Incidence,Risk Factors,and Prognosis of Patients with Hepatocellular Carcinoma and Brain Metastases

Objective Brain metastases significantly impact the clinical course of patients with hepatocellular carcinoma(HCC).This study aimed to examine the age-related incidence,demographics,and survival of patients with HCC and brain metastases.Methods Data of HCC patients from 2010 to 2015 in the Surveillance,Epidemiology,and End Results(SEER)Registry were screened for the presence of brain metastases.They were stratified by age and ethnicity.Multivariable logistic and Cox regression analyses were used to identify factors associated with brain metastases and those with overall survival(OS)and liver cancer-specific survival(CSS),respectively.Results A total of 141 HCC patients presenting with brain metastases were identified,accounting for 0.35% of all HCC patients and 2.37% of patients with metastatic disease.Among all HCC patients,the incidence rate was the highest among patients aged 30-49 years old(0.47%).Ethnicity was not associated with the presence of brain metastases at the time of HCC diagnosis.However,African-American patients presented with a significantly lower disease-specific survival[median time:1 month;interquartile range(IQR):0-3.0 months].Initial lung or bone metastasis was independently associated with an increased risk of the presence of brain metastases[odds ratio(OR):12.62,95% confidence interval(CI):8.40-18.97]but was not associated with a worse OS or CSS among those with brain metastases.Conclusion This study identified the age-related incidence and risk factors of brain metastases in HCC patients.These results may contribute to the consideration of brain screening among patients with initial metastatic HCC with lung or bone metastases,and influence the counseling of this patient population regarding their prognosis.

Selection criteria for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer

Peritoneal carcinomatosis in gastric cancer is associated with a dismal prognosis.Systemic chemotherapy is not effective because of the existence of a blood-peritoneal barrier.Cytoreductive surgery and intraperitoneal chemotherapy can improve survival and quality of life in selected patients.Patient selection for this multimodal approach is one of the most critical issues,and calls for interdisciplinary evaluation by radiologists,medical and surgical oncologists,and anaesthetists.This article sets forth criteria for selection of gastric cancer patients suffering from peritoneal carcinomatosis.

Laparoscopic surgery for benign and malign diseases of the digestive system:Indications,limitations,and evidence

The laparoscopic technique was introduced in gastrointestinal surgery in the mid 1980s.Since then,the development of this technique has been extraordinary.Triggered by technical innovations(stapling devices or coagulation/dissecting devices),nowadays any type of gastrointestinal resection has been successfully performed laparoscopically and can be performed laparoscopically dependent on the patient’s condition.This summary gives an overview over 30 years of laparoscopic surgery with focus on today’s indications and evidence.Main indications remain the more common procedures,e.g.,appendectomy,cholecystectomy,bariatric procedures or colorectal resections.For all these indications,the laparoscopic approach has become the gold standard with less perioperative morbidity.Regarding oncological outcome there have been several highquality randomized controlled trials which demonstrated equivalency between laparoscopic and open colorectal resections.Less common procedures like esophagectomy,oncological gastrectomy,liver and pancreatic resections can be performed successfully as well by anexperienced surgeon.However,the evidence for these special indications is poor and a general recommendation cannot be given.In conclusion,laparoscopic surgery has revolutionized the field of gastrointestinal surgery by reducing perioperative morbidity without disregarding surgical principles especially in oncological surgery.

Biliary complications following liver transplantation: Singlecenter experience over three decades and recent risk factors

AIM To identify independent risk factors for biliary complications in a center with three decades of experience in liver transplantation.METHODS A total of 1607 consecutive liver transplantations were analyzed in a retrospective study. Detailed subset analysis was performed in 417 patients, which have been transplanted since the introduction of Model of End-Stage Liver Disease(MELD)-based liver allocation. Risk factors for the onset of anastomotic biliary complications were identified with multivariable binary logisticregression analyses. The identified risk factors in regression analyses were compiled into a prognostic model. The applicability was evaluated with receiver operating characteristic curve analyses. Furthermore, Kaplan-Meier analyses with the log rank test were applied where appropriate. RESULTS Biliary complications were observed in 227 cases(14.1%). Four hundred and seventeen(26%) transplantations were performed after the introduction of MELD-based donor organ allocation. Since then, 21%(n = 89) of the patients suffered from biliary complications, which are further categorized into anastomotic bile leaks [46%(n = 41)], anastomotic strictures [25%(n = 22)], cholangitis [8%(n = 7)] and non-anastomotic strictures [3%(n = 3)]. The remaining 18%(n = 16) were not further classified. After adjustment for all univariably significant variables, the recipient MELD-score at transplantation(P = 0.006; OR = 1.035; 95%CI: 1.010-1.060), the development of hepatic artery thrombosis post-operatively(P = 0.019; OR = 3.543; 95%CI: 1.233-10.178), as well as the donor creatinine prior to explantation(P = 0.010; OR = 1.003; 95%CI: 1.001-1.006) were revealed as independent risk factors for biliary complications. The compilation of these identified risk factors into a prognostic model was shown to have good prognostic abilities in the investigated cohort with an area under the receiver operating curve of 0.702.CONCLUSION The parallel occurrence of high recipient MELD and impaired donor kidney function should be avoided. Risk is especially increased when post-transplant hepatic artery thrombosis occurs.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: Where are we?

Peritoneal surface malignancies are generally associated with poor prognosis. In daily clinical routine, systemic chemotherapy is still considered the only reasonable therapy despite of encouraging results of cytoreductive surgery (CRS) along with intraperitoneal hyperthermic chemotherapy (HIPEC). The Achilles heel of CRS and HIPEC is appropriate patient selection and precise surgical technique preventing patients from excessive morbidity and mortality. Given these findings, new concepts of second look surgery for high risk patients allow detection of peritoneal spread ahead of clinical symptoms or presence of peritoneal masses reducing perioperative morbidity. In addition, personalized intraperitoneal chemotherapy might further improve outcome by appreciating individual tumor biology. These days, every physician should be aware of CRS and HIPEC for treatment of peritoneal surface malignancies. Since there is now sufficient data for the superiority of CRS and HIPEC to systemic chemotherapy in selected patients, our next goal should be providing this strategy with minimal morbidity and mortality even in the presence of higher tumor load.

Hepatic encephalopathy before and neurological complications after liver transplantation have no impact on the employment status 1 year after transplantation

AIM To investigate the impact of hepatic encephalopathybefore orthotopic liver transplantation(OLT) and neurological complications after OLT on employment after OLT.METHODS One hundred and fourteen patients with chronic liver disease aged 18-60 years underwent neurological examination to identify neurological complications, neuropsychological tests comprising the PSE-SyndromeTest yielding the psychometric hepatic encephalopathy score, the critical flicker frequency and the Repeatable Battery for the Assessment of Neuropsychological Status(RBANS), completed a questionnaire concerning their occupation and filled in the short form 36(SF-36) to assess health-related quality of life before OLT and 12 mo after OLT, if possible. Sixty-eight(59.6%) patients were recruited before OLT, while on the waiting list for OLT at Hannover Medical School [age: 48.7 ± 10.2 years, 45(66.2%) male], and 46(40.4%) patients were included directly after OLT. RESULTS Before OLT 43.0% of the patients were employed. The patients not employed before OLT were more often non-academics(employed: Academic/non-academic 16(34.0%)/31 vs not employed 10(17.6%)/52, P = 0.04), had more frequently a history of hepatic encephalopathy(HE)(yes/no; employed 15(30.6%)/34 vs not employed 32(49.2%)/33, P = 0.05) and achieved worse results in psychometric tests(RBANS sum score mean ± SD employed 472.1 ± 44.5 vs not employed 443.1 ± 56.7, P = 0.04) than those employed. Ten patients(18.2%), who were not employed before OLT, resumed work afterwards. The patients employed after OLT were younger [age median(range, min-max) employed 47(42, 18-60) vs not employed 50(31, 29-60), P = 0.01], achieved better results in the psychometric tests(RBANS sum score mean ± SD employed 490.7 ± 48.2 vs not employed 461.0 ± 54.5, P = 0.02) and had a higher health-related quality of life(SF 36 sum score mean ± SD employed 627.0 ± 138.1 vs not employed 433.7 ± 160.8; P < 0.001) compared to patients not employed after OLT. Employment before OLT(P < 0.001), age(P < 0.01) and SF-36 sum score 12 mo after OLT(P < 0.01) but not HE before OLT or neurological complications after OLT were independent predictors of the employment status after OLT.CONCLUSION HE before and neurological complications after OLT have no impact on the employment status 12 mo after OLT. Instead younger age and employment before OLT predict employment one year after OLT.

Changes of duplex parameters and splenic size in liver transplant recipients during a long period of observation

AIM: To assess the changes of portal and arterial velocities, resistance index, spleen and liver size during a long observation period (13.7 years) after orthotopic liver transplantation (OLT).METHODS: Two hundred and sixty patients were recruited retrospectively for this study and divided into groups with defined time intervals after OLT. The cross-sectional changes of portal and arterial velocities,resistance index, spleen and liver size between the defined time intervals were studied. The complications detected by ultrasound were compared to gold standard methods.RESULTS: The mean values for liver size were all within the normal range. The splenic size decreased between the time intervals 100 and 1 000 d after OLT (t;P＜0.01).While portal and arterial flow velocities decreased up to 5.5 years (t; portal velocity P＜0.01, maximal systolic velocity P=0.05, maximal end diastolic velocity P＜0.01),RI increased during this interval (t:P＜0.01). Higher RIvalues were found in older patients (r = 0.24, P＜0.001).CONCLUSION: The arterial and portal velocities show adaptation processes continuing over the course of many years after OLT and are reported for the first time. The vascular complications detected by ultrasound occur mostly up to 100 d after OLT.

Significance of multivisceral resections in oncologic surgery: A systematic review of the literature

BACKGROUND Multivisceral resections (MVR) are often necessary to reach clear resections margins but are associated with relevant morbidity and mortality. Factors associated with favorable oncologic outcomes and elevated morbidity rates are not clearly defined. AIM To systematically review the literature on oncologic long-term outcomes and morbidity and mortality in cancer surgery a systematic review of the literature was performed. METHODS PubMed was searched for relevant articles (published from 2000 to 2018). Retrieved abstracts were independently screened for relevance and data were extracted from selected studies by two researchers. RESULTS Included were 37 studies with 3112 patients receiving MVR for colorectal cancer (1095 for colon cancer, 1357 for rectal cancer, and in 660 patients origin was not specified). The most common resected organs were the small intestine, bladder and reproductive organs. Median postoperative morbidity rate was 37.9%(range: 7% to 76.6%) and median postoperative mortality rate was 1.3%(range: 0% to 10%). The median conversion rate for laparoscopic MVR was 7.9%(range: 4.5% to 33%). The median blood loss was lower after laparoscopic MVR compared to the open approach (60 mL vs 638 mL). Lymph-node harvest after laparoscopic MVR was comparable. Report on survival rates was heterogeneous, but the 5-year overall-survival rate ranged from 36.7% to 90%, being worst in recurrent rectalcancer patients with a median 5-year overall survival of 23%. R0 -resection, primary disease setting and no lymph-node or lymphovascular involvement were the strongest predictors for long-term survival. The presence of true malignant adhesions was not exclusively associated with poorer prognosis. Included were 16 studies with 1.600 patients receiving MVR for gastric cancer. The rate of morbidity ranged from 11.8% to 59.8%, and the main postoperative complications were pancreatic fistulas and pancreatitis, anastomotic leakage, cardiopulmonary events and post-operative bleedings. Total mortality was between 0% and 13.6% with an R0 -resection achieved in 38.4% to 100% of patients. Patients after R0 resection had 5-year overall survival rates of 24.1% to 37.8%. CONCLUSION MVR provides, in a selected subset of patients, the possibility for good long-term results with acceptable morbidity rates. Unlikelihood of achieving R0 -status, lymphovascular- and lymph -node involvement, recurrent disease setting and the presence of metastatic disease should be regarded as relative contraindications for MVR.

Glycogen metabolism-mediated intercellular communication in the tumor microenvironment influences liver cancer prognosis

Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq data were obtained from ten HCC tumor samples totaling 64,545 cells and 65 glycogen metabolism genes were analyzed bya nonnegative matrix factorization(NMF).The prognosis and immune response of new glycogen TME cell dusters were predicted by using HCC and immunotherapy cohorts from public databases.HOC single cell analysis was divided into fibroblasts,NT T cells,macrophages,endothelial clls,and B cells,which were separately divided into new cell clusters by glycogen metabolism gene annotation.Pseudo temporal trajectory analysis demonstrated the temporal differentiation trajectory of different glycogen subtype cell dusters.Cellular communication analysis revealed extensive interactions between endothelial cells with glycogen metabolizing TME cell.related subtypes and diferent glycogen subtype cell clusters.SCENIC analysis of transcription factors upstream of TME cell clusters with different glycogen metabolism.In addition,TME cell dusters of glycogen metabolism were found to be enriched in expression in CAF subtypes,CD8 depleted,M1,and M2 types.Bulk seq analysis showed the prognostic signifcance of glycogen metabolism.mediated TME cell dusters in HCC,while a significant immune response was found in the immunotherapy cohort in patients treated with immune checkpoint blockade(ICB),especially for CAFs,T cells,and macrophages In summary,our study reveals for the first time that glycogen metabolism mediates intercellular communication in the hepatocellular carcinoma microenvironment while elucidating the anti-tumor mechanisms and immune prognostic responses of different subtypes of cell dusters.

Prognostic value of site-specific metastases in pancreatic adenocarcinoma: A Surveillance Epidemiology and End Results database analysis

AIM To evaluate the prognostic value of site-specific metastases among patients with metastatic pancreaticc arcinoma registered within the Surveillance, Epidemiology and End Results(SEER) database.METHODS SEER database(2010-2013) has been queried through SEER*Stat program to determine the presentation, treatment outcomes and prognostic outcomes of metastatic pancreatic adenocarcinoma according to the site of metastasis. In this study, metastatic pancreatic adenocarcinoma patients were classified according to the site of metastases(liver, lung, bone, brain and distant lymph nodes). We utilized chi-square test to compare the clinicopathological characteristics among different sites of metastases. We used Kaplan-Meier analysis and log-rank testing for survival comparisons. We employed Cox proportional model to perform multivariate analyses of the patient population; and accordingly hazard ratios with corresponding 95%CI were generated. Statistical significance was considered if a two-tailed P value < 0.05 was achieved. RESULTS A total of 13233 patients with stage Ⅳ pancreatic cancer and known sites of distant metastases were identified in the period from 2010-2013 and they were included into the current analysis. Patients with isolated distant nodal involvement or lung metastases have better overall and pancreatic cancer-specific survival compared to patients with isolated liver metastases(for overall survival: lung vs liver metastases: P < 0.0001; distant nodal vs liver metastases: P < 0.0001)(for pancreatic cancer-specific survival: lung vs liver metastases: P < 0.0001; distant nodal vs liver metastases: P < 0.0001). Multivariate analysis revealed that age < 65 years, white race, being married, female gender; surgery to the primary tumor and surgery to the metastatic disease were associated with better overall survival and pancreatic cancer-specific survival.CONCLUSION Pancreatic adenocarcinoma patients with isolated liver metastases have worse outcomes compared to patients with isolated lung or distant nodal metastases. Further research is needed to identify the highly selected subset of patients who may benefit from local treatment of the primary tumor and/or metastatic disease.

Impact of body composition on survival and morbidity after liver resection in hepatocellular carcinoma patients

Background: Hepatocellular carcinoma is the most common innate liver tumor. Due to improved surgical techniques, even extended resections are feasible, and more patients can be treated with curative intent. As the liver is the central metabolic organ, preoperative metabolic assessment is crucial for risk stratification. Sarcopenia, obesity and sarcopenic obesity characterize body composition and metabolic status. Here we present the impact of body composition on survival after liver resection in patients with hepatocellular carcinoma. Methods: A retrospective database analysis of 70 patients who were assigned for liver resection due to hepatocellular carcinoma was conducted. For assessment of sarcopenia and obesity, skeletal muscle surface area was measured at lumbar vertebra 3 level(L3) in preoperative four-phase contrast enhanced abdominal CT scans, and L3 muscle index and body fat percentage were calculated. Results: Univariate analysis comparing the survival curves using the score test demonstrated superior postoperative overall survival for sarcopenic( P = 0.035) and sarcopenic obese( P = 0.048) patients as well as a trend favoring obese( P = 0.130) subjects. Whereas multivariate analysis could not identify significant difference in postoperative survival regarding sarcopenia, obesity or sarcopenic obesity. Only large tumor size, multifocal disease and male gender were risk factors for long-term survival. Conclusions: Sarcopenia, obesity and sarcopenic obesity are indeed no risk factors for poor postoperative survival in this study. Our data do not support the evaluation of sarcopenia, obesity and sarcopenic obesity before liver resection in hepatocellular carcinoma patients.

Grade of donor liver microvesicular steatosis does not affect the postoperative outcome after liver transplantation

BACKGROUND:The potential effect of graft steatosis on the postoperative liver function is discussed controversially. The present study aimed to evaluate the effect of the donor liver microvesicular steatosis on the postoperative outcome after liver transplantation.METHODS:Ninety-four patients undergoing liver transplantation at the University Hospital Aachen were included in this study. The patient cohort was divided into three groups according to the grade of microvesicular steatosis(MiS):MiS <30%(n=27), MiS 30%-60%(n=41) and MiS >60%(n=26).The outcomes after liver transplantation were evaluated, including the 30-day and 1-year patient and graft survival rates and the incidences of early allograft dysfunction(EAD) and primary nonfunction(PNF). RESULTS:The incidences of EAD and PNF did not differ significantly between the groups. We observed 5 cases of PNF,one occurred in the MiS <30% group and 4 in the MiS 30%-60% group. The 30-day and 1-year graft survivals did not differ significantly between groups. The 30-day patient survival rates were 100% in all groups. The 1-year patient survival rates were 94.4% in the MiS <30% group, 87.9% in the MiS 30%-60% group and 90.9% in the MiS >60% group.CONCLUSION:Microvesicular steatosis of donor livers has no negative effect on the postoperative outcome after liver transplantation.

Decision modelling for economic evaluation of liver transplantation

As the gap between a shortage of organs and the immense demand for liver grafts persists, every available donor liver needs to be optimized for utility, urgency and equity. To overcome this challenge, decision modelling might allow us to gather evidence from previous studies as well as compare the costs and consequences of alternative options. For public health policy and clinical intervention assessment, it is a potentially powerful tool. The most commonly used types of decision analytical models include decision trees, the Markov model, microsimulation, discrete event simulation and the system dynamic model. Analytic models could support decision makers in the field of liver transplantation when facing specific problems by synthesizing evidence, comprising all relevant options, generalizing results to other contexts, extending the time horizon and exploring the uncertainty. For modeling studies of economic evaluation for transplantation, understanding the current nature of the disease is crucial, as well as the selection of appropriate modelling techniques. The quality and availability of data is another key element for the selection and development of decision analytical models. In addition, good practice guidelines should be complied, which is important for standardization and comparability between economic outputs.

Concept of histone deacetylases in cancer:Reflections on esophageal carcinogenesis and treatment

Esophageal cancer (EC) presents a high mortality rate, mainly due to its aggressive nature. Squamous cell carcinoma is the most common histological type world-wide, though, a continuous increase in esophageal adenocarcinomas has been noted in the past decades. Common risk factors associated with EC include smoking, alcohol consumption, gastroesophageal reflux disease, Barrett's esophagus and obesity. In an effort to overcome chemotherapy resistance in oncology, it was discovered that histone acetylation/deacetylation equilibrium is altered in carcinogenesis, leading to changes in chromatin structure and altering expression of genes important in the cell cycle, differentiation and apoptosis. Based on this knowledge, histone acetylation was addressed as a potential novel chemotherapy drug target to repress cancer cell proliferation. There are four classes of histone deacetylases (HDACs) inhibitors with a variety of different mechanisms of actions that render them possible anticancer drugs. They arrest the cell cycle, inhibit differentiation and angiogenesis and induce apoptosis. They do not necessarily act on histone proteins, since they can also exert indirect anti-cancer effects, by modifying various cellular proteins.In addition,HDACs have also been associated with increased chemotherapy resistance.Based on the literature,HDACs have been associated with EC,with surveys revealing that increased expression of certain HDACs correlates with advanced TNM stages,tumor grade,metastatic potential and decreased 5-year overall and disease-free survival.The aim of this survey is to elucidate the molecular identity and mechanism of action of HDAC inhibitors as well as verify their potential utility as anti-cancer agents in esophageal cancer.

Management of primary retroperitoneal synovial sarcoma: A case report and review of literature

BACKGROUND Synovial sarcoma(SS) is a rare type of soft tissue sarcoma that is usually developed from areas where synovial tissue exists, especially at the extremities.Nevertheless, several cases of retroperitoneal SS(RSS) have been described. We herein report a case of RSS presented in our institution.CASE SUMMARY A 69-year-old female patient was admitted with a large, palpable, firm mass in the right abdominal space SS. Computerized tomography scan depicted a concentric, sharply marinated retro-peritoneal lesion which was displacing the right kidney and the lower edge of the liver. Subsequently, the patient underwent surgical excision of the mass with additional right nephrectomy and resection of the right adrenal gland and a part of the diaphragm. The final histological diagnosis of the tumour was grade II monophasic RSS.CONCLUSION RSS is encountered in the biphasic type, the monophasic fibrous, and the monophasic epithelial category as well. Relevant clinical manifestations are not always documented at early stages. Therefore, the final diagnosis is posed after complete histological examination taking into consideration the results of immunochemistry and genetic analysis. Therapeutic approach happens often late when metastases at the lungs and the liver are apparent. Thus, 5-year survival rates remain low.

Orthotopic liver transplantation for giant liver haemangioma: A case report

In liver haemangiomas, the risk of complication rises with increasing size, and treatment can be obligatory. Here we present a case of a 46-year-old female who suffered from a giant haemangioma causing severe portal hypertension and vena cava compression, leading to therapy refractory ascites, hyponatremia and venostasis-associated thrombosis with pulmonary embolism. The patients did not experience tumour rupture or consumptive coagulopathy. Surgical resection was impossible because of steatosis of the non-affected liver. Orthotopic liver transplantation was identified as the only treatment option. The patient's renal function remained stable even though progressive morbidity and organ allocation were improbable according to the patient's lab model for end-stage liver disease(lab MELD) score. Therefore, non-standard exception status was approved by the European organ allocation network "Eurotransplant". The patient underwent successful orthotopic liver transplantation 16 mo after admission to our centre. Our case report indicates the underrepresentation of morbidity associated with refractory ascites in the lab MELD-based transplant allocation system, and it indicates the necessity of promptly applying for non-standard exception status to enable transplantation in patients with a severe clinical condition but low lab MELD score. Our case highlights the fact that liver transplantation should be considered early in patients with non-resectable, symptomatic benign liver tumours.

Immunological aspects of liver cell transplantation

Within the field of regenerative medicine, the liver is of major interest for adoption of regenerative strategies due to its well-known and unique regenerative capacity. Whereas therapeutic strategies such as liver resection and orthotopic liver transplantation(OLT) can be considered standards of care for the treatment of a variety of liver diseases, the concept of liver cell transplantation(LCTx) still awaits clinical breakthrough. Success of LCTx is hampered by insufficient engraftment/long-term acceptance of cellular allografts mainly due to rejection of transplanted cells. This is in contrast to the results achieved for OLT where longterm graft survival is observed on a regular basis and, hence, the liver has been deemed an immuneprivileged organ. Immune responses induced by isolated hepatocytes apparently differ considerably from those observed following transplantation of solid organs and, thus, LCTx requires refined immunological strategies to improve its clinical outcome. In addition, clinical usage of LCTx but also related basic research efforts are hindered by the limited availability of high quality liver cells, strongly emphasizing the need for alternative cell sources. This review focuses on the various immunological aspects of LCTx summarizing data available not only for hepatocyte transplantation but also for transplantation of non-parenchymal liver cells and liver stem cells.

Ventilation after pancreaticoduodenectomy increases perioperative mortality: Identification of risk factors and their relevance in Germany that do not apply in England

Background:Pre-operative risk factors for post-operative ventilation and their influence on survival after pancreaticoduodenectomy for malignancy are unknown.Methods:Totally 391 patients operated in Hannover,Germany were investigated with multivariable logistic regression and Cox regression modeling to identify independent risk factors for post-operative ventilation≥6 h,patient survival and 90-day mortality.And 84 patients operated in Birmingham,United Kingdom were analyzed to assess the external relevance of findings.Results:Longer operations,history of thrombosis,intra-operative blood transfusion,lower estimated glomerular filtration rates(eGFR)and higher values of the age at operation divided by the Horovitz Quotient independently increased the risk of post-operative ventilation≥6 h in German patients(n=108;27.6%)(P<0.050).Blood transfusion and lower pre-operative eGFR levels increased the risk of early death in German patients significantly and independently of established prognostic factors.A history of thrombosis and lower eGFR levels were also independent significant risk factors for 90-day mortality in German patients but not in English patients.None of the English patients received post-operative ventilation.Significantly more German patients were>75 years,had a history of thrombosis,received blood transfusions,and had significantly worse lung function parameters.pT4 tumors were detected in 18 German patients(4.6%),but not in the English patients.Conclusions:Identified risk factors for post-operative ventilation are clinically relevant in Germany but not in England and may be used to lower mortality risk.The German and the English cohorts displayed significant differences in the approach to patient selection and early post-operative extubation.

Gender differences in trauma,shock and sepsis

Despite efforts in prevention and intensive care, trauma and subsequent sepsis are still associated with a high mortality rate. Traumatic injury remains the main cause of death in people younger than 45 years and is thus a source of immense social and economic burden. In recent years, the knowledge concerning gender medicine has continuously increased. A number of studies have reported gender dimorphism in terms of response to trauma, shock and sepsis.However, the advantageous outcome following trauma-hemorrhage in females is not due only to sex. Rather, it is due to the prevailing hormonal milieu of the victim. In this respect, various experimental and clinical studies have demonstrated beneficial effects of estrogen for the central nervous system, the cardiopulmonary system, the liver, the kidneys, the immune system, and for the overall survival of the host. Nonetheless, there remains a gap between the bench and the bedside. This is most likely because clinical studies have not accounted for the estrus cycle. This review attempts to provide an overview of the current level of knowledge and highlights the most important organ systems responding to trauma, shock and sepsis. There continues to be a need for clinical studies on the prevailing hormonal milieu following trauma, shock and sepsis.

Bias-Variation Dilemma Challenges Clinical Trials: Inherent Limitations of Randomized Controlled Trials and Meta-Analyses Comparing Hernia Therapies

Purpose:Evaluation of hernia therapies according to the current rules of Evidence Based Medicine is widely reduced to results of RCTs or meta-analyses. RCTs have been accepted as a most important tool to confirm a superior effect of an intervention. Unfortunately, in hernia surgery, comparisons of RCTs and correspondingly their use in meta-analyses, are not, surprisingly often, able to confirm any significant impact of a specific procedure due to intrinsic restrictions in a multi-causal setting with its web of influences. Methods:Based on our own experiences of clinical studies in surgery, the present article outlines several situations, with their respective reasons, which argue the severe limitations of RCTs and meta-analysis to define an optimum treatment. Results:Meta-analyses accumulate the variations of each trial, which then may cover any clear causal relationship. RCTs usually are dealing with subgroups of standard patients thus excluding the majority of our patients. Low statistical power of current cohort sizes restricts the analysis of subgroups or of effects with low incidences. Simple comparisons of means frequently are hampered by nonlinear relationships to outcome. The relevance of a specific variable is difficult to separate from other influences. The limited surveillance period of studies ignores a delayed change in outcome. Randomization cannot guarantee a standardized patient’s condition. All the arguments have to be considered as a crucial and fundamental consequence of the bias-variance dilemma or principle of uncertainty in medicine, and underline the many limitations of RCTs to evaluate any specific impact of hernia therapies on e.g. infection, pain or recurrence. Conclusions: Many surgical issues cannot be and should not be investigated by RCTs, in particular, if a marked patients’ heterogeneity has to be considered or the low incidences of the outcome readout cannot be addressed with sufficient statistical power without getting lost in the variation mire. Registries with their non-restricted data-acquisition should be regarded as reliable alternatives for postoperative outcome quality surveillance studies.