Decreased mebrofenin uptake in patients with non-colorectal liver tumors requiring liver volume augmentation-a single-center analysis.

BACKGROUND: Posthepatectomy liver failure (PHLF) remains a life-threatening complication after hepatectomy. To reduce PHLF, a preoperative assessment of liver function is indispensable. For this purpose, 99mTc-mebrofenin hepatobiliary scintigraphy with SPECT (MSPECT) can be used. The aim of the current study was to evaluate the predictive value of MSPECT for PHLF in patients with non-colorectal liver tumors (NCRLT) compared to patients with colorectal liver metastasis (CRLM) undergoing extended liver resection. METHODS: We included all patients undergoing extended liver resections via two-stage procedures between January 2019 and December 2021 at the University Medical Center Hamburg-Eppendorf, Germany. All patients received a preoperative MSPECT. RESULTS: Twenty patients were included. In every fourth patient, PHLF was observed. Four patients had PHLF grade C. There were no differences between patients with CRLM and NCRLT regarding PHLF rate and future liver remnant (FLR) volume. Patients with CRLM had higher mebrofenin uptake in the FLR compared to those with NCRLT (2.49%/min/m2 vs. 1.51%/min/m2; p = 0.004). CONCLUSION: Mebrofenin uptake in patients with NCRLT was lower compared to those patients with CRLM. However, there was no difference in the PHLF rate and FLR volume. Cut-off values for the mebrofenin uptake might need adjustments for different surgical indications, surgical procedures, and underlying diseases.

Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma.

Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values <0.05 considered significant. K3326X and I157T were associated with increased risk of developing sporadic PDAC (odds ratio (ORdom ) = 1.78, 95% confidence interval (CI) = 1.26-2.52, p = 1.19 × 10-3 and ORdom = 1.74, 95% CI = 1.15-2.63, p = 8.57 × 10-3 , respectively). Neither mutation was significantly associated with risk of developing early-onset PDAC. This retrospective study demonstrates novel risk estimates of K3326X and I157T in sporadic PDAC which suggest that upon validation and in combination with other established genetic and non-genetic risk factors, these mutations may be used to improve pancreatic cancer risk assessment in European populations. Identification of carriers of these risk alleles as high-risk groups may also facilitate screening or prevention strategies for such individuals, regardless of family history.

A hairy cavity: endoscopic therapy of a presacral recurrence of a complex pilonidal sinus.

BACKGROUND: Recently, minimally invasive techniques to avoid radical excisions of the pilonidal sinus with long-lasting secondary wound healing were developed. We describe a rare case of an intrapelvic, pararectal recurrence of a pilonidal sinus, who was innovatively treated with flexible endoscopy. CASE PRESENTATION: A 43-year-old Caucasian man presented with an intrapelvic, pararectal recurrence of a primarily wide-stretched pilonidal sinus, originally located in the sacrococcygeal region and spreading laterally to the gluteal region and intrapelvic to the presacral area. No connection to the bowel was evident. Up until presentation in the endoscopic department, a total of five attempts of surgical resection were performed, always confirming the diagnosis of a pilonidal sinus. Endoscopic therapy consisted of a combination of debridement, laser ablation and endoscopic vacuum therapy. After completion of APC and VAC therapy, the patient irrigated the abscess cavity for a further 2 weeks with a rinsing syringe. The resulting deep scar at the gluteal fistula was resected after secondary wound healing was completed. Two years after the end of the therapy, no recurrence was evident. CONCLUSION: Flexible endoscopy is, with its multiple therapeutic applications, an effective tool even in very complex inflammatory fistula and abscesses. Correctly indicated, it is with its minimally invasive character an excellent alternative to open surgical approaches.

Diverse prognostic value of the GTn promoter polymorphism in squamous cell and adeno carcinoma of the oesophagus.

The basal transcription of heme oxygenase-1 (HO-1) regulation is dependent upon a GT repeat germ line polymorphism (GTn) in the promoter of the HO-1 gene. We determined the prognostic value of HO-1 promoter polymorphism on the natural postoperative course of complete resected oesophageal cancer. Genomic DNA from 297 patients was amplified by polymerase chain reaction and sequenced. The results were correlated with clinicopathological parameters, disseminated tumour cells in bone marrow (DTC) and clinical outcome. Depending on short allele with <25 and long allele with ≥25, GTn repeats three genotypes (SS, SL and LL) were defined. A diverse role of GTn was evident in squamous cell carcinoma (SCC) and adenocarcinoma (AC). In SCC, the SS genotype presented less advanced tumours with lower rate DTC in bone marrow and relapse compared with L-allele carriers. In contrast, AC patients with the SS genotype displayed a complete opposing tumour characteristic. The disease-free (DFS) and overall survival (OS) in SCC patients was markedly reduced in LL genotypes (p < 0.001). In AC contrarily the SS genotype patients displayed the worst DFS and OS (p < 0.001). GTn is a strong prognostic factor with diverse prognostic value for recurrence and survival in AC and SCC.

Non-trauma Emergency Pancreatoduodenectomies: A Single-Center Retrospective Analysis.

OBJECTIVE: To retrospectively assess the frequency and indications for emergency pancreatoduodenctomies in a tertiary referral center. METHODS: Pancreatoduodenectomies between January 2005 and January 2014 were retrospectively assessed for emergency indications defined as surgery following unplanned hospital admission in less than 24 h. Data on indications and on the intraoperative as well as the post-operative course were collected. RESULTS: Out of 583 pancreatoduodenectomies during the interval, a total of 10 (1.7 %) were performed as an emergency surgery. Indications included uncontrollable bleeding, duodenal and proximal jejunal perforations, and endoscopic retrograde cholangiopancreatography-related complications. Three of the 10 (30.0 %) patients died during the hospital course. In one patient, an intraoperative mass transfusion was necessary. No intraoperative death occurred. All but one patient were American Society of Anesthesiologists class three or higher. In two cases, the pancreatic remnant was left without anastomosis for second-stage pancreatojejunostomy. Median operation time was 326.5 min (SD 100.3 min). Hospital stay of the surviving patients was prolonged (median 43.0 days; SD 24.0 days). CONCLUSION: Emergency pancreatoduodenectomies are non-frequent, have a diverse range of indications and serve as an ultima ratio to cope with severe injuries and complications around the pancreatic head area.

[Neuroendocrine tumours of the GI tract--data from the German NET Registry]. / Neuroendokrine Tumoren des Verdauungstrakts - Daten des deutschen NET-Registers.

BACKGROUND: Neuroendocrine tumours (NET) are rare and heterogeneous neoplasia. To obtain valid data on epidemiology, diagnostics, therapy, prognosis and risk factors is the aim of the German NET registry. PATIENTS AND METHODS: Data from 2009 histologically proven NET were collected from 35 NET centres between 1999 and 2010. Data collection has been performed prospectively since 2004. Results: Median follow-up was 34.5 months and median age at diagnosis 56.4 years. Primary tumour localisations were pancreas (34.2%), midgut (5.8%), stomach (6.5%), bowel (6.9%), duodenum (4.8%) and neuroendocrine CUP (12.6%). Synchronous metastases were seen in 46% and second malignancies in 12%. From 860 patients, 402 (46.7%) had functional tumours with the following hormone excess syndromes: carcinoid syndrome (19.1%; n = 164), persistent hyperinsulinaemic hypoglycaemia (17.7%; n = 152), Zollinger- Ellison syndrome (7.1%; n = 61), glucagonoma (0.7%; n = 15), Verner-Morrison syndrome (0.4%; n = 8) and somatostatinoma syndrome(0.1%; n = 2). Surgical therapy was performed in 78%, therapy with somatostatin receptor analogues(SSA) in 28%, peptide radioreceptor therapy (PRRT) in 19%, chemotherapy in 18% and interferon therapy in 6.5%. Only surgery was done in 47%, whereas 53% received a second therapy. General mortality rate during follow-up was 14.9%. The tumour-specific survival rates for 2, 5 and 10 years were 94, 85 and 70%. The 5-year survival is dependent on the surgical or non-surgical therapy (82 versus 61%, p < 0.001) and also on the primary tumour site (90/30% for midgut, 85/65% for pancreas, p < 0.001). Grading (G1, G2, G3) based on proliferation index Ki-67 recommended by the ENETS guidelines and WHO classification is highly correlated to the 5-year survival rate (88, 82, 33%, p < 0.001). CONCLUSION: The German NET registry provides valid multicentric data on NET in Germany. Surgical therapy is the most frequent and important therapy with good clinical outcome. In non-resectable, metastatic tumours, systemic therapies are common. Continuation and evaluation of the new WHO and TNM classifications for NET and their therapies will be a future focus of the registry.

Limits of surgery for pancreatic cancer.

Pancreatic cancer patients often present in an already advanced state of disease and the therapeutic approach is an interdisciplinary challenge. Surgery is an integral part in a potentially curative setting, yet in such advanced disease surgery can reach its limits. The technical feasibility has to be weighted against potential harms and the oncological reasonableness. In locally advanced disease, limits of surgery could be pushed as evidence grew. A venous vascular tumor infiltration nowadays does not preclude patients from surgery, as venous resections can be safely performed and survival rates are not inferior to patients with standard resections. Multivisceral resections have an increased risk of morbidity and mortality, but can improve overall survival. The resection and reconstruction of tumor infiltrated arteries is technically feasible, but these procedures have a high rate of associated morbidity and mortality with an unclear oncological benefit and therefore are generally not recommended. This also holds true for intentional palliative R2-resections, which do not offer a survival benefit but decrease the quality of life and have higher morbidity and mortality rates than palliative bypass procedures. A synchronous resection of the primary tumor and intraabdominal metastases in an olgiometastatic disease only offers a questionable oncological benefit and the evidence for this approach is scarce. Therefore, surgery in a metastatic disease is generally not recommended and has to be discussed interdisciplinary on a highly individual basis.Key words: pancreatic cancer multivisceral resection staging.

Presence of the coxsackievirus and adenovirus receptor (CAR) in human neoplasms: a multitumour array analysis.

BACKGROUND: The Coxsackie- and Adenovirus Receptor (CAR) has been assigned two crucial attributes in carcinomas: (a) involvement in the regulation of growth and dissemination and (b) binding for potentially therapeutic adenoviruses. However, data on CAR expression in cancer types are conflicting and several entities have not been analysed to date. METHODS: The expression of CAR was assessed by immunohistochemical staining of tissue microarrays (TMA) containing 3714 specimens derived from 100 malignancies and from 273 normal control tissues. RESULTS: The expression of CAR was detected in all normal organs, except in the brain. Expression levels, however, displayed a broad range from being barely detectable (for example, in the thymus) to high abundance expression (for example, in the liver and gastric mucosa). In malignancies, a high degree of variability was notable also, ranging from significantly elevated CAR expression (for example, in early stages of malignant transformation and several tumours of the female reproductive system) to decreased CAR expression (for example, in colon and prostate cancer types). CONCLUSION: Our results provide a comprehensive insight into CAR expression in neoplasms and indicate that CAR may offer a valuable target for adenovirus-based therapy in a subset of carcinomas. Furthermore, these data suggest that CAR may contribute to carcinogenesis in an entity-dependent manner.

VEGFR-2, CXCR-2 and PAR-1 germline polymorphisms as predictors of survival in pancreatic carcinoma.

BACKGROUND: Hypoxic environment of pancreatic cancer (PC) implicates high vascular in-growth, which may be influenced by angiogenesis-related germline polymorphisms. Our purpose was to evaluate polymorphisms of vascular endothelial growth factor receptor 2 (VEGFR-2), CXC chemokine receptor 2 (CXCR-2), proteinase-activated receptor 1 (PAR-1) and endostatin (ES) as prognostic markers for disease-free (DFS) and overall survival (OS) in PC. PATIENTS AND METHODS: Genotyping of 173 patients, surgically treated for PC between 2004 and 2011, was carried out by TaqMan(®) genotyping assays or polymerase chain reaction. Chi-square test, Kaplan-Meier estimator and Cox regression hazard model were used to assess the prognostic value of selected polymorphisms. RESULTS: VEGFR-2 -906 T/T and PAR-1 -506 Del/Del genotypes predicted longer DFS (P = 0.003, P = 0.014) and OS (VEGFR-2 -906, P = 0.011). CXCR-2 +1208 T/T genotype was a negative predictor for DFS (P < 0.0001). Combined analysis for DFS and OS indicated that patients with the fewest number of favorable genotypes simultaneously present (VEGFR-2 -906 T/T, CXCR-2 +1208 C/T or C/C and PAR-1 -506 Del/Del) were at the highest risk for recurrence or death (P < 0.0001). CONCLUSION: VEGFR-2 -906 C>T, CXCR-2 +1208 C>T and PAR-1 -506 Ins/Del polymorphisms are potential predictors for survival in PC.

Surgery of esophageal cancer.

BACKGROUND: Surgery is the only option for curative treatment in patients with esophageal carcinoma. Despite the debates related to the peri-operative therapy regime, a generally accepted consensus on surgical approach is not reached yet. The debate focuses mainly on pros and cons between radical transthoracic resection and the (limited) transhiatal resection in the last decade. METHODS: The PubMed database was searched for randomized trials, meta-analyses, and retrospective single-center studies. The search terms were "esophageal carcinoma," "esophageal junction carcinomas," "transhiatal," "transthoracic," "morbidity," "mortality," and "surgery." RESULTS: The radical transthoracic approach should be the standard of care for esophageal carcinoma since it does not go along with an increased risk of postoperative morbidity or mortality but reveals an improved survival. Patient-related co-morbidities are the most influencing factors for the postoperative outcome. For type II esophageal junction carcinoma, treatment options from transhiatal extended gastrectomy to esophagectomy with hemigastrectomy or esophagogastrectomy with colonic interposition are existing. In type III esophagogastric junction carcinomas, the transhiatal extended gastrectomy is the standard of care, and the minimally invasive approach should be performed in specialized centers. CONCLUSION: Based on current available study results, this expert review provides a decision support for the best surgical strategy depending on tumor localization and patients' characteristics.

Adjusting the RAPID score with 2 additional variables significantly increases its predictive value in patients with empyema.

Pleural empyema is a serious condition leading to a significant burden on health care systems due to protracted hospitalisations. Treatment ranges from non-surgical interventions such as antibiotic therapy and chest tube placement to thoracoscopic or open surgery. Various risk factors which impact outcomes have been investigated. The RAPID (renal, age, purulence, infection source, and dietary factors) score is a clinical risk score which identifies patients at risk of death and may be used to formulate individual treatment strategies accordingly. All patients undergoing surgical interventions for empyema at a major tertiary medical centre in Germany from 2017 to 2020 were analysed. The aim was to identify perioperative risk factors which significantly impact treatment outcomes but are currently not included in the RAPID score. 245 patients with pleural empyema surgically treated at the Department of General, Visceral and Thoracic Surgery at the University Medical Centre, Hamburg, Germany (admitted from January 2017 to April 2020) were retrospectively analysed. All patients which received either minimally invasive or open thoracic surgery were included. Epidemiological as well as perioperative data was analysed to identify risk factors which impact long-term overall outcomes. 90-day mortality rate was the primary endpoint. The mean age was 59.4 years with a bimodal distribution. There was a male predominance across the cohort (71.4% compared to 28.6%), with no significant differences across ages below or above 60 years. 53 (21.6%) patients died within the first 90 days. Diabetes type 1 and 2, renal replacement therapy, immunosuppression, postoperative bleeding, intraoperative transfusion as well as microbiologically confirmed bacterial invasion of the pleura all led to higher mortality rates. Higher RAPID scores accurately predicted higher 90-day mortality rates. Modifying the RAPID score by adding the comorbidities diabetes and renal replacement therapy significantly increased the predictive value of the score. We demonstrated various perioperative and patient related risk-factors not included in the RAPID score which negatively impact postoperative outcome in patients receiving surgical treatment for pleural empyema. These should be taken into consideration when deciding on the best course of treatment. If confirmed in a prospective study including non-surgical patients with a significantly larger cohort, it may be worth considering expanding the RAPID score to include these.

Pupil evaluation in addition to Glasgow Coma Scale components in prediction of traumatic brain injury and mortality.

BACKGROUND: Early diagnosis and prediction of traumatic brain injury (TBI) is essential for determining treatment strategies and allocating resources. This study evaluated the predictive accuracy of Glasgow Coma Scale (GCS) verbal, motor and eye components alone, or in addition to pupil size and reactivity, for TBI. METHODS: A retrospective cohort analysis of data from 51 425 severely injured patients registered in the Trauma Registry of the German Society for Trauma Surgery from 1993 to 2009 was undertaken. Only directly admitted patients alive on admission and with complete data on GCS, pupil size and pupil reactivity were included. The unadjusted predictive roles of GCS components and pupil parameters, alone or in combination, were modelled using area under the receiver operating characteristic (AUROC) curve analyses and multivariable logistic regression regarding presence of TBI and death. RESULTS: Some 24 115 patients fulfilled the study inclusion criteria. Best accuracy for outcome prediction was found for pupil reactivity (AUROC 0.770, 95 per cent confidence interval 0.761 to 0.779) and GCS motor component (AUROC 0.797, 0.788 to 0.805), with less accuracy for GCS eye and verbal components. The combination of pupil reactivity and GCS motor component (AUROC 0.822, 0.814 to 0.830) outmatched the predictive accuracy of GCS alone (AUROC 0.808, 0.800 to 0.815). Pupil reactivity and size were significantly correlated (r(s) = 0.56, P < 0.001). Patients displaying both unequal pupils and fixed pupils were most likely to have TBI (95.1 per cent of 283 patients). Good outcome (Glasgow Outcome Scale score 4 or more) was documented for only 1929 patients (8.0 per cent) showing fixed and bilateral dilated pupils. CONCLUSION: The best predictive accuracy for presence of TBI was obtained using the GCS components. Pupil reactivity together with the GCS motor component performed best in predicting death.

Staging and outcome depending on surgical treatment in adenocarcinomas of the oesophagogastric junction.

BACKGROUND: Owing to controversial staging and classification of adenocarcinoma of the oesophago-gastric junction (AOG) before surgery, the choice of appropriate surgical approach remains problematic. In a retrospective study, preoperative staging of AOG and the impact of preoperative misclassification on outcome were analysed. METHODS: Data from patients with AOG were analysed from a prospectively collected database with regard to surgical treatment, preoperative and postoperative staging, and outcome. RESULTS: One-hundred and thirty patients with Siewert types I and II AOG who did not have neoadjuvant treatment were included in the study: 41 patients with an AOG type I who underwent oesophagectomy, 51 patients with an AOG staged before surgery as type I who underwent oesophagectomy but in whom the final histology showed a type II tumour, and 38 patients whose tumours were staged as AOG type II before and after operation who underwent gastrectomy. Among patients who had an oesophagectomy, lymph node metastases (P = 0.022), tumour relapse (P = 0.009) and recurrent distant metastases (P = 0.028) were significantly more frequent in patients with AOG type II; those with AOG type II had shorter overall survival than those with type I tumours (P = 0.024). Among those with AOG type II, recurrence-free survival was significantly shorter after oesophagectomy compared with extended gastrectomy (P = 0.019). Thoracoabdominal oesophagectomy had a favourable influence on outcome compared with the transhiatal approach. CONCLUSION: Accurate preoperative staging of AOG and appropriate surgical therapy are crucial for outcome. AOG type II is a more aggressive tumour with higher recurrence rates than AOG type I. These patients therefore benefit from more radical surgical treatment.

Losses at chromosome 4q are associated with poor survival in operable ductal pancreatic adenocarcinoma.

Here we tested the prognostic impact of genomic alterations in operable localized pancreatic ductal adenocarcinoma (PDAC). Fifty-two formalin-fixed and paraffin-embedded primary PDAC were laser micro-dissected and were investigated by comparative genomic hybridization after whole genome amplification using an adapter-linker PCR. Chromosomal gains and losses were correlated to clinico-pathological parameters and clinical follow-up data. The most frequent aberration was loss on chromosome 17p (65%) while the most frequent gains were detected at 2q (41%) and 8q (41%), respectively. The concomitant occurrence of losses at 9p and 17p was found to be statistically significant. Higher rates of chromosomal losses were associated with a more advanced primary tumor stage and losses at 9p and 18q were significantly associated with presence of lymphatic metastasis (chi-square: p = 0.03, p = 0.05, respectively). Deletions on chromosome 4 were of prognostic significance for overall survival and tumor recurrence (Cox-multivariate analysis: p = 0.026 and p = 0.021, respectively). In conclusion our data suggest the common alterations at chromosome 8q, 9p, 17p and 18q as well as the prognostic relevant deletions on chromosome 4q as relevant for PDAC progression. Our comprehensive data from 52 PDAC should provide a basis for future studies with a higher resolution to discover the relevant genes located within the chromosomal aberrations identified.

Endoscopic ultrasound staging in gastric cancer: Does it help management decisions in the era of neoadjuvant treatment?

BACKGROUND AND STUDY AIMS: Endoscopic ultrasonography (EUS) has been shown to be the most accurate test for locoregional staging of upper gastrointestinal tumors; however, recent studies have questioned its accuracy level in daily clinical application. The present retrospective study analyzes the accuracy of EUS in guiding interdisciplinary treatment decisions. PATIENTS AND METHODS: 123 primarily operated patients (63 % men, mean age 61.4 years) were included; only cases with tumor-free resection margins and without evidence of distant metastases were selected. EUS and histopathological findings were compared. Main outcome parameter was the distinction between tumors to be primarily operated (T1 /2N0) and those to be treated by neoadjuvant or perioperative chemotherapy (T3/4, or any N + ), based on an assumed algorithm for treatment stratification. RESULTS: Overall staging accuracy of EUS was 44.7 % for T and 71.5 % for N status irrespective of tumor location. Overstaging was the main problem (44.9 % for T, 42.9 % for N staging). The overall EUS classification was correct in 79.7 % (accuracy), with a sensitivity 91.9 % and specificity 51.4 %; only 19 out of 37 cases with histopathological T1/2N0 were correctly classified by EUS. Positive and negative predictive values of EUS in diagnosing advanced tumor stage for assignment to neoadjuvant therapy were 81.4 % and 73.1 %, respectively. CONCLUSIONS: Whereas EUS has a high sensitivity in the diagnosis of locally advanced gastric cancer, endosonographic overstaging of T2 cancers appears to be a frequent problem. EUS stratification between local (T1 /2N0) and advanced (T3/4 or any N + ) tumors would thus result in incorrect assignment to neoadjuvant treatment in half of cases.

Arterial en bloc resection for pancreatic carcinoma.

BACKGROUND: Surgery for locally advanced pancreatic cancer with arterial involvement of the hepatic artery, coeliac trunk and superior mesenteric artery (SMA) is highly controversial. In a retrospective review, the benefits and harms of arterial en bloc resection (AEBR) for pancreatic adenocarcinoma with arterial involvement were analysed. METHODS: Patients were divided into three groups: 29 patients who had pancreatic resection and AEBR (group 1), 449 who had pancreatic resection with no arterial resection or reconstruction (group 2), and 40 with unresectable tumours who underwent palliative bypass (group 3). RESULTS: Eighteen patients underwent reconstruction of the hepatic artery, eight of the coeliac trunk and three of the SMA. Additional reconstruction of portal vein was required in 15 patients and of adjacent visceral organs in 19. Perioperative morbidity and mortality rates were higher in group 1 than in group 2 (P = 0·031 and P = 0·037 respectively). Additional portal vein resection was an independent predictor of morbidity (P < 0·001). Median overall survival was similar for groups 1 and 2 (14·0 versus 15·8 months; P = 0·152), and lower for group 3 (7·5 months; P = 0·028 versus group 1). CONCLUSION: In selected patients AEBR can result in overall survival comparable to that obtained with standard resection and better than that after palliative bypass. Nevertheless, AEBR is associated with significantly higher morbidity and mortality rates, counterbalancing the overall gain in survival and limiting the overall oncological benefit.

Is Toupet fundoplication the procedure of choice for treating gastroesophageal reflux disease? Results of a prospective randomized experimental trial comparing three major antireflux operations in a porcine model.

BACKGROUND: Gastroesophageal reflux disease (GERD) is among the most common dysfunctions of the upper gastrointestinal tract. It interferes with quality of life and is a risk factor for the development of adenocarcinoma in the lower esophagus. Laparoscopic fundoplication is an effective treatment of GERD, but the physiologic mechanisms of the different available procedures had not been investigated to date. METHODS: In this study, 28 German Landrace pigs underwent baseline manometry and 24-h pH monitoring followed by myotomy to induce reflux esophagitis. After new-onset reflux was proved, the pigs were randomized to groups based on four treatments: total fundoplication, anterior hemifundoplication, posterior hemifundoplication, and control. On days 10 and 60 after the intervention, the effectiveness of the different fundoplication modifications was compared with that of the control subjects by 24-h pH monitoring manometry. Finally, the pigs were killed, after which the minimum volume and pressure required to breach the gastroesophageal junction were recorded. RESULTS: After myotomy, a significant increase in the reflux could be confirmed. The findings after fundoplication showed a significant decrease in the fraction of time that the pH fell below four and an increase in the vector volume compared with the measurement after myotomy. Total fundoplication and posterior hemifundoplication were highly effective, whereas measurements after anterior fundoplication still showed increased fraction times. Pharmacologic stimulation with pentagastrin showed an increase in the vector volume of the esophageal sphincter. CONCLUSIONS: Total fundoplication and posterior hemifundoplication are potent operations for the treatment of GERD. Anterior hemifundoplication reduces the reflux as well, but the effects are significantly less than with total and posterior fundoplication. Pharmacologic stimulation showed excellent results after posterior hemifundoplication, and a tendency to overcorrection was shown after total fundoplication.

[Perioperative fluid management]. / Perioperatives Volumenmanagement.

An appropriate perioperative infusion management is pivotal for the perioperative outcome of the patient. Optimization of the perioperative fluid treatment often results in enhanced postoperative outcome, reduced perioperative complications and shortened hospitalization. Hypovolemia as well as hypervolemia can lead to an increased rate of perioperative complications. The main goal is to maintain perioperative euvolemia by goal-directed therapy (GDT), a combination of fluid management and inotropic medication, to optimize perfusion conditions in the perioperative period; however, perioperative fluid management should also include the preoperative and postoperative periods. This encompasses the preoperative administration of carbohydrate-rich drinks up to 2 h before surgery. In the postoperative period, patients should be encouraged to start per os hydration early and excessive i.v. fluid administration should be avoided. Implementation of a comprehensive multimodal, goal-directed fluid management within an enhanced recovery after surgery (ERAS) protocol is efficient but the exact status of indovodual items remains unclear at present.

Lack of prognostic significance of serum DNA methylation of DAPK, MGMT, and GSTPI in patients with non-small cell lung cancer.

BACKGROUND AND OBJECTIVES: To further improve the screening, diagnosis and therapy of patients with non-small cell lung cancer (NSCLC) additional diagnostic tools are desperately warranted. Aim of this study was to investigate the potential of the DNA methylation of DAPK, MGMT, and GSTPI in serum of patients with NSCLC as a prognostic molecular marker in this disease. METHODS: Seventy-six patients with NSCLC were included in this study. The analysis of DNA methylation in serum of patients was performed on pre-operative samples. Following DNA isolation and bisulfite-treatment, DNA methylation was analyzed by quantitative-methylation-specific real-time PCR with beta-actin as the internal reference gene. RESULTS: DNA methylation was detectable with following frequencies: DAPK 68.4%, MGMT 7.9%, GSTPI 0%. There were no associations between DNA methylation status and histology, tumor stage, grading or gender detectable. With a mean follow-up of 19.7 months the median survival was 26.3 months. There were no associations between the status of DNA methylation in patient's serum and prognosis detectable. CONCLUSION: The analysis of DNA methylation in serum of patients with NSCLC by quantitative-methylation-specific real-time PCR is technically feasible. Although our results suggest quantification of DNA methylation in serum not of prognostic significance in this disease, further studies are warranted to determine the future potential of this molecular approach.