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The treatment of peritoneal surface malignancies ranges from palliative care to full cytoreductive surgery (CRS) and Heated Intraperitoneal Chemotherapy HIPEC. Ongoing monitoring of patient recruitment and volume is usually carried out through dedicated registries. With multiple registries available worldwide, we sought to investigate the nature, extent and value of existing worldwide CRS and HIPEC registries.METHODS: A questionnaire was sent out to all known major treatment centres. The questionnaire covers: general purpose of the registry; inclusion criteria in the registry; the date the registry was first established; volume of patients in the registry and description of the data fields in the registries. Finally, the population size of the catchment area of the registry was collected.RESULTS: 27 questionnaires where returned. National databases are established in northwest European countries. There are five international general databases. Most database collect data on patients who have undergone an attempt to CRS and HIPEC. Two registries collect data on all patients with peritoneal carcinomatosis regardless the treatment. Most registries are primarily used for tracking outcomes and complications. When correlating the number of cases of CRS and HIPEC that are performed to the catchment area of the various registry, a large variation in the number of performed procedures related to the overall population was noted, ranging from 1.3 to 57 patients/million year with an average of 15 patients/1 million year.CONCLUSION: CRS and HIPEC is a well-established treatment for peritoneal surface malignancies worldwide. However, the coverage as well as the registration of treatment procedures differs widely. The most striking difference is the proportion of HIPEC procedures per capita which ranges from 1.3 to 57 patients per million. This suggests either a difference in patient selection, lack of access to HIPEC centres or lack of appropriate data collection.

Patients with peritoneal metastases of gastric cancer have a poor prognosis with a median survival of 7 months. A benefit of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) could be shown in several selected patient cohorts but remains controversial. The aim of this study was, to reflect the results of a national German HIPEC registry initiated by the German Society of General and Visceral Surgery (DGAV). The DGAV HIPEC registry StuDoQ|Peritoneum documents patients with peritoneal malignancy contributed from 52 hospitals. All consecutive documented patients from 2011 until 2016 (n = 3078) were treated with CRS and HIPEC and were analysed. A total of 315 (10%) suffered from gastric cancer and were analysed. A complete data set of 235 patients was available for this study, including 113 male (48.1%) and 122 female (51.9%) patients with a median age of 53.4 years (SD ± 11.9). The median PCI was 8.0 (range 1–30). A complete cytoreduction was achieved in 121 patients (71.6%). Postoperative complications (Clavien–Dindo grades 3–4) occurred in 40 patients (17%). The median overall survival (OS) time was 13 months. The 5-year survival rate was 6%. According to the PCI from 0–6 (n = 74); 7–15 (n = 70) and 16–39 (n = 24) the median OS differs significantly (18 months vs. 12 months vs. 5 months; p = 0.002). CRS and HIPEC in selected patients with gastric cancer and peritoneal spread can improve survival when they are treated in centers. An accurate staging and patient selection are of major importance to achieve long-term survival.

In recent years, there has been a significant change in the treatment recommendations for acute diverticulitis. In order to provide the right treatment to the individual patient, it is therefore important to classify the stage of the disease accurately, after taking various aspects into consideration.Patients treated for acute diverticulitis in Würzburg University Hospital during 2010 to 2014 were included. Inclusion criteria were the presence of a computer tomography for disease classification.More than half of the patients examined (n = 135, 52.9%) had acute uncomplicated diverticulitis on admission; 112 (43.2%) had a covered perforation (small paracolic abscess n = 63, 24,3%; large abscess n = 49, 18,9%) and 12 (4.6%) a free perforation. In a total of 150 (57.9%) patients, this was the first episode of diverticulitis, with a covered (66.1%) or a free perforation (75.0%) occurring at a higher than average rate as the first manifestation. Nearly two-thirds (66.4%, n = 168) of patients underwent sigmoid resection during follow-up.Despite current trends towards more conservative therapy of acute diverticulitis, sigmoid resection remains a corner stone of successful therapy throughout all types of acute diverticulitis. The indication of sigmoid resection nowadays requires profound knowledge of the individual prognosis for recurrent diverticulitis and quality of life.In den vergangenen Jahren gab es einen deutlichen Wandel in den Therapieempfehlungen der akuten Divertikulitis. Die stadiengerechte Therapie orientiert sich an der neuen Klassifikation der Divertikelkrankheit aus der aktuellen Leitlinie.Erfasst wurden alle Patienten, die in den Jahren 2010 bis 2014 wegen einer akuten Divertikulitis im Universitätsklinikum Würzburg behandelt wurden. Einschlusskriterium für die Auswertung war das Vorhandensein einer Computertomografie zur Stadieneinteilung.Gut die Hälfte der untersuchten Patienten (n = 135, 52,9%) hatte bei Aufnahme eine akute unkomplizierte Divertikulitis, 112 (43,2%) wiesen eine gedeckte Perforation (Mikroabszess n = 63, 24,3%; bzw. Makroabszess n = 49, 18,9%), 12 Patienten (4,6%) eine freie Perforation auf. Bei insgesamt 150 (57,9%) Patienten war es der 1. Schub einer Divertikulitis, eine gedeckte (66,1%) oder eine freie Perforation (75,0%) trat dabei überdurchschnittlich häufig als Erstmanifestation auf. Knapp zwei Drittel (66,4%, n = 168) der Patienten wurden im Verlauf sigmareseziert.Trotz des Trends hin zu einer konservativen Therapie der akuten Divertikulitis bleibt die (elektive) Sigmaresektion nach wie vor ein zentraler Bestandteil in der Therapie über alle Stadien hinweg. Die Indikationsstellung ist jedoch heutzutage deutlich differenzierter und erfordert neben der individuellen Klassifikation der Entzündungssituation auch Kenntnisse über die individuelle krankheitsspezifische Prognose in Bezug auf Rezidivwahrscheinlichkeit und Lebensqualität.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are performed for well-selected patients with peritoneal surface malignancies. This combined treatment is potentially associated with an increased rate of complications. The aim of this paper was to analyze the morbidity and mortality of CRS and HIPEC in the German national registry. We present a retrospective analysis of 2149 consecutive patients from 52 hospitals. The data were prospectively documented in the DGAV StuDoQ Registry between February 2011 and December 2016. Almost two-thirds of all patients had a colorectal malignancy; therefore, the most frequently performed resections were colectomies (54%) and rectal resections (30%). Only 36.2% of all patients had no anastomosis, and fewer than 20% of all patients were older than 70 years of age (16.4%). Enteric fistula and anastomotic leaks occurred in 10.5% of all cases. The reoperation rate was 14.6% (95% confidence interval [CI] 11.51–18.1). Major grade 3 and 4 complications (Clavien–Dindo classification) occurred in 19.3% of all patients, half of which were due to surgical complications. The overall 30-day postoperative hospital mortality was 2.3% (95% CI 1.02–3.85). Multivariate analysis showed an increased risk for morbidity associated with pancreatic resections (odds ratio [OR] 2.4), rectal resection (OR 1.5), or at least one anastomosis (OR 1.35), and mortality with reoperation (OR 8.7) or age > 70 years (OR 3.35). CRS and HIPEC are associated with acceptable morbidity and low mortality. These results show that CRS and HIPEC can be safely performed nationwide when close mentoring by experienced centers is provided.

Background Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as parts of an interdisciplinary treatment concept including systemic chemotherapy can improve survival of selected patients with peritoneal metastatic colorectal cancer (pmCRC). Nevertheless, the sequence of the therapeutic options is still a matter of debate. Thus, the COMBATAC (COMBined Anticancer Treatment of Advanced Colorectal cancer) trial was conducted to evaluate a combined treatment regimen consisting of preoperative systemic polychemotherapy + cetuximab followed by CRS + HIPEC and postoperative systemic polychemotherapy + cetuximab. Patients and Methods The COMBATAC trial is a prospective, multicenter, open-label, single-arm, single-stage phase 2 trial. Twenty-six patients with synchronous or metachronous colorectal or appendiceal peritoneal carcinomatosis were included. Enrollment was terminated prematurely by the sponsor because of slow recruitment. Progression-free survival as primary end point and overall survival were estimated by the Kaplan-Meier method. Also evaluated were morbidity according to Common Terminology Criteria for Adverse Events v4.0 and feasibility of the combined treatment concept. Results Median progression-free survival for the intention-to-treat population (n = 25) was 14.9 months. Median overall survival was not reached during the study duration. Ninety-two adverse events were documented in 16 patients, including 14 serious adverse events in 9 patients. The overall morbidity rate was 64%, and the grade 3/4 morbidity rate was 44%. Of all grade 3/4 morbidity events, 36.4% were related to systemic chemotherapy and 22.7% to surgery, whereas 40.9% were not directly related. There was no treatment-related mortality. Conclusion The results of the COMBATAC trial show that the multimodal treatment concept consisting of perioperative systemic chemotherapy and CRS + HIPEC is safe and feasible. Progression-free survival in selected patients with colorectal or appendiceal peritoneal metastasis might be improved.

Due to its primarily extraperitoneal location, potential affection of the anorectal continence and different metastatic behavior the rectal carcinoma (RC) is classified and treated as an independent disease. Over the past few decades various trials have led to improved multimodal therapies (including radiation, chemotherapy and surgery) for locally advanced rectal cancer and significant changes in the management of this disease whereas the benefit of adjuvant chemotherapy remains unclear. Based on a prospective tumor register of the University Hospital of Wuerzburg data of 263 patients having undergone neoadjuvant therapy and surgical resection for locally advanced rectal cancer were retrieved from the Wuerzburg International database (WID) between October 1992 and September 2013 analyzing the overall survival according to the application of an adjuvant therapy. The cohort consisted of 263 patients with a median age of 65 years (27–89 years), mostly male gender (n = 191; 72.6%) and an ASA performance score of II or III. 143 patients (54.3%) received an adjuvant therapy. Those patients have been significant younger (median 10 years; p

Tumor involvement of the peritoneum-peritoneal carcinomatosis-is a heterogeneous form of cancer that had been generally regarded as a sign of systemic tumor disease and as a terminal condition. The multimodal treatment approach for patients with peritoneal carcinomatosis, which had been conceived and developed, consists of what is known as cytoreductive surgery, followed by hyperthermic intraperitoneal chemotherapy (HIPEC). Depending on the tumor mass as assessed intraoperatively and the histopathological differentiation, patients who undergo cytoreductive surgery and HIPEC have a significant survival benefit. Mean increases in the survival period ranging from six months to up to four years have now been reported. In view of the substantial logistic effort and the extent of the surgery involved, this treatment approach represents a major challenge both for patients and for surgical oncologists, as well as for the members of the overall interdisciplinary structure required, which includes oncology, anesthesiology and intensive care, psycho-oncology, and patient management. The surgical procedures alone may take 8-14 hr. The present paper provides an overview of the basis for the approach and the use of specialized classifications and quantitative prognostic indicators.

Background The learning curves for cytoreductive surgery with intraperitoneal chemotherapy for treatment of pseudomyxoma peritonei (PMP) were explored between international centres/surgeons to identify institutional or other factors that might affect performance. Methods Data from patients with PMP treated with the combined procedure across 33 international centres between 1993 and 2012 were analysed retrospectively. A risk-adjusted sequential probability ratio test was conducted after defining the target outcome as early oncological failure (disease progression within 2 years of treatment), an acceptable risk for the target outcome (odds ratio) of 2, and type I/II error rates of 5 per cent. The risk prediction model was elaborated and patients were evaluated sequentially for each centre/surgeon. The learning curve was considered to be overcome and proficiency achieved when the odds ratio for early oncological failure became smaller than 2. Results Rates of optimal cytoreduction, severe postoperative morbidity and early oncological failure were 84·4, 25·7 and 29·0 per cent respectively. The median annual centre volume was 17 (range 6–66) peritoneal malignancies. Only eight of the 33 centres and six of 47 surgeons achieved proficiency after a median of 100 (range 78–284) and 96 (86–284) procedures respectively. The most important institutional factor affecting surgical performance was centre volume. Conclusion The learning curve is extremely long, so centralization and/or networking of centres is necessary to assure quality of services. One centre for every 10–15 million inhabitants would be ideal.

The human dopamine D2 receptor gene ( DRD2 ) is considered a candidate gene for neuro-psychiatric diseases. We typed three new DNA sequence variants in DRD2 intron 4, intron 6 and exon 8, in combination with the known TaqI A restriction fragment length polymorphism (RFLP) and exon 7 311 Ser/Cys in 106 unrelated psychiatrically healthy Caucasians. Based on the genotypic data we delineated 10 distinct DRD2 haplotypes and their genetic relationship. Our data provide evidence that the Taq A1 allele and the 311 Cys variant are components of different groups of haplotypes though both variants have been speculated to be associated with alcoholism or schizophrenia in recent studies. Therefore we conclude that the prior knowledge of the frequencies and genetic relationships of DRD2 haplotypes will lead to the selection of more suitable intragenic markers for future association studies.

To investigate a potential mode of noninvasive screening for colorectal cancer, we evaluated the hypermethylation of the secreted frizzled-related protein-1 gene promoter in human stool DNA. In stool samples from 36 patients with colorectal neoplasia (7 adenoma, 29 colorectal cancer) and 17 healthy control subjects, isolated DNA was treated with sodium bisulfite and analyzed by methylation-specific polymerase chain reaction with primers specific for methylated or unmethylated promoter sequences of the secreted frizzled-related protein-1 gene. Hypermethylation of the secreted frizzled-related protein-1 promoter was present in the stool DNA of patients with adenoma and colorectal cancer. A sensitivity of 89 percent and specificity of 86 percent were achieved in the detection of colorectal neoplasia. The difference in hypermethylation status of the secreted frizzled-related protein-1 promoter between the patients with colorectal neoplasia and the control group was statistically highly significant (P

The present study was performed to test the hypotheses that allelic variants at the human dopamine D2 receptor gene locus (DRD2) confer susceptibility to alcoholism or are associated with clinical subtypes of alcoholism. We investigated an A --> G substitution polymorphism in the 3'-untranslated region of exon 8 (E8) of DRD2 with allele frequencies of f(G) = 0.295 - 0.329. No significant association of the DRD2 genotype or allele frequencies with alcoholism was found in an association study including 283 alcoholics and 146 non-alcoholic controls. However, the frequent homozygous E8 A/A genotype with f(AA) = 0.47 - 0.48 was associated with increased anxiety and depression scores in alcoholics during the follow up after clinical detoxification treatment. In addition, E8 A/A was associated with increased suicide attempts and showed a tendency towards more severe withdrawal symptoms, early relapse and reduced responsiveness to the dopaminergic agonist apomorphine. Regression analysis revealed the DRD2 E8 genotype as the only significant factor determining withdrawal severity in female alcoholics. The findings suggest an influence of the DRD2 genotype on the neuropharmacological effects of chronic alcohol exposure and the clinical course of alcoholism.

Computer programs which can be used as an aid to diagnose multiple congenital anomaly syndromes have been used for many years, but up to now they have been evaluated very rarely. The diagnostic abilities of three of these systems [LDDB (London Dysmorphology Database), POSSUM (Pictures of Standard Syndromes and Undiagnosed Malformations), and SYNDROC] were analyzed. All three programs are based on an algorithm which defines a diagnosis by a set of phenotypic components all having the same weight (descriptive algorithm). A second algorithm is applied by SYNDROC to rank competing diagnoses in order of probability. This pseudo-Bayesian algorithm provides a coefficient of certitude (CC). For a test the clinical findings of 102 patients who had received a firm diagnosis were used. Two search strategies were tried: "novice's strategy" with all findings taken for a search and "expert's strategy" with a selected set of anomalies. Only those diagnoses that were suggested with the 1st rank, defined as the highest degree of agreement, or the highest CC were studied. The greatest resemblance between suggestions of the databases and the clinical diagnosis was obtained with the expert strategy. The highest number of matches were produced by SYNDROC (80 with expert strategy) and the lowest by POSSUM (54 with novice strategy). The overall agreement between the databases is about 40% for the 1st rank. This number reflects that different authors use different pivotal signs for the description of a syndrome. With the pseudo-Bayesian algorithm 59 cases obtained the highest CC value. Great difficulties exist with the subjective estimates for the calculation of these values; the absolute CC values seem to be meaningless. A small number of unusual cases with special combinations of anomalies provide serious problems for correct diagnosis.