Georg Kähler

NOTES—case report of a unidirectional flexible appendectomy

BackgroundNatural orifice transluminal endoscopic surgery (NOTES) refers to a new surgical procedure using flexible endoscopes in the abdominal cavity. With this procedure, access is gained by way of organs which are reached through a natural, already-existing external orifice. The hoped-for advantages associated with this method include the reduction of post-operative wound pain, shorter convalescence, avoidance of wound infection and abdominal-wall hernias as well as the absence of scars. We performed a trans-vaginal appendectomy on a human subject.Materials and methodsIn experimental operations on animals, we first evaluated the trans-vaginal access site. After them, we started first operation in human. The procedure was carried out under preventive administration of antibiotics. We used a therapeutic single-canal gastroscope. The appendix was located after exploration of the abdomen. After preparation of the mesenteriolum, ligature of the appendix base was performed by means of endoloop, followed by transsection with scissors. Recovery of the specimen was achieved by pulling it out with the instrument.ResultsOn the evening of the day on which surgery had taken place, administration of nourishment was begun. After the procedure, the patient reported slight soreness in the muscles of the abdominal wall; she felt otherwise perfectly well.InterpretationIn the space of a year, the first operations have been performed on human subjects by a few select work groups. NOTES procedures are still in the initial stages of clinical development. Until they can be introduced into surgical daily routine, further improvements are required as to equipment, technology and operative procedure.

KRAS and BRAF mutations and PTEN expression do not predict efficacy of cetuximab-based chemoradiotherapy in locally advanced rectal cancer.

PURPOSE Mutations in KRAS and BRAF genes as well as the loss of expression of phosphatase and tensin homolog (PTEN) (deleted on chromosome 10) are associated with impaired activity of antibodies directed against epidermal growth factor receptor in patients with metastatic colorectal cancer. The predictive and prognostic value of the KRAS and BRAF point mutations as well as PTEN expression in patients with locally advanced rectal cancer (LARC) treated with cetuximab-based neoadjuvant chemoradiotherapy is unknown. METHODS AND MATERIALS We have conducted phase I and II trials of the combination of weekly administration of cetuximab and irinotecan and daily doses of capecitabine in conjunction with radiotherapy (45 Gy plus 5.4 Gy) in patients with LARC (stage uT3/4 or uN+). The status of KRAS and BRAF mutations was determined with direct sequencing, and PTEN expression status was determined with immunohistochemistry testing of diagnostic tumor biopsies. Tumor regression was evaluated by using standardized regression grading, and disease-free survival (DFS) was calculated according to the Kaplan-Meier method. RESULTS A total of 57 patients were available for analyses. A total of 31.6% of patients carried mutations in the KRAS genes. No BRAF mutations were found, while the loss of PTEN expression was observed in 9.6% of patients. Six patients achieved complete remission, and the 3-year DFS rate was 73%. No correlation was seen between tumor regression or DFS rate and a single marker or a combination of all markers. CONCLUSIONS In the present series, no BRAF mutation was detected. The presence of KRAS mutations and loss of PTEN expression were not associated with impaired response to cetuximab-based chemoradiotherapy and 3-year DFS.

Expression of Transketolase like gene 1 (TKTL1) predicts disease-free survival in patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy

BackgroundFor patients with locally advanced rectal cancer (LARC) neoadjuvant chemoradiotherapy is recommended as standard therapy. So far, no predictive or prognostic molecular factors for patients undergoing multimodal treatment are established. Increased angiogenesis and altered tumour metabolism as adaption to hypoxic conditions in cancers play an important role in tumour progression and metastasis. Enhanced expression of Vascular-endothelial-growth-factor-receptor (VEGF-R) and Transketolase-like-1 (TKTL1) are related to hypoxic conditions in tumours. In search for potential prognostic molecular markers we investigated the expression of VEGFR-1, VEGFR-2 and TKTL1 in patients with LARC treated with neoadjuvant chemoradiotherapy and cetuximab.MethodsTumour and corresponding normal tissue from pre-therapeutic biopsies of 33 patients (m: 23, f: 10; median age: 61 years) with LARC treated in phase-I and II trials with neoadjuvant chemoradiotherapy (cetuximab, irinotecan, capecitabine in combination with radiotherapy) were analysed by quantitative PCR.ResultsSignificantly higher expression of VEGFR-1/2 was found in tumour tissue in pre-treatment biopsies as well as in resected specimen after neoadjuvant chemoradiotherapy compared to corresponding normal tissue. High TKTL1 expression significantly correlated with disease free survival. None of the markers had influence on early response parameters such as tumour regression grading. There was no correlation of gene expression between the investigated markers.ConclusionHigh TKTL-1 expression correlates with poor prognosis in terms of 3 year disease-free survival in patients with LARC treated with intensified neoadjuvant chemoradiotherapy and may therefore serve as a molecular prognostic marker which should be further evaluated in randomised clinical trials.

Perioperative and Oncological Outcome of Laparoscopic Resection of Gastrointestinal Stromal Tumour (GIST) of the Stomach

Background. Surgery remains the only curative treatment for gastrointestinal stromal tumour (GIST). Resection needs to ensure tumour-free margins while lymphadenectomy is not required. Thus, partial gastric resection is the treatment of choice for small gastric GISTs. Evidence on whether performing resection laparoscopically compromises outcome is limited. Methods. We compiled patients undergoing laparoscopic resection of suspected gastric GIST between 2003 and 2007. Follow-up was performed to obtain information on tumour recurrence. Results. Laparoscopic resection with free margins was performed in 21/22 patients. Histology confirmed GIST in 17 cases, 4 tumours were benign neoplasms. Median operation time and postoperative stay for GIST patients were 130 (range 80–201) mins and 7 (range 5–95) days. Two patients experienced stapler line leakage necessitating surgical revision. After median follow-up of 18 (range 1–53) months, no recurrence occurred. Conclusions. Laparoscopic resection of gastric GISTs yields good perioperative outcomes. Oncologic outcome needs to be assessed with longer follow-up. For posterior lesions, special precaution is needed. Laparoscopic resection could become standard for circumscribed gastric GISTs if necessary precautions for oncological procedures are observed.

Effectivity of current sterility methods for transgastric NOTES procedures: results of a randomized porcine study.

BACKGROUND AND AIM Natural-orifice transluminal endoscopic surgery (NOTES) is an emerging transluminal technique in which interventions are carried out by entering the abdominal cavity via a natural orifice such as the stomach. Infection is a potential risk of the procedure, and the potential pathogens are different from those encountered with skin incisions. Currently, available data regarding prophylactic anti-infective treatment are limited. We compared the effectiveness of topical antimicrobial lavage of mouth and stomach and proton pump inhibitor therapy with gastric cleansing with sterile saline solution in preventing NOTES-related contamination and infection. METHODS A randomized survival swine study was performed. Eight pigs underwent preparation with intravenously administered proton pump inhibitors, mouth and gastric lavage (chlorhexidine), and gastric irrigation (diluted neomycin), plus single-shot intravenous antibiotics. Control group (n = 8) underwent gastric cleansing with sterile saline solution. Peritoneal biopsy, multiple smears, and dilutions for cultures were taken and incubated. The swine were sacrificed after 14 days. Bacterial load was expressed in colony-forming units (CFU). RESULTS One pig died due to gallbladder perforation after 3 days, 2/15 swine presented minor clinical signs of infection in the 14-day follow-up (all 3 pigs were in the control group). Mean C-reactive protein levels were 5.7 +/- 2.4 g/dL (therapy group) and 12.2 +/- 3.8 g/dL (control) ( P = 0.17). Bacterial growth was seen in 1/8 swine (therapy group) and 6/8 swine (control group) ( P = 0.002). Bacterial load was 282 CFU/mL (therapy) vs. 3.2 x 10 (5) CFU/mL (control) ( P = 0.023) in the follow-up. CONCLUSION The use of intravenous antibiotics in addition to topical antimicrobial lavage of mouth and stomach and treatment with proton pump inhibitors decreased the peritoneal bacterial load to almost zero and this was associated with a significantly lower peritoneal infection rate compared with saline-only lavage.

Endoskopisches Operieren über natürliche Körperöffnungen (NOTES) in Deutschland: Zusammenfassung der Arbeitsgruppensitzungen der „D-NOTES 2009”

The D-NOTES-group met in June 2009 for an evaluation of ongoing preclinical and clinical activities in natural orifice endoscopic surgery and the further coordination of research in Germany. Different working groups with various topics were formed. Consensus statements among various participants with different scientific and medical background were initiated. In summary, important topics were handled such as the correct handling of bacterial contamination and related complications, the question of the ideal entry point and a secure closure, interdisciplinary cooperation, and matters related to training and education. Furthermore, participants agreed on terminological basics. A to-do-list for medical engineering was formulated.

Malignant gastroduodenal obstruction: retrospective comparison of endoscopic and surgical palliative therapy.

Abstract Introduction. Endoscopic stenting (ES) is a minimally invasive alternative to surgical gastroenterostomy (GE) for palliation of malignant gastroduodenal obstructions. This consecutive, retrospective analysis compares the clinical outcome of all patients undergoing ES or GE in the same period. Methods. ES was performed at the Endoscopy Department, University Hospital Mannheim or at the Interdisciplinary Endoscopy Department, University Hospital Hamburg-Eppendorf. GE was performed at the Surgical Department, University Hospital Mannheim. All palliative ES or GE on patients with malignant gastroduodenal obstruction without earlier gastric resections between January 2001 and April 2007 were evaluated. Main outcome measurements were ability of solid food intake (gastric outlet obstruction score), persistence of nausea and vomiting (gut function score), length of hospital stay, morbidity, mortality and re-interventions. Results. A total of 44 ES and 43 GE were performed. Nausea and vomiting – measured by means of the gut function score – persisted in significantly more patients in the GE group than in those who underwent stent placement (p = 0.0102). The gastric outlet obstruction score at discharge from the hospital revealed no significant difference in the ability of solid food intake between the groups. The hospital stay was significantly longer in the GE group (p = 0.0003). There was no significant difference in mortality and the rates of complications and re-interventions. Conclusion. In this study, ES is a generally equivalent – and in several points superior – alternative to GE for palliation of malignant gastroduodenal obstruction. ES seems to be the less invasive alternative for symptomatic patients. GE has good results in patients with longer survival and can be practiced within abdominal explorations.

A Composite Adenoendocrine Carcinoma of the Stomach Arising from a Neuroendocrine Tumor

Gastric neuroendocrine tumors (carcinoids) are relatively uncommon neoplasms. Some 70 to 80% of these lesions occur in patients with autoimmune body gastritis. This disorder, however, is also a risk factor for the development of conventional gastric adenocarcinomas. We report a case of a patient with autoimmune body gastritis and a well-differentiated neuroendocrine tumor of the stomach, which was removed with endoscopic full-thickness resection in sano upon signs of invasive growth several years after its first diagnosis. Histological examination surprisingly showed a composite glandular-endocrine gastric carcinoma. We discuss the histopathological genesis of the tumor and provide evidence that endoscopic full-thickness resection might be an oncologically appropriate minimally invasive treatment for such gastric lesions.

Gastrointestinal endoscopy in a low budget context: delegating EGD to non-physician clinicians in Malawi can be feasible and safe

Gastrointestinal endoscopy is rarely performed in low-income countries in sub-Saharan Africa. One reason is the lack of available medical doctors and specialists in these countries. At Zomba Central Hospital in Malawi, clinical officers (non-physician clinicians with 4 years of formal training) were trained in upper gastrointestinal endoscopy. Prospectively recorded details of 1732 consecutive esophagogastroduodenoscopies (EGDs) performed between September 2001 and August 2010 were analyzed to evaluate whether upper gastrointestinal endoscopy can be performed safely and accurately by clinical officers. A total of 1059 (61.1%) EGDs were performed by clinical officers alone and 673 (38.9%) were carried out with a medical doctor present who performed or assisted in the procedure. Failure and complication rates were similar in both groups (P=0.105). Endoscopic diagnoses for frequent indications were generally evenly distributed across the two groups. The main difference was a higher proportion of normal findings and a lower proportion of esophagitis in the group with a doctor present, although this was significant only in patients who had presented with epigastric/abdominal pain (P<0.001). In conclusion, delegating upper gastrointestinal endoscopy to clinical officers can be feasible and safe in a setting with a shortage of medical doctors when adequate training and supervision are provided.

Absorbable ligation loops for flexible endoscopy: a necessary tool for natural orifice transluminal endoscopic surgery

BACKGROUND One of the main challenges of natural orifice transluminal endoscopic surgery (NOTES) remains the development of safe and reliable tools. In this study, we introduce the first absorbable ligatures specifically designed for NOTES. OBJECTIVE To determine the feasibility of a new absorbable ligation loop (NOTES loop) and to compare this new type of suture with the nonabsorbable loop (Endoloop) most commonly used until now. DESIGN Prospective, comparative animal trial/survival animal study (observation period 21 days) with subsequent histopathological assessment (blinded observer design). SETTING Veterinarian center. SUBJECTS This study used 12 female domestic piglets. INTERVENTION Every pig underwent two transgastric uterine horn ligations, one with an absorbable loop and one with a nonabsorbable loop. Additional uterine horn resections on both sides were done on 6 pigs. MAIN OUTCOME MEASUREMENTS Intervention success, loop reliability, foreign-body reaction, extent of inflammatory response (μm). RESULTS Transgastric flexible intra-abdominal ligation of the uterine horns was performed safely with both loops in all cases. During a 3-week observation period, 11 of 11 NOTES loops and 10 of 11 Endoloops were reliable. Microscopically, foreign-body reaction was minimal around both sutures (P = .303). The overall inflammatory response was larger around the Endoloops (P = .046). Uterine horn resection had an influence on the extent of inflammation. LIMITATIONS Animal study. CONCLUSION Ligation was feasible with both loops. The absorbable loops were reliable during a 3-week observation period and can be recommended for use during NOTES appendectomies.