Neurogenic appendicopathy: A rare differential diagnosis of acute appendicitis.

AIM OF THE STUDY: In histologically non-inflamed but clinically suspect appendices, changes described as neurogenic appendicopathy with fibrous or fibrolipomatous obliterations can be observed. The purpose of this study was to analyse the incidence of these entities of the appendix in a longitudinal patient cohort. PATIENTS AND METHODS: This is a retrospective single-centre study of 457 patients undergoing laparoscopic appendectomy from 2017 to 2020 due to suspected acute appendicitis. RESULTS: In 72 patients (15.8%) with clinically suspected acute appendicitis, the appendix showed no distinct signs of acute inflammation during the procedure. In 43 patients, histological analysis revealed neurogenic appendicopathy or fibrous and fibrolipomatous obliteration. Female gender (P=0.088), younger age (P<0.0001), longer pain duration (P<0.0001) and repetitive pain episodes were more frequent in these patients than in those with acute appendicitis. Inflammation markers were also decreased in the group of patients with neurogenic appendicopathy (leukocytes 9.8±3.5 vs. 13.0±4.5 G/L and C-reactive protein 38.7±60.7 vs. 59.4±70.5mg/L). CONCLUSION: Neurogenic appendicopathy with fibrous/fibrolipomatous obliteration is a differential diagnosis of acute appendicitis that can only be confirmed by pathology. Female gender, young age, prolonged duration with repetitive episodes of pain, and relatively low inflammatory markers are evocative of this diagnosis.

Liver resection and transplantation in Caroli disease and syndrome.

INTRODUCTION: Caroli disease (CD) is a congenital dilatation of the intrahepatic bile ducts. In combination with liver fibrosis or cirrhosis, it is called Caroli syndrome (CS). Infectious complications and intrahepatic cholangiocarcinoma are secondary problems. The aim of this study was to analyse the clinical pattern and outcome in patients with CD/CS who underwent liver surgery. METHODS: Between January 2004 and December 2016, 21 patients with CD/CS were treated with liver resection or transplantation (LTX) and post-operative data of patients with CD/CS were retrospectively analysed in a database. RESULTS: Two patients underwent LTX, and 19 patients underwent liver resection due to CD/CS. During follow-up, one patient developed lung cancer nine years after LTX. Patients resected due to CD/CS were predominantly females (74%) with an overall low incidence of co-morbidities. The median post-operative Clavien-Dindo score was 1 (range: 0-3). There was no death during a median follow-up period of over five years. In four patients, cholangiocarcinoma was confirmed. Tumor recurrence was seen in three patients, and was treated with chemotherapy or repeated liver resection. CONCLUSIONS: LTX and liver resections due to CD/CS are rare and associated with an acceptable post-operative morbidity and low mortality. Surgical treatment should be performed as early as possible to avoid recurrent episodes of cholangitis or carcinogenesis.

Randomized clinical trial comparing liver resection with and without perioperative assessment of liver function.

BACKGROUND: Liver function tests may help to predict outcomes after liver surgery. The aim of this study was to evaluate the clinical impact on postoperative outcome and patient management of perioperative liver function testing using the LiMAx® test. METHODS: A multicentre RCT was conducted in six academic liver centres. Patients with intrahepatic tumours scheduled for open liver resection of at least one segment were eligible. Patients were randomized to undergo additional perioperative liver function tests (LiMAx® group) or standard care (control group). Patients in the intervention arm received two perioperative LiMAx® tests, one before the operation for surgical planning and another after surgery for postoperative management. The primary endpoint was the proportion of patients transferred directly to a general ward. Secondary endpoints were severe complications, length of hospital stay (LOS) and length of intermediate care/ICU (LOI) stay. RESULTS: Some 148 patients were randomized. Thirty-six of 58 patients (62 per cent) in the LiMAx® group were transferred directly to a general ward, compared with one of 60 (2 per cent) in the control group (P < 0·001). The rate of severe complications was significantly lower in the LiMAx® group (14 per cent versus 28 per cent in the control group; P = 0·022). LOS and LOI were significantly shorter in the LiMAx® group (LOS: 10·6 versus 13·3 days respectively, P = 0·012; LOI: 0·8 versus 3·0 days, P < 0·001). CONCLUSION: Perioperative use of the LiMAx® test improves postoperative management and reduces the incidence of severe complications after liver surgery. Registration number: NCT01785082 ( https://clinicaltrials.gov).

[Precancerous and early stage cancer of the bile duct system]. / Präkanzerosen und Frühkarzinome des Gallengangsystems.

Early stage cancer of the bile duct system is still difficult to diagnose. In cases of suspect lesions a stepwise diagnostic procedure consisting of computed tomography (CT), magnetic resonance imaging (MRI) with MR cholangiography (MRC) and possibly endoscopic retrograde cholangiopancreatography (ERCP) with brush cytology should immediately be carried out. If there is a sufficient suspicion for premalignancy or early stage cancer the indications for surgical intervention should clearly be defined. Only resection can lead to a decrease in the recurrence rate and a better long-term outcome. If the patient is in a functionally nonresectable condition the possibility of liver transplantation should be considered.

[Puberty is a major factor in pilonidal sinus disease : Gender-specific investigations of case number development in Germany from 2007 until 2015]. / Die Pubertät ist ein wichtiger Faktor bei der Pilonidalsinuserkrankung : Geschlechtsspezifische Untersuchung der Fallzahlentwicklung in Deutschland 2007 bis 2015.

BACKGROUND: Pilonidal sinus disease is an acute abscess-forming or chronic subacute inflammation, characterized by a fistula system with typical ostia. Treatment is primarily surgical. OBJECTIVE: This study aimed to investigate and evaluate the evolution of pilonidal sinus disease in Germany on the basis of data provided by the Federal Statistical Office in Germany (Statistisches Bundesamt). MATERIAL AND METHODS: From the diagnosis data of hospital inpatients generated by the Federal Statistical Office in Germany the data on the International Classification of Diseases (ICD) code L05 for pilonidal sinus from 2007 to 2015 were extracted and processed. RESULTS AND DISCUSSION: The number of cases increased from 25,835 cases in 2007 to 31,033 cases in 2011, followed by a decrease to 30,235 cases in 2015. Considering the number of patients under 20 years of age, there was also an increase from 40 cases per 100,000 population in 2007 to 50 cases per 100,000 population in 2013. Ever since, the case numbers have remained relatively constant and have reached a plateau. The maximum number of case numbers was in the age group of 20-24 years. The female age group 10-14 years old is the only group among all investigated age groups with more cases than the respective male age group. The investigated data did not permit any epidemiological conclusions for pilonidal sinus disease because outpatient cases have not been included. The higher incidence in the female age group 10-14 years old could be explained by the earlier onset of adolescence. Thus, adolescence appears to have a major impact on the development of pilonidal sinus disease.

Effects of methylene-blue staining on the extent of pilonidal sinus excision.

OBJECTIVE: We aimed to examine the effects of methylene-blue staining (MBS) on the volume of specimens after excision of pilonidal sinuses. METHOD: This was a retrospective analysis of 135 excised specimens after pilonidal sinus (PS) surgery. All patients underwent procedures at the Department of Surgery of University Hospital Jena between 2000 and 2010. All specimens were measured in three dimensions. To calculate the volumes of excised specimens, we used a model of a hemi-ellipsoid. Demographic information (age, height, weight, body mass index, smoking status) were also obtained for all patients. RESULTS: Excised specimens with MBS had significantly larger volumes (p<0.001) as reflected in length (p=0.001), width (p=0.001), and depth (p=0.017) of the excised specimen compared with specimens that were not stained with methylene blue (MB). In addition, the volume was larger in subjects with a recurrent PS (p=0.021), which was predominantly the case in female subjects (p=0.025). CONCLUSION: These data suggest that excised specimens with MBS had significantly larger volumes of the excised specimen compared with specimens that were not stained with MB. MBS of a fistula system could enable such a system to be marked sufficiently, thereby facilitating complete resection of a PS.

Total Thyroidectomy for Amiodarone-induced Thyrotoxicosis in the Hyperthyroid State.

Amiodarone is a potent antiarrhythmic agent, indicated for the treatment of refractory arrhythmias, which may lead to thyrotoxicosis. In these patients, thyroidectomy is a valid therapeutic option. Antithyroid therapy in the immediate preoperative setting and the subsequently accepted minimal delay until thyroidectomy have not been clearly defined yet. The aim of the present study was to show, that total thyroidectomy under general anaesthesia in patients with amiodarone-induced thyrotoxicosis (AIT) is safe without necessarily obtaining an euthyroid state preoperatively.We conducted a retrospective cohort study of prospectively gathered data on 11 patients undergoing total thyroidectomy under general anaesthesia between January 2008 and December 2013 for AIT at our University Hospital.All patients were preoperatively treated with carbimazole, steroids and ß-receptor antagonists. Additionally, 3 patients received potassium perchlorate and in one patient carbimazole was changed to propylthiouracil. Plasmapheresis was performed in 3 patients. Only one patient was euthyroid at the time of operation. There were no significant intra- and postoperative complications, especially no signs of thyroid storm. One patient could postoperatively be removed from the cardiac transplant waiting list due to improved cardiac function.Improvements in the interdisciplinary surgical management for AIT between cardiologists, endocrinologists, anaesthetists and endocrine surgeons provide the basis of safe total thyroidectomy under general anaesthesia in hyperthyroid state. Early surgery without long delay for medical antithyroid treatment (with its potential negative side effects) is recommended.

[Classic Limberg Flap Procedure for Treatment of a Sacrococcygeal Pilonidal Sinus Disease - Explanation of the Surgical Technique]. / Klassische Rautenplastik nach Limberg zur Behandlung einer sakrokokzygealen Pilonidalsinuserkrankung - Erklärung der OP-Technik.

INTRODUCTION: Sacrococcygeal pilonidal sinus disease is frequently encountered in surgical practice. Besides excision only, the current pilonidal sinus guideline of the Association of the Scientific Medical Societies in Germany (AWMF-S3) also recommends plastic surgical procedures such as the cleft-lift operation described by Bascom, the Karydakis flap procedure and, due to the low recurrence rates, the Limberg flap procedure, for the treatment of this disease. INDICATION: In our case we show the surgical procedure performed on a 23-year-old male patient, who was previously treated for an acute abscess-forming sacrococcygeal pilonidal sinus. METHOD: Our video shows the fasciocutaneous rhombic flap procedure described by Limberg step by step. CONCLUSION: The Limberg flap procedure is a simple operation for the treatment of sacrococcygeal pilonidal sinus disease.

[Sequential intervention with primary excision and Limberg plastic surgery procedure for treatment of sacrococcygeal pilonidal sinus : Results of a pilot study]. / Zweizeitiges Verfahren mit primärer Exzision und Limberg-Plastik zur Therapie eines sakrokokzygealen Pilonidalsinus : Ergebnisse einer Pilotstudie.

BACKGROUND: The current German S3 guidelines recommend radical excision for pilonidal sinus disease. Furthermore, the Karydakis operation and the plastic surgery procedure according to Limberg are also recommended. Contrary to the S2 guidelines of 2008, these two plastic surgery procedures for coverage are recommended for the treatment of the first-time manifestation of this disease. Most studies on the classical Limberg plastic surgical procedure are comparative in nature and describe a simultaneous intervention from which patients with an abscess are excluded. AIM: The aim of this present study was to analyze the results of a sequential procedure including primary excision followed by a Limberg plastic surgery procedure for the treatment of acute abscesses and chronic pilonidal sinus disease. MATERIAL AND METHODS: From July 2010 to June 2013 a total of 50 patients with pilonidal sinus disease were treated at the University Hospital Jena with an initial radical excision. In accordance with the Association of the Scientific Medical Societies in Germany (AWMF) guidelines which were valid during that time, patients were offered plastic surgery coverage for recurrence prophylaxis and in cases of recurrence a Limberg plastic surgery procedure was recommended. RESULTS: Of the 50 patients 22 opted for a Limberg plastic surgery procedure during the interval. The mean follow-up after the Limberg plastic surgery procedure was 20.1 months (range 2-36 months). During the follow-up period, there were no recurrences (0 %) but four major complications (18.2 %) and one minor complication (4.5 %) were observed. CONCLUSION: This concept can be applied in cases of acute abscess formation and in chronic pilonidal sinus disease. The patient's decision with respect to a Limberg plastic surgery procedure for recurrence prophylaxis does not have to be made immediately. In addition, the Limberg plastic surgery procedure is performed in an infection-free stage. The second inpatient stay, second surgical procedure and prolonged time off work are a disadvantage.

An exclusion mechanism in ion exchange chromatography.

Protein dynamic binding capacities on ion exchange resins are typically expected to decrease with increasing conductivity and decreasing protein charge. There are, however, conditions where capacity increases with increasing conductivity and decreasing protein charge. Capacity measurements on two different commercial ion exchange resins with three different monoclonal antibodies at various pH and conductivities exhibited two domains. In the first domain, the capacity unexpectedly increased with increasing conductivity and decreasing protein charge. The second domain exhibited traditional behavior. A mechanism to explain the first domain is postulated; proteins initially bind to the outer pore regions and electrostatically hinder subsequent protein transport. Such a mechanism is supported by protein capacity and confocal microscopy studies whose results suggest how knowledge of the two types of IEX behavior can be leveraged in optimizing resins and processes.

An ancestral nuclear protein assembly: crystal structure of the Methanopyrus kandleri histone.

Eukaryotic histone proteins condense DNA into compact structures called nucleosomes. Nucleosomes were viewed as a distinguishing feature of eukaryotes prior to identification of histone orthologs in methanogens. Although evolutionarily distinct from methanogens, the methane-producing hyperthermophile Methanopyrus kandleri produces a novel, 154-residue histone (HMk). Amino acid sequence comparisons show that HMk differs from both methanogenic and eukaryotic histones, in that it contains two histone-fold ms within a single chain. The two HMk histone-fold ms, N and C terminal, are 28% identical in amino acid sequence to each other and approximately 21% identical in amino acid sequence to other histone proteins. Here we present the 1.37-A-resolution crystal structure of HMk and report that the HMk monomer structure is homologous to the eukaryotic histone heterodimers. In the crystal, HMk forms a dimer homologous to [H3-H4](2) in the eukaryotic nucleosome. Based on the spatial similarities to structural ms found in the eukaryotic nucleosome that are important for DNA-binding, we infer that the Methanopyrus histone binds DNA in a manner similar to the eukaryotic histone tetramer [H3-H4](2).

Membrane ion-exchange chromatography for process-scale antibody purification.

The large-scale production of recombinant monoclonal antibodies demands economical purification processes with high throughputs. The potential for ion-exchange membrane adsorbers to replace traditional ion-exchange columns was evaluated. Breakthrough capacities of commercially available cation-exchange membranes were determined as a function of flow-rate and layer number. Due to economic and process restrictions, cation-exchange membranes may not currently be advantageous for process-scale antibody purification in a bind and elute mode. However, anion-exchange membranes in a flow-through mode may provide a reasonable alternative to columns for the removal of low levels of impurities such as DNA, host cell protein, and virus.

Expanded bed adsorption in the purification of monoclonal antibodies: a comparison of process alternatives.

Expanded bed adsorption (EBA) was examined as the initial capture/purification step in the purification of monoclonal antibodies from Chinese hamster ovary (CHO) cultures. Two process alternatives each using EBA were compared to a conventional Protein A process without EBA. One alternative used Protein A affinity EBA followed by packed-bed cation and anion-exchange steps. The other alternative used cation-exchange EBA as the capture step followed by packed-bed Protein A and anion-exchange steps. The process using Protein A EBA produced comparable purity (host cell protein, DNA, Protein A, antibody aggregate) to the conventional process. However, the Protein A EBA column showed a significant decrease in dynamic capacity with a limited number of cycles. The process using cation EBA achieved comparable levels of host cell proteins (HCP) and DNA but not antibody aggregate or leached Protein A compared to the conventional process.

Expanded bed protein A affinity chromatography of a recombinant humanized monoclonal antibody: process development, operation, and comparison with a packed bed method.

We show that expanded bed protein A affinity chromatography using Streamline rProtein A media is an efficient method for purifying a recombinant humanized monoclonal antibody from unclarified Chinese hamster ovary cell culture fluid and that it provides purification performance comparable to using a packed bed. We determined that the dynamic capacity of the expanded bed media is related to flow rate (measured in column volumes per hour) by a power function, which allows a high capacity at a low flow rate. At 250 cm h-1 with a 25 cm bed height (10 column volumes h-1), the dynamic capacity is 30 g l-1. The yield and purity (measured by the amount of host cell proteins, DNA, SDS-PAGE, and turbidity) of the antibody purified by expanded bed is comparable to the yield and purity obtained on a standard packed bed method using Prosep A media.

Performance comparison of protein A affinity-chromatography sorbents for purifying recombinant monoclonal antibodies.

We describe the performance characteristics of five Protein A affinity-chromatography sorbents (Sepharose Fast Flow, Poros 50, Poros LP, Prosep and Streamline) for purifying a recombinant humanized monoclonal antibody from clarified Chinese hamster ovary cell culture fluid. We measured the dynamic capacity at varying flow rates, maximum capacity, pressure drop and production rate. For purified antibody, we measured yield and purity (by SDS/PAGE, the amount of DNA, the amount of host-cell proteins and the amount of Protein A). We found that, whereas all sorbents provided significant and essentially equivalent antibody purification, there were differences in capacity and pressure drop, which affected the production rate and had implications for process applications.

Real-time control of antibody loading during protein A affinity chromatography using an on-line assay.

We show that an on-line chromatographic assay can reliably control antibody loading in real-time during protein A affinity chromatography purification of a recombinant antibody from clarified Chinese hamster ovary cell culture fluid. The on-line assay directly sampled preparative column effluent and provided real-time measurement of antibody breakthrough during loading. The on-line assay used protein A immobilized on perfusion chromatography media, equilibrated with phosphate-buffered saline at pH 7.2 and eluted with phosphate-buffered saline at pH 2.2. The assay reliably ended loading at 1% breakthrough with minimal yield loss. Reproducible yield and purity were obtained over 23 consecutive cycles. Yield remained constant while breakthrough capacity and the antibody concentration in the load changed.

Real-time monitoring of recombinant antibody breakthrough during protein A affinity chromatography.

An on-line assay was developed to monitor antibody breakthrough in real time during Protein A affinity chromatography of recombinant antibodies. When loading cell culture fluid on to a Protein A affinity column, antibody breakthrough cannot be measured by UV absorbance because of the flow-through of UV-absorbing impurities. An assay using perfusion chromatography media with immobilized Protein A is a rapid, antibody-specific assay. It directly samples preparative column effluent, allowing real-time measurement of antibody breakthrough during loading of Protein A affinity chromatography. Breakthrough curves were generated for three column media at five flow rates, showing the effects of diffusion on the shape of the breakthrough curve. The breakthrough curves were used to measure dynamic capacity.

Non-flammable preparative reversed-phase liquid chromatography of recombinant human insulin-like growth factor-I.

Acetonitrile is used as an eluent for reversed-phase chromatography. However, because it is a flammable solvent, using acetonitrile on a large scale requires expensive equipment and facilities specially designed for flammable solvents. Using a non-flammable solvent as an eluent eliminates this expense. A method was developed to purify recombinant human insulin-like growth factor I by reversed-phase high-performance liquid chromatography using gradient elution with hexylene glycol, a non-flammable replacement for acetonitrile. The separation produced equivalent yield, purity and throughput as reversed-phase chromatography using elution with acetonitrile.