Age and manifestation related symptoms in familial adenomatous polyposis

BACKGROUND: To identify early symptoms of familial adenomatous polyposis with a view to improve early diagnosis and treatment. Diagnosis on the basis of genetic testing is usually limited to where there is a known family history, so FAP is more usually diagnosed on clinical grounds. Except for those identified via FAP registers, the majority of patients are symptomatic at the time of diagnosis. METHODS: We undertook a retrospective study of 143 FAP patients treated at the Department of Surgery, University of Erlangen between 1971 and 2000. We identified patterns of symptoms, endoscopic findings and extracolonic manifestations in three age groups. RESULTS: FAP was diagnosed clinically on the basis of symptoms in 84% (120/143) of these patients. Most presented with intestinal symptoms such as colonic bleeding (68%) and diarrhea (42%). All but one of the patients between 20 and 40 years old had rectal polyps (98.7%, 75/76), whereas in those over 40 years old the prevalence was 76% (35/46). Non-specific symptoms such as abdominal pain, fatigue and bloating were less frequent and were mainly reported by patients older than 40. CONCLUSION: The commonest presenting features of FAP are alteration of bowel habit and rectal bleeding, but both are found in many other conditions. Patients with these findings need immediate endoscopy to allow prompt diagnosis and prophylactic surgery

Pioneering Robotic Liver Surgery in Germany: First Experiences with Liver Malignancies

Background Minimally invasive liver surgery is growing worldwide with obvious benefits for the treated patients. These procedures maybe improved by robotic techniques, which add several innovative features. In Germany, we were the first surgical department implementing robotic assisted minimally invasive liver resections. Material and methods Between June 2013 and March 2015, we performed robotic based minimally invasive liver resections in nine patients with malignant liver disease. Five off these patients suffered from primary and four from secondary liver malignancies. We retrospectively analyzed the perioperative variables of these patients and the oncological follow up. Results Mean age of the patients was 63 years (range 45–71). One patient suffered from intrahepatic cholangiocellular, four from hepatocellular carcinoma, and four patients from colorectal liver metastases. In six patients, left lateral liver resection, in two cases single segment resection, and in one case minimally invasive guided liver ablation were performed. Five patients underwent previous abdominal surgery. Mean operation time was 312 min (range 115–458 min). Mean weight of the liver specimens was 182 g (range 62–260 g) and mean estimated blood loss was 251 ml (range 10–650 ml). The mean tumor size was 4.4 cm (range 3.5–5.5 cm). In all cases, R0 status was confirmed with a mean margin of 0.6 cm (range 0.1–1.5 cm). One patient developed small bowel fistula on postoperative day 5, which could be treated conservatively. No patient died. Mean hospital stay of the patients was 6 days (range 3–10 days). During a mean follow up of 12 months (range 1–21 months), two patients developed tumor recurrence. Conclusion Robotic-based liver surgery is feasible in patients with primary and secondary liver malignancies. To achieve perioperative parameters comparable to open settings, the learning curve must be passed. Minor liver resections are good candidates to start this technique. But the huge benefits of robotic-based liver resections should be expected in extended procedures beyond minor liver resections with the currently available technology

Mannan-binding lectin and procalcitonin measurement for prediction of postoperative infection

INTRODUCTION: Postoperative infection is a major cause of morbidity and mortality. We investigated two serum markers for their ability to identify patients at risk for postoperative infection. Mannan-binding lectin (MBL) is a central molecule of the innate immune system and MBL deficiency is known to predispose to infection. Procalcitonin (PCT) is a sensitive marker for bacterial infection. METHODS: We investigated 162 patients undergoing elective surgery for cancer of the gastrointestinal tract. Patients were classified as having no complications (group A), having infection for unknown reason (group B) or having sepsis after events like aspiration or anastomotic leakage (group C). Analysis was done pre- and postoperatively for serum levels of MBL, PCT and C-reactive-protein. DNA was preoperatively sampled and stored and later analysed for genetic polymorphisms of MBL. RESULTS: The preoperative serum levels of MBL were significantly lower in group B patients than in group A patients (1332 ± 466 ng/ml versus 2523 ± 181 ng/ml). PCT measured on day one post-surgery was significantly higher in group B patients than in group A (3.33 ± 1.08 ng/ml versus 1.38 ± 0.17 ng/ml). Patients with an aberrant MBL genotype had a significantly higher risk of postoperative infections than wild-type carriers (p < 0.05). CONCLUSION: Preoperative MBL and early postoperative PCT measurement may help identify patients at risk for postoperative infection

The importance of radiological controls of anastomoses after upper gastrointestinal tract surgery - a retrospective cohort study

<p>Abstract</p> <p>Introduction</p> <p>This study was designed to analyze whether routine radiological controls of anastomoses in the upper gastrointestinal tract an early detection of anastomotic leaks.</p> <p>Patients and Methods</p> <p>135 patients who underwent upper gastrointestinal tract surgery were retrospectively analyzed. Patients in the first group (n = 55) underwent routine radiological control of the anastomoses. In the second group (n = 80) the radiological control was only performed in case of clinical symptoms or signs of anastomotic leaks.</p> <p>Results</p> <p>The incidence of anastomotic leaks in the patients seen by us was 5.2%, equivalent to 7 of 135 patients In Group 1 leaks were seen in 4 of 55 patients (7,2%) in group 2 leaks were seen in 3 of 80 (3,8%). The radiological control of the anastomoses with contrast swallow showed the leakage in two cases. Twice the results were false negative. The sensitivity of computed tomography was 100%.</p> <p>Discussion</p> <p>Routine radiological control of anastomoses with contrast swallow only has low sensitivity. This procedure should not be performed routinely any more.</p> <p>The radiological control should be used in cases with signs of anastomotic leakage or with postoperatively impaired gastrointestinal passage.</p

CC Chemokine Receptor 7–dependent and –independent Pathways for Lymphocyte Homing: Modulation by FTY720

Cognate interaction of chemokine receptor CCR7 on lymphocytes with its ligands CCL19 and CCL21 expressed on high endothelial venules (HEVs) is essential for effective migration of T and B cells across HEVs into secondary lymphoid organs. Plt mice, which lack expression of CCL19 and CCL21-ser, both ligands for CCR7 on HEVs, as well as CCR7-deficient mice, have a defective cell migration and reduced homing of lymphocytes. FTY720, a novel immunosuppressant, causes a reduction of lymphocytes in peripheral blood and tissues and their sequestration into lymphoid tissues. In this study we demonstrate that FTY720 rescues the homing defect in both CCR7−/− mice and plt mice. After FTY720 treatment, the number of CD4+ and CD8+ T cells as well as B cells in peripheral blood is reduced while pertussis toxin–sensitive homing into peripheral lymph nodes, mesenteric lymph node, and Peyer's patches is increased. Immunohistology demonstrates that FTY720 enables these cells to enter lymphoid tissue through HEVs. Thus, our data suggest an alternative G-αi-dependent, CCR7-CCL19/CCL21-independent mechanism for lymphocyte homing through HEVs which is strongly augmented in the presence of FTY720

Long-Term Relapse-Free Survival by Interdisciplinary Collaboration in a Patient with Metastatic Pancreatic Cancer (UICC IV)

Introduction: The prognostic outlook for patients suffering from pancreatic cancer is generally poor. Particularly in cases of advanced and metastatic disease, long-term relapse-free survival may be achieved only in a few cases. Case Report: A 45-year-old patient presented with metastatic pancreatic cancer. Liver metastases had been intra-operatively confirmed by histology. Prior to initiating treatment, a portacath was surgically implanted. Subsequently, the patient received a weekly dose of 1,000 mg/m2 gemcitabine combined with 2,000 mg/m2 high-dose 5-fluorouracil as a 24-hour infusion for palliative treatment. As the patient was suffering from a stenosis of the ductus hepaticus communis, an endoprosthesis was primarily implanted. After 18 applications of chemotherapy during which only low toxic side effects such as nausea, vomiting and alopecia (NCI-CTC grade 1) presented, a partial remission of the primary tumor was observed. In the course of chemotherapy treatment, the carbohydrate antigen 19-9 tumor marker value normalized. Thus, the interdisciplinary tumor board of the University of Erlangen decided to perform a laparoscopy to evaluate the status of liver metastases after palliative chemotherapy treatment. Subsequently, the primary tumor could be completely resected (pT2, pN0, pM0, L0, V0, G2, R0); liver metastases were not observed. Eight years after the initial diagnosis, the patient is relapse-free, professionally fully integrated and presents with an excellent performance status. Conclusion: Patients suffering from metastatic pancreatic cancer may benefit from treatment combinations with palliative intent. In singular cases, patients may even have a curative treatment option, provided a close interdisciplinary collaboration exists

Identification of Predictive Markers for Response to Neoadjuvant Chemoradiation in Rectal Carcinomas by Proteomic Isotope Coded Protein Label (ICPL) Analysis

Neoadjuvant chemoradiation (nCRT) is an established procedure in stage union internationale contre le cancer (UICC) II/III rectal carcinomas. Around 53% of the tumours present with good tumor regression after nCRT, and 8%-15% are complete responders. Reliable selection markers would allow the identification of poor or non-responders prior to therapy. Tumor biopsies were harvested from 20 patients with rectal carcinomas, and stored in liquid nitrogen prior to therapy after obtaining patients’ informed consent (Erlangen-No.3784). Patients received standardized nCRT with 5-Fluoruracil (nCRT I) or 5-Fluoruracil ± Oxaliplatin (nCRT II) according to the CAO/ARO/AIO-04 protocol. After surgery, regression grading (Dworak) of the tumors was performed during histopathological examination of the specimens. Tumors were classified as poor (Dworak 1 + 2) or good (Dworak 3 + 4) responders. Laser capture microdissection (LCM) for tumor enrichment was performed on preoperative biopsies. Differences in expressed proteins between poor and good responders to nCRT I and II were identified by proteomic analysis (Isotope Coded Protein Label, ICPL™) and selected markers were validated by immunohistochemistry. Tumors of 10 patients were classified as histopathologically poor (Dworak 1 or 2) and the other 10 tumor samples as histopathologically good (Dworak 3 or 4) responders to nCRT after surgery. Sufficient material in good quality was harvested for ICPL analysis by LCM from all biopsies. We identified 140 differentially regulated proteins regarding the selection criteria and the response to nCRT. Fourteen of these proteins were synchronously up-regulated at least 1.5-fold after nCRT I or nCRT II (e.g., FLNB, TKT, PKM2, SERINB1, IGHG2). Thirty-five proteins showed a complete reciprocal regulation (up or down) after nCRT I or nCRT II and the rest was regulated either according to nCRT I or II. The protein expression of regulated proteins such as PLEC1, TKT, HADHA and TAGLN was validated successfully by immunohistochemistry. ICPL is a valid method to identify differentially expressed proteins in rectal carcinoma tissue between poor vs. good responders to nCRT. The identified protein markers may act as selection criteria for nCRT in the future, but our preliminary findings must be reproduced and validated in a prospective cohort

A new survival model for hyperthermic intraperitoneal chemotherapy (HIPEC) in tumor-bearing rats in the treatment of peritoneal carcinomatosis

BACKGROUND: Cytoreduction followed by hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in patients with peritoneal carcinomatosis of colorectal origin. Animal models are important in the evaluation of new treatment modalities. The purpose of this study was to devise an experimental setting which can be routinely used for the investigation of HIPEC in peritoneal carcinomatosis. METHODS: A new peritoneal perfusion system in tumor bearing rats were tested. For this purpose CC531 colon carcinoma cells were implanted intraperitoneally in Wag/Rija rats. After 10 days of tumor growth the animals were randomized into three groups of six animals each: group 1: control (n = 6), group 2: HIPEC with mitomycin C in a concentration of 15 mg/m(2 )(n = 6), group III: mitomycin C i.p. as monotherapy in a concentration of 10 mg/m(2 )(n = 6). After 10 days, total tumor weight and the extent of tumor spread, as classified by the modified Peritoneal Cancer Index (PCI), were assessed by autopsy of the animals. RESULTS: No postoperative deaths were observed. Conjunctivitis, lethargy and loss of appetite were the main side effects in the HIPEC group. No severe locoregional or systemic toxity was observed. All control animals developed massive tumor growth. Tumor load was significantly reduced in the treatment group and was lowest in group II. CONCLUSION: The combination of hyperthermia with MMC resulted in an increased tumoricidal effect in the rat model. The presented model provides an opportunity to study the mechanism and effect of hyperthermic intraperitoneal chemotherapy and new drugs for this treatment modality