Johannes C. Lauscher

Development of a clinical trial to determine whether watchful waiting is an acceptable alternative to surgical repair for patients with oligosymptomatic incisional hernia: study protocol for a randomized controlled trial

BackgroundIncisional hernia is a frequent complication in abdominal surgery. This article describes the development of a prospective randomized clinical trial designed to determine whether watchful waiting is an acceptable alternative to surgical repair for patients with oligosymptomatic incisional hernia.Methods/DesignThis clinical multicenter trial has been designed to compare watchful waiting and surgical repair for patients with oligosymptomatic incisional hernia. Participants are randomized to watchful waiting or surgery and followed up for two years. The primary efficacy endpoint is pain/discomfort during normal activities as a result of the hernia or hernia repair two years after enrolment, as measured by the hernia-specific Surgical Pain Scales (SPS). The target sample size of six hundred thirty-six patients was calculated to detect non-inferiority of the experimental intervention (watchful waiting) in the primary endpoint. Sixteen surgical centers will take part in the study and have submitted their declaration of commitment giving the estimated number of participating patients per year. A three-person data safety monitoring board will meet annually to monitor and supervise the trial.DiscussionTo date, we could find no published data on the natural course of incisional hernias. To our knowledge, watchful waiting has never been compared to standard surgical repair as a treatment option for incisional hernias. A trial to compare the outcome of the two approaches in patients with oligosymptomatic incisional hernias is urgently needed to provide data that can facilitate the choice between treatment options. If watchful waiting was equal to surgical repair, the high costs of surgical repair could be saved. The design for such a trial is described here.This multicenter trial will be funded by the German Research Foundation (DFG). The ethics committee of the Charité has approved the study protocol. Approval has been obtained from ten study sites at time of this submission. The electronic Case Report Forms have been created. The first patient was to be randomized November 14th, 2011. An initiation meeting took place in Berlin January 9th, 2012.Trial RegistrationClinicalTrials.gov: NCT01349400

Laparoscopic and open inguinal hernia repair with alloplastic material: do the subjective and objective parameters differ in the long-term course?

Introduction Management with alloplastic materials has become the standard procedure in inguinal hernia surgery. The aim of this study was to evaluate the long-term results after laparoscopic and open groin hernia repair with alloplastic material in a large patient population. Materials and Methods We included patients in the study who underwent elective laparoscopic total extraperitoneal (TEP) inguinal hernia repair or Lichtenstein surgery between January 1998 and December 2004 for either unilateral or bilateral inguinal hernia. Patient data were recorded by a prospective online data recording system and evaluated after a minimum follow-up time of 12 (12 to 103) months by standardized questionnaires. Both objective (chronic pain, chronic dysesthesia, recurrence, and postoperative recovery) and subjective (cosmetic result, scar formation, and the choice of surgical procedure) parameters were surveyed. Results Seven hundred eighty-two patients with 923 inguinal hernias underwent surgery in the study period. Five hundred fifty-three patients returned the questionnaire; 62 died during the follow-up. In the remaining 491 patients, TEP was used in 292 patients (375 hernias) and the Lichtenstein procedure in 199 patients (206 hernias). TEP was significantly superior to the Lichtenstein procedure for 2 objective parameters: chronic dysesthesia and return to normal work. Regarding the subjective parameters, TEP was superior in the cosmetic results and the choice of surgical procedure. 3.1% of the patients after TEP versus 8.5% after Lichtenstein were dissatisfied with the cosmetic result (P=0.008). If secondary inguinal hernia surgery were required, 89.4% of the patients would choose TEP again versus 76.1% the Lichtenstein procedure (P<0.001). Conclusions Whereas the Lichtenstein procedure was not significantly better in any of the evaluated parameters, TEP was superior especially in the subjective parameters.

Antiproliferative and apoptotic effects of telmisartan in human colon cancer cells

Telmisartan is an angiotensin I (AT1) receptor blocker used in the treatment of essential hypertension, with partial peroxisome proliferator-activated receptor γ (PPARγ) agonism. In prior studies, PPARγ activation led to apoptosis and cell cycle inhibition in various cancer cells. The aim of the present study was to investigate the potential antiproliferative and apoptotic effects of telmisartan by partially activating PPARγ. HT-29, SW-480 and SW-620 cells were incubated with telmisartan (0.2–5 μM) or the full agonist, pioglitazone (0.2–5.0 μM). The antiproliferative and apoptotic effects of telmisartan in the human colon cancer cells were significant at therapeutic serum concentrations, and telmisartan exhibited a potency at least equivalent to the full PPARγ agonist, pioglitazone. The antiproliferative and apoptotic effects of pioglitazone in the human colon cancer cells were not completely deregulated by PPARγ blockade with GW9662. In the telmisartan-treated cells, PPARγ blockade resulted in an increased antiproliferative and apoptotic effect. These effects are not entirely explained by PPARγ activation, however, possible hypotheses that require further experimental investigation are as follows: i) Ligand-independent PPARγ activation through the activation-function 1 domain; ii) a PPARγ-independent mechanism; or iii) independent antiproliferative and apoptotic effects through GW9662.

Endo-β-N-acetylglucosaminidase H de-N-glycosylation in a domestic microwave oven: application to biomarker discovery.

Sample preparation is the rate-limiting step in glycan analysis workflows. Among all of the steps, enzymatic digestions, which are usually performed overnight, are the most time-consuming. In the current study, we report an economical and fast preparation of N-glycans from serum, including microwave-assisted enzymatic digestion in the absence of denaturing chemicals and solvents during the release. To this end, we used a household microwave oven to accelerate both pronase and endo-β-N-acetylglucosaminidase H (Endo H) digestions. Purification was then performed using self-made SP20SS and carbon tips. We were able to prepare samples in 55 min instead of 21 h. Finally, the method was applied in the context of oncological biomarker discovery exemplarily to ovarian and colon cancer. We observed a significant downregulation of sialylated hybrid structures in ovarian cancer samples using capillary electrophoresis-laser-induced fluorescence (CE-LIF). Furthermore, sepsis, a systemic inflammatory response syndrome, was also included in the study to understand whether the changes observed in ovarian cancer patients were due to the cancer itself or to the inflammation that usually accompanies its development. Because sialylated hybrid structures were upregulated in sepsis samples, the downregulation of these structures in ovarian cancer is specific to the cancer itself and, therefore, could be used as a biomarker.

Association Between Activation of Atypical NF-kappa B1 p105 Signaling Pathway and Nuclear beta-Catenin Accumulation in Colorectal Carcinoma

Recent studies have demonstrated that increased expression of coding region determinant‐binding protein (CRD‐BP) in response to β‐catenin signaling leads to the stabilization of β‐TrCP1, a substrate‐specific component of SCF E3 ubiquitin ligase complex, resulting in an accelerated degradation of IκBα and activation of canonical nuclear factor‐κB (NF‐κB) pathway. Here, we show that the noncanonical NF‐κB1 p105 pathway is constitutively activated in colorectal carcinoma specimens, being particularly associated with β‐catenin‐mediated increased expression of CRD‐BP and β‐TrCP1. In the carcinoma tissues exhibiting high levels of nuclear β‐catenin the phospho‐p105 levels were increased and total p105 amounts were decreased in comparison to that of normal tissue indicating an activation of this NF‐κB pathway. Knockdown of CRD‐BP in colorectal cancer cell line SW620 resulted in significantly higher basal levels of both NF‐κB inhibitory proteins, p105 and IκBα. Furthermore decreased NF‐κB binding activity was observed in CRD‐BP siRNA‐transfected SW620 cells as compared with those transfected with control siRNA. Altogether, our findings suggest that activation of NF‐κB1 p105 signaling in colorectal carcinoma might be attributed to β‐catenin‐mediated induction of CRD‐BP and β‐TrCP1.

Zehn Jahre „Praktischer Kurs für Viszeralchirurgie Warnemünde“

BACKGROUND Skill courses for surgery offer a good but cost and personnel-intensive possibility to obtain practical and theoretical knowledge by the employment of a close teacher-pupil contact of a large group of surgeons. The goal of the study presented here was to evaluate the satisfaction and benefits of the practical course for visceral surgery in Warnemünde after 10 years of course experience. MATERIAL AND METHODS All participants in the annual course for visceral surgery were included since 1999. During this 1-week course conventional and laparoscopic exercises are performed under direct guidance of an experienced tutor. The participants are divided into 3 groups based on their surgical experience (e.g. <3 years, 3-5 years, >5 years). All participants received a standardised questionnaire before and after successful course completion for the collection of relevant data (e.g. demography, training, surgical experience and course evaluation). RESULTS A total of 1,062 participants (435 female, 627 male, mean age 37 years) participated in the course. The average surgical experience of the participants was 5 years. Of the participants 489 came from a hospital of basic medical care, 499 from a hospital of maximum medical care and 74 from a university hospital. Of the participants 96% had no or only little experience with skill courses (1,020 out of 1,065) and 827 participants had no or only few possibilities for training outside of the operation room (78%). The conventional part of the course was evaluated by 77% of the participants as very good and by 50% as very good for the laparoscopic part. Only 8.3% of the participants were willing to finance the costs of the course by themselves. CONCLUSIONS The practical course for visceral surgery leads to a subjective success in learning. Participation in the course leads to a high satisfaction and offers a cost-intensive possibility for a standardised surgical training. But there are too few experiences with skill courses and possibilities for surgical training outside the operation room so far.

Pain and dysesthesia following total extraperitoneal hernia repair

INTRODUCTION Minimally invasive repair with alloplastic material for inguinal hernia has become a method with few complications and a low recurrence rate. Persistent pain and dysesthesia years after the procedure are however of growing clinical interest. It is still unknown to what degree initial pain or dysesthesia change in the long term. Therefore this study was done to evaluate patient complaints following total extraperitoneal repair (TER) over a long observation period. MATERIALS AND METHODS Included in the study were patients from January 2000 to December 2006 who were treated electively for uni- or bilateral inguinal hernia using TER. Exclusion criteria were emergency procedures, incarcerated hernia, and scrotal hernia. The patient data were collected using a prospective online data system and evaluation of long-term results via standardized questionnaires determining persisting pain, dysesthesia, physical limitations from the surgery, satisfaction with the operation, and recurrences. The patients were grouped according to length of follow-up after surgery: 12-36 months (group 1), 37-60 months (group 2), and 61-96 months (group 3). RESULTS Since January 2000, 484 patients 18 to 97 years old with 620 inguinal hernias were operated. Of those, 349 were evaluated for this study (proportion of returned questionnaires: 72.1%). No significant differences were noted in patient characteristics or early postoperative complications. The percentage of patients suffering from relevant pain (moderate to severe) dropped significantly: 10.3% (group 1) vs 1.0% (group 2) (P<0.05) and 3.4% (group 3) (P<0.05). No significant differences were found concerning dysesthesia (19.6% in group 1 vs 19.2% in group 3). There were no significant differences in satisfaction with the operation, as 73.8% in group 1, 67.7% in group 2, and 73.3% in group 3 were very satisfied with the results. The number of recurrences increased during the observation period: 1.9% in group 1, 3.1% in group 2, and 5.5% in group 3 (P>0.05). CONCLUSIONS Total extraperitoneal repair is a reliable method with low recurrence rate and high patient satisfaction. A relevant proportion of patients complain however of pain and dysesthesia persisting over years. The data from this study show that in the long term, pain incidence drops significantly while the rate of dysesthesia remains constant. Long follow-up is needed to evaluate the long-term course of persistent pain. For more precise understanding of the long-term results of herniotomy, prospective randomized studies are needed with accordingly long follow-up.

["Practical course for visceral surgery in Warnemünde" 10 years on. Significance and benefits of a surgical training course].

BACKGROUND Skill courses for surgery offer a good but cost and personnel-intensive possibility to obtain practical and theoretical knowledge by the employment of a close teacher-pupil contact of a large group of surgeons. The goal of the study presented here was to evaluate the satisfaction and benefits of the practical course for visceral surgery in Warnemünde after 10 years of course experience. MATERIAL AND METHODS All participants in the annual course for visceral surgery were included since 1999. During this 1-week course conventional and laparoscopic exercises are performed under direct guidance of an experienced tutor. The participants are divided into 3 groups based on their surgical experience (e.g. <3 years, 3-5 years, >5 years). All participants received a standardised questionnaire before and after successful course completion for the collection of relevant data (e.g. demography, training, surgical experience and course evaluation). RESULTS A total of 1,062 participants (435 female, 627 male, mean age 37 years) participated in the course. The average surgical experience of the participants was 5 years. Of the participants 489 came from a hospital of basic medical care, 499 from a hospital of maximum medical care and 74 from a university hospital. Of the participants 96% had no or only little experience with skill courses (1,020 out of 1,065) and 827 participants had no or only few possibilities for training outside of the operation room (78%). The conventional part of the course was evaluated by 77% of the participants as very good and by 50% as very good for the laparoscopic part. Only 8.3% of the participants were willing to finance the costs of the course by themselves. CONCLUSIONS The practical course for visceral surgery leads to a subjective success in learning. Participation in the course leads to a high satisfaction and offers a cost-intensive possibility for a standardised surgical training. But there are too few experiences with skill courses and possibilities for surgical training outside the operation room so far.

Beobachtung vs. Operation oligosymptomatischer Narbenhernien

INTRODUCTION Incisional hernias are one of the the most frequent complications in visceral surgery and incisional hernia repair has a relevant complication rate. Therefore, there have to be solid indications before carrying out incisional hernia repair. To date, there is a lack of evidence concerning the correct indications for surgical repair of incisional hernias. The AWARE trial compares watchful waiting to surgical repair of incisional hernias. MATERIAL AND METHODS The AWARE trial is a prospective randomized multicenter trial. Patients with asymptomatic or oligosymptomatic incisional hernia are randomized into the watchful waiting or the surgical repair group with a follow-up of 2 years. The primary endpoint is pain during normal activities due to the hernia or the hernia repair after 2 years measured on the hernia-specific surgical pain scale (SPS). RESULTS In this study 36 centers are participating throughout Germany, more than 1600 patients had been screened up to 31 December 2014 and 234 (14.6%) of the screened patients could be recruited. CONCLUSION The AWARE study will provide evidence concerning the two therapeutic options of watchful waiting and surgical repair of incisional hernia.

Stump closure in laparoscopic appendectomy. Influence of endoloop or linear stapler on patient outcome

BACKGROUND Even though laparoscopic appendectomy is one of the most frequent procedures in abdominal surgery, the technique of appendiceal stump closure is still not standardized. The aim of this retrospective study was to analyze the effect of the use of endoloops or linear staplers for appendiceal stump closure concerning surgical site infections (SSI) and intra-abdominal abscesses (IAA). PATIENTS AND METHODS All laparoscopic appendectomies between January 1st 2007 and May 31st 2010 were split into an endoloop group (ELG) and a linear stapler group (LSG). The groups were compared with respect to the outcome parameters SSI and IAA. RESULTS A total of 430 appendectomies were performed in the study period of which 105 operations were conducted laparoscopically. In this study 47.6 % (n = 50) were alloted to the LSG and 52.4 % (n = 55) to ELG. In LSG 3.1 % (n = 1) developed an SSI versus 10.0 % (n = 4, p = 0.254) in ELG. No IAAs occurred in LSG compared to 2 (5.1 %, p = 0.499) in ELG. CONCLUSION The use of EL for appendiceal stump closure is safe and cost effective for low-grade appendicitis but high-grade appendicitis should be treated with LS.