A flexible implant for acute intrapancreatic electrophysiology.

Microelectrode arrays (MEAs) have proven to be a powerful tool to study electrophysiological processes over the last decades with most technology developed for investigation of the heart or brain. Other targets in the field of bioelectronic medicine are the peripheral nervous system and its innervation of various organs. Beyond the heart and nervous systems, the beta cells of the pancreatic islets of Langerhans generate action potentials during the production of insulin. In vitro experiments have demonstrated that their activity is a biomarker for blood glucose levels, suggesting that recording their activity in vivo could support patients suffering from diabetes mellitus with long-term automated read-out of blood glucose concentrations. Here, we present a flexible polymer-based implant having 64 low impedance microelectrodes designed to be implanted to a depth of 10 mm into the pancreas. As a first step, the implant will be used in acute experiments in pigs to explore the electrophysiological processes of the pancreas in vivo. Beyond use in the pancreas, our flexible implant and simple implantation method may also be used in other organs such as the brain.

Impact of preoperative body mass index and weight loss on morbidity and mortality following colorectal cancer-a retrospective cohort study.

PURPOSE: Body weight and preoperative weight loss (WL) are controversially discussed as risk factors for postoperative morbidity and mortality in colorectal cancer surgery. The objective of this study is to determine whether body mass index (BMI) or WL is associated with a higher postoperative complication rate. METHODS: In this retrospective cohort study, data analysis of 1241 consecutive patients undergoing colorectal cancer surgery in an 11-year period was performed. The main outcome measures were wound infections (WI), anastomotic leakages (AL), and in-house mortality. RESULTS: A total of 697 (56%) patients with colon and 544 (44%) with rectum carcinoma underwent surgery. The rate of WI for each location increased with rising BMI. The threshold value was 28.8 kg/m2. Obese patients developed significantly more WI than normal-weight patients did following rectal resection (18.0% vs. 8.2%, p = 0.018). Patients with preoperative WL developed significantly more AL following colon resections than did patients without preoperative WL (6.2% vs. 2.5%, p = 0.046). In-house mortality was significantly higher in obese patients following colon resections than in overweight patients (4.3% vs. 0.4%, p = 0.012). Regression analysis with reference to postoperative in-house mortality revealed neither increased BMI nor WL as an independent risk factor. CONCLUSIONS: Increased preoperative BMI is associated with a higher WI rate. AL rate after colon resection was significantly higher in patients showing preoperative WL. Preoperative BMI and WL are therefore risk factors for postoperative morbidity in this study. Nevertheless, this has to be further clarified by means of prospective studies. Trial registration DRKS00025359, 21.05.2021, retrospectively registered.

Early postoperative endoscopic evaluation of rectal anastomoses: a prospective cross-sectional study.

BACKGROUND: Reported incidence of anastomotic leakage (AL) of rectal anastomoses is up to 29% with an overall mortality up to 12%. Nevertheless, there is no uniform evidence-based diagnostic procedure for early detection of AL. The objective of this prospective clinical trial was to demonstrate the diagnostic value of early postoperative flexible endoscopy for rectal anastomosis evaluation. METHODS: Flexible endoscopy between 5 and 8th postoperative day was performed consecutively in 90 asymptomatic patients. Sample size calculation was made using the two-stage Simon design. Diagnostic value was measured by management change after endoscopic evaluation. Anastomoses were categorized according to a new classification. Study is registered in German Clinical Trials Register (DRKS00019217). RESULTS: Of the 90 anastomoses, 59 (65.6%) were unsuspicious. 20 (22.2%) were suspicious with partial fibrin plaques (n = 15), intramural hematoma and/or local blood coagulum (n = 4) and ischemic area in one. 17 of these anastomoses were treated conservatively under monitoring. In three a further endoscopic re-evaluation was performed and as consequence one patient underwent endoscopic vacuum therapy. 11 (12.2%) AL were detected. Here, two could be treated conservatively under monitoring, four with endoscopic vacuum therapy and five needed revision surgery. No intervention-related adverse events occurred. A change in postoperative management was made in 31 (34.4%) patients what caused a significant improvement of diagnosis of AL (p < 0.001). CONCLUSIONS: Early postoperative endoscopic evaluation of rectal anastomoses is a safe procedure thus allows early detection of AL. Early treatment for suspicious anastomoses or AL could be adapted to avoid severe morbidity and mortality.

Evaluation of different setting configurations with a new developed telemedical interface of a parallel kinematic robotic system - An experimental development study.

BACKGROUND: For development of a minimally invasive intracorporal micromanipulator, a master-slave telemanipulation system was required. METHODS: Different input positions for a tablet-based input device with a heads-up centred screen were evaluated. Personal preference was assessed using a questionnaire. Then, the most ergonomic and intuitive position was compared to a surgical reference position based on laparoscopic sigmoid resection. RESULTS: After comparing a 45°, 75° (pitch) and 60°/20° (pitch/yaw) to a 60° reference position no significant differences in processing time and number of failures could be demonstrated. Study participants indicated the 60°/20° position as the most comfortable in the questionnaire. This was therefore compared with the laparoscopic reference position, both sitting and standing. Here, the laparoscopic sitting position was perceived to be the most ergonomic. CONCLUSIONS: The developed input device offers a maximum of flexibility and individualisation to reach ergonomic and intuitive conditions. General recommendations regarding an optimal setting cannot be given, based on our results.

[Laparoscopic Heller Myotomy in the Treatment of Achalasia]. / Laparoskopische Heller-Myotomie zur Therapie der Achalasie.

BACKGROUND: Achalasia refers to a primary oesophageal motility disorder characterised by the absence of peristalsis and incomplete or complete lack of relaxation of the lower oesophageal sphincter. The cardinal symptom is dysphagia. The therapeutic goal is surgical or interventional repair of the oesophageal outflow tract at the level of the oesophagogastric junction. INDICATION: We present the case of a 24-year-old patient with dysphagia accompanied by regurgitations, odynophagia as well as an unintentional weight loss over two years. METHODS: The video describes the preoperative imaging as well as endoscopic findings and demonstrates the technique of laparoscopic Heller myotomy followed by Dor fundoplication. CONCLUSIONS: Concerning the therapy of classic achalasia, laparoscopic Heller myotomy followed by Dor fundoplication - despite controversies regarding peroral endoscopic myotomy as an alternative therapeutic option - can be considered as an established standard procedure.

The rate of cholangiocarcinoma in Caroli Disease A German multicenter study.

BACKGROUND: Caroli Disease (CD) and Caroli Syndrome (CS) are rare disorders presenting with dilation of the intrahepatic bile ducts. CD/CS are associated with cholangiocarcinoma (CCA). However, the true incidence of CCA is still unclear, although it may serve as an indication for surgery. In this paper, we analyzed (I) the incidence of CCA in German centers, (II) reviewed our single center population together with its clinical presentation and (III) performed a thorough literature review. METHODS: 17 large HPB-centers across Germany were contacted and their patients after surgical treatment due to CD/CS with histopathology were included. Medline search for all studies published in English or German literature was performed. Patients who underwent surgery at our department between 2012 and 2020 due to CD or CS were analyzed. RESULTS: In the multicenter study, 79 patients suffered from CD and 119 patients from CS, with a total number of 198 patients. In 14 patients, CCA was found (Overall: 7,1%; CD: 6,3%, CS 7,6%). Between 2012 and 2020, 1661 liver resections were performed at our department. 14 patients underwent surgery due to CD or CS. Histological examination showed synchronous cholangiocarcinoma in one patient. The literature review revealed a CCA-rate of 7,3% in large series, whereas in case reports a rate of 6,8% was found. CONCLUSION: There is risk of malignant transformation and patients with CD might also benefit from resection due to improvement of symptoms. Therefore, resection is strongly advised. As certain patients with CS require transplantation, treatment should not be guided by the relatively low rate of CCA but by the concomitant diseases that come along with hepatic failure.

Reducing Degrees of Freedom in Surgical Suturing: Implications for Minimally Invasive Device Development-A Prospective Experimental Study.

Open surgery allows the use of all 6 degrees of freedom (DOF; x-y-z and roll-pitch-yaw), whereas laparoscopy requires working under limitation to 4 axes. We present a prospective experimental study evaluating translational and rotational DOF restriction in surgical suturing tasks. An experimental platform included a kinematic structure that limited the maneuverability of the surgical instruments. The subjects (n=20) worked in a randomized order using (1) 6DOF, (2) 4DOF with 3 translational and 1 rotational DOF (4TRANS), and (3) 4DOF with 1 translational and 3 rotational DOF (4ROT). The time required to perform each task was recorded. Suturing and knot tying were significantly faster under 6DOF compared with 4ROT (both P<0.001) and 4TRANS (both P<0.001). Assessment of subjective difficulty and impairment showed most favorable results for 6DOF. The advantage of rotational compared with translational DOF should be considered in the development of future surgical devices.

Detection of adverse events leading to inadvertent injury during laparoscopic cholecystectomy using convolutional neural networks.

Uncontrolled movements of laparoscopic instruments can lead to inadvertent injury of adjacent structures. The risk becomes evident when the dissecting instrument is located outside the field of view of the laparoscopic camera. Technical solutions to ensure patient safety are appreciated. The present work evaluated the feasibility of an automated binary classification of laparoscopic image data using Convolutional Neural Networks (CNN) to determine whether the dissecting instrument is located within the laparoscopic image section. A unique record of images was generated from six laparoscopic cholecystectomies in a surgical training environment to configure and train the CNN. By using a temporary version of the neural network, the annotation of the training image files could be automated and accelerated. A combination of oversampling and selective data augmentation was used to enlarge the fully labeled image data set and prevent loss of accuracy due to imbalanced class volumes. Subsequently the same approach was applied to the comprehensive, fully annotated Cholec80 database. The described process led to the generation of extensive and balanced training image data sets. The performance of the CNN-based binary classifiers was evaluated on separate test records from both databases. On our recorded data, an accuracy of 0.88 with regard to the safety-relevant classification was achieved. The subsequent evaluation on the Cholec80 data set yielded an accuracy of 0.84. The presented results demonstrate the feasibility of a binary classification of laparoscopic image data for the detection of adverse events in a surgical training environment using a specifically configured CNN architecture.

[Robotic Assisted Proctocolectomy with Ileal Pouch-Anal Anastomosis in a Case of Suspected Hereditary Polyposis]. / Roboterassistierte Proktokolektomie mit ileopouchanaler Anastomose bei Verdacht auf hereditäre Polyposis.

BACKGROUND: Various forms of hereditary polyposis have been described in the literature. Classical familial adenomatous polyposis (FAP) is a rare, autosomal dominantly inherited disease which is caused by a germline mutation in the adenomatous polyposis coli gene (APC). Patients with this diagnosis successively develop multiple polyps of the colon. Left untreated, FAP almost inevitably leads to malignant transformation. INDICATION: We present the case of a 37-year-old patient with histologically confirmed, stenotic adenocarcinoma of the descending colon and an initially suspected hereditary polyposis due to multiple polyps in the descending and sigmoid colon. METHODS: The video describes the preoperative imaging as well as endoscopic findings and demonstrates the technique of a two-stage, robotically assisted proctocolectomy with ileal pouch-anal anastomosis (IPAA) and the creation of a temporary loop ileostomy. CONCLUSIONS: With respect to the surgical treatment of classic FAP, restorative proctocolectomy (RPC) with ileal J-pouch construction can be regarded as an established standard procedure, despite controversy regarding various technical aspects. Minimally invasive strategies should be considered as an equivalent option compared to conventional techniques.

Therapy of pessary-induced rectovaginal fistula and pelvic organ prolapse in elderly patients by vaginal approach and modified LeFort colpocleisis: a case series.

PURPOSE: Pelvic organ prolapse (POP) presents a common benign condition in women associated with reduced quality of life (QoL). The use of pessaries is considered a first-line treatment of POP. However, pessaries can cause perforations into adjacent organs resulting in fistulas. We present a series of three cases of rectovaginal fistulas (RVF) due to pessary perforation. METHODS: Three consecutive cases of pessary-induced RVF in patients with POP stage IV were assessed between September 2016 and September 2019. Consensus for therapeutic strategy was reached by an interdisciplinary board. RESULTS: The RVF were located in the posterior vaginal wall and had a diameter of up to 60 mm. In one of three patients, a two-step approach was chosen with the ostomy being performed at the same time as fistula closure and modified LeFort colpocleisis. It was followed by ostomy closure 3 months later. In two patients, a three-step approach was chosen with the ostomy performed separately due to a local tissue inflammation around RVF. Neither fistula nor POP recurrences have occurred so far. CONCLUSION: Combined temporary gastrointestinal diversion, RVF closure and POP therapy can be performed as a two- or three-stage approach. Lack of evidence and standardized algorithms in RVF therapy make further clinical studies essential. We encourage the preoperative assessment of any case of complex rectovaginal fistula by an interdisciplinary board for determining an individualized treatment.

ALPPS for Locally Advanced Intrahepatic Cholangiocarcinoma: Did Aggressive Surgery Lead to the Oncological Benefit? An International Multi-center Study.

BACKGROUND: ALPPS is found to increase the resectability of primary and secondary liver malignancy at the advanced stage. The aim of the study was to verify the surgical and oncological outcome of ALPPS for intrahepatic cholangiocarcinoma (ICC). METHODS: The study cohort was based on the ALPPS registry with patients from 31 international centers between August 2009 and January 2018. Propensity score matched patients receiving chemotherapy only were selected from the SEER database as controls for the survival analysis. RESULTS: One hundred and two patients undergoing ALPPS were recruited, 99 completed the second stage with median inter-stage duration of 11 days. The median kinetic growth rate was 23 ml/day. R0 resection was achieved in 87 (85%). Initially high rates of morbidity and mortality decreased steadily to a 29% severe complication rate and 7% 90-day morbidity in the last 2 years. Post-hepatectomy liver failure remained the main cause of 90-day mortality. Multivariate analysis revealed insufficient future liver remnant at the stage-2 operation (FLR2) to be the only risk factor for severe complications (OR 2.91, p = 0.02). The propensity score matching analysis showed a superior overall survival in the ALPPS group compared to palliative chemotherapy (median overall survival: 26.4 months vs 14 months; 1-, 2-, and 3-year survival rates: 82.4%, 70.5% and 39.6% vs 51.2%, 21.4% and 11.3%, respectively, p < 0.01). The survival benefit, however, was not confirmed in the subgroup analysis for patients with insufficient FLR2 or multifocal ICC. CONCLUSION: ALPPS showed high efficacy in achieving R0 resections in locally advanced ICC. To get the most oncological benefit from this aggressive surgery, ALPPS would be restricted to patients with single lesions and sufficient FLR2.

Novel box trainer for taTME - prospective evaluation among medical students.

BACKGROUND: Transanal total mesorectal excision (taTME) has been subject to extensive research and increasing clinical application. It allows further reduction of trauma by accessing via a natural orifice. Manifold platforms and instruments have been introduced and heterogeneity in surgical techniques exists. Because of the technique's complexity there is a persistent need for dedicated training devices and concepts. MATERIALS AND METHODS: The key steps of taTME were analyzed and a box trainer with three modules resembling these steps was designed and manufactured. Twenty-one surgically inexperienced medical students performed five repetitions of the three tasks with the new box trainer. Time and error count were analyzed for assessment of a learning curve. RESULTS: A significant reduction of processing time could be demonstrated for tasks 1-3 (p < 0.001; p < 0.001; p = 0.001). The effect size was high for comparison of repetition 1 and 5 and decreased over the course (task 1: r = 0.88 vs. r = 0.21; task 2: r = 0.86 vs. r = 0.23; task 3: r = 0.74 vs. r = 0.44). Also, a significant reduction of errors was demonstrated for tasks 1 and 2. The decrease of effect size was analogously demonstrated. CONCLUSIONS: The trainer might help to reduce the use of animal models for testing of platforms and instruments as well as gaining first-hand experience in transanal rectal resection.

[First Robotic Assisted Resection of a Retrorectal Tailgut Cyst - Video Case Report of a 27-Year-Old Female Patient]. / Roboterassistierte Resektion einer retrorektalen Tailgut-Zyste ­ erstbeschreibender Videofallbericht einer 27-jährigen Patientin.

PURPOSE: Tailgut cysts are a rare form of retrorectal tumours. They are also referred to as cystic hamartomas and predominantly affect female patients. Malignant transformation is thought to occur in 2 - 10% of cases, but there is scant further evidence. Besides the risk of malignant transformation, the feared complications include infection, difficulties in defecation, or potential dystocia necessitating in sano resection. INDICATION: We describe the case of a 27-year-old female patient presenting with a prolapsing round structure during defaecation. MRI, endosonography and transrectal drainage were carried out to exclude malignancy. We performed resection of the retrorectal tailgut cyst by robotic surgery. To the authors knowledge, this access has not previously been described for tailgut cyst resection. METHOD: Our video shows preoperative diagnostic testing, endoscopic drainage and robotic resection of the tailgut cyst. An intraoperative lesion of the dorsal rectum was successfully closed by suture. CONCLUSIONS: Different surgical techniques have been described for tailgut cyst resection. That with the widest application is posterior/sacral access, followed by abdominal and transrectal techniques. There are no published reports of robotic resection. We chose the robotic approach, as this is the surgeon's preferred technique for minimally invasive surgery of the pelvis.

Resection for Klatskin tumors: technical complexities and results.

Klatskin's tumors, actually-redefined as perihilar cholangiocarcinoma (phCCA) do represent 50-70% of all CCAs and develop in a context of chronic inflammation and cholestasis of bile ducts. Surgical resection provides the only chance of cure for this disease but is technically challenging because of the complex, intimate and variable relationship between biliary and vascular structures at this location. Five years survival rates range between 25-45% (median 27-58 months) in case of R0 resection and 0-23% (median 12-21 months) in case of R1 resection respectively. It should be noted that the major costs of high radicality are represented by relative high morbidity and mortality rates (i.e., 20-66% and 0-9% respectively). Considering the fact that radical resection may represent the only curative treatment of phCCA, we focused our review on surgical planning and techniques that may improve resectability rates and outcomes for locally advanced phCCA. The surgical treatment of phCCA can be successful when following aspects have been fulfilled: (I) accurate preoperative diagnostic aimed to identify the tumor in all its details (localization and extension) and to study all the risk factors influencing a posthepatectomy liver failure (PHLF): i.e., liver volume, liver function, liver quality, haemodynamics and patient characteristics; (II) High end surgical skills taking in consideration the local extension of the tumor and the vascular invasion which usually require an extended hepatic resection and often a vascular resection; (III) adequate postoperative management aimed to avoid major complications (i.e., PHLF and biliary complications). These are technically challenging operations and must be performed in a high volume centres by hepato-biliary-pancreas (HBP)-surgeons with experience in microsurgical vascular techniques.

6-Hydroxydopamine leads to T2 hyperintensity, decreased claudin-3 immunoreactivity and altered aquaporin 4 expression in the striatum.

The neurotoxin 6-hydroxydopamine (6-OHDA) is frequently used in animal models to mimic Parkinson's disease. Imaging studies describe hyperintense signalling in regions close to the site of the 6-OHDA injection in T2-weighted (T2w) magnetic resonance imaging (MRI). The nature of this hyperintense signal remains elusive and still is matter of discussion. Here we demonstrate hyperintense signalling in T2w MRI and decreased apparent diffusion coefficient (ADC) values following intraventricular injection of 6-OHDA. Moreover, we show decreased GFAP immunoreactivity in brain regions corresponding to the region revealing the hyperintense signalling, probably indicating a loss of astrocytes due to a toxic effect of 6-OHDA. In the striatum, where no hyperintense signalling in MRI was observed following intraventricular 6-OHDA injection, immunohistochemical and molecular analyses revealed an altered expression of the water channel aquaporin 4 and the emergence of vasogenic edema, indicated by an increased perivascular space. Moreover, a significant decrease of claudin-3 immunoreactivity was observed, implying alterations in the blood brain barrier. These findings indicate that intraventricular injection of 6-OHDA results (1) in effects close to the ventricles that can be detected as hyperintense signalling in T2w MRI accompanied by reduced ADC values and (2) in effects on brain regions not adjacent to the ventricles, where a disturbance of water homeostasis occurs. We clearly demonstrate that 6-OHDA leads to brain edema that in turn may affect the overall results of experiments (e.g. behavioral alterations). Therefore, when using 6-OHDA in Parkinson's models effects that are not mediated by degeneration of catecholaminergic neurons have to be considered.

Effect of 6-hydroxydopamine (6-OHDA) on proliferation of glial cells in the rat cortex and striatum: evidence for de-differentiation of resident astrocytes.

Reactive astrogliosis is the universal response to any brain insult. It is characterized by cellular hypertrophy, up-regulation of the astrocyte marker glial fibrillary acidic protein (GFAP), and proliferation. The source of these proliferating cells is under intense debate. Progenitor cells derived from the subventricular zone (SVZ), cells positive for chondroitin sulfate proteoglycan (NG2(+)), and de-differentiated astrocytes have been proposed as the origin of proliferating cells following injury. We have analyzed the effect of intraventricular-applied 6-hydroxydopamine (6-OHDA) on the proliferation and morphology of astrocytes in rat cortex and striatum by means of immunohistochemistry and confocal laser microscopy. At 4 days post-lesion, GFAP expression increased markedly. A subpopulation of the GFAP(+) cells co-expressed Ki-67, indicating that these cells were proliferating. To investigate whether these cells (1) arose from migrating SVZ progenitor cells, (2) derived from NG2(+) progenitor cells, or (3) de-differentiated from resident astrocytes, we studied the expression of the migration marker doublecortin (Dcx), the oligodendrocyte progenitor marker NG2, and the progenitor markers Nestin and Pax6. The proliferating Ki-67(+) cells co-expressed Nestin and Pax6, whereas no co-expression of Ki-67 with NG2 or the migration marker Dcx was observed. Thus, resident astrocytes de-differentiate, in response to the intraventricular application of 6-OHDA, to a phenotype resembling radial glia cells, which represent transient astrocyte precursors during development. An understanding of the mechanisms of the de-differentiation of mature astrocytes might be useful for designing new approaches to cell therapy in neurodegenerative diseases such as Parkinson's disease.