Case report: acute abdominal pain in a 37-year-old patient and the consequences for his family.

BACKGROUND: Hereditary diffuse gastric cancer is a rare condition that accounts for approximately 1-3% of all gastric cancer cases. Due to its rapid and invasive growth pattern, it is associated with a very poor prognosis. As a result, comprehensive genetic testing is imperative in patients who meet the current testing criteria in order to identify relatives at risk. This case report illustrates the substantial benefit of genetic testing in the family of a patient diagnosed with hereditary diffuse gastric cancer. CASE PRESENTATION: A 37-year-old patient was admitted to the emergency department with acute abdominal pain. Following explorative laparoscopy, locally advanced diffuse gastric cancer was diagnosed. The indication for genetic testing of CDH1 was given due to the patient's young age. A germline mutation in CDH1 was identified in the index patient. As a result, several family members underwent genetic testing. The patient's father, brother and one aunt were identified as carriers of the familial CDH1 mutation and subsequently received gastrectomy. In both the father and the aunt, histology of the surgical specimen revealed a diffuse growing adenocarcinoma after an unremarkable preoperative gastroscopy. CONCLUSION: Awareness and recognition of a potential hereditary diffuse gastric cancer can provide a substantial health benefit not only for the patient but especially for affected family members.

Multi-omic based molecular profiling of advanced cancer identifies treatable targets and improves survival in individual patients.

A proof-of-concept study was conducted to assess whether patients with advanced stage IV cancer for whom predominantly no standard therapy was available could benefit from comprehensive molecular profiling of their tumor tissue to provide targeted therapy. Tumor samples of 83 patients were collected under highly standardized conditions and analyzed using immunohistochemistry, next-generation sequencing and phosphoprotein profiling. Expression and phosphorylation of key oncogenic pathways were measured to identify targets at the (phospho-) proteomic level. At genomic level, 50 oncogenes and tumor suppressor genes were analyzed. Based on molecular profiling, targeted therapies were decided by the attending oncologist. Accordingly, 28 patients who met the defined criteria fell in two equal-sized groups. One group received targeted therapies while the other did not. Following six months of treatment, disease control was achieved by 49% of patients receiving targeted therapy (complete remission, 14%; partial remission, 21%; stable disease, 14%; disease progression, 36%; death, 14%) and 21% of patients receiving non-targeted therapy (stable disease, 21%; disease progression, 64%; death, 14%). Individual patients experienced dramatic responses to a therapy which otherwise would not have been applied. This approach clarifies the value of multi-omic molecular profiling for cancer diagnostics.

Surgical procedures and postsurgical tissue processing significantly affect expression of genes and EGFR-pathway proteins in colorectal cancer tissue.

An understanding of tissue data variability in relation to processing techniques during and postsurgery would be desirable when testing surgical specimens for clinical diagnostics, drug development, or identification of predictive biomarkers. Specimens of normal and colorectal cancer (CRC) tissues removed during colon and liver resection surgery were obtained at the beginning of surgery and postsurgically, tissue was fixed at 10, 20, and 45 minutes. Specimens were analyzed from 50 patients with primary CRC and 43 with intrahepatic metastasis of CRC using a whole genome gene expression array. Additionally, we focused on the epidermal growth factor receptor pathway and quantified proteins and their phosphorylation status in relation to tissue processing timepoints. Gene and protein expression data obtained from colorectal and liver specimens were influenced by tissue handling during surgery and by postsurgical processing time. To obtain reliable expression data, tissue processing for research and diagnostic purposes needs to be highly standardized.

Transvaginal specimen removal after laparoscopic distal pancreatic resection.

PURPOSE: Transvaginal specimen removal has been introduced 20 years ago but then abandoned. With the advent of transvaginal interventions following the introduction of natural orifice transluminal endoscopic surgery, renewed interest was generated for hybrid procedures with minimal access for the intervention and use of transvaginal (TV) specimen removal. We present the first such series after laparoscopic distal pancreatectomy. METHODS: In seven subsequent women (median age 48 years) with body and tail pancreatic tumors undergoing laparoscopic distal pancreatectomy, the new method of TV specimen removal was applied. The patients' data and the technical successes as well as intra- and postprocedural complications were recorded prospectively. The patients were followed after discharge for gynecological examination. RESULTS: Specimen removal consisting of the pancreas and spleen in five and the pancreas only in two cases was technically successful; no intraoperative complications were encountered. Postoperative complications consisted of one case of intra-abdominal hemorrhage and one case of pancreatic fistula, attributable to the resection and not to TV specimen removal. Gynecological follow-up was normal in all seven patients. CONCLUSIONS: The technique of TV specimen removal is feasible and safe also after laparoscopic distal pancreatectomy. It may help to further diminish the access trauma of laparoscopic pancreatic surgery.

The EURO-NOTES clinical registry for natural orifice transluminal endoscopic surgery: a 2-year activity report.

BACKGROUND: The EURO-NOTES Clinical Registry (ECR) was established as a European database to allow the monitoring and safe introduction of Natural Orifice Transluminal Endoscopic Surgery (NOTES). The aim of this study was to analyze different techniques applied and relative results during the first 2 years of the ECR. METHODS: The ECR was designed as a voluntary database with online access. All members of the European Society for Gastrointestinal Endoscopy and the European Association for Endoscopic Surgery were requested to participate in the registry. Demographic and therapy data as well as data on the postoperative course are recorded in the ECR in an anonymous way. RESULTS: A total of 533 patients who underwent NOTES procedures were included in the study. Four different hybrid techniques for 435 cholecystectomies were described, registering postoperative complications in 2.8% of patients, addition of a single trocar in 5.3%, and conversions to laparoscopy in 0.5%. Both flexible endoscopic and rigid laparoscopic cholecystectomy techniques proved to be safe and effective with minor differences. There was a shorter operative time in the rigid laparoscopic group. Thirty-three appendectomies were reported by transgastric and transvaginal techniques, with transvaginal techniques scoring shorter operative time and hospital stay, but with a frequent need to add more trocars. Overall complications occurred in 14.7% of patients but they did not differ significantly among the different techniques. One transvaginal and 31 transanal sigmoidectomies were included for prolapse and diverticulitis, with four postoperative complications (12.5%), but none needing further treatment. Twenty peroral esophageal myotomies were included with three postoperative complications (15.0%), but none needing further treatment. CONCLUSIONS: Five years since the introduction of NOTES into clinical practice, hybrid techniques have gained considerable clinical application. Several NOTES hybrid cholecystectomy and appendectomy techniques are practicable and safe alternatives to laparoscopic procedures. Also, sigmoidectomies and peroral esophageal myotomies were described, proving feasibility and safety. Nevertheless, the real benefit of NOTES for patients still needs to be assessed.

Is the transvaginal route appropriate for intra-abdominal NOTES procedures? Experience and follow-up of 222 cases.

BACKGROUND: Since 2007, natural orifice transluminal endoscopic surgery (NOTES) has been applied in humans. We performed this prospective study to evaluate the transvaginal route in terms of risks, complication rate, and long-term side effects such as dyspareunia. METHODS: From June 2007 to September 2011, we performed 222 transvaginal hybrid NOTES procedures: 220 transvaginal cholecystectomies (TVC) and 2 transvaginal appendectomies (TVA). All patients were asked to present to our associated gynecologists within 1 week for an examination. After at least 3 months, the patients were interviewed using a standard questionnaire. RESULTS: All operations could be successfully performed in this technique except two cases, which were converted to conventional laparoscopic cholecystectomy. The only intraoperative complication was the puncture of the urine bladder. We observed two postoperative complications: one biliary fistula 3 days after TVC, and one abscess in the Douglas pouch 3 weeks after TVC. The gynecological examinations revealed no abnormalities. The interview (median postoperative time, 6 months) with a follow-up rate of 93 % revealed no pain in the pelvis, dyspareunia, or sexual dysfunction after TVC. CONCLUSIONS: The transvaginal route is appropriate for NOTES procedures; there is only a minor and acceptable rate of intra- and postoperative morbidity.

NOTES cholecystectomy: matched-pair analysis comparing the transvaginal hybrid and conventional laparoscopic techniques in a series of 216 patients.

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) is currently a very important topic for both gastroenterologists and surgeons. We have developed a technique of transvaginal hybrid NOTES cholecystectomy (TVC) that leaves no visible scar and is applicable to daily use. This technique is compared to the conventional laparoscopic cholecystectomy (CLC) in a matched-pair analysis. METHODS: From June 2007 until February 2009, 108 NOTES cholecystectomies were performed. For a matched-pair analysis we first selected a group of 192 female patients who had undergone CLC and who were operated on by the same group of surgeons in the same time period. Then 108 pairs who had TVC were matched according to the degree of inflammation of the gallbladder and age. We were able to contact 208 patients at least 3 months after surgery. Hence, the study analysis was performed with 100 complete pairs. RESULTS: All 200 cholecystectomies were performed successfully without conversion. The TVC procedure was significantly longer than CLC (52 vs. 35 min, p<0.001). There were no intraoperative complications in either group. There were no significant differences with respect to reoperations, wound infections, consumption of analgesic drugs, length of hospital stay, and sick leave. Seventy-five TVC and 73 CLC patients had sexual intercourse after the operation without any complaints. CONCLUSION: We present here the largest series of NOTES for cholecystectomy published to date and the first comparative study with the gold standard. The TVC technique is as successful as the CLC, it causes no more complications than CLC, especially with respect to the vaginal approach, it is more time-consuming to perform, but has an ideal cosmetic result, i.e., no visible scar.

The German registry for natural orifice translumenal endoscopic surgery: report of the first 551 patients.

OBJECTIVE: To analyze patient outcome in the first 14 months of the German natural orifice translumenal endoscopic surgery (NOTES) registry (GNR). SUMMARY BACKGROUND DATA: NOTES is a new surgical concept, which permits scarless intra-abdominal operations through natural orifices, such as the mouth, vagina, rectum, or urethra. The GNR was established as a nationwide outcome database to allow the monitoring and safe introduction of this technique in Germany. METHODS: The GNR was designed as a voluntary database with online access. All surgeons in Germany who performed NOTES procedures were requested to participate in the registry. The GNR recorded demographical and therapy data as well as data on the postoperative course. RESULTS: A total of 572 target organs were operated in 551 patients. Cholecystectomies accounted for 85.3% of all NOTES procedures. All procedures were performed in female patients using transvaginal hybrid technique. Complications occurred in 3.1% of all patients, conversions to laparoscopy or open surgery in 4.9%. In cholecystectomies, institutional case volume, obesity, and age had substantial effect on conversion rate, operation length, and length of hospital stay, but no effect on complications. CONCLUSIONS: Despite the fact that NOTES has just recently been introduced, the technique has already gained considerable clinical application. Transvaginal hybrid NOTES cholecystectomy is a practicable and safe alternative to laparoscopic resection even in obese or older patients.

Single-access surgery laparoscopic cholecystectomy and appendectomy.

The objective of this study was to achieve an ideal cosmetic result and minimize the access trauma to the abdominal wall. The authors developed a technique to perform cholecystectomies and appendectomies with only one incision in the umbilicus. With the upcoming idea of Natural Orifice Transluminal Endoscopic Surgery (NOTES) in the recent years and noticing the lack of feasibility of the technique for the daily routine beside the technique described by these authors, another development was raising the interest of the surgeons around the world. The single-access surgery through the umbilicus is a technique, that can be used in the daily routine and provides the best cosmetic results. Furthermore, injury of the abdominal wall is located at only one site, which might reduce the rate of trocar hernias and abdominal wall infections. Two 5.5-mm trocars were inserted through an incision at the upper edge of the umbilicus. After perforation of the abdominal wall with a stylet of a 5.5-mm trocar, a curved grasper was inserted, without the use of a trocar, into the abdominal cavity. The use of curved instruments facilitates better triangulation and instrument handling. No gas leakage was observed due to the nonexistence of a trocar. Dissection of the Calot' s triangle or appendix vessels can be done with standard instruments. The curved grasper allows retraction of the gallbladder or appendix. The specimen can be removed through the umbilical incision. The authors present a single-access surgery technique for cholecystectomies and appendectomies using curved instruments. The single-access surgery with parallel inserted curved instruments is feasible. No additional complications are related to this modification other than those known to be associated with laparoscopic surgery. This method offers an almost scarless surgery. Whether other advantages such as less trocar hernias, wound infections, and/or a faster recovery can be achieved, it has not yet to be proven.

Laparoscopic Toupet fundoplication.

This article and video presents our Toupet procedure. It is a modern adaptation of Toupet's original technique. Toupet described his technique of fundoplication in 1963 (Toupet, Mem Aca Chir 89:394, 1963). He had little experience but saw the importance of a partial wrap to avoid postoperative dysphagia. He recommended closure of the hiatus only in case of large hernias and never divided the short gastric vessels. If we talk about a Toupet procedure today, we mean a posterior partial fundoplication. In contrary to his original technique, we have learned that hiatal closure is important to avoid recurrent hernia and that the wrap in most cases can be tailored more nicely if the short gastric vessels are divided. This modern adaptation of the Toupet's operation is a very successful tool to treat gastro-oesophageal reflux disease.

Detection of colorectal adenoma and cancer based on transthyretin and C3a-desArg serum levels.

Colorectal cancer is the second leading cause of cancer death, and it develops from benign colorectal adenomas in over 95% of patients. Early detection of these cancer precursors by screening tests and their removal can potentially eradicate more than 95% of colorectal cancers before they develop. To discover sensitive and specific biomarkers for improvement of pre-clinical diagnosis of colorectal adenoma and cancer, we analysed in two independent studies (n = 87 and n = 83 patients) serum samples from colorectal cancer (stage III), colorectal adenoma and control patients using SELDI-TOF-MS. Extensive statistical analysis was performed to establish homogeneous patient groups based on their clinical data. Two biomarkers that were each able to distinguish control patients from either colorectal adenoma or colorectal cancer patients (p<0.001) were identified as transthyretin (pre-albumin) and C3a-desArg by MS/MS and were further validated by antibody-based assays (radial immunodiffusion, ELISA). A combination of both proteins clearly indicated the presence of colorectal adenoma or carcinoma. Using a cut-off of <0.225 g/L for transthyretin and >1974 ng/mL for C3a-desArg, we found a sensitivity and specificity for colorectal adenoma of 96% and 70%, respectively.

Tissue ischemia time affects gene and protein expression patterns within minutes following surgical tumor excision.

The aim of this study was to determine the impact of ischemia on gene and protein expression profiles of healthy and malignant colon tissue and, thus, on screening studies for identification of molecular targets and diagnostic molecular patterns. Healthy and malignant colon tissue were snap-frozen at various time points (3-30 min) after colon resection. Gene and protein expression were determined by microarray (HG-U133A chips) and surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) technology (CM10 chips, SAX2 chips, and IMAC3Ni chips), respectively. Real-time reverse transcription PCR (RT-PCR) was used for comparative measurement of expression of particular genes. Initial changes of gene and protein expression profiles were already observed 5-8 min after colon resection. Fifteen minutes after surgery, 10%-15% of molecules, and after 30 min, 20% of all detectable genes and proteins, respectively, differed significantly from the baseline values. Significant changes of expression were found in most functional groups. As confirmed by real-time RT-PCR, this included not only known hypoxia-related molecules (HIF-1 alpha, c-fos, HO-1) but also cytoskeletal genes (e.g., CK20) and tumor-associated antigens (e.g., CEA). In conclusion, preanalytical factors, such as tissue ischemia time, dramatically affect molecular data. Control of these variables is mandatory to obtain reliable data in screening programs for molecular targets and diagnostic molecular patterns.