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Purpose: Ex vivo hepatectomy is the incorporation of liver transplant techniques in the non-transplant setting, providing opportunity for locally advanced tumors found conventionally unresectable. Because the procedure is rare and reports in the literature are limited, we sought to perform a systematic review and meta-analysis investigating technical variations of ex vivo hepatectomies. Methods: In the literature, there is a split in those performing the procedure between venovenous bypass (VVB) and temporary portacaval shunts (PCS). Of the 253 articles identified on the topic of ex vivo resection, 37 had sufficient data to be included in our review. Results: The majority of these procedures were performed for hepatic alveolar echinococcosis (69%) followed by primary and secondary hepatic malignancies. In 18 series, VVB was used, and in 18, a temporary PCS was performed. Comparing these two groups, intraoperative variables and morbidity were not statistically different, with a cumulative trend in favor of PCS. Ninety-day mortality was significantly lower in the PCS group compared to the VVB group (p=0.03). Conclusion: In order to better elucidate these differences between technical approaches, a registry and consensus statement are needed. [ABSTRACT FROM AUTHOR]

Background: Portal vein embolization (PVE) is widely used to promote the hypertrophy of a future liver remnant (FLR) and reduce posthepatectomy liver failure. The aim of this study was to evaluate the efficacy of transileocecal portal embolization (TIPE) associated with staging laparoscopy (hybrid lap-TIPE) for a planned hepatectomy in advanced hepatobiliary cancers. Methods: The hybrid lap-TIPE procedure consisted of staging laparoscopy for complete screening of the abdominal cavity with cytoreductive surgery and subsequent TIPE. Data on hybrid lap-TIPE, performed between March 2013 and February 2020, were collected retrospectively. Results: Hybrid lap-TIPE was conducted for 52 patients, and a subsequent TIPE was accomplished in 42 patients (80.8%), since staging laparoscopy detected latent or unresectable factors in 13 patients (25.0%), among which 2 patients with hepatocellular carcinoma and 1 with colorectal liver metastasis received laparoscopic cytoreductive surgery for latent lesions in the FLR. Finally, radical hepatectomy was completed in 36 patients (69.2%), including 3 patients who underwent cytoreductive surgery. The most common operation was an extended right hepatectomy (50.0%), followed by right hepatectomy (30.6%), including 3 hepatopancreatoduodenectomies. The overall morbidity associated with hybrid lap-TIPE and hepatectomy was 7.1% and 41.7%, respectively. The mortality associated with hybrid lap-TIPE and hepatectomy was 0% and 5.6%, respectively. The rates of 2-year survival and 2-year disease-free survival were 64.8% and 61.9%, respectively, after hepatectomy. Conclusions: Hybrid lap-TIPE is safe and could be a useful treatment option for patients with advanced hepatobiliary cancer because it can help to identify optimal candidates for PVE followed by a planned hepatectomy. [ABSTRACT FROM AUTHOR]

Purpose: Increased model for end-stage liver disease (MELD) score measured in the early postoperative course is associated with one-year mortality and graft loss. However, the correlation with postoperative complications has not been investigated. The aim of this study was to investigate the association between postoperative MELD score and subsequent complications. Methods: Adult liver transplant recipients transplanted from January 2011 until December 2016 were included. MELD score days 1–5 were correlated with complications day 6–30, subdivided into type and severity according to Clavien-Dindo classification. Results: We included 246 adult liver transplant recipients. Between days 6 and 30, 671 complications occurred in 201 of the patients (82%) corresponding to 64% of all postoperative complications in the whole postoperative period (days 0–30). In multivariate analyses adjusted for recipient gender and age, preoperative MELD score, and Eurotransplant Donor Risk Index, postoperative MELD score was significantly associated with having one or more complications, any type of complication except cardiovascular and renal complications, and complication severity. Conclusions: Postoperative MELD score days 1–5 were associated with complications arising in the subsequent period 6–30 days after transplantation. An increased MELD score should heighten the clinician's awareness of a possible complication. [ABSTRACT FROM AUTHOR]

Purpose: Temporary portal decompression (TPD) during liver transplantation (LT) remains a divisive technical issue in the liver transplant community. In this video-based article, we show the technical details of the different techniques used for TPD during LT. Methods: An early portal section, before liver mobilization, should be preferred in order to achieve hepatectomy of a totally devascularized liver. Portal decompression can be achieved through direct right portocaval shunts and indirect portosystemic shunts (i.e., mesentericosaphenous and portosaphenous shunts). Results: The preference for direct portocaval or indirect portosystemic shunts is tailored on patients and anatomical characteristics. Each of these three techniques presents specific indications, limitations, and advantages. Conclusion: TPD during LT can be achieved through different techniques that aim to facilitate the recipient hepatectomy, reduce the blood loss, and maintain hemodynamic stability. [ABSTRACT FROM AUTHOR]

Purpose: Almost 50% of patients diagnosed with colorectal cancer (CRC) will develop liver metastasis (LM). Although their only long-term curative treatment is surgery, less than half of these patients can be eventually resected. Therefore, palliative chemotherapy is offered as a definitive option, though with poor results. Recently, the University of Oslo group has published encouraging results in the treatment of these patients with liver transplantation (LT), whereby worldwide interest in this option has been renewed. Methods: A literature review of LT for patients with unresectable colorectal metastasis was performed. This included information regarding patient selection, complications, overall survival (OS) and disease-free survival (DFS), immunosuppression, chemotherapy, and description of the ongoing trials. Results: Improvements in OS and DFS have been observed in consecutive published prospective trials, as patient selection has been refined. Papers reporting OS of patients who randomly presented similar selection criteria also exhibited good results. Conclusion: LT within the available therapeutic options in patients with CRC-LM seems to be a compelling alternative in carefully selected patients. The ongoing trials will provide valuable information regarding selection criteria, immunosuppressive therapy and different modalities of adjuvant chemotherapy, which are, to our knowledge, the vital platform of LT in CRC-LM. Although some of the developing techniques involve living donors, graft availability for these patients remains a matter of major concern. [ABSTRACT FROM AUTHOR]

Approximately 10% of patients with ascites associated with cirrhosis fail to respond to dietary rules and diuretic treatment and therefore present with refractory ascites. In order to avoid iterative large-volume paracentesis in patients with contraindication to TIPS, the automated low flow ascites pump system (Alfapump) was developed to pump ascites from the peritoneal cavity into the urinary bladder, where it is eliminated spontaneously by normal micturition. This manuscript reports the surgical technique for placement of the Alfapump. [ABSTRACT FROM AUTHOR]

Background: Liver transplantation (LT) is the only cure for patients diagnosed with unresectable hepatocellular carcinoma (HCC), and HCC has become the leading indication for LT in the USA. The shortage of liver grafts results in a significant waiting time for LT with the risk of tumour progression. Treating HCCs during the waiting time prior to transplantation (bridging therapy) is an attractive strategy to reduce the risk of exceeding the tumour criteria for transplantation. Studies on bridging therapy are heterogenous and due to ethical issues, mostly of retrospective design. Purpose: We summarize the main studies and methods that have been reported on bridging therapies for patients with HCC waiting for a LT. Conclusion: During the waiting period for LT, patients with HCC at risk for tumour progression and therefore bridging therapy is recommended for patients with an estimated waiting time of ≥6 months. Bridging therapy for patients with HCC prior to LT mainly include locoregional therapies (LRTs), with transarterial chemoembolization (TACE) being the most common, followed by radio frequency ablation (RFA). Because of a continuous enhancement of therapy options, including a more precise adjustment of external radiotherapy, further possibilities for an individualized bridging therapy for patients with HCC have been developed. Patients with compensated liver cirrhosis and small tumour size are preferably treated with RFA, whereas patients with larger tumour size but compensated liver function are treated with TACE/TARE. Patients with uncompensated liver cirrhosis and larger tumour size can nowadays be successfully bridged to LT with external radiotherapy without increasing the risk for further deterioration of liver function. [ABSTRACT FROM AUTHOR]

Purpose: Women represent up to 60 % of students entering the medical profession in many countries in the world. However, the proportion of women to men is not accordingly balanced among surgical residents and especially in leadership positions in surgery. Therefore, we investigated the career goals as well as family and lifestyle priorities of female surgeons in German liver transplant centers. Methods: A standardized questionnaire was developed using the web-based survey tool SurveyMonkey®. Questionnaires were distributed electronically to 180 female surgeons in 24 German liver transplant centers. A total of 81 completed questionnaires were analyzed. Results: Female surgeons in German liver transplant centers are eager to assume leadership positions and do not wish to follow traditional role models. After finishing training, most female surgeons plan to continue working at a university hospital. About 80 % of the respondents intend to continue working full time and wish to combine career and family. Conclusions: This is the first survey on career intentions of female surgeons in Germany. In the face of gender changes in the medical profession, we were able to demonstrate that female surgeons are willing to fill leadership positions. Individual and institutional creative modifications are necessary if the advancement of women in surgery is to be promoted. [ABSTRACT FROM AUTHOR]

Purpose: Postoperative complications may have not only immediate but also long-term effects on the outcomes. Here, we analyzed the effect of postoperative complications requiring a reoperation (grade 3b) within the first 30 days on patients' and graft survival following liver transplantation. Methods: Graft and patient survival in relation to donor and recipient variables and the need of reoperation for complications of 277 consecutive liver transplants performed from January 2007 to December 2012 were analyzed. Results: Two hundred seventy-seven liver transplants were performed in 252 patients. Overall patient and graft survival at 1, 2, and 3 years were significantly reduced in patients requiring a reoperation. The labMELD score was significantly elevated ( p = 0.04) and cold ischemia time was prolonged ( p = 0.03) in recipients undergoing reoperations. Kaplan-Meier curves indicate that complications impact the outcome primarily within the first 3 months after transplantation. In multivariate analyses, the actual need of reoperation ( p < 0.001), the labMELD score ( p = 0.05), cold ischemia time ( p = 0.02), and the need for hemodialysis pre-transplant ( p = 0.05) were the only variables which correlated with the overall survival. Conclusion: Postoperative complications resulting in reoperations have a significant impact on the outcome primarily in the early phase after liver transplantation. Successful management of postoperative complications is key to every successful liver transplant program. [ABSTRACT FROM AUTHOR]

The article presents abstracts on medical topics which include ALKBH3-dependent DNA alkylation repair promotes cancer cell proliferation, Functional of chondrogenic progenitor cells in rheumatoid arthritis (RA), and Influence of extrinsic innervation on intestinal carcinogenesis in APCmin mice.

Purpose: The purpose of this study is to review indications and results of surgical treatments of hepatocellular carcinoma (HCC). This tumor, which represents one of the most common malignancies worldwide, is characterized by its prominent development in patients with chronic liver disease (CLD). Liver transplantation (LT) is considered as the ideal treatment of limited HCC removing both tumor(s) and the pre-neoplasic underlying diseased liver. However, this treatment, which is not available in many countries, is restricted to patients with minimum risk of tumor recurrence under immunosuppression. The risk of recurrence is minimized in patients fulfilling the Milan criteria with a tendency to accept slight expansion of size in patients with favourable natural history and low AFP level. Increasing duration in the waiting list before LT leads several teams to use neoadjuvant therapies such as percutaneous ablation, TACE and liver resection. Liver resection in cirrhotic patients with good liver function remains the most available efficient treatment of patients with HCC. Better liver function assessment, understanding of the segmental liver anatomy with more accurate imaging studies and surgical technique refinements are the most important factors that have contributed to reduce mortality with an expecting 5 years survival of 70%. There is considerable interest in combined treatment associating resection and LT. Transplantable patients with good liver function should be considered for liver resection as primary therapy and for LT in case of tumor recurrence. This salvage strategy is refined using pathological analysis of the resected specimen which identifies histological pejorative factors allowing selecting patients who should transplanted before recurrence. Conclusions: The improvement of survival in HCC patients after surgical treatment results from refinements in surgical technique and better identification of adverse prognostic factors. [ABSTRACT FROM AUTHOR]

Background: Angiogenesis, the formation of new blood vessels from the endothelium of the existing vasculature, describes a crucial process in tumor growth, disease progression, and metastasis. Therefore, the upcoming strategy of inhibiting tumor angiogenesis has generated different treatment modalities, which have been transferred into clinical practice in recent years. Currently, this concept is applied to target the vasculature of different visceral tumors and intensive clinical research has just started. Materials and methods: This review summarizes the modifications of systemic treatment of visceral tumors by targeting the vasculature in the past years. Moreover, novel targets and treatment strategies will be discussed to evaluate future directions. Results: Leading antiangiogenic drugs combined with systemic chemotherapy have been applied with increasing success during the last years. Therefore, the concept of combining vascular targeting agents with established chemotherapeutic regimens has been increasingly adopted into the therapies of different visceral tumors. Conclusion: Targeting the vasculature of visceral tumors in combination with established standard tumor therapies includes major clinical potential for future therapy concepts. [ABSTRACT FROM AUTHOR]

Introduction: Surgical therapy remains the only curative option for pancreatic ductal adenocarcinoma. But even after complete resection, almost all patients suffer from local tumor recurrence. Current standard adjuvant therapy with gemcitabine does not impressively affect the recurrence rate. The aim of this study was to evaluate a novel anti-angiogenic adjuvant treatment strategy by targeting the vascular endothelial growth factor receptor (VEGFR). We assayed the effects of a novel VEGFR inhibitor (ZK261991) on pancreatic carcinoma. ZK261991 is a highly selective and potent VEGFR-kinase inhibitor, which is orally available. Methods: We used a previously established nude mouse orthotopic pancreatic cancer resection model. Subcutaneous donor tumor fragments (1 mm) derived from human pancreatic cancer cell lines HPAF-2 and AsPC-1 were implanted in the pancreatic tail of 48 nude mice. Fourteen days afterwards, all mice underwent a histologically confirmed curative tumor resection followed by daily adjuvant oral therapy with ZK261991 (50 mg/kg; n = 24) vs. placebo ( n = 24). The mice were sacrificed after 12 weeks of therapy or in case of defined endpoints. All sacrificed mice underwent autopsy. A dissemination score (local and systemic tumor spread), size of recurrent tumor mass, survival, and weight loss/gain were surveyed. Results: Kaplan-Meier analysis of survival showed a significant benefit for mice treated with ZK261991 after HPAF-2 tumor resection: 83.8 days (95% CI 73.9-93.6) vs. 60.9 days (95% CI 48.9-73.0), p = 0.006. Adjuvant treatment with ZK261991 of AsPC-1-derived tumors showed a tendency towards a benefit compared to control but no significant difference: 75.8 days (95% CI 59.7-91.9) vs. 65.7 days (95% CI 51.6-79.7). There were no significant differences in dissemination score and size of recurrent tumor mass between the treatment groups. Conclusion: Adjuvant anti-angiogenic therapy with the novel VEGFR-inhibitor ZK261991 resulted in a significant survival benefit after curative tumor resection in a clinically relevant orthotopic animal model of pancreatic cancer. Combination of anti-angiogenic treatment with cytotoxic agents may further improve the results of adjuvant therapy. [ABSTRACT FROM AUTHOR]

The purpose of this review is to highlight the molecular mechanisms leading to the development and progression of pancreatic ductal adenocarcinoma (PDAC) with particular emphasis on tumor cell proliferation, local invasion, and metastasis. Recent advances in the field of PDAC biology have shed light on the molecular events that trigger PDAC initiation and maintenance. It is now clear that apart from the genetic alterations within the tumor cells, interactions of the tumor with its environment are necessary for proliferation and invasion. Interestingly, a number of developmental signaling pathways are reactivated in PDAC. Progress has also been made in the understanding of the molecular events that govern the process of metastasis. Although our understanding of the mechanisms underlying PDAC pathobiology are more advanced than ever, little progress has been made in the clinical treatment of PDAC, and successful bench-to-bedside transfer of knowledge to boost new treatment options is still unsatisfying. [ABSTRACT FROM AUTHOR]

Since the discovery of cancer cells with stem-like characteristics in hematopoietic malignancies and, more recently, in solid tumors, enormous attention has been paid to the stem-cell nature of pancreatic cancer. Among the most important properties of cancer stem cells their high capacity for tumorigenicity as well as their ability to metastasize is under special research interest today. Here, we give a brief overview of main components used to confirm the stem-cell-like behavior of putative cancer stem cells and discuss markers and methods for identifying them in pancreatic cancer. Finally, the review provides some new suggestions as to how specifically target these cells and improve current therapy regimens. The cancer stem-cell hypothesis is a fundamentally different model of carcinogenesis composed of two separate but dependent on each other characteristics of stem cells—aberrant activation of their tightly regulated processes of self-renewal and differentiation and their resistance towards chemo- and radiotherapy. The cancer stem cells may further be identified based on their expression of cell surface markers or their functional characteristics. The concept of molecular targeting of such highly tumorigenic cancer cells aimed to sensitize tumors toward conventional therapies and effectively abrogate tumor growth and metastasis. The presence of cancer stem cells in pancreatic tumors has prognostic relevance and influences therapeutic response. Evidence suggests that metastatic potential may be conferred to these highly tumorigenic cells as well. A better understanding of the biological behavior of these cells may further improve therapeutic approaches and outcomes in patients with this devastating disease. [ABSTRACT FROM AUTHOR]

The first successful renal transplant was carried out more than five decades ago between identical twins. At these early days, acute rejection was the limiting factor. Due to tremendous progress in immunosuppressive therapy and surgical technique, today, renal transplantation is the gold standard therapy for patients with end-stage renal disease. In fact, in comparison with chronic hemodialysis, renal transplantation offers an increase in quality of life while reducing comorbidities associated with dialysis treatment. Despite numerous beneficial achievements, no further improvement regarding patient outcome can be observed over the last two decades. Graft survival rates remain unchanged. The leading causes for graft loss are chronic allograft nephropathy and death with functioning graft. This might be related to a constant increase of the proportion of donors presenting extended donor criteria as well as a more liberal acceptance of candidates for a renal transplant. In the near future, one has to focus more closely on the posttransplant patient care to minimize factors associated with chronic allograft damage. These include post-transplant diabetes, hyperlipidemia, high blood pressure, cytomegalovirus infection, etc. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer responsible for over 20% of deaths due to gastrointestinal malignancies. PDAC is usually diagnosed at an advanced stage which, in part, helps to explain its high resistance to chemotherapy and radiotherapy. In addition, the cancer cells in PDAC have a high propensity to metastasize and to aberrantly express several key regulators of angiogenesis and invasion. Chemotherapy has only provided a modest impact on mean survival and often induces side effects. Targeting angiogenesis alone or in combination with other modalities should be investigated to determine if it may provide for increased survival. This review summarizes the alterations in PDAC that play a critical role in angiogenesis and provides an overview of current and therapeutic strategies that may be useful for targeting angiogenesis in this malignancy. [ABSTRACT FROM AUTHOR]

The article presents abstracts of medical research. They include "QUERCETIN PROTECTS HUMAN HEPATOCYTES FROM OXIDATIVE STRESS BY INDUCING HEME OXYGENASE-1 VIA THE MAPK/NRF2 PATHWAYS," "BLOCKADE OF THE HEPATIC ARTERIAL BUFFER RESPONSE BY NITRIC OXIDE REDUCES ORGAN FAILURE AND ENHANCES REGENERATION IN REDUCED-SIZE LIVERS," and "RAPAMYCIN REDUCES CYCLOSPORINE-INDUCED THICKENING OF VASCULAR ANASTOMOSES BY INHIBITING PERICYTES AFTER HEART TRANSPLANTATION IN RATS."

While early surgical success made organ transplantation possible in the 1950s and 1960s, the breakthrough in clinical organ transplantation was achieved through the discovery and invention of modern immunosuppressive agents in the early/mid-1980s. Especially during the 1990s, a large array of immunosuppressants has expanded the armamentarium used to prevent and treat allograft rejection, resulting in an excellent short-term and an acceptable long-term outcome. However, these drugs have potent but still non-specific immunosuppressive properties and frequently show severe acute and chronic side effects, sometimes questioning the overall success. As the “Holy-Grail” of the transplant community, the induction of “true donor-specific tolerance” has not been achieved yet; current immunosuppressive strategies, in particular in Europe, include “individually tailored immunosuppressive” protocols, mostly based on specific immunologic and non-immunologic risk factors. These protocols allow for optimal immunosuppressive protocols for each patient group according to their needs by choosing the most suitable, well-tolerated combination of agents and the most effective doses to avoid acute rejection episodes (incidence and severity) and minimise drug-related toxicity to reduce long-term drug-related morbidity and mortality. Nevertheless, transplant recipient are still being forced to take a life-long course of chemical immunosuppressive agents to keep their graft, knowing about the possible life-threatening side effects. We review current trends of immunosuppressive protocols in liver and kidney transplantation, focusing on calcineurin-inhibitor-sparing protocols, mammalian-target-of-rapamycin (mTOR) inhibitor based-protocols and corticosteroid-avoidance protocols, being aware of the fact, that most of these strategies could be applicable for other transplanted organs, too. Finally, we describe future trends and new developments that are rising on the horizon. [ABSTRACT FROM AUTHOR]

Angiogenesis, the formation of new blood vessels from the endothelium of the existing vasculature, is fundamental in tumor growth, progression, and metastasis. Inhibiting tumor angiogenesis is a promising strategy for treatment of cancer and has been successfully transferred from preclinical to clinical application in recent years. Whereas conventional therapeutic approaches, e.g. chemotherapy and radiation, are focussing on tumor cells, antiangiogenic therapy is directed against the tumor supplying blood vessels. This review will summarize important molecular mechanisms of tumor angiogenesis and advances in the design of antiangiogenic drugs. Furthermore, clinical implications of antiangiogenic therapy in surgical oncology will be discussed. First antiangiogenic drugs have been approved for treatment of advanced solid tumors in several countries. Leading antiangiogenic drugs are designed to inhibit vascular endothelial growth factor-mediated tumor angiogenesis. Combining antiangiogenic agents with conventional chemotherapy or radiation is currently investigated clinically with great emphasis to realize a multimodal tumor therapy, targeting both the tumor cell and tumor vascular compartment. Antiangiogenic tumor therapy represents a promising strategy for treatment of cancer and will most likely exhibit its clinical potential in combination with established standard tumor therapies in the future. [ABSTRACT FROM AUTHOR]

The article presents abstracts of surgical research. They include "Positive implication of applying extended donor criteria in liver transplantation," "Taurine protects kidney from ischemia/reperfusion injury after transplantation," and "Alloplastic material induces zonal regulation of matrix metalloproteinase-2 gene expression by macrophages and fibroblasts."

Presents abstracts of lectures from all surgical specialities with emphasis on tissue engineering and molecular biology in surgery, presented during the September 2005 Annual Meeting on Surgical Research.

Background. Organ transplantation is a standard procedure today. Due to immunosuppressive drugs and increasing survival after organ transplantation, patients with transplanted organs carry an increased risk of developing malignant tumours. Accordingly, more patients with malignant tumours after transplantation will be faced by general or oncology surgeons. We report the case of a 48-year-old patient with advanced rectal cancer 6.5 years after pancreas–kidney-transplantation for type I diabetes. Method. The patient was treated with neo-adjuvant radio-chemotherapy, followed by low anterior rectal resection with total mesorectal excision. Consecutively, a solitary hepatic metastasis, a solitary pulmonary metastasis and a chest wall metastasis were resected over the course of 13 months. Result. The patient eventually died of metastasized cancer 32 months after therapy had been initiated, his organ grafts functioning well until his death. Conclusion. Our case report provides evidence that transplantation patients should receive standard oncology treatment, including neo-adjuvant treatment, so long as their general condition and organ graft functions allow us to do so, although a higher degree of morbidity might be encountered. [ABSTRACT FROM AUTHOR]