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Effective patient selection is key in minimizing perioperative morbidity and mortality scores to evaluate the extent of peritoneal disease and help identify patients most likely to benefit from CRS and HIPEC. Although prolonged survival is often the focus of treatment, this must be balanced against impaired quality of life. In this chapter we summarize the most frequently used scoring systems for patients with peritoneal malignancy.

Zusammenfassung Hintergrund 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. Patienten und Methode 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. Ergebnisse 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. Diskussion und Schlussfolgerung 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.

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.

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.

Aim The aim of this official guideline published by the German Society of Gynecology and Obstetrics (DGGG) and coordinated with the German Society of Urology (DGU) and the German Society of Reproductive Medicine (DGRM) is to provide consensus-based recommendations, obtained by evaluating the relevant literature, on counseling and fertility preservation for prepubertal girls and boys as well as patients of reproductive age. Statements and recommendations for girls and women are presented below. Statements or recommendations for boys and men are not the focus of this guideline. Methods This S2k guideline was developed at the suggestion of the guideline commission of the DGGG, DGU and DGRM and represents the structured consensus of representative members from various professional associations (n = 40). Recommendations The guideline provides recommendations on counseling and fertility preservation for women and girls which take account of the patient's personal circumstances, the planned oncologic therapy and the individual risk profile as well as the preferred approach for selected tumor entities. Ziel Das Ziel dieser offiziellen Leitlinie, die von der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG) publiziert und zusammen mit der Deutschen Gesellschaft für Urologie (DGU) sowie Deutschen Gesellschaft für Reproduktionsmedizin (DGRM) koordiniert wurde, ist es, durch die Evaluation der relevanten Literatur konsensbasierte Handlungsempfehlungen für die Beratung und den Einsatz von fertilitätserhaltenden Maßnahmen bei präpubertären Mädchen und Jungen sowie für Patienten/-innen im reproduktiven Alter zu geben. Im Folgendem werden die Statements und Empfehlungen für Mädchen und Frauen dargestellt. Die Statements und Empfehlungen für Jungen und Männer sind nicht Inhalt dieser Publikation. Methoden Diese S2k-Leitlinie wurde durch einen strukturierten Konsens von repräsentativen Mitgliedern verschiedener Fachgesellschaften (n = 40) im Auftrag der Leitlinienkommission der DGGG, DGU und DGRM entwickelt. Empfehlungen Es werden Empfehlungen zur Beratung und dem Einsatz von fertilitätserhaltenden Maßnahmen bei Patientinnen unter Berücksichtigung der Lebensumstände, der geplanten onkologischen Therapie und des individuellen Risikoprofils dargestellt sowie über das Vorgehen bei ausgewählten Tumorentitäten.

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

Background: At present, there are only few objective quality criteria for the treatment of peritoneal carcinomatosis using cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion (HIPEC). Method and Results: However, because this therapy is associated with significant morbidity and mortality, such quality criteria are quite important. Accreditation of peritoneal carcinomatosis centers by the German Society for General and Visceral Surgery was a first step towards establishing these clinics. Conclusion: One key requirement for accreditation is membership in the German Peritoneal Carcinomatosis Registry. This prospective database provides a collation and evaluation of the epidemiological and therapeutic factors relating to this disease.

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.

Hyperthermic isolated limb perfusion (HILP) is considered an established treatment for multiple locoregional intransit metastases in malignant melanoma of the extremities. Various mechanisms such as the expression of chemoresistance genes and heat shock proteins by the tumor may be responsible for varying response rates and locoregional recurrences of the treatment. The aim of the experimental animal study was to investigate the direct impact of HILP on such mechanisms of resistance. Tissue temperature, administration of the cytostatic drug, and duration of perfusion were varied. Expression of the chemoresistance genes mdr1, mrp1, mrp2, and lrp and of heat shock protein 72 (HSP72) in the tumor tissue was analysed using RT-PCR and western blot analysis. The untreated SK-MEL-3 tumor expressed mdr1, mrp1, and lrp, but not mrp2. Neither variation of temperature, administration of the cytostatic drug, nor duration of perfusion changed the expression of this “resistance pattern”. In contrast to the cytostatic drug, hyperthermia causes a persistent induction of HSP72. Both observations could offer a potential explanation for failure of HILP in malignant melanoma.

There is controversy about the effect of the influence of hyperthermia and chemotherapeutic agents on the healing of intestinal anastomosis. The effects of hyperthermic intraperitoneal chemoperfusion (HIPEC) of wound healing after colonic anastomosis were investigated in a rat model.Thirty-six Wag/Rija rats were randomized into three groups of 12 animals each: group I: control (only colonic anastomosis was performed) (n = 12); group II: HIPEC (mitomycin C in a concentration of 20 mg/m(2) (n = 12) colonic anastomosis was performed before HIPEC; group III: HIPEC (mitomycin C in a concentration of 20 mg/m(2) (n = 12) colonic anastomosis was performed after HIPEC. Bursting pressure and bursting sites were recorded 4 and 10 days after intervention. Collagen deposits, inflammation and foreign body reactions were evaluated.Lower bursting pressure and lost of collagen were found in both HIPEC groups and compared with the control group. There was almost no difference between both HIPEC groups. They were noted overwhelmingly at the anastomosis in the HIPEC group. The degree of collagen accumulation was well-correlated with bursting pressure.These results have shown that hyperthermic intraperitoneal chemoperfusion (HIPEC) impairs wound healing in colonic anastomosis in rats.

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.

Published cases of familial unilateral terminal transverse defects are scarce. We report on a morphologically similar defect of the hand in a father and his daughter. The hand anomaly is similar in both, but on the opposite side. Thalidomide was taken in the sensitive period of the pregnancy by the father's mother. To our knowledge this is the second description of unilateral terminal aphalangia in successive generations. In order to evaluate the possible genetic basis we analyze epidemiological studies in respect to the recurrence risk of cases with isolated limb reduction defects. We compare reports of familial occurrence concerning the degree of relationship as well as the pattern of malformation. The latter seems to be an important aspect from an evolutionary and a developmental viewpoint. For our observation an autosomal dominant transmission is the most likely although multifactorial determination cannot be excluded.

We report on a Yugoslavian sibpair with postaxial acrofacial dysostosis type Genee-Wiedemann with some novel signs which broaden the spectrum of this syndrome. The manifestations of the present cases are compared with those of the previously described patients. Life expectancy, change of symptoms over time, and the mode of inheritance are discussed.

Objective: To determine if hyperthermic intraperitoneal chemoperfusion (HIPEC) of colonic anastomoses is detrimental to subsequent anastomotic healing. Methods: 24 Wag/Rija rats were randomized into four groups of six animals each: group 1: control (n = 6), group 2: HIP (n = 6), group 3: HIPEC with mitomycin C in a concentration of 30 mg/m2 (n = 6), group 4: mitomycin i.p. in a concentration of 20 mg/m2 (n = 6). In all animals colon anastomosis approximataly 3 cm proximal to the peritoneal reflection was performed. After 10 days, the anastomic breaking strength and the number of anastomic complications were observed. Results: No postoperative deaths were reported. The postoperative morbidity rate was 18,7%. No severe locoregional or systemic toxity was observed. In HIPEC treated animals bursting pressure of anastomoses was lower than in group I. No significant difference in bursting pressure were found in groups I, II and IV. In group III one animal had a covered perforation and one animal showed extensive adhesions. Conclusion: The healing of colonie anastomoses did not differ between group I, II and IV. In contrast, anastomotic complications were significantly more common in HIPEC animals.

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.

Laser-induced thermotherapy (LITT) or interstitial laser thermotherapy is an in situ ablation technique for the treatment of malignant tumors of the liver. 1,2 The potential of LITT is that laser light is directly transmitted through flexible bare fibers into the tumor tissue with high precision. The biologic effect of the laser light is based on the transformation of laser photon energy into heat by the absorption of tissue-specific chromophores. The aim is to induce uniform coagulation necrosis of the treatment volume. 3 Of great importance to the method’s success is the size of the induced coagulation necrosis, which must contain the whole volume of the tumor tissue. This lesion size largely depends on the temperature distribution in the target volume, which is determined partly by the blood perfusion in the target organ. 4,5 In organs with a high blood perfusion, such as the liver, a cooling effect results because of the temperature difference between the hyperthermic area and blood. 6,7 Temporary interruption of hepatic blood flow by occlusion of hepatic inflow vessels (Pringle maneuver) during LITT has been proven to increase its efficacy. 8–11 The Pringle maneuver usually requires laparotomy 10,11 or at least laparoscopy 12 and may therefore be difficult to repeat in cases of insufficient therapy. LITT, however, can be applied percutaneously without laparotomy or laparoscopy and can thus be easily repeated. 1,2 An alternative to the temporary interruption of hepatic arterial blood flow to liver tumors is the application of degradable starch microspheres (DSM), as used for chemoembolization. 13,14 The purpose of this study was to assess the effect of combined LITT and DSM on intrahepatic temperature distribution and tumor response in rats with liver tumors.

Editor,—In a recent paper Narchi and Kulaylat1 analysed the prevalence (erroneously termed incidence2) of trisomy 21 in children of mothers with diabetes (7/1870) and in non-diabetic mothers (28/20 430) and found it to be significantly higher in the former. All seven cases in the diabetes group occurred in mothers with gestational diabetes. The authors concluded, that: (1) Maternal gestational diabetes is an independent risk factor for Down’s syndrome, irrespective of maternal age, as in an analysis of their data stratified by age, all five age groups showed a higher relative risk for Down’s syndrome in diabetic mothers; (2) Down’s syndrome should be added to the list of congenital anomalies known to occur more frequently in infants of diabetic mothers. Table 2 in their paper does not fully support their hypothesis. As can be seen from their data, age is a confounding factor for gestational diabetes …