Kim C. Honselmann

Long-term mortality and quality of life in intensive care patients treated for pneumonia and/or sepsis: Predictors of mortality and quality of life in patients with sepsis/pneumonia.

PURPOSE The purpose of this study is to evaluate long-term mortality and quality of life (QoL) of intensive care patients with pneumonia and/or sepsis 1 year after discharge and to identify potential predictors for these outcome measures. METHODS This retrospective cohort study analyzed all patients admitted to the intensive care unit (ICU) of a German university hospital with diagnosis of pneumonia and/or sepsis between 2008 and 2009. Quality of life was assessed by telephone interview or mail using the standardized EuroQol 5-dimension questionaire. RESULTS Of 1406 patients treated in the ICU within the observational period, 217 met the inclusion criteria. Whereas in-hospital mortality differed significantly between pneumonia (17%) and sepsis (46%) (P < .001), 1-year mortality was not statistically significant (51% and 65%, P = .057). A high Simplified Acute Physiology Score (SAPS) II value was associated with high in-hospital mortality but failed to predict 1-year mortality. Quality of life, measured 1 year after discharge by visual analog scale (VAS), was 50% ± 25%, which was significantly lower than in a matched control group (70% ± 20%; P < .001). A high SAPS II score on admission did not correlate with VAS but was an independent predictor of a low EuroQol 5-dimension index. CONCLUSIONS The high post-ICU mortality of patients with pneumonia and sepsis emphasizes the need to focus on long-term follow-up in ICU studies and demonstrates that even when sepsis signs are missing, critically ill patients due to pneumonia have high 1-year mortality. Simplified Acute Physiology Score II does not predict long-term mortality, but a low SAPS II on admission might be useful to identify patients with good physical status after 1 year. TAKE HOME MESSAGE Hospital mortality of patients treated for pneumonia and/or sepsis is high and increases significantly within the first year after discharge. The SAPS II predicts in-hospital mortality and the physical components of QoL but not long-term mortality. TWEET One-year mortality of ICU pneumonia patients is equally high as in sepsis patients. Simplified Acute Physiology Score II cannot predict long-term mortality but can predict QoL.

Regulation Mechanisms of the Hedgehog Pathway in Pancreatic Cancer: A Review

Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of death from cancer. Its 5-year survival rate is less than 5%. This poor prognosis is mostly due to the cancers early invasion and metastasis formation, leading to an initial diagnosis at an advanced incurable stage in the majority of patients. The only potentially curative treatment is radical surgical resection. The effect of current chemotherapeutics or radiotherapy is limited. Novel therapeutic strategies are therefore much needed. One of the hallmarks of PDAC is its abundant desmoplastic (stromal) reaction. The Hedgehog (Hh) signaling pathway is critical for embryologic development of the pancreas. Aberrant Hh signaling promotes pancreatic carcinogenesis, the maintenance of the tumor microenvironment and stromal growth. The canonical Hh-pathway in the tumor stroma has been targeted widely but has not yet lead to hopeful clinical results. Targeting both the tumor and its surrounding stroma through Hh pathway inhibition by also targeting non-canonical pathways as apparent in the tumor cell may therefore be a novel treatment strategy for PDAC.

Tumor engraftment in patient-derived xenografts of pancreatic ductal adenocarcinoma is associated with adverse clinicopathological features and poor survival

Patient-derived xenograft (PDX) tumors are powerful tools to study cancer biology. However, the ability of PDX tumors to model the biological and histological diversity of pancreatic ductal adenocarcinoma (PDAC) is not well known. In this study, we subcutaneously implanted 133 primary and metastatic PDAC tumors into immunodeficient mice. Fifty-seven tumors were successfully engrafted and even after extensive passaging, the histology of poorly-, moderately-, and well-differentiated tumors was maintained in the PDX models. Moreover, the fibroblast and collagen contents in the stroma of patient tumors were recapitulated in the corresponding PDX models. Analysis of the clinicopathological features of patients revealed xenograft tumor engraftment was associated with lymphovascular invasion (P = 0.001) and worse recurrence-free (median, 7 vs. 16 months, log-rank P = 0.047) and overall survival (median, 13 vs. 21 months, log-rank P = 0.038). Among successful engraftments, median time of growth required for reimplantation into new mice was 151 days. Reflective of the inherent biological diversity between PDX tumors with rapid (<151 days) and slow growth, differences in their growth were maintained during extensive passaging. Rapid growth was additionally associated with lymph node metastasis (P = 0.022). The association of lymphovascular invasion and lymph node metastasis with PDX formation and rapid growth may reflect an underlying biological mechanism that allows these tumors to adapt and grow in a new environment. While the ability of PDX tumors to mimic the cellular and non-cellular features of the parental tumor stroma provides a valuable model to study the interaction of PDAC cells with the tumor microenvironment, the association of successful engraftment with adverse clinicopathological features suggests PDX models over represent more aggressive forms of this disease.

Association Between Changes in Body Composition and Neoadjuvant Treatment for Pancreatic Cancer

Importance Sarcopenia and sarcopenic obesity have been associated with poor outcomes in unresectable pancreatic cancer (PC). Neoadjuvant treatment (NT) is used increasingly to improve resectability; however, its effects on fat and muscle body composition have not been characterized. Objectives To evaluate whether NT affects muscle mass and adipose tissue in patients with borderline resectable PC (BRPC) and locally advanced PC (LAPC) and determine whether there were potential differences between patients who ultimately underwent resection and those who did not. Design, Setting, and Participants In this retrospective cohort study conducted at 4 academic medical centers, 193 patients with BRPC and LAPC undergoing surgical exploration after NT who had available computed tomographic scans (both at diagnosis and preoperatively) and confirmed pancreatic ductal adenocarcinoma were evaluated. The study was conducted from January 2013 to December 2015. Data analysis was performed from September 2016 to May 2017. Measurement of body compartments was evaluated with volume assessment software before and after NT. A radiologist blinded to the patient outcome assessed the areas of skeletal muscle, total adipose tissue, and visceral adipose tissue through a standardized protocol. Exposures Receipt of NT. Main Outcomes and Measures Achievement of pancreatic resection at surgical exploration after the receipt of NT. Results Of the 193 patients with complete radiologic imaging available after NT, 96 (49.7%) were women; mean (SD) age at diagnosis was 64 (11) years. Most patients received combined therapy with fluorouracil, irinotecan, oxaliplatin, leucovorin, and folic acid (124 [64.2%]) and 86 (44.6%) received chemoradiotherapy as well. The median interval between pre-NT and post-NT imaging was 6 months (interquartile range [IQR], 4-7 months). All body compartments significantly changed. The adipose compound decreased (median total adipose tissue area from 284.0 cm2; IQR, 171.0-414.0 to 250.0 cm2; IQR, 139.0-363.0; P < .001; median visceral adipose tissue area from 115.2 cm2; IQR, 59.9-191.0 to 97.7 cm2; IQR, 48.0-149.0 cm2; P < .001), whereas the lean mass slightly improved (median skeletal muscle from 122.1 cm2; IQR, 99.3-142.0 to 123 cm2; IQR 104.8-152.5 cm2; P = .001). Surgical resection was achievable in 136 (70.5%) patients. Patients who underwent resection had experienced a 5.9% skeletal muscle area increase during NT treatment, whereas those who did not undergo resection had a 1.7% decrease (P < .001). Conclusions and Relevance Patients with PC experience a significant loss of adipose tissue during neoadjuvant chemotherapy, but no muscle wasting. An increase in muscle tissue during NT is associated with resectability.

Neoadjuvant Therapy in Pancreatic Cancer: Review Article

CONTEXT Pancreatic cancer is still associated with a high mortality and morbidity for affected patients. To this date the role of neoadjuvant therapy in the standard treatment of pancreatic cancer remains elusive. The aim of our study was to review the latest results and current approaches in neoadjuvant therapy of pancreatic cancer. METHODS We performed a literature review for neoadjuvant therapy in pancreatic cancer. We divided the results into resectable disease and local advanced pancreatic cancer. RESULTS Neoadjuvant therapy in pancreatic cancer is safe. But currently no standard guidelines exist in neoadjuvant approaches on pancreatic cancer. For local advanced pancreatic cancer the available data tends to show a positive effect on survival rates for neoadjuvant approaches. CONCLUSION For resectable disease we found no benefit of neoadjuvant therapy. The negative or positive effects of neoadjuvant treatment in pancreatic cancer remain unclear for the lack of sufficient and prospective data.

Perioperative and Long-term Oncological Results of Minimally Invasive Pancreatoduodenectomy as Hybrid Technique – A Matched Pair Analysis of 120 Cases

Background Laparoscopic pancreatoduodenectomy is a highly challenging procedure. The aim of this study was to analyse post-operative morbidity and mortality as well as long term overall survival in patients undergoing hybrid LPD, as compared to open pancreaticoduodenecomy (OPD) in a single surgeon series. Methods Patients undergoing pancreatoduodenectomy (PD) in the period from 2000 to 2015 were identified from a prospectively maintained database. All LPD procedures were performed by one specialised pancreatic surgeon (TK). Patients were matched 1 : 1 for age, sex, BMI, ASA, histological diagnosis, pancreatic texture and portal venous resection (PVR). All LPD procedures were performed as hybrid LPD – combining laparoscopic resection and open reconstruction via mini laparotomy. Results A total of 549 patients were identified, including 489 patients in the OPD group and 60 patients in the LPD group. 60 patients were identified who underwent LPD between 2010 and 2015 versus 60 OPD patients operated in the same period. Median overall operation time was shorter in the LPD group than with OPD patients (LPD 352 vs. OPD 397 min; p = 0.002). Overall transfusion units were lower in the LPD group (LPD range 0 – 4 vs. OPD range 0 – 11; p = 0.032). Intensive care unit stay (LPD 1 vs. OPD 6 d; p = 0.008) and overall hospital stay (OHS: LPD 14 vs. OPD 18 d; p = 0.012) were shorter in the LPD groups than in the OPD group. As regards postoperative complications, LPD was associated with reduced rates of clinically relevant grade B/C postoperative pancreatic fistula (LPD 15 vs. OPD 36%; p = 0.036) and grade B/C delayed gastric emptying (LPD 8 vs. OPD 20%; p = 0.049). A total of 56 patients were diagnosed with malignant disease. The number of harvested lymph nodes and R0-resection rates were equal for LPD and OPD patients. LPD patients showed a trend to improved median overall survival (LPD mean 56 months vs. OPD mean 48 months; p = 0.056). Conclusion Hybrid LPD is a safe procedure associated with a reduction in clinically relevant postoperative complications and allows faster recovery. Long term oncological outcome of hybrid LPD for malignant disease is equal to that with the standard open approach.

The Extracellular Matrix and Pancreatic Cancer: A Complex Relationship

Pancreatic ductal adenocarcinoma (PDAC) has an extraordinarily dense fibrotic stroma that impedes tumor perfusion and delivery of anticancer drugs. Since the extracellular matrix (ECM) comprises the bulk of the stroma, it is primarily responsible for the increased interstitial tissue pressure and stiff mechanical properties of the stroma. Besides its mechanical influence, the ECM provides important biochemical and physical cues that promote survival, proliferation, and metastasis. By serving as a nutritional source, the ECM also enables PDAC cells to survive under the nutrient-poor conditions. While therapeutic strategies using stroma-depleting drugs have yielded disappointing results, an increasing body of research indicates the ECM may offer a variety of potential therapeutic targets. As preclinical studies of ECM-targeted drugs have shown promising effects, a number of clinical trials are currently investigating agents with the potential to advance the future treatment of PDAC. Thus, the present review seeks to give an overview of the complex relationship between the ECM and PDAC.

Hybrid Laparoscopic Duodenopancreatectomy

Laparoscopic pancreatoduodenectomy is currently limited to a few tertiary centers worldwide. The slow distribution of this technique since its first description by Gagner and Pomp (Gagner 1994) more than twenty years ago is due to numerous reasons: (1) In contrast to laparoscopic distal pancreatectomy, the laparoscopic pancreatic head resection is characterized by a complex reconstruction involving the pancreatic anastomosis as well as the biliojejunal anastomosis. (2) The technical prerequisites for dissectors and instrumentation have only been developed during the past few years. (3) The combination of laparoscopic proficiency with profound expertise in pancreatic surgery has only just emerged in this new generation of surgeons. In summary, there has been a very dynamic development of the laparoscopic pancreatic head resection during the past few years. There have been published series with over 50 patients demonstrating the feasibility and safety of this technique in specialized centers. In highly specialized teams this technique is even advanced towards more complex surgeries including portal vein resection as well as laparoscopic portal vein reconstruction [1]. The rapid development of this field can be noted when highlighting the number of cases published between January 2012 and June 2013, which exceed the numbers of the 15 years prior [2].

Familienfreundlich und gendergerecht – Die Chirurgie der Zukunft

Eine familienfreundliche und gendergerechte Chirurgie – wie soll das gehen? Das Projekt FamSurg bietet Antworten, damit Vereinbarkeit von Familie und Beruf in diesem Fachgebiet kein Widerspruch bleiben muss.