Pancreatic head resection for carcinoma of the ampulla vateri - better long-term prognosis, but more postoperative complications.

BACKGROUND: Pancreatoduodenectomies are complex surgical procedures with a considerable morbidity and mortality even in high-volume centers. However, postoperative morbidity and long-term oncological outcome are not only affected by the surgical procedure itself, but also by the underlying disease. The aim of our study is an analysis of pancreatoduodenectomies for patients with pancreatic ductal adenocarcinoma (PDAC) and ampullary carcinoma (CAMP) concerning postoperative complications and long-term outcome in a tertiary hospital in Germany. METHODS: The perioperative and oncological outcome of 109 pancreatic head resections performed for carcinoma of the ampulla vateri was compared to the outcome of 518 pancreatic head resections for pancreatic ductal adenocarcinoma over a 20 year-period from January 2002 until December 2021. All operative procedures were performed at the University Hospital Freiburg, Germany. Patient data was analyzed retrospectively, using a prospectively maintained SPSS database. Propensity score matching was performed to adjust for differences in surgical and reconstruction technique. Primary outcome of our study was long-term overall survival, secondary outcomes were postoperative complications and 30-day postoperative mortality. Postoperative complications like pancreatic fistula (POPF), postpancreatectomy hemorrhage (PPH) and delayed gastric emptying (DGE) were graded following current international definitions. Survival was estimated using Kaplan Meier curves and log-rank tests. A p-value < 0.05 was considered statistically significant. RESULTS: Operation time was significantly longer in PDAC patients (432 vs. 391 min, p < 0.001). The rate of portal vein resections was significantly higher in PDAC patients (p < 0.001). In CAMP patients, a pancreatogastrostomy as reconstruction technique was performed more frequently compared to PDAC patients (48.6% vs. 29.9%, p < 0.001) and there was a trend towards more laparoscopic surgeries in CAMP patients (p = 0.051). After propensity score matching, we found no difference in DGE B/C and PPH B/C (p = 0.389; p = 0.517), but a significantly higher rate of clinically relevant pancreatic fistula (CR-POPF) in patients with pancreatoduodenectomies due to ampullary carcinoma (30.7% vs. 16.8%, p < 0.001). Long-term survival was significantly better in CAMP patients (42 vs. 24 months, p = 0.003). CONCLUSION: Patients with pancreatoduodenectomies due to ampullary carcinomas showed a better long-term oncological survival, by reason of the better prognosis of this tumor entity. However, these patients often needed a more elaborated postoperative treatment due to the higher rate of clinically relevant pancreatic fistula in this group.

Surgical complications requiring late surgical revisions after pancreatoduodenectomy increase postoperative morbidity and mortality.

BACKGROUND: Pancreatoduodenectomies are complex surgical procedures with considerable postoperative morbidity and mortality. Here, we describe complications and outcomes in patients requiring surgical revisions following pancreatoduodenectomy. METHODS: A total of 1048 patients undergoing a pancreatoduodenectomy at our institution between 2002 and 2019 were analyzed retrospectively. All patients with surgical revisions were included. Revisions were divided into early and late using a cut-off of 5 days after the first surgery. Statistical significance was examined by using chi-square tests and Fisher's exact tests. Survival analysis was performed using Kaplan-Meier curves and log-rank tests. RESULTS: A total of 150 patients with at least 1 surgical revision after pancreatoduodenectomy were included. Notably, 64 patients had a revision during the first 5 days and were classified as early revision. Compared with the 86 patients with late revisions, we found no differences concerning wound infections, delayed gastric emptying, or acute kidney failure. After late revisions, we found significantly more cases of sepsis (31.4% late versus 15.6% early, p = 0.020) and reintubation due to respiratory failure (33.7% versus 18.8%, p = 0.031). Postoperative mortality was significantly higher within the late revision group (23.2% versus 9.4%, p = 0.030). CONCLUSION: Arising complications after pancreatoduodenectomy should be addressed as early as possible as patients requiring late surgical revisions frequently developed septic complications and multiorgan failure.

Surgical pancreatic biopsies for cases with locally advanced pancreatic cancer with inconclusive histology after interventional biopsy.

Background: Histopathological confirmation of malignancy is mandatory in patients with unresectable pancreatic cancer before initiation of palliative chemotherapy. When interventional biopsy proves unsuccessful, laparoscopic or open surgical biopsies become necessary. Methods: 66 consecutive surgical biopsies of the pancreas performed at a single institution between 01/2010 and 04/2020 were analyzed retrospectively. We analyzed sensitivity of histopathological confirmation of malignancy as well as complication rates of laparoscopic and open surgical biopsies in patients with suspected advanced pancreatic cancer after unsuccessful interventional biopsies. Results: 8 complications were observed in 46 patients requiring only a pancreatic biopsy (17.4 %) while in 13 of 20 patients complications were observed when additional procedures were necessary (65 %). Major complications CD ≥ III were observed in the "biopsy +/- port" group in 4 of 46 patients and in the "biopsy + additional procedure" cohort in 9 of 20 patients (8.7 vs. 45 %, p < 0.001). Despite the trend to reduced perioperative complications in laparoscopic biopsies, the reduction did not reach statistical significance when compared to open resections (11.1 vs. 26.3 %, p = 0.18). Surgical pancreatic biopsies reached a sensitivity regarding the correct definite histopathological result of 90.32 %, specificity was 100 %. Conclusion: Both laparoscopic and open biopsies can be performed at acceptable complication rates CD ≥ III of 8.7 % and present a valuable option after failure of image-guided techniques for biopsy. Additional operative measures in locally advanced pancreatic carcinoma ought to be critically reflected due to a substantially higher complication rate CD ≥ III of 45 %. Key message: Laparoscopic and open surgical biopsies in patients with unresectable pancreatic cancer demonstrate a high diagnostic sensitivity at acceptable complication rates. This finding is important because it provides further support for surgical biopsies to avoid delay before initiation of palliative therapy.

Immune changes induced by periampullary adenocarcinoma are reversed after tumor resection and modulate the postoperative survival.

BACKGROUND: Tumor growth encompasses multiple immunologic processes leading to impaired immunity. Regarding cancer surgery, the perioperative period is characterized by additional immunosuppression, which may contribute to poorer outcomes. In this exploratory study, we assessed plasma parameters characterizing the perioperative immunity with a particular focus on their prognostic value. PATIENTS AND METHODS: 31 patients undergoing pancreatoduodenectomy were enrolled (adenocarcinoma of the pancreatic head and its periampullary region: n = 24, benign pancreatic diseases n = 7). Abundance and function of circulating immune cells and the plasma protein expression were analyzed in blood samples taken pre- and postoperatively using flow cytometry, ELISA and Proximity Extension Assay. RESULTS: Prior to surgery, an increased population of Tregs, a lower level of intermediate monocytes, a decreased proportion of activated T-cells, and a reduced response of T-cells to stimulation in vitro were associated with cancer. On the first postoperative day, both groups showed similar dynamics. The preoperative alterations did not persist six weeks postoperatively. Moreover, several preoperative parameters correlated with postoperative survival. CONCLUSION: Our data suggests systemic immunologic changes in adenocarcinoma patients, which are reversible six weeks after tumor resection. Additionally, the preoperative immune status affects postoperative survival. In summary, our results implicate prognostic and therapeutic potential, justifying further trials on the perioperative tumor immunity to maximize the benefit of surgical tumor therapy.

Molecular Mechanisms of Tumor Immunomodulation in the Microenvironment of Colorectal Cancer.

Colorectal cancer remains one of the most important health challenges in our society. The development of cancer immunotherapies has fostered the need to better understand the anti-tumor immune mechanisms at play in the tumor microenvironment and the strategies by which the tumor escapes them. In this review, we provide an overview of the molecular interactions that regulate tumor inflammation. We particularly discuss immunomodulatory cell-cell interactions, cell-soluble factor interactions, cell-extracellular matrix interactions and cell-microbiome interactions. While doing so, we highlight relevant examples of tumor immunomodulation in colorectal cancer.

The clinical impact of preoperative biliary drainage on isolated infectious complications (iiC) after pancreatic head resection-a retrospective study.

BACKGROUND: The perioperative morbidity after pancreatoduodenectomy (PD) is mostly influenced by intraabdominal complications which are often associated with infections. In patients with preoperative biliary drainage (PBD), the risk for postoperative infections may be even elevated. The aim of this study is to explore if isolated infectious complications without intraabdominal focus (iiC) can be observed after PD and if they are associated to PBD and antibiotic prophylaxis with potential conclusions for their treatment. METHODS: During a 10-year period from 2009 to 2019, all consecutive PD were enrolled prospectively in a database and analyzed retrospectively. Bacteriobilia (BB) and Fungibilia (FB) were examined by intraoperatively acquired smears. A perioperative antibiotic prophylaxis was performed by Ampicillin/Sulbactam. For this study, iiC were defined as postoperative infections like surgical site infection (SSI), pneumonia, unknown origin etc. Statistics were performed by Fisher's exact test and Mann Whitney U test. RESULTS: A total of 426 PD were performed at the Vivantes Humboldt-hospital. The morbidity was 56% (n = 238). iiC occurred in 93 patients (22%) and accounted for 38% in the subgroup of patients with postoperative complications. They were not significantly related to BB and PBD but to FB. The subgroup of SSI, however, had a significant relationship to BB and FB with a poly microbial profile and an accumulation of E. faecalis, E. faecium, Enterobacter, and Candida. BB was significantly more frequent in longer lay of PBD. Resistance to standard PAP and co-existing resistance to broad spectrum antibiotics is frequently found in patients with iiC. The clinical severity of iiC was mostly low and non-invasive therapy was adequate. Their treatment led to a significant prolongation of the hospital stay. CONCLUSIONS: iiC are a frequent problem after PD, but only in SSI a significant association to BB and FB can be found in our data. Therefore, the higher resistance of the bacterial species to routine PAP, does not justify broad spectrum prophylaxis. However, the identification of high-risk patients with BB and PBD (length of lay) is recommended. In case of postoperative infections, an early application of broad-spectrum antibiotics and adaption to microbiological findings from intraoperatively smears may be advantageous.

Clinical characteristics and outcome of patients with acute mesenteric ischemia: a retrospective cohort analysis.

BACKGROUND: Acute mesenteric ischemia (AMI) is an uncommon, but life-threatening clinical entity due to late diagnosis resulting in irreversible ischemic bowel necrosis. The most common causes of AMI are the embolic occlusion and the acute thrombosis of the mesenteric circulation. Typical treatment is composed of an early revascularization of the mesenteric circulation followed by abdominal surgery for resection of nonviable intestine and restoration of the intestinal continuity, but the mortality rates remain high. METHODS: A retrospective cohort analysis was conducted, aiming to evaluate clinical characteristics, performed surgical procedures and outcomes of patients with acute mesenteric ischemia who underwent emergency abdominal surgery at a high volume surgical center in Germany. RESULTS: Overall, 53 patients were identified with the intraoperatively proven diagnosis of AMI. Overall hospital mortality was with 62% comparable to the literature. Nineteen patients presented with an intraoperatively verified complete and non-reversible intestinal infarction without any angiographic or surgical option for a revascularization of the mesenteric circulation or an option for intestinal resection. From the rest of the patients, 14 underwent intestinal resection of the ischemic area without restoration of intestinal continuity; the other 20 underwent resection with a primary anastomosis to restore intestinal continuity. The mortality rate of these patients with curative-intended surgery remained high (41% of patients died). Pre- and postoperative hyperlactatemia were associated with lower survival of these patients. CONCLUSION: AMI remains a life-threatening abdominal emergency. Therapeutic approaches are highly depended on acting surgeon's decision, being affected by subjectively rated bowel viability and physical condition of the affected patient. Only selected patients with good bowel viability appear to be suitable for receiving primary anastomosis. The results clearly indicate the need for further research to develop therapeutic approaches for a better management of AMI and to improve outcome of affected patients.

Stent-Associated Infectious Complications After Pancreatoduodenectomies Can Be Prevented by Perioperative Antibiotic Therapy: An Analysis of Single-Center Standards.

OBJECTIVES: Perioperative morbidity after pancreatoduodenectomies is still high. One potentially responsible factor is the insertion of bile duct stents before surgery. In our single-center study, we evaluated the influence of preoperative bile duct stenting combined with perioperative antibiotic therapy versus primary surgery in carcinoma patients. METHODS: Clinical data of 973 patients undergoing pancreatoduodenectomy at the University Hospital Freiburg from 2002 to 2018 were explored retrospectively. Postoperative pancreatic fistula, delayed gastric emptying (DGE), and postpancreatectomy hemorrhage (PPH) were graded by current international definitions. Patients with pancreatic ductal adenocarcinoma or periampullary carcinoma were included. RESULTS: We included 634 patients of whom 372 (58.7%) were treated with preoperative bile duct stenting. No difference concerning postoperative pancreatic fistula was observed (P = 0.479). We found more wound infections (stent 18.4%, no stent 11.1%, P = 0.008) but a significantly lower rate of PPH and DGE in stented patients (PPH 7.5% vs 11.9%, P = 0.044; DGE 16.5% vs 22.5%, P = 0.039). Surprisingly, intra-abdominal abscesses were reduced in stented patients (9.4% vs 15.0%, P = 0.022), just as insufficiencies of the biliodigestive anastomosis (P = 0.021). CONCLUSIONS: Perioperative antibiotic therapy seems to reduce the risk for severe intra-abdominal infectious complications in stent-bearing patients.

Current Insights: The Impact of Gut Microbiota on Postoperative Complications in Visceral Surgery-A Narrative Review.

Postoperative complications are a major problem occurring in up to 50% of patients undergoing major abdominal surgery. Occurrence of postoperative complications is associated with a significantly higher morbidity and mortality in affected patients. The most common postoperative complications are caused by an infectious genesis and include anastomotic leakage in case of gastrointestinal anastomosis and surgical site infections. Recent research highlighted the importance of gut microbiota in health and disease. It is plausible that the gut microbiota also plays a pivotal role in the development of postoperative complications. This narrative review critically summarizes results of recent research in this particular field. The review evaluates the role of gut microbiota alteration in postoperative complications, including postoperative ileus, anastomotic leakage, and surgical site infections in visceral surgery. We tried to put a special focus on a potential diagnostic value of pre- and post-operative gut microbiota sampling showing that recent data are inhomogeneous to identify a high-risk microbial profile for development of postoperative complications.

Curative-intent pancreas resection for pancreatic metastases: surgical and oncological results.

BACKGROUND: Pancreatic metastasis is a rare cause for pancreas surgery and often a sign of advanced disease no chance of curative-intent treatment. However, surgery for metastasis might be a promising approach to improve patients' survival. The aim of this study was to analyze the surgical and oncological outcome after pancreatic resection of pancreatic metastasis. METHODS: This is a retrospective cohort analysis of a prospectively-managed database of patients undergoing pancreatic resection at the University of Freiburg Pancreatic Center from 2005 to 2017. RESULTS: In total, 29 of 1297 (2%) patients underwent pancreatic resection due to pancreatic metastasis. 20 (69%) patients showed metastasis of renal cell carcinoma (mRCC), followed by metastasis of melanoma (n = 5, 17%), colon cancer (n = 2, 7%), ovarian cancer (n = 1, 3%) and neuroendocrine tumor of small intestine (n = 1, 3%). Two (7%) patients died perioperatively. Median follow-up was 76.4 (range 21-132) months. 5-year and overall survival rates were 82% (mRCC 89% vs. non-mRCC 67%) and 70% (mRCC 78% vs. non-mRCC 57%), respectively. Patients with mRCC had shorter disease-free survival (14 vs. 22 months) than patients with other primary tumor entities. CONCLUSION: Despite malignant disease, overall survival of patients after metastasectomy for pancreatic metastasis is acceptable. Better survival appears to be associated with the primary tumor entity. Further research should focus on molecular markers to elucidate the mechanisms of pancreatic metastasis to choose the suitable therapeutic approach for the individual patient.

Sclerosing angiomatoid nodular transformation of the spleen, a rare cause for splenectomy: Two case reports.

BACKGROUND: Sclerosing angiomatoid nodular transformation (SANT) is a rare benign disease of the spleen with unknown origin. Clinical symptoms are inhomogeneous, and suspicious splenic lesion often found incidentally, leading to splenectomy, as malignancy cannot securely be ruled out. Diagnosis is made histologically after resection. CASE SUMMARY: Two cases of German, white, non-smoking, and non-drinking patients of normal weight are presented. The first one is a 26-year-old man without medical history who was exhibiting an undesired weight loss of 10 kg and recurring vomiting for about 18 mo. The second one is a 65-year-old woman with hypertension who had previously undergone gynecological surgery, suffering from a lasting feeling of abdominal fullness. Both showed radiologically an inhomogeneous splenic lesion leading to splenectomy approximately 6 and 9 wk after surgical presentation. Both diagnoses of SANT were made histologically. Follow-up went well, and both were treated according to the recommendation for asplenic patients. CONCLUSION: SANT is a rare cause of splenectomy and an incidental histological finding. Further research should focus on clinical and radiological diagnosis of SANT as well as on treatment of patients with asymptomatic and small findings.

Adjuvant chemotherapy after surgery for pancreatic ductal adenocarcinoma: retrospective real-life data.

BACKGROUND: The recommendation for postoperative chemotherapy in pancreatic ductal adenocarcinoma (PDAC) is based on prospective randomized trials. However, patients included in clinical trials do not often reflect the overall patient population treated in clinical practice. MATERIALS AND METHODS: A retrospective review of all patients undergoing pancreas resection for PDAC between 2001 and 2013 was performed. Follow-up data from oncologists, general practitioners, or hospital patient files were available for 92% of patients. RESULTS: A total of 251 patients were included in our analysis. Chemotherapy was recommended for 223 patients, but 86 patients did not follow the recommendation. The application of the recommended chemotherapy, consisting of 6 cycles of gemcitabine, was only applied to 45 patients. Forty patients received the recommended number of cycles with dose reduction or prolonged intervals between cycles, and adjuvant chemotherapy was terminated prior to the intended completion of all 6 cycles in 54 patients. Survival of patients after adjuvant chemotherapy was increased compared to that of patients without chemotherapy (with recurrence 25.6 vs. 14.3 months, p = 0.001, and without recurrence 27.4 vs. 14.3 months, p <  0.001). Terminating chemotherapy prior to completion (p = 0.009) as well as a lower number of chemotherapy cycles (p = 0.026) was associated with a decreased survival. CONCLUSION: Adjuvant chemotherapy improves overall and disease-free survival after curative pancreatic resection, but only a small fraction of patients completes the recommended 6 cycles of adjuvant chemotherapy. Our data indicates that performance status of patients after pancreas resections for PDAC requires not only highly biologically active but also well-tolerated adjuvant chemotherapy regimens.

Recurring Anastomotic Leak-A Prospective Clinicopathological Investigation of a Distinct Disease Pattern.

BACKGROUND: Intestinal anastomotic insufficiency (AI) is a common problem in visceral surgery associated with overexpression of matrix metalloproteinases (MMPs). In some patients it occurs more than once. The etiology of recurring anastomotic insufficiency (RAI) is not understood yet and should be addressed as an independent disease entity. MATERIALS AND METHODS: Thirty nine consecutive patients with AI were treated at our university center and were included in this prospective study. Clinical data were evaluated by correlative statistical analysis to identify independent risk factors for RAI. Patients were divided in two groups: 18 patients had a single operative revision until restoration (group SAI), and 21 patients had two or more revisions (group RAI). Anastomotic tissue samples as well as untouched bowel wall were collected during reoperations for analysis of MMPs and tissue inhibitor of metalloproteinases (TIMP2). Clinical data were correlated with pathological observations. RESULTS: Significant differences of clinical and molecular pathological data were found between the two groups. Transfusion of red blood cells until the first reoperation and alcohol abuse led to RAI and were the only independent risk factors for RAI in multivariate analysis. Overexpression of MMP-8, -9, and -13 in anastomotic tissue correlated with the administration of red blood cells during initial operation. Reduced expression of TIMP2 was frequent in nearly all patients without differences throughout the subgroups. CONCLUSIONS: RAI seems to have an independent disease pattern. Transfusion of blood products is not only a known risk factor for AI but seems to significantly disturb the anastomotic healing process leading to RAI.

Minimally Invasive versus Open Distal Pancreatectomy for Ductal Adenocarcinoma (DIPLOMA): A Pan-European Propensity Score Matched Study.

OBJECTIVE: The aim of this study was to compare oncological outcomes after minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) in patients with pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Cohort studies have suggested superior short-term outcomes of MIDP vs. ODP. Recent international surveys, however, revealed that surgeons have concerns about the oncological outcomes of MIDP for PDAC. METHODS: This is a pan-European propensity score matched study including patients who underwent MIDP (laparoscopic or robot-assisted) or ODP for PDAC between January 1, 2007 and July 1, 2015. MIDP patients were matched to ODP patients in a 1:1 ratio. Main outcomes were radical (R0) resection, lymph node retrieval, and survival. RESULTS: In total, 1212 patients were included from 34 centers in 11 countries. Of 356 (29%) MIDP patients, 340 could be matched. After matching, the MIDP conversion rate was 19% (n = 62). Median blood loss [200 mL (60-400) vs 300 mL (150-500), P = 0.001] and hospital stay [8 (6-12) vs 9 (7-14) days, P < 0.001] were lower after MIDP. Clavien-Dindo grade ≥3 complications (18% vs 21%, P = 0.431) and 90-day mortality (2% vs 3%, P > 0.99) were comparable for MIDP and ODP, respectively. R0 resection rate was higher (67% vs 58%, P = 0.019), whereas Gerota's fascia resection (31% vs 60%, P < 0.001) and lymph node retrieval [14 (8-22) vs 22 (14-31), P < 0.001] were lower after MIDP. Median overall survival was 28 [95% confidence interval (CI), 22-34] versus 31 (95% CI, 26-36) months (P = 0.929). CONCLUSIONS: Comparable survival was seen after MIDP and ODP for PDAC, but the opposing differences in R0 resection rate, resection of Gerota's fascia, and lymph node retrieval strengthen the need for a randomized trial to confirm the oncological safety of MIDP.

Bio-absorbable sealants for reinforcing the pancreatic stump after distal pancreatectomy are critical.

BACKGROUND: Bio-absorbable sealants are widely used to reduce the rate and severity of postoperative pancreatic fistulas after distal pancreatectomy. However, numerous clinical trials have failed to demonstrate their clinical benefit. We therefore investigated stability and bio-compatibility of absorbable sealants in vitro and in vivo. METHODS: In vitro, polymerized compounds were incubated in pancreatic juice before their stability was tested. In vivo, two compounds were used to seal the pancreatic stump after distal pancreatectomy in nine pigs. Burst pressure of the pancreatic stump, surgical outcome, histology of the pancreatic stump, systemic inflammation, and drain fluid was examined. RESULTS: Products based on fibrin or collagen were unstable in the presence of active pancreatic enzymes and completely dissolved within 2 h. Sealants using chemical cross-linking of proteins showed improved stability for 7 days. In vivo, application of polyethylenglycol-based sealant leads to complete closure of the pancreatic duct after 5 days, while a glutaraldehyde-based sealant prevented physiological closure of the pancreatic main duct. CONCLUSIONS: Many compounds used clinically to reinforce the pancreatic stump after distal pancreatectomy are inadequate due to instability in the presence of pancreatic enzymes. While selected bio-absorbable sealants inhibited the natural healing of the pancreatic stump, polyethylenglycol-based sealants should be tested in further clinical trials.

Oncological outcome of laparoscopically assisted pancreatoduodenectomy for ductal adenocarcinoma in a retrospective cohort study.

INTRODUCTION: Laparoscopic resections of the pancreatic head are increasingly performed. Several studies show that they are comparable to open operations in terms of postoperative morbidity. However, since a substantial proportion of pancreatic head resections are necessary for pancreatic adenocarcinoma the oncologic safety and outcome of minimally invasive operations is of interest. In this study we evaluated oncologic outcome and survival after laparoscopically assisted pancreatic head resection for ductal adenocarcinoma. METHODS: Perioperative and oncological outcome of sixty-two laparoscopically assisted pancreatic head resections for pancreatic ductal adenocarcinoma performed between 2010 and 2016 was compared to outcome of 278 open resections between 2001 and 2016 in a retrospective study. Data was continuously collected in a prospectively maintained database. RESULTS: Operation time was significantly longer in the laparoscopic group (477 vs. 428 min. p < 0.001). Tumor size, lymph node yield and lymph node state and need of portal vein resection were comparable. There was a higher rate of free resection margins in the laparoscopic group (87% vs. 71%, p < 0.01). There was no difference in postoperative mortality and morbidity. Patients with laparoscopic resection stayed in hospital significantly shorter (median 14 vs. 16 days, p < 0.003). Postoperative survival after 5 years was not different in both groups. CONCLUSION: Laparoscopically assisted resection of adenocarcinoma of the pancreatic head is equal to open resection concerning oncologic outcome and actuarial survival. However, minimally invasive resection shortened the hospital stay. However, further evaluations with a longer follow up time are needed.

The predominance of a naive T helper cell subset in the immune response of experimental acute pancreatitis.

INTRODUCTION: In necrotizing acute pancreatitis (NAP), systemic inflammatory response syndrome (SIRS) and the compensatory anti-inflammatory response syndrome (CARS) decide overall outcome and mortality. In patients, low lymphocyte counts were found, but T-helper cells seemed to conversely increase. Our aim was to further categorize T-helper cells within the context of NAP induced SIRS and CARS. METHODS: NAP was induced by injection of sodium-taurocholate into the common bile duct of male BALB/c mice; sham treated animals received saline infusion. The animals were sacrificed at 6, 12, 24 and 48 h later. Lymphocytes from blood, liver and spleen were isolated and examined by flow cytometry. Staining was performed for CD4, CD8, CD19, CD45RB, CD25, CD69, and CD152. CD4+ cells were sorted for their CD45RB expression and sought for gene regulation associated to TH1/TH2 cells by quantitative RT-PCR. RESULTS: In NAP, CD4+ was solely increased in all compartments. CD8+ remained without substantial alterations. CD45RB showed significant expression in RBhigh in T-helper cells, confirmed by the CD45RBhigh/low ratio (Liver, 24 h: NAP 2.2, SHAM 0.6; p < 0.001). CD45RBhigh and -low cells were not associated to patterns of TH1/TH2 expression. In NAP, CCR4 expression was significantly decreased within RBhigh cells (fold change: 0.04, p < 0.05), while TLR6 showed significant overexpression (fold change: 2.36, p < 0.05). CONCLUSION: T-helper cells increase in NAP, leaning towards CD45RBhigh expression. They resemble naive T-cells, in which NAP leads to expression profiles associated with an innate immune response. This suggests new findings in immunological pathomechanisms of NAP.

The prognostic influence of intrapancreatic tumor location on survival after resection of pancreatic ductal adenocarcinoma.

BACKGROUND: The prognosis of pancreatic ductal adenocarcinoma (PDAC) is worse when the tumor is located in the pancreatic body or tail, compared to being located in the pancreatic head. However, for localized, resectable tumors survival seems to be at least similar. METHODS: We analyzed and compared the outcome after pancreatoduodenectomy (PD) and distal pancreatectomy (DP) for PDAC at our institution. Clinical, pathological and survival data from patients undergoing pancreatic resection for PDAC 1994-2014 were explored retrospectively, accessing a prospective pancreatic database. Patients receiving primary total pancreatectomy were excluded. RESULTS: Four hundred and thirteen patients were treated for PDAC: 347 (84%) underwent PD and 66 (16%) DP. Tumors located in the pancreatic body and tail were significantly larger than their counterparts located in the head (30.6 mm vs. 41.2 mm; p < 0.001). However, distal tumors had significantly less nodal involvement (71% vs. 57%; p = 0.03). Portal-vein resection (PVR) was performed more often in PD, multivisceral resection (MVR) was more frequent in DP (37% vs. 14% and 4% vs. 29%; p < 0.001). Rates for negative resection margins and tumor grading were similar. Postoperative complication rates including morbidity, rates of re-operation and mortality were comparable. Long-term outcome revealed no significant difference between PD and DP with 5-year survival rates of 17.8 and 22% respectively (p = 0.284). Multivariate analysis confirmed positive resection margin, positive nodal status, extended resection (PVR, MVR) and lack of adjuvant/additive chemotherapy as independent risk factors for poor survival after pancreatic resection. CONCLUSION: Patients with resectable pancreatic ductal adenocarcinoma located in the body and tail of the pancreas display a similar postoperative oncological outcome despite larger tumors when compared to patients with resectable tumors located in the pancreatic head.

Organ-specific monocyte activation in necrotizing pancreatitis in mice.

BACKGROUND: Acute necrotizing pancreatitis (NAP) induces a systemic inflammatory response syndrome. We investigated the underlying changes of monocytes using different activation markers. MATERIALS AND METHODS: A retrograde injection of 2 mL/kg bodyweight of sodium taurocholate into the common bile duct of BALB/c mice induced NAP, whereas sham-operated animals (SOP) were treated with saline. After 6, 12, 24, and 48 h, histologic alterations, pancreatic enzymes, and interleukin 6 in serum, albumin, and myeloperoxidase (MPO) in bronchoalveolar lavage fluid were examined. Isolation of mononuclear cells from the blood, spleen, and liver and the subsequent determination of macrophages (F4/80) and their activation marker CD121b and MHCII (1Ad) were performed by fluorescence-activated cell sorting (FACS analyses). RESULTS: After pancreatitis induction, pancreatic enzymes (amylase: SOP 7008 U/L, NAP 37,044 U/L, P < 0.001) and histologic pancreatic damage (SOP 0.80 ± 1.92, NAP 19.6 ± 0.64, P < 0.001) developed instantly. Pulmonary vascular damage and MPO were detected between 6 and 12 h after onset (6 h albumin SOP 132.0 ± 12.0 µg/mL, NAP 267.2 ± 49.6 µg/mL; P < 0.05; MPO SOP 0.23 ± 0.20 ng/mL, NAP 11.29 ± 3.12 ng/mL, P < 0.01). Blood levels of interleukin 6 increased after 12-24 h (12 h SOP 584 ± 300 pg/mL; NAP 2169 ± 942 pg/mL, P < 0.05), whereas monocytes increased fourfold within 48 h (P < 0.05). Furthermore, pancreatitis increased the percentage of activated monocytes in the blood (6 h and/or 48 h: MHCII (1Ad) 2196%/5.65%; CD121b 51,654%/82,146%). Similar observations were made for monocytes from the liver and spleen. CONCLUSIONS: Although inflammatory mediators increased during 24 h after pancreatitis induction, monocyte activation lasted for at least 48 h. The latter is not limited to blood but also detected in isolated liver and spleen monocytes.

The chemokine ligand CXCL16 is an indicator of bacterial infection in necrotizing pancreatitis.

OBJECTIVES: Current guidelines tell us that intervention in severe necrotizing pancreatitis ought to be performed as late as possible. However, when pancreatic necrosis becomes infected, the necrotic tissue needs to be removed. Unfortunately, bacterial infection can only be proven by invasive methods. METHODS: Necrotizing pancreatitis with sterile or infected necrosis was induced in mice. Mice serum samples were examined by antibody-based protein array. After identifying candidate proteins that showed strong regulation, the serum concentration of these proteins was examined by sandwich ELISA. Then, human serum samples were collected from patients with mild pancreatitis, severe pancreatitis with and without pancreatic necrosis and patients with microbiologically proven infection of pancreatic necrosis. These serum samples were then analyzed by sandwich ELISA. RESULTS: In mice 6 proteins were strongly up-regulated and were further investigated by ELISAs. Of these proteins, CXCL16 and TRANCE (RANKL) concentrations were analyzed in human serum samples. CXCL16 and TRANCE were increased in patients with pancreatic necrosis and abdominal infection. Receiver operated characteristics showed that CXCL16 was superior in predicting infected pancreatic necrosis when compared to C-reactive protein and TRANCE. CONCLUSIONS: Serum CXCL16 is increased in severe pancreatitis with infected pancreatic necrosis and identifies patients who benefit from surgical necrosectomy.