Impact of the COVID-19 Pandemic on Surgical Oncology in Europe: Results of a European Survey.

BACKGROUND: The first COVID-19 pandemic wave hit most of the health-care systems worldwide. The present survey aimed to provide a European overview on the COVID-19 impact on surgical oncology. METHODS: This anonymous online survey was accessible from April 24 to May 11, 2020, for surgeons (n = 298) who were contacted by the surgical society European Digestive Surgery. The survey was completed by 88 surgeons (29.2%) from 69 different departments. The responses per department were evaluated. RESULTS: Of the departments, 88.4% (n = 61/69) reported a lower volume of patients in the outpatient clinic; 69.1% (n = 47/68) and 75.0% (n = 51/68) reported a reduction in hospital bed and the operating room capacity, respectively. As a result, the participants reported an average reduction of 29.3% for all types of oncological resections surveyed in this questionnaire. The strongest reduction was observed for oncological resections of hepato-pancreatico-biliary (HPB) cancers. Of the interviewed surgeons, 68.7% (n = 46/67) agreed that survival outcomes will be negatively impacted by the pandemic. CONCLUSION: The first COVID-19 pandemic wave had a significant impact on surgical oncology in Europe. The surveyed surgeons expect an increase in the number of unresectable cancers as well as poorer survival outcomes due to cancellations of follow-ups and postponements of surgeries.

The COVID-19 pandemic: impact on surgical departments of non-university hospitals.

BACKGROUND: During the first wave of the COVID-19 pandemic, German health care centres were restructured for the treatment of COVID-19 patients. This was accompanied by the suspension of the surgical programme. The aim of the survey was to determine the effects of COVID-19 on surgical care in non-university hospitals in Germany. METHODS: This cross-sectional study was based on an anonymous online survey, which was accessible from April 24th to May 10th, 2020 for surgeons of the Konvent der leitenden Krankenhauschirurgen (Convention of leading Hospital Surgeons) in Germany. The analysis comprised of 22.8% (n = 148/649) completed surveys. RESULTS: Communication and cooperation with authorities, hospital administration and other departments were largely considered sufficient. In the early phase of the COVID-19 pandemic, 28.4% (n = 42/148) of the respondents complained about a short supply of protective equipment available for the hospital staff. 7.4% (n = 11/148) of the participants stated that emergency operations had to be postponed or rescheduled. A decreased quantity of emergency surgical procedures and a decreased number of surgical emergency patients treated in the emergency room was reported in 43.9% (n = 65/148) and 63.5% (n = 94/148), respectively. Consultation and treatment of oncological patients in the outpatient clinic was decreased in 54.1% (n = 80/148) of the surveyed hospitals. To increase the capacity for COVID-19 patients, a reduction of bed and operating room occupancy of 50.8 ± 19.3% and 54.2 ± 19.1% were reported, respectively. Therefore, 90.5% (n = 134/148) of all participants expected a loss of revenue of 28.2 ± 12.9% in 2020. CONCLUSION: The first wave of the COVID-19 pandemic had a significant impact on surgical care in Germany. The reduction in the bed and the operating room capacity may have lead to considerable delays in urgent and semi-elective surgical interventions. In addition to the risk of worsening patient care, we anticipate severe financial damage to the clinics in 2020 and beyond. National and supranational planning is urgently needed to ensure the surgical care of patients during the ongoing COVID-19 pandemic.

Practical guideline on obesity care in patients with gastrointestinal and liver diseases - Joint ESPEN/UEG guideline.

BACKGROUND: Patients with chronic gastrointestinal disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean gastrointestinal patients. The present guideline addresses this question according to current knowledge and evidence. OBJECTIVE: The present practical guideline is intended for clinicians and practitioners in general medicine, gastroenterology, surgery and other obesity management, including dietitians and focuses on obesity care in patients with chronic gastrointestinal diseases. METHODS: The present practical guideline is the shortened version of a previously published scientific guideline developed according to the standard operating procedure for ESPEN guidelines. The content has been re-structured and transformed into flow-charts that allow a quick navigation through the text. RESULTS: In 100 recommendations (3× A, 33× B, 24 × 0, 40× GPP, all with a consensus grade of 90% or more) care of gastrointestinal patients with obesity - including sarcopenic obesity - is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially metabolic associated liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician. CONCLUSION: The present practical guideline offers in a condensed way evidence-based advice how to care for patients with chronic gastrointestinal diseases and concomitant obesity, an increasingly frequent constellation in clinical practice.

European guideline on obesity care in patients with gastrointestinal and liver diseases - Joint European Society for Clinical Nutrition and Metabolism / United European Gastroenterology guideline.

BACKGROUND: Patients with chronic gastrointestinal (GI) disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean GI patients. The present guideline addresses this question according to current knowledge and evidence. OBJECTIVE: The objective of the guideline is to give advice to all professionals working in the field of gastroenterology care including physicians, surgeons, dietitians and others how to handle patients with GI disease and obesity. METHODS: The present guideline was developed according to the standard operating procedure for European Society for Clinical Nutrition and Metabolism guidelines, following the Scottish Intercollegiate Guidelines Network grading system (A, B, 0, and good practice point [GPP]). The procedure included an online voting (Delphi) and a final consensus conference. RESULTS: In 100 recommendations (3x A, 33x B, 24x 0, 40x GPP, all with a consensus grade of 90% or more) care of GI patients with obesity - including sarcopenic obesity - is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially fatty liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician. CONCLUSION: The present guideline offers for the first time evidence-based advice how to care for patients with chronic GI diseases and concomitant obesity, an increasingly frequent constellation in clinical practice.

European guideline on obesity care in patients with gastrointestinal and liver diseases - Joint ESPEN/UEG guideline.

BACKGROUND: Patients with chronic gastrointestinal (GI) disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean GI patients. The present guideline addresses this question according to current knowledge and evidence. OBJECTIVE: The objective of the guideline is to give advice to all professionals working in the field of gastroenterology care including physicians, surgeons, dietitians and others how to handle patients with GI disease and obesity. METHODS: The present guideline was developed according to the standard operating procedure for ESPEN guidelines, following the Scottish Intercollegiate Guidelines Network (SIGN) grading system (A, B, 0, and good practice point (GPP)). The procedure included an online voting (Delphi) and a final consensus conference. RESULTS: In 100 recommendations (3x A, 33x B, 24x 0, 40x GPP, all with a consensus grade of 90% or more) care of GI patients with obesity - including sarcopenic obesity - is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially fatty liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician. CONCLUSION: The present guideline offers for the first time evidence-based advice how to care for patients with chronic GI diseases and concomitant obesity, an increasingly frequent constellation in clinical practice.

Nerve growth factor and artemin are paracrine mediators of pancreatic neuropathy in pancreatic adenocarcinoma.

OBJECTIVE: To further characterize the neurotrophic attributes of pancreatic cancer (PCa). SUMMARY BACKGROUND DATA: PCa is characterized by neuropathic alterations which are resulting in pancreatic pain. To further characterize pancreatic neuropathy, we aimed: to analyze whether neuropathic alterations in PCa are only limited to the tumor-core or whether they are similarly encountered in neural structures in the noncancerous pancreas, to demonstrate whether PCa features neurotrophic attributes and finally to identify responsible neurotrophic molecules. METHODS: Nerve density and area were quantified in normal pancreas (NP, n=45), histologically "normal" pancreas next to pancreatic cancer (NNPCa, n=61) and PCa (n=97). Growth-associated protein-43, nerve growth factor (NGF), and Artemin expressions were assessed by Immunohistochemistry, Western-Blot, and quantitative real time polymerase chain reaction-analyses. Isolated myenteric plexus of newborn rats were exposed to NP, NNPCa, and PCa tissue extracts and supernatants of Panc1 and T3M4 cancer cells with or without Artemin and NGF depletion, followed by neurite density analysis. RESULTS: Dense neural networks and enlarged nerves were not only detected in PCa but were also present in NNPCa. Growth-associated protein-43, NGF, and Artemin expressions were absent/weak in NP, but increased in both NNPCa and PCa and were closely associated with intrapancreatic neuropathy. PCa and NNPCa tissue extracts and Panc1/T3M4 supernatants noticeably increased neurite density in myenteric plexus-cultures, which were attenuated by depletion of NGF and Artemin. CONCLUSIONS: The neurotrophic effects of PCa extend into the peritumoral "normal" pancreatic areas without neuro-cancer interactions. The neurotrophic characteristics of PCa can be mimicked by in vitro analyses and reveal NGF and Artemin as potential key players in the generation of pancreatic neuropathy in PCa.

Pancreatic neuropathy and neuropathic pain--a comprehensive pathomorphological study of 546 cases.

BACKGROUND & AIMS: Chronic pancreatitis (CP) and pancreatic adenocarcinoma (PCa) are characterized by intrapancreatic neural alterations and pain. Our aims were to: (a) Investigate whether neuropathic changes like pancreatic neuritis, increased neural density, and hypertrophy are phenomena only in CP or whether they are also evident in other pancreatic disorders as well, (b) study possible variations in neural cancer cell invasion among malignant pancreatic tumors, and (c) explore whether these neuropathic changes contribute to pain sensation. METHODS: Neuropathic changes were studied in PCa (n=149), in CP (n=141), in pancreatic tumors (PTm) including serous/mucinous cystadenomas, invasive/noninvasive intraductal papillary mucinous neoplasias, benign/malignant neuroendocrine tumors, ampullary cancers (n=196), and in normal pancreas (n=60). The results were correlated with GAP-43 expression, tissue inflammation, pancreatic neuritis, neural invasion, fibrosis, desmoplasia, pain, and patient survival. RESULTS: Increased neural density and hypertrophy were only detected in PCa and CP and were strongly associated with GAP-43 over expression and abdominal pain. The severity of pancreatic neuritis was strongest in PCa and was closely linked to changes in neural density and hypertrophy. The aggressiveness of neural cancer cell invasion was most prominent in PCa and was related to neuropathic changes, desmoplasia, and pain. Severe and enduring pain were strongly associated with poor prognosis in PCa patients. CONCLUSIONS: Enhanced neural density and hypertrophy are only typical features of CP and PCa among all investigated pancreatic disorders. Such neuropathic changes, including damage to nerves by inflammatory and/or cancer cells, seem to enhance and generate pancreatic neuropathic pain.

T-Tube or no T-tube in the reconstruction of the biliary tract during orthotopic liver transplantation: systematic review and meta-analysis.

The routine use of a T-tube in reconstruction of the biliary tree during orthotopic liver transplantation (OLT) is controversial. A systematic review of the literature on the use of a T-tube in reconstruction of the biliary tree was performed. Retrospective studies were only reviewed, whereas prospective randomized studies were included in the meta-analysis. An analysis of 196 studies revealed that 91 studies investigated the use of a T-tube in OLT. Fifteen retrospective studies compared different groups and were thus considered relevant; 6 prospective studies were identified, of which 5 were randomized controlled trials with a total of 639 patients. The results of the randomized controlled trials were meta-analyzed. The odds ratio (OR) for biliary complications was 1.15 [95% confidence interval (CI) = 0.28-4.72], and this revealed that there were no differences in the rate of overall biliary complications whether or not a T-tube was used (Z = 0.19, P = 0.85). A detailed analysis of the biliary complications revealed that biliary leaks developed in 24 patients in the T-tube group versus 22 patients in the no-T-tube group (OR = 1.17, 95% CI = 0.4-3.47, Z = 0.29, P = 0.77). Biliary strictures were significantly more common in the group of patients who underwent reconstruction without a T-tube (14 versus 31 events; OR = 0.46, 95% CI = 0.23-0.9, Z = 2.26, P = 0.02). In conclusion, although reconstruction of the biliary tree with a T-tube prevents the occurrence of biliary strictures and may have the potential to reduce long-term morbidity with respect to late strictures, there is no clear evidence in favor of using a T-tube during OLT.

[Effects of the SARS-CoV-2 pandemic on surgery - a national cross-sectional study]. / Auswirkungen der SARS-CoV-2-Pandemie auf die Chirurgie ­ Eine nationale Querschnittsstudie.

BACKGROUND AND AIMS: From the beginning of the SARS-CoV­2 pandemic the German healthcare system focused on the treatment of COVID-19 patients. This was accompanied by the suspension of all elective operations. The aim of this study was to investigate the impact of the SARS-CoV­2 pandemic on general and visceral surgery in university hospitals in Germany. METHODS: This cross-sectional study was based on an anonymous survey, which was accessible online from 3 April 2020 to 17 April 2020 for the surgical departments of university hospitals in Germany. In total 73% (n = 29/40) of the hospitals participated in the survey. RESULTS: Cooperation with the authorities and the hospital administration was generally considered adequate; however, only 3% (1/29) and 7% (2/29) fully agreed with the statement that the health authorities at the federal and state level, respectively, were supportive of general and visceral surgery. The hospital directors expect an average loss of revenues of 28 ± 16%. There was an average reduction in beds or operating room capacity of 38% and 45%, respectively. In addition, 11% of the medical personnel in general and visceral surgery were reallocated to other departments. CONCLUSION: The SARS-CoV­2 pandemic has a significant impact on academic general and visceral surgery in Germany. The reduction in beds and operating room capacity can lead to considerable delays in urgent surgical interventions and financial burdens in 2020 and subsequent years.

Neural fractalkine expression is closely linked to pain and pancreatic neuritis in human chronic pancreatitis.

The chemokine fractalkine induces migration of inflammatory cells into inflamed tissues, thereby aggravating inflammatory tissue damage and fibrosis. Furthermore, fractalkine increases neuropathic pain through glial activation, which can be diminished by blocking of its receptor, CX3CR1, through neutralizing antibodies. As chronic pancreatitis (CP) is characterized by tissue infiltration of inflammatory cells, fibrosis, pancreatic neuritis and severe pain, the roles of fractalkine and CX3CR1 were investigated in CP (n=61) and normal pancreas (NP, n=21) by QRT-PCR, western blot and immunohistochemistry analyses. Their expression correlated with the severity of pancreatic neuritis, fibrosis, intrapancreatic nerve fiber density and hypertrophy, pain, CP duration and with the amount of inflammatory cell infiltrate immuno-positive for CD45 and CD68. To investigate the influence of fractalkine on pancreatic fibrogenesis, human pancreatic stellate cells (hPSCs) were isolated from patients with CP, incubated with fractalkine and then Collagen-1 and alpha-smooth muscle actin (alpha-SMA) expressions were measured. CX3CR1, but not fractalkine, mRNA was overexpressed in CP. In contrast, the protein levels of both CX3CR1 and fractalkine were upregulated. Neuro-immunoreactivity for fractalkine and CX3CR1 was strongest in patients suffering from severe pain and pancreatic neuritis. Long-term suffering from CP was noticeably related to increased neural immunoreactivity of fractalkine. Furthermore, fractalkine and CX3CR1 mRNA overexpressions were associated with enhanced lymphocyte and macrophage infiltration. Advanced fibrosis was associated with increased fractalkine expression, whereas in vitro fractalkine had no significant impact on collagen-1 and alpha-SMA expressions in hPSCs. Therefore, pancreatic fractalkine expression appears to be linked to visceral pain and to the recruitment of inflammatory cells into the pancreatic tissue and nerve fibers, with subsequent pancreatic neuritis. However, pancreatic fibrogenesis is probably indirectly influenced by fractalkine. Taken together, these novel findings suggest that CX3CR1 represents a potential novel therapeutic target to reduce inflammation and modulate pain in CP.

Pancreatic neuropathy results in "neural remodeling" and altered pancreatic innervation in chronic pancreatitis and pancreatic cancer.

OBJECTIVES: Chronic pancreatitis (CP) and pancreatic cancer (PCa) are characterized by intrapancreatic neuropathic alterations, including increased neural density and hypertrophy, pancreatic neuritis and neural invasion (NI) by cancer cells in PCa. The aim of this study was to identify the influence of these neuropathic changes on the quality of pancreatic innervation, intrapancreatic glia, and visceral pain. METHODS: Pancreatic nerve fiber qualities were characterized by immunohistochemical visualization of various markers, including those for sympathetic (tyrosine hydroxylase, TH) and cholinergic innervation (choline acetyltransferase, ChAT), as well as the glial transcription factor, Sox10, and the neuroepithelial progenitor cell marker, Nestin, in normal pancreas (NP, n=16), CP (n=20), and PCa (n=20) patients. The neural immunoreactivity scores of these markers were correlated with the severity of intrapancreatic neuropathic changes and with abdominal pain sensation of patients. RESULTS: Pancreatic sympathetic innervation was significantly reduced in CP and PCa, whereas parasympathetic innervation did not show major changes. Nestin neuro-immunoreactivity was stronger, and Sox10-immunoreactivity was weaker in CP and PCa than in NP. Pancreatic sympathetic and cholinergic innervation was noticeably decreased in patients with severe pancreatic neuritis, NI by cancer cells, or abdominal pain. Moreover, the neural immunoreactivity for Sox10 and Nestin also varied with intrapancreatic neuropathic alterations and abdominal pain. CONCLUSIONS: The quality of intrapancreatic nerve fibers and the activation state of intrapancreatic glia in CP and PCa are strikingly different from those in normal pancreas. This novel phenomenon of "neural remodeling" shows how pancreatic neuropathic pain and "visceral neuropathy" are associated with altered pancreatic innervation in CP and PCa.

Cannabinoids in pancreatic cancer: correlation with survival and pain.

Cannabinoids exert antiproliferative properties in a variety of malignant tumors, including pancreatic ductal adenocarcinoma (PDAC). In our study, we quantitatively evaluated the immunoreactivity for cannabinoid-1 (CB1) and cannabinoid-2 (CB2) receptors as well as for the endocannabinoid metabolizing enzymes fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MGLL). Furthermore, quantitative real-time RT-PCR for CB1, CB2, FAAH and MGLL in normal pancreas and pancreatic cancer tissues was performed. Levels of endocannabinoids were determined by liquid chromatography/mass spectrometry. Immunoreactivity scores and QRT-PCR expression levels were correlated with the clinico-pathological (TNM, survival, pain) status of the patients. Evaluation of endocannabinoid levels revealed that these remained unchanged in PDAC compared to the normal pancreas. Patients with high CB1 receptor levels in enlarged nerves in PDAC had a lower combined pain score (intensity, frequency, duration; p = 0.012). There was a significant relationship between low CB1 receptor immunoreactivity or mRNA expression levels (p = 0.0011 and p = 0.026, respectively), or high FAAH and MGLL cancer cell immunoreactivity (p = 0.036 and p = 0.017, respectively) and longer survival of PDAC patients. These results are underlined by a significant correlation of high pain scores and increased survival (p = 0.0343). CB2 receptor immunoreactivity, CB2 receptor, FAAH and MGLL mRNA expression levels did not correlate with survival. Therefore, changes in the levels of endocannabinoid metabolizing enzymes and cannabinoid receptors on pancreatic cancer cells may affect prognosis and pain status of PDAC patients.

Neural invasion in pancreatic cancer: a mutual tropism between neurons and cancer cells.

Neural invasion by pancreatic cancer cells (PCC) worsens the prognosis and frequently limits curative resection. We established a novel in-vitro model in which T3M4-PCCs were co-cultured with either isolated myenteric plexus cells (MP) or dorsal root ganglia (DRG) of newborn rats within a three-dimensional extracellular matrix gel. The close vicinity of MP or DRG to T3M4-PCCs induced early morphologic changes on T3M4-PCCs at the migration front prior to the migration process with elongated and neurite-targeting PCCs, compared to round and non-grouping at the non-migrating front. T3M4-PCCs built cancer-cell clusters around the DRG or MP, a process which was accelerated by increasing number of T3M4-PCCs or neurons. These findings indicate that neuro-cancer interactions start prior to PCC migration and induce evident changes in cancer and nerve biology. These findings can be reproduced within the introduced 3D in-vitro migration assay which allows investigation in the early pathogenesis of neural PCC invasion.

Pancreatic pain.

Abdominal pain is an important clinical symptom in pancreatic diseases. There is increasing evidence that pain in chronic pancreatitis and pancreatic cancer is triggered by pancreatic neuropathy. Damage to intrapancreatic nerves seems to support the maintenance and exacerbation of neuropathic pain. In chronic pancreatitis, intrapancreatic nerves are invaded by immune cells. This observation led to the hypothesis that neuro-immune interactions play a role in the pathogenesis of chronic pancreatitis and the accompanying abdominal pain syndrome. Similarly, pancreatic cancer cells infiltrate the perineurium of local nerves, which may in part explain the severe pain experienced by the patients. Furthermore, perineural invasion extending into extrapancreatic nerves may preclude curative resection and thus often leads to local recurrence. In recent years, the involvement of a variety of neurotrophins and neuropeptides in the pathogenesis of pancreatic pain was discovered. This review summarises recent data on the mechanisms of neuropathy and pain generation in pancreatic disorders.

Resection of primary pancreatic cancer and liver metastasis: a systematic review.

Resection of liver metastases for locally resectable pancreatic cancer has rarely been performed. Recently, promising results regarding morbidity and mortality as well as long-term survival have been shown. Thus, we conducted a systematic review of the literature on pancreatic cancer resection with associated liver metastasis resection. There are 3 case reports and 18 studies including less than 10 patients. Only three studies are larger series with 10 or more patients in whom pancreatic resections and hepatic metastasectomies were performed. Here, morbidity and mortality ranged from 24.1 to 26% and from 0 to 4.3%, respectively. Median survival was reported to be between 5.8 and 11.4 months. In total, all identified studies included 103 patients in whom a metastasis resection was performed. Liver metastasis resection for locally resectable pancreatic cancer can be performed in selected cases with low morbidity and mortality. Overall survival in cases with one or few liver metastases which are concomitantly resected seems to be comparable to cases without evidence of metastasis. Therefore, randomized controlled clinical trials will have to be initiated to determine the value of such resections and to identify factors which will allow for selection of patients in whom the extension of the resectability criteria might confer a survival benefit.

R2 resection in pancreatic cancer--does it make sense?

BACKGROUND: The goal of surgical treatment in patients with pancreatic cancer is the complete resection of tumor tissue; however, the intraoperative appraisal of resectability can be difficult. Extensive surgical exploration for definitive clear resectability may lead to R2 resections in single cases. PATIENTS: We analyzed 38 patients with pancreatic cancer with remaining macroscopic tumor tissue after pancreatic resection, as R0 resection was not possible. Patients were compared to 46 patients with unresectable cancer without distant metastases or peritoneal carcinomatosis, in which a bypass procedure was performed. RESULTS: Operating time and hospital stay were significantly longer after R2 resection. Intraoperative blood loss was significantly higher; and severe surgical complications and the need for relaparotomy were significantly more frequent after R2 resection. The 30-day mortality rate was higher after R2 resection; this difference was not statistically significant. Median survival was comparable in both groups. Two years after surgery, 22.6% of the patients after R2 resection were still alive compared to 10.9% after bypass surgery. CONCLUSION: Tumor debulking is not a treatment option in patients with advanced pancreatic cancer, but the patient is not at a disadvantage compared to bypass procedures if tumor tissue remains and R0 resection cannot be achieved after surgical exploration.

Association of axon guidance factor semaphorin 3A with poor outcome in pancreatic cancer.

Neural alterations and aberrantly expressed nerve-specific factors promoting tumor progression are known to contribute to pancreatic cancer's extremely poor prognosis. Despite hints that axon guidance factor semaphorin 3A (SEMA3A) may function as a tumor inhibitor, its clinical importance and therapeutic potential have not yet been explored. The present study investigated the role of SEMA3A and its receptors-plexins A1-A4 (PLXNA1-A4) and neuropilin-1 (NRP1)-in pancreatic cancer. QRT-PCR and immunohistochemical analyses revealed overexpression of SEMA3A, NRP1 and PLXNA1 in metaplastic ducts, malignant cells and nerves of cancerous specimens, and showed that elevated levels of corresponding mRNA (6.8-fold, 2.0-fold and 1.5-fold, respectively) clearly correlated with negative clinicopathological manifestations such as shorter survival (SEMA3A and PLXNA1) and a lesser degree of tumor differentiation (NRP1) in Stages I-III patients. High SEMA3A expression in pancreata of Stage IV M1 patients and in peritoneal metastases, and consequent functional studies indicated that poor clinical outcome might be related to the ability of SEMA3A to promote dissemination and invasiveness of pancreatic cancer cells through activation of multiple pathways involving Rac1, GSK3b or p42/p44 MAPK, but not E- to N-cadherin switch, MMP-9 or VEGF induction. Thus, this study is the first to quantify expression of the SEMA3A system in human malignancy and to show that overexpression of SEMA3A by nerves and transformed cells leads to a SEMA3A-rich environment which may favor malignant activities of tumor cells. Furthermore, negative clinicopathological correlations suggest that SEMA3A might represent a novel intervention target but not a treatment option for pancreatic cancer patients.

Effect of antecolic reconstruction on delayed gastric emptying after the pylorus-preserving Whipple procedure.

HYPOTHESIS: Antecolic duodenojejunostomy prevents delayed gastric emptying (DGE) after a pylorus-preserving Whipple (ppW) procedure better than retrocolic duodenojejunostomy. DESIGN: A single operation team's experience with antecolic and retrocolic duodenojejunostomy in ppW is analyzed on a prospective database using univariate and multivariate models. SETTING: Tertiary referral center that focuses on pancreatic diseases. PATIENTS AND INTERVENTIONS: One hundred consecutive patients undergoing a ppW procedure with retrocolic reconstruction between January 1, 1996, and December 31, 2001, and 100 consecutive patients undergoing a ppW procedure with antecolic reconstruction between January 1, 2002, and December 31, 2003. Characteristics such as median age, median hospital stay, sex, diagnosis, previous operations, blood loss, surgical and medical complications, American Society of Anesthesiologists risk groups, stent implantation, and especially DGE were matched for the comparison groups. MAIN OUTCOME MEASURES: We compared DGE, characteristics, and perioperative variables in patients with antecolic vs retrocolic reconstruction after ppW. RESULTS: The DGE occurred significantly more often in patients with retrocolic reconstruction than in those with antecolic reconstruction (P < .001). The antecolic and retrocolic study groups were comparable in age (P = .25), sex (P = .48), and postoperative surgical (P = .19) and medical (P = .054) complications. The univariate analysis between patients with and without DGE did not show significant differences regarding diagnosis, previous operations, blood loss, surgical and medical complications, American Society of Anesthesiologists classification, or stent implantation. In the multivariate analysis, only the type of reconstruction (P = .006) and sex (P = .04) seemed to affect DGE. CONCLUSION: We recommend antecolic duodenjejunostomy in patients undergoing a ppW procedure regardless of their diagnosis.

Native ureteropyelostomy: an effective therapy for urinary tract complications following kidney transplantation.

BACKGROUND: Urinary tract complications are relevant sources of morbidity and mortality after kidney transplantation. Incidence is reported within 3-14% in recent studies. Secondary ureteropyelostomy using the native ureter is a surgical option to treat severe urinary tract complications after kidney transplantation.The aim of this study was to evaluate the outcome after ureteropyelostomy using the native ureter in the management of urinary tract complications after kidney transplantation. METHODS: A single centre, retrospective clinical review of prospectively collected data of all patients who received kidney transplantation or combined kidney-pancreas transplantation between January 2001 and June 2009 was performed. All patients who underwent surgical therapy for urinary tract complications were identified and followed up to evaluate graft function and survival. RESULTS: Six hundred forty-six patients received kidney transplantation or combined kidney/pancreas transplantation. Twenty-six patients (4%) had to undergo re-operation due to severe urinary tract complications after kidney transplantation. Sixteen of the 26 patients (62%) received ureteropyelostomy using the ipsilateral native ureter. This reconstructive operation was successful in 14 of 16 patients (87.5%). Two patients needed to be re-operated for surgical complications. CONCLUSION: Ureteropyelostomy using the native ureter to treat ureter-related urinary tract complications after kidney transplantation can be performed safely and result in good graft and patient survival.