performed for treatment of carcinoma oesophagus. In this article, we overview the different types of minimally invasive oesophagectomies we used in our experience. To present an overview of the different types of minimally invasive oesophagectomies used to treat carcinoma oesophagus and to propose a simple working algorithm for surgical management of carcinoma oesophagus, a retrospective review of patients with carcinoma oesophagus who were operated at this centre during the period 1997-2009 was made. Data regarding type of surgery, level of growth, type of carcinoma, and complications were reviewed. A total of 463 patients underwent minimally invasive oesophagectomy for carcinoma oesophagus. Of these, 121 patients (26%) were female. There were no conversions. The mean age of patients was 61.6 years (range 36 years-77 years). Most patients (n = 330; 71%) had squamous cell carcinoma while 133 patients (29%) had adenocarcinoma. Overall mortality was 0.9%. Overall morbidity was 16%. Minimally invasive approaches to oesophagectomy are safe and the type of approach has to be tailored for the histology, level and stage of growth.

Evolution in techniques of laparoscopic pancreaticoduodenectomy: a decade long experience from a tertiary center.

BACKGROUND: Laparoscopic pancreaticoduodenectomy is a technically demanding surgery performed only at few centers in the world. This article aims to describe the evolution of the technique and summarizes the results in our institute over the years. METHODS: Prospective data of patients undergoing laparoscopic pancreaticoduodenectomy from March 1998 to January 2009 was retrospectively reviewed. RESULTS: There were a total of 75 patients (22 females and 53 males) with a mean age of 62 (range, 28-76) years. Conversion rate was 0%, overall postoperative morbidity was 26.7% and mortality rate was 1. 33%. Pancreatic fistula was seen in 6.67%. The mean operating time was 357 min (range 270-650), and the mean blood loss was 74 ml (range 35-410). The average time to the first bowel movement was 3 days and mean hospital stay was 8.2 days (range 6-42). Resected margins were positive in 2.6% of cases. The mean number of retrieved lymph nodes for the malignant lesions was 14 (range 8-22). CONCLUSION: Laparoscopic pancreaticoduodenectomy can be safely performed by highly skilled laparoscopic surgeons. This technique can achieve adequate margins and follow oncological principles. Randomized comparative trials are needed to establish the superiority of laparoscopy versus open surgery.

Transumbilical flexible endoscopic cholecystectomy in humans: first feasibility study using a hybrid technique.

BACKGROUND: Natural-orifice transluminal endoscopic surgery (NOTES) procedures have been tested using numerous approaches, mainly in animals. In humans, only cholecystectomy has been assessed, using a combined transvaginal and transumbilical approach. We present another variant of a hybrid technique for cholecystectomy, namely the combination of a flexible transumbilical double-channel endoscope and a 3-mm rigid transcutaneous trocar placed in the left hypochondrium for liver retraction. PATIENTS AND METHODS: The procedure was attempted in 10 well-selected young patients (M : F = 4 : 6, mean age 29.5 years). Instruments used through the two working channels of the endoscope were either a grasping forceps or snare for grasping and pulling and a hot-biopsy forceps for cold and hot preparation and dissection. Endoclips were used for cystic duct and artery closure. Postoperative analgesia consisted of one intravenous dose of analgesic, followed by oral administration for one further day. Follow-up visits were scheduled at 7 days, 30 days, 90 days, and 6 months. RESULTS: In 4 of the 10 cases the operation had to be converted to conventional laparoscopic cholecystectomy due to difficulty in dissection (in 2 cases) or uncontrollable hemorrhage (2 cases). The mean operating time was 148 minutes. Of the 6 cases in which the procedure was finished by the new approach, cystic artery bleeding occurred in 1 and was successfully clipped. One further patient had a postoperative cystic duct leak with a bilioma, successfully treated by endoscopic retrograde cholangiopancreatography with stenting. Five of the six patients reported themselves as satisfied at 3- or 6-month follow-up. CONCLUSIONS: So far, our endoscope-based transumbilical cholecystectomy technique has not yielded satisfactory results in humans. Further instrument and accessory improvements may increase both success rate and acceptance. Scarless surgery without the inherent risks of a transluminal approach may then become feasible.

Laparoscopic anterior resection and total mesorectal excision for rectal cancer: a prospective nonrandomized study.

BACKGROUND: The purpose of this study was to present our experience of laparoscopic total mesorectal resection, including ultralow resection and coloanal anastomosis. MATERIALS AND METHODS: Between 1993 and 2005, patients fit for general anesthesia, with resectable cancers, and with lower edge of tumor beyond 5 cm of the anal verge were subjected to laparoscopic anterior resection with sphincter preservation. Double stapling technique is used to establish bowel continuity. RESULTS: A total of 170 patients, 88 males and 82 females, were subjected to successful laparoscopic anterior resection, which included high anterior resection (n=90), low anterior resection (n=52), ultralow anterior resection (n=20), and coloanal anastomosis (n=8). The average age of patients was 58.4 years (12-90 years). Mean operating time was 130 min and mean hospital stay was 7 days. The morbidity was 13.5% with nil mortality. With an average follow-up of 49 months (range 9 years to 3 months), 9 patients developed local recurrence and 45 patients developed distant metastasis. CONCLUSION: In selected cases, laparoscopic anterior resection is possible for all levels of rectal tumors, allowing sphincter preservation and maintaining oncological safety.

Laparoscopic distal pancreatectomy: results of a prospective non-randomized study from a tertiary center.

BACKGROUND: Though laparoscopic distal pancreatectomy for benign conditions was first described in the early 1990s, it has not become as popular as other laparoscopic surgeries. Published literature on this topic consists of several case reports and a handful of small series. We present our experience, which, to the best of our knowledge, is the largest series reported to date. METHODS: Since 1998, 22 patients have undergone distal pancreatectomy at our institute. The technique of distal pancreatosplenectomy, as well as spleen-preserving distal pancreatectomy, is described. RESULTS: Four males and 18 females in the age range of 12-69 years underwent operation. Splenic preservation was possible in 7 patients. The tumor diameter ranged from 2.1 cm to 7.4 cm. The mean operating time was 215 min. The mean length of incision required for specimen retrieval was 3.4 cm. All patients were started on a liquid diet on the first postoperative day. The median hospital stay was 4 days. One patient developed a pancreatic fistula that was managed conservatively. At the end of an average follow-up of 4.6 years, no recurrence has been reported. CONCLUSIONS: Laparoscopic distal pancreatectomy is a safe procedure, with minimal morbidity, rapid recovery, and short hospital stay. In appropriate cases, splenic preservation is feasible.

Palanivelu hydatid system for safe and efficacious laparoscopic management of hepatic hydatid disease.

BACKGROUND: Hydatid disease, being endemic in several areas of the world, is of interest even to surgeons in non-endemic areas because they may encounter the disease due to ease and rapidity of travel as well as immigration. We describe a new device for laparoscopic management of hepatic hydatid disease. METHODS: The special trocar-cannula system--the Palanivelu hydatid system (PHS)--and the technique of operation are described. A total of 75 patients were operated on using this technique. RESULTS: In 83.3% of patients, only evacuation of the hydatid cyst by the PHS was done. In 13.7%, this was followed by left lobectomy because the cysts were large, occupying almost the entire left lobe of the liver. The remnant cavity was dealt with by omentoplasty. The average follow-up period was 5.9 years, during which there were no recurrences. CONCLUSIONS: PHS is successful in preventing spillage, evacuating the contents of hydatid cysts, performing transcystic fenestration, and for dealing with cyst-biliary communications.

Laparoscopic management of hepatic hydatid disease.

BACKGROUND: Hydatid disease is an endemic condition in several parts of the world. Owing to ease of travel, even surgeons in nonendemic areas encounter the disease and should be aware of its optimum treatment. A safe, new method of laparoscopic management of hepatic hydatid disease is described along with a review of the relevant literature. METHODS: Sixty-six cases of hepatic hydatid disease were operated on laparoscopically using the Palanivelu Hydatid System. The special trocar-cannula system used and the technique of operation are described. RESULTS: The majority of the patients presented with pain. Most of the patients had only a single cyst. The right lobe of the liver was most commonly involved. Cysts were bilateral in 4 patients. In 83.3%, simply evacuation of the hydatid cyst by the Palanivelu Hydatid System was done. In 13.7%, this was followed by a left lobectomy, as the cysts were large occupying almost the entire left lobe of the liver. The remnant cavity was dealt with by omentoplasty. The average follow-up period is 5.8 years. There have been no recurrences to date. CONCLUSION: We recommend Palanivelu Hydatid System for management of hepatic hydatid disease. We have found its efficacy to be optimum for preventing spillage, evacuating hydatid cyst contents, performing transcystic fenestration, and for dealing with cyst-biliary communications.

Laparoscopic lateral pancreaticojejunostomy: a new remedy for an old ailment.

BACKGROUND: Lateral pancreaticojejunostomy is considered as the standard surgery for chronic pancreatitis. Yet there are very few reports of this procedure being done laparoscopically. We present our experience with laparoscopic lateral pancreaticojejunostomy till date and describe our technique. MATERIAL AND METHOD: Since 1997, we have done 12 laparoscopic lateral pancreatojejunostomies. There were 9 females and 3 males and the average age was 29.3 years. The indication for surgery in all patients was intractable abdominal pain and significant weight loss. Additionally, two patients were also suffering from pancreatic ascites. RESULTS: The average diameter of the pancreatic duct was 14.7 mm. We used a four-port technique. All surgeries were completed without any conversion to open surgery. Post-operatively, there were no major morbidity and nil mortality. The average operating time was 172 minutes. Post-operative stay was short (average 5 days) and on median follow-up of 4.4 years, 83.3% patients had complete pain relief while 16.7% had partial relief. All patients had significant weight gain. CONCLUSIONS: Laparoscopic lateral pancreaticojejunostomy is safe, effective and feasible in experience hands. Mastery of intracorporeal knotting and suturing techniques is mandatory before embarking on this surgery.

Twenty years after Erich Muhe: Persisting controversies with the gold standard of laparoscopic cholecystectomy.

This review article is a tribute to the genius of Professor Erich Muhe, a man ahead of his times. We trace the development of laparoscopic cholecystectomy and detail the tribulations faced by Muhe. On the occasion of the twentieth anniversary of the first laparoscopic cholecystectomy, we take another look at some of the controversies surrounding this gold standard in the management of gallbladder disease.

Late rejection after transabdominal pre-peritoneal inguinal repair: laparoscopic extraction of mesh.

We report a 29-year-old man who developed mesh rejection 3 years after laparoscopic transabdominal pre-peritoneal inguinal repair. The mesh, which was lying in a fluid cavity adherent to the urinary bladder and right iliac vessel, was removed laparoscopically.

Imaging of pancreatic adenocarcinoma with emphasis on multidetector CT.

Pancreatic adenocarcinoma is the fourth most frequent cause of cancer-related death. The incidence is increasing and the overall survival has altered little in recent years. Moreover, patients usually present late with inoperable disease and curative resection by standard pancreatico-duodenectomy (Whipple's procedure) is associated with significant morbidity. It should only be attempted in that small group of patients lacking radiological evidence of advanced disease. Despite the recent advances in body magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS), computed tomography (CT) is the mainstay of staging in most centres and the recent development of multidetector CT machines (MDCT) has raised hope of an improvement in preoperative staging. This review focuses on the CT of pancreatic adenocarcinoma with particular emphasis on examination technique and on those criteria that determine resectability.