Value of sarcopenia in the resection of colorectal liver metastases-a systematic review and meta-analysis.

Introduction: Sarcopenia is defined as a decline in muscle function as well as muscle mass. Sarcopenia itself and sarcopenic obesity, defined as sarcopenia in obese patients, have been used as surrogates for a worse prognosis in colorectal cancer. This review aims to determine if there is evidence for sarcopenia as a prognostic parameter in colorectal liver metastases (CRLM). Methods: PubMed, Embase, Cochrane Central, Web of Science, SCOPUS, and CINAHL databases were searched for articles that were selected in accordance with the PRISMA guidelines. The primary outcomes were overall survival (OS) and disease-free survival (DFS). A random effects meta-analysis was conducted. Results: After eliminating duplicates and screening abstracts (n = 111), 949 studies were screened, and 33 publications met the inclusion criteria. Of them, 15 were selected after close paper review, and 10 were incorporated into the meta-analysis, which comprised 825 patients. No significant influence of sarcopenia for OS (odds ratio (OR), 2.802 (95% confidence interval (CI), 1.094-1.11); p = 0.4) or DFS (OR, 1.203 (95% CI, 1.162-1.208); p = 0.5) was found, although a trend was defined toward sarcopenia. Sarcopenia significantly influenced postoperative complication rates (OR, 7.905 (95% CI, 1.876-3.32); p = 0.001) in two studies where data were available. Conclusion: Existing evidence on the influence of sarcopenia on postoperative OS as well as DFS in patients undergoing resection for CRLM exists. We were not able to confirm that sarcopenic patients have a significantly worse OS and DFS in our analysis, although a trend toward this hypothesis was visible. Sarcopenia seems to influence complication rates but prospective studies are needed.

Use of LigaSure vessel sealing system versus conventional axillary dissection in breast cancer patients: a retrospective comparative study.

BACKGROUND: In locally advanced breast cancer, axillary lymph node dissection remains a pivotal component of surgical therapy. Apart from this, it has been mostly replaced by sentinel node biopsy. Complications after axillary dissection include wound infection, neuropathy, lymphedema and-most frequently-seroma. In this retrospective multi-centre study, we compared the use of LigaSureTM with monopolar electrocautery regarding perioperative outcome. METHODS: A retrospective data analysis from female breast cancer patients who underwent axillary dissection at two breast centres in Austria that are using two different surgical techniques was performed for this study. We compared the rate of complications and re-operations, length of hospital stay, time to drain removal, total drain fluid, seroma formation after drain removal, number of seroma aspirations and total seroma fluid. RESULTS: Seventy one female patients with a median age of 63 (30-83) were included in this study. In 35 patients LigaSureTM and in 36 monopolar cautery was used for axillary dissection. There was no significant difference regarding intraoperative complications and rate of re-operations between the two groups (2.9 vs. 5.6%; p = 1 and 2.9 vs. 13.9%; p = 0.199). The time to drain removal and the length of hospital stay was similar in both groups. A significant difference in the occurence of postoperative wound infection could also not be shown. However, we found a significantly smaller total drain fluid in the LigaSureTM-group compared to the cautery-group (364.6 ml vs. 643.4 ml; p = 0.004). Seroma formation after drain removal was more frequent in the LigaSureTM-group (68.6 vs. 41.7%; p = 0.032) with a higher number of outpatient seroma aspirations (2.0 vs. 0.9; p = 0.005). CONCLUSION: LigaSureTM and monopolar cautery provide equivalent techniques in axillary lymph node dissection with comparable postoperative outcomes.

Metachronous hepatic resection for liver only pancreatic metastases.

BACKGROUND: The value of liver resection (LR) for metachronous pancreatic ductal adenocarcinoma (PDAC) metastases remains controversial. However, in light of increasing safety of liver resections, surgery might be a valuable option for metastasized PDAC in selected patients. METHODS: We performed a retrospective, multicenter study including patients undergoing hepatectomy for metachronous PDAC liver metastases between 2004 and 2015 to analyze postoperative outcome and overall survival. All patients were operated with curative intent. Patients with oligometastatic metachronous liver metastasis with definitive chemotherapy (n = 8) served as controls. RESULTS: Overall 25 patients in seven centers were included in this study. The median age at the time of LR was 63.8 years (56.9-69.9) and the median number of metastases in the liver was 1 (IQR 1-2). There were eight non-anatomical resections (32%), 15 anatomical minor (60%) and 2 major LR (8%). Postoperative complications occurred in eleven patients (eight Clavien-Dindo grade I complications (32%) and three grade IIIa complications (12%), respectively). The 30-day mortality was 0%. The median length of stay was 8.6 days (IQR 5-11). Median overall survival following LR was 36.8 months compared to 9.2 months in patients with metachronous liver metastasis with chemotherapy (p = 0007). DISCUSSION: Liver resection for metachronous PDAC metastasis is safe and feasible in selected patients. To address general applicability and to find factors for patient selection, larger trials are urgently warranted.

Non-obstetric surgery during pregnancy - an eleven-year retrospective analysis.

BACKGROUND: Diagnosis and management of non-obstetric abdominal pathologies during pregnancy are clinically challenging for both obstetricians and general surgeons. Our aim was to evaluate the outcome of pregnant patients who had undergone non-obstetric abdominal surgery. METHODS: We retrospectively reviewed 76 pregnant patients who had required surgery for non-obstetric abdominal pathologies during pregnancy at our department from January 2005 to December 2015. Data were collected retrospectively from medical records as well as from our institutional perinatal database. We evaluated data for clinical presentation, perioperative management, preterm labor, and maternal and fetal outcomes. RESULTS: The patients' mean age was 29 (interquartile range IQR 25-33) years. Indications for surgery were acute appendicitis in 63%, adnexal pathology in 11%, cholecystolithiasis in 5% and other indications in 21%; surgery was performed in an elective setting in 18% and in an emergent/urgent setting in 82%. In five cases, complications, three of them oncological, called for further surgery. Ninety-seven percent of operations were conducted under general anesthesia. Median skin-to-skin time was 50 (37-80) minutes, median in-hospital stay was 4 (3.5-6) days, and 5 % required postoperative intensive care. Preterm labor occurred in 15%, miscarriage in 7% (none of them directly related to abdominal surgery). CONCLUSION: Abdominal surgery for non-obstetric pathology during pregnancy can be performed safely, if mandatory, without increases in maternal and fetal pathology, miscarriage, and preterm birth rates.

Randomized clinical trial of the effect of a fibrin sealant patch on pancreatic fistula formation after pancreatoduodenectomy.

BACKGROUND: The potential for a fibrin sealant patch to reduce the risk of postoperative pancreatic fistula (POPF) remains uncertain. The aim of this study was to evaluate whether a fibrin sealant patch is able to reduce POPF in patients undergoing pancreatoduodenectomy with pancreatojejunostomy. METHODS: In this multicentre trial, patients undergoing pancreatoduodenectomy were randomized to receive either a fibrin patch (patch group) or no patch (control group), and stratified by gland texture, pancreatic duct size and neoadjuvant treatment. The primary endpoint was POPF. Secondary endpoints included complications, drain-related factors and duration of hospital stay. Risk factors for POPF were identified by logistic regression analysis. RESULTS: A total of 142 patients were enrolled. Forty-five of 71 patients (63 per cent) in the patch group and 40 of 71 (56 per cent) in the control group developed biochemical leakage or POPF (P = 0·392). Fistulas were classified as grade B or C in 16 (23 per cent) and ten (14 per cent) patients respectively (P = 0·277). There were no differences in postoperative complications (54 patients in patch group and 50 in control group; P = 0·839), drain amylase concentration (P = 0·494), time until drain removal (mean(s.d.) 11·6(1·0) versus 13·3(1·3) days; P = 0·613), fistula closure (17·6(2·2) versus 16·5(2·1) days; P = 0·740) and duration of hospital stay (22·1(2·2) versus 18·2(0·9) days; P = 0·810) between the two groups. Multivariable logistic regression analysis confirmed that obesity (odds ratio (OR) 5·28, 95 per cent c.i. 1·20 to 23·18; P = 0·027), soft gland texture (OR 9·86, 3·41 to 28·54; P < 0·001) and a small duct (OR 5·50, 1·84 to 16·44; P = 0·002) were significant risk factors for POPF. A patch did not reduce the incidence of POPF in patients at higher risk. CONCLUSION: The use of a fibrin sealant patch did not reduce the occurrence of POPF and complications after pancreatoduodenectomy with pancreatojejunostomy. Registration number: 2013-000639-29 (EudraCT register).

Low skeletal muscle mass outperforms the Charlson Comorbidity Index in risk prediction in patients undergoing pancreatic resections.

INTRODUCTION: Low skeletal muscle mass is a known predictor of morbidity and mortality in patients undergoing major pancreatic surgeries. We sought to combine low skeletal muscle mass with established risk predictors to improve their prognostic capacity for postoperative outcome and morbidity. METHODS: As established parameters to predict preoperative mortality risk for patients, the ASA classification and the Charlson Comorbidity Index (CCI) were used. The Hounsfield Units Average Calculation (HUAC) was measured to define low skeletal muscle mass in 424 patients undergoing pancreatic resections for malignancies. Patients in the lowest sex-adjusted quartile for HUAC were defined as having low skeletal muscle mass (muscle wasting). Multivariable Cox regression analysis was utilized to identify preoperative risk factors associated with postoperative morbidity. RESULTS: Median patient age was 63 years (19-87), 47.9% patients were male, and half the cohort had multiple comorbidities (Charlson Comorbidity Index [CCI]>6, 63.2%), 30-day mortality was 5.8% (n = 25). Median HUAC was 19.78 HU (IQR: 15.94-23.54) with 145 patients (34.2%) having low skeletal muscle mass. Preoperative frailty defined by low skeletal muscle mass was associated with an increased risk for postoperative complications (OR 1.55, CI 95% 0.98-2.45, p = 0.014), and a higher 30-day mortality (HR 5.17, CI 95% 1.57-16.69, p = 0.004). With an AUC of 0.85 HUAC showed the highest predictability for 30-day mortality (CI 95% 0.78-0.91, p = 0.0001). Patients with CCI ≥6 and low skeletal muscle mass defined by the HUAC had a 9.78 higher risk of dying in the immediate postoperative phase (HR 9.78, CI 95% 2.98-12.2, p = 0.0001). CONCLUSION: Low skeletal muscle mass predicts postoperative mortality and complications best and it should be incorporated to conventional risk scores to identify high risk patients.

Validation of C-reactive protein levels as a prognostic indicator for survival in a large cohort of pancreatic cancer patients.

BACKGROUND: Recent evidence indicates that the host inflammatory response has an important role in the tumour progression. Elevated C-reactive protein (CRP) levels have been previously associated with poor prognosis in several cancer types including small-scale studies in pancreatic cancer (PC) patients. The purpose of the present study was to validate the prognostic impact of plasma CRP levels at date of diagnosis on cancer-specific survival (CSS) in a large cohort of PC patients. METHODS: Data from 474 consecutive patients with adenocarcinoma of the pancreas, treated between 2004 and 2012 at a single centre, were evaluated retrospectively. CSS was analysed using the Kaplan-Meier method. To evaluate the prognostic significance of plasma CRP levels, univariate and multivariate Cox analyses were applied. RESULTS: High plasma CRP levels at diagnosis were significantly associated with well-established prognostic factors, including high tumour stage and tumour grade and the administration of chemotherapy (P<0.05). In univariate analysis, we observed that a high plasma CRP level was a consistent factor for poor CSS in PC patients (hazard ratio (HR)=2.21; 95% confidence interval (CI)=1.68-2.92, P<0.001). In multivariate analysis, tumour stage, grade, administration of chemotherapy, a high neutrophil-lymphocyte ratio and the highest quartile of CRP levels (HR=1.60, 95% CI=1.16-2.21; P=0.005) were identified as independent prognostic factors in PC patients. CONCLUSION: In conclusion, we confirmed a significant association of elevated CRP levels with poor clinical outcome in PC patients. Our results indicate that the plasma CRP level might represent a useful marker for patient stratification in PC management.

Increased neutrophil-lymphocyte ratio is a poor prognostic factor in patients with primary operable and inoperable pancreatic cancer.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) has been proposed as an indicator of systemic inflammatory response. Previous findings from small-scale studies revealed conflicting results about its independent prognostic significance with regard to different clinical end points in pancreatic cancer (PC) patients. Therefore, the aim of our study was the external validation of the prognostic significance of NLR in a large cohort of PC patients. METHODS: Data from 371 consecutive PC patients, treated between 2004 and 2010 at a single centre, were evaluated retrospectively. The whole cohort was stratified into two groups according to the treatment modality. Group 1 comprised 261 patients with inoperable PC at diagnosis and group 2 comprised 110 patients with surgically resected PC. Cancer-specific survival (CSS) was assessed using the Kaplan-Meier method. To evaluate the independent prognostic significance of the NLR, the modified Glasgow prognostic score (mGPS) and the platelet-lymphocyte ratio univariate and multivariate Cox regression models were applied. RESULTS: Multivariate analysis identified increased NLR as an independent prognostic factor for inoperable PC patients (hazard ratio (HR)=2.53, confidence interval (CI)=1.64-3.91, P<0.001) and surgically resected PC patients (HR=1.61, CI=1.02-2.53, P=0.039). In inoperable PC patients, the mGPS was associated with poor CSS only in univariate analysis (HR=1.44, CI=1.04-1.98). CONCLUSION: Risk prediction for cancer-related end points using NLR does add independent prognostic information to other well-established prognostic factors in patients with PC, regardless of the undergoing therapeutic modality. Thus, the NLR should be considered for future individual risk assessment in patients with PC.

Low expression of the putative tumour suppressor spinophilin is associated with higher proliferative activity and poor prognosis in patients with hepatocellular carcinoma.

BACKGROUND: Spinophilin, a multifunctional intracellular scaffold protein, is reduced in certain types of cancer and is regarded as a novel putative tumour suppressor protein. However, the role of spinophilin in hepatocellular carcinoma (HCC) has never been explored before. METHODS: In this study, we determined for the first time the expression pattern of spinophilin in human HCC by immunohistochemistry and quantitative reverse transcriptase-PCR analysis. In addition, we performed immunohistochemical analysis of p53, p14(ARF) and the proliferation marker Ki-67. Kaplan-Meier curves and multivariate Cox proportional models were used to study the impact on clinical outcome. Small interfering RNA (siRNA) was used to silence spinophilin and to explore the effects of reduced spinophilin expression on cellular growth. RESULTS: In our study, complete loss of spinophilin immunoreactivity was found in 44 of 104 HCCs (42.3%) and reduced levels were found in an additional 37 (35.6%) cases. After adjusting for other prognostic factors, multivariate Cox regression analysis identified low expression of spinophilin as an independent prognostic factor with respect to disease-free (hazard ratio (HR)=1.8; 95% confidence interval (CI)=1.04-3.40; P=0.043) and cancer-specific survival (HR=2.0; CI=1.1-3.8; P=0.025). Reduced spinophilin expression significantly correlated with higher Ki-67 index in HCC (P=0.014). Reducing spinophilin levels by siRNA induced a higher cellular growth rate and increased cyclin D2 expression in tumour cells (P<0.05). CONCLUSION: This is the first study of the expression pattern and distribution of spinophilin in HCC. According to our data, the loss of spinophilin is associated with higher proliferation and might be useful as a prognostic marker in patients with HCC.

Opportunistic cytomegalovirus infection causing colonic perforation in a patient with systemic lupus erythematosus.

We present the case of a 58-year-old woman with a long-standing history of systemic lupus erythematosus (SLE) who developed a cytomegalovirus (CMV) infection with colonic perforation and subsequent purulent peritonitis whilst using combined immunosuppressive therapy. The pathogenesis and the clinical presentation of this unique case is discussed in detail. Opportunistic infection should always be kept in mind in SLE patients presenting with fever. Viral serology should be routinely performed in these patients, especially when immunosuppressive therapy is given, to avoid delay in instituting adequate management and therapy.

Serum albumin, subjective global assessment, body mass index and the bioimpedance analysis in the assessment of malnutrition in patients up to 15 years after liver transplantation.

BACKGROUND: The subjective global assessment (SGA) or the body mass index (BMI) is used to determine the nutritional state after LTX. Bioelectrical impedance analysis (BIA) is used as tool to determine body composition by nutritional care professionals. METHODS: BIA, SGA, BMI, and serum albumin (SA) levels were performed to assess malnutrition following liver transplantation. BIA measurement was used as reference standard to determine existing malnutrition. A phase angle (PA) <5 was used to define potentially existing chronic disease-related malnutrition as a standard. All other measured parameters were compared with respect to their prognostic accuracy regarding the prediction of malnutrition as compared to the mentioned standard. RESULTS: Seventy-one recipients (51 men, 20 women) were included. Median age was 58, weight 77 kg, BMI 26 kg/m(2) , PA 4.1°, and SA 4.3 g/dL. According to the Nutritional Risk Screening 2002, 9.4% (6/71), to BMI 15.4% (11/71), to SA 30.9% (22/71), and to BIA 36.5% (28/71) of the patients were malnourished. PA did not correlate with BMI or NA, there was a significant correlation with SA (p = 0.001). Univariate analysis revealed SA as independent predictor for malnutrition. ROC analysis for all parameters revealed a significantly (p < 0.05) better area under the receiver operating characteristic curve for SA (0.812) than for BMI (0.603) for the prediction of malnutrition. CONCLUSION: SGA or BMI calculation alone does not suffice to evaluate the nutritional status. SA seems to play a crucial role in the prediction of severe disease-related malnutrition in this special patient cohort.

[Abdominal wall closure by incisional hernia and herniation after laparostoma]. / Bauchdeckenverschluss bei Narbenhernien und Herniationen nach Laparostoma.

As hernias and abdominal wall defects have a variety of etiologies each with its own complications and comorbidities in various constellations, efficient treatment requires patient-oriented management. There is no recommended standard treatment and the very different clinical pictures demand an individualized interdisciplinary approach. Particularly in the case of complicated hernias, the planning of the operation should focus on the problems posed by the individual patient. Treatment mainly depends on the etiology of the hernia, immediate or long-term complications and the efficiency of individual repair techniques. Abdominal wall repair for recurrent herniation requires direct closure of the fascia generally using the sublay technique with a lightweight mesh. It is still unclear whether persistent inflammation, mesh dislocation, fistula formation or other long-term complications are due to certain materials or to the surgical technique. With mesh infections it has been shown to be advantageous to remove a polytetrafluoroethylene (PTFE) mesh, while the combination of systemic and local treatment appears to suffice for a polypropylene or polyester mesh. Heavier meshes in the sublay position or plastic reconstruction with autologous tissue are indicated as substitutes for the abdominal wall for giant hernias, repeated recurrences and large abdominal wall defects. A laparostoma is increasingly more often created to treat septic intra-abdominal processes but is very often responsible for a complicated hernia. If primary repair of the abdominal wall is not an option, resorbable material or split skin is used for coverage under the auspices of a planned hernia repair.

Management of pancreatic trauma and its consequences--guidelines or individual therapy?

BACKGROUND/AIMS: Diagnosis of pancreatic trauma and its complications may be difficult due to non-specific signs and symptoms and treatment recommendations are not unequivocal. METHODOLOGY: Clinical data of a series of 47 patients with pancreatic trauma were analyzed; most of them were polytraumatized and treated by an interdisciplinary team. RESULTS: The most common causes were traffic accidents and sport injuries with 66% and 15%, respectively. Concomitant injuries were seen in 96% (nonpancreatic intra-abdominal injuries 85% including spleen 38% and liver 34%, extra-abdominal injuries 70%). Concomitant liver injuries were treated conservatively in 31% and operatively in 69% (including hepatic packing in 38%). Concomitant splenic injuries were usually very severe and could be managed conservatively in only 11%. All patients with pancreatic injuries grade III, IV or V (17%) according to the American Association of Surgical Trauma Classification required surgery, endoscopic treatment or interventional radiology. The most common posttraumatic complications were necrotizing pancreatitis (15%), pseudocyst formation (9%), abscesses (6%) and fistulas (4%). CONCLUSIONS: The status of the pancreatic duct is the crucial point for management of pancreatic trauma and should be assessed as early as possible. Treatment has to be tailored to the individual situation, especially in patients with severe concomitant injuries or prolonged course.

Expression of IGF-I, IGF-II, and IGF-IR in gallbladder carcinoma. A systematic analysis including primary and corresponding metastatic tumours.

AIMS: The insulin-like growth factor (IGF) system has been implicated in tumour development and progression. This study was designed to analyse the expression of the IGF-I receptor (IGF-IR) and its ligands (IGF-I, IGF-II) in gallbladder cancer. METHODS: IGF-I, IGF-II, and IGF-IR immunoreactivity was investigated in 57 gallbladder carcinomas and corresponding lymph node (n = 11) and hepatic (n = 7) metastases using a tissue microarray technique and correlated with tumour stage, grade, and patient outcome. RESULTS: Cancer tissue allowing a reliable evaluation of IGF-I, IGF-II, and IGF-IR was present in 55 of 57 primary tumours and 17 of 18 metastases. IGF-I and IGF-II immunoreactivity was seen in 25 and 14 of the 55 primary tumours, in addition to six and three of the 17 metastases, respectively. No associations with tumour stage, grade, or prognosis were detected. IGF-IR was expressed in 52 of 55 primary tumours and all 17 metastases. IGF-IR staining intensity decreased with tumour cell dedifferentiation. Moreover, IGF-IR expression in less than 50% of cancer cells was an independent marker of poor prognosis in multivariate analysis (risk ratio, 4.0; 95% confidence interval, 1.4 to 11.2; p = 0.01). CONCLUSIONS: The expression of IGF-IR and its ligands provides evidence for the existence of an auto/paracrine loop of tumour cell stimulation in gallbladder cancer and makes this type of cancer a candidate for therapeutic strategies aimed at interfering with the IGF pathway. The recognition of IGF-IR as a new independent prognostic biomarker may help to identify patients who might benefit from adjuvant treatment.

Treatment of patients with pyogenic liver abscess.

BACKGROUND: Pyogenic liver abscess (PLA) remains a serious disease with a mortality of 6-14%. METHODS: Clinical data of 76 patients with PLA were analyzed. Treatment options comprised antibiotics, percutaneous puncture/drainage, endoscopic papillotomy/stenting and/or surgery as indicated. RESULTS: Fifty-eight patients (76%) had single and 18 patients multiple PLA (right lobe: 65%; both lobes: 22%). The most frequent etiologies were: biliary (38%), hematogenous and posttraumatic (11%). Factors associated with the need for surgery included gallbladder empyema, biliary fistulas, malignancy, perforation, multicentricity, vascular complications and foreign bodies (e.g. infected ventriculo-peritoneal shunt, toothpick). CONCLUSIONS: Microbiological testing provides important information for treatment monitoring and modification. Complementary assessment of risk factors for a complicated course is crucial for timely identification of patients requiring additional treatment.

Analysis of KIT (CD117) expression in gallbladder carcinomas by tissue microarray.

AIMS: KIT (CD117) is a transmembrane tyrosinase-kinase receptor which has been related to cell proliferation, differentiation, adhesion and control of apoptosis. If present, KIT may provide a suitable target for tumour therapy. In this study, we report the presence of KIT in primary and metastatic gallbladder carcinomas. METHODS: Formalin-fixed and paraffin-embedded specimens of 57 primary gallbladder carcinomas and 18 corresponding metastases were stained using a tissue microarray technique and two different antibodies. RESULTS: Only three tumours stained for KIT. With a polyclonal antibody only one well differentiated papillary adenocarcinoma was immunoreactive. With a monoclonal antibody two additional poorly differentiated tubular adenocarcinoma showed weak and focal immunostaining. CONCLUSIONS: KIT immunoreactivity is infrequent in gallbladder carcinoma. Thus, routine screening of tumour tissues for KIT by immunohistochemistry appears to be cost-ineffective and cannot be recommended. Moreover, the lack of substantial KIT immunoreactivity in both primary and metastatic gallbladder carcinoma tissues does not provide a rationale to investigate imatinib mesylate therapy in clinical trials including patients with advanced disease.