Thoracic Epidural Analgesia Is Not Associated With Improved Survival After Pancreatic Surgery: Long-Term Follow-Up of the Randomized Controlled PAKMAN Trial.

BACKGROUND: Perioperative thoracic epidural analgesia (EDA) and patient-controlled intravenous analgesia (PCIA) are common forms of analgesia after pancreatic surgery. Current guidelines recommend EDA over PCIA, and evidence suggests that EDA may improve long-term survival after surgery, especially in cancer patients. The aim of this study was to determine whether perioperative EDA is associated with an improved patient prognosis compared to PCIA in pancreatic surgery. METHODS: The PAKMAN trial was an adaptive, pragmatic, international, multicenter, randomized controlled superiority trial conducted from June 2015 to October 2017. Three to five years after index surgery a long-term follow-up was performed from October 2020 to April 2021. RESULTS: For long-term follow-up of survival, 109 patients with EDA were compared to 111 patients with PCIA after partial pancreatoduodenectomy (PD). Long-term follow-up of quality of life (QoL) and pain assessment was available for 40 patients with EDA and 45 patients with PCIA (questionnaire response rate: 94%). Survival analysis revealed that EDA, when compared to PCIA, was not associated with improved overall survival (OS, HR, 1.176, 95% HR-CI, 0.809-1.710, P = .397, n = 220). Likewise, recurrence-free survival did not differ between groups (HR, 1.116, 95% HR-CI, 0.817-1.664, P = .397, n = 220). OS subgroup analysis including only patients with malignancies showed no significant difference between EDA and PCIA (HR, 1.369, 95% HR-CI, 0.932-2.011, P = .109, n = 179). Similar long-term effects on QoL and pain severity were observed in both groups (EDA: n = 40, PCIA: n = 45). CONCLUSIONS: Results from this long-term follow-up of the PAKMAN randomized controlled trial do not support favoring EDA over PCIA in pancreatic surgery. Until further evidence is available, EDA and PCIA should be considered similar regarding long-term survival.

Outcomes and risks in palliative pancreatic surgery: an analysis of the German StuDoQ|Pancreas registry.

BACKGROUND: Non-resectability is common in patients with pancreatic ductal adenocarcinoma (PDAC) due to local invasion or distant metastases. Then, biliary or gastroenteric bypasses or both are often established despite associated morbidity and mortality. The current study explores outcomes after palliative bypass surgery in patients with non-resectable PDAC. METHODS: From the prospectively maintained German StuDoQ|Pancreas registry, all patients with histopathologically confirmed PDAC who underwent non-resective pancreatic surgery between 2013 and 2018 were retrospectively identified, and the influence of the surgical procedure on morbidity and mortality was analyzed. RESULTS: Of 389 included patients, 127 (32.6%) underwent explorative surgery only, and a biliary, gastroenteric or double bypass was established in 92 (23.7%), 65 (16.7%) and 105 (27.0%). After exploration only, patients had a significantly shorter stay in the intensive care unit (mean 0.5 days [SD 1.7] vs. 1.9 [3.6], 2.0 [2.8] or 2.1 [2.8]; P < 0.0001) and in the hospital (median 7 days [IQR 4-11] vs. 12 [10-18], 12 [8-19] or 12 [9-17]; P < 0.0001), and complications occurred less frequently (22/127 [17.3%] vs. 37/92 [40.2%], 29/65 [44.6%] or 48/105 [45.7%]; P < 0.0001). In multivariable logistic regression, biliary stents were associated with less major (Clavien-Dindo grade ≥ IIIa) complications (OR 0.49 [95% CI 0.25-0.96], P = 0.037), whereas-compared to exploration only-biliary, gastroenteric, and double bypass were associated with more major complications (OR 3.58 [1.48-8.64], P = 0.005; 3.50 [1.39-8.81], P = 0.008; 4.96 [2.15-11.43], P < 0.001). CONCLUSIONS: In patients with non-resectable PDAC, biliary, gastroenteric or double bypass surgery is associated with relevant morbidity and mortality. Although surgical palliation is indicated if interventional alternatives are inapplicable, or life expectancy is high, less invasive options should be considered.

Outcome Quality After Colorectal Cancer Resection in Certified Colorectal Cancer Centers­Patient-Reported and Short-Term Clinical Outcomes.

BACKGROUND: In this observational study, patient-reported outcomes and short-term clinical outcome parameters in patients with colorectal cancer were studied 12 months after the start of treatment. Outcomes were also compared across German Certified Colorectal Cancer Centres. METHODS: Data were collected from 4239 patients with colorectal cancer who had undergone elective tumor resection in one of 102 colorectal cancer centers and had responded to a quality-of-life questionnaire before treatment (EORTC QLQ-C30 and -CR29). 3142 (74.1%) of these patients completed a post-treatment questionnaire 12 months later. Correlation analyses were calculated and case-mix adjusted comparisons across centers were made for selected patient-reported outcomes, anastomotic insufficiency, and 30-day-mortality. RESULTS: At 12 months, mild improvements were seen in mean quality-of-life scores (66 vs. 62 points), constipation (16 vs. 19), and abdominal pain (15 vs. 17). Worsening was seen in physical function (75 vs. 82) and pain (22 vs. 19). Better patient-reported outcomes at 12 months were associated with better scores before treatment. Better results in at least three of the five scores were associated with male sex, higher educational level, higher age, and private health insurance. Major worsening of fecal incontinence was seen among patients with rectal cancer without a stoma. The largest differences across centers were found with respect to physical function. Anastomotic insufficiency was found in 4.3% of colon cancer patients and 8.2% of rectal cancer patients. 1.9% of patients died within 30 days after their resection. CONCLUSION: Clinicians can use these findings to identify patients at higher risk for poorer patient-reported outcomes. The differences among cancer centers that were found imply that measures for quality improvement would be desirable.

Risk Factor Identification for Delayed Gastric Emptying after Distal Pancreatectomy-An Evaluation of 1688 Patients Based on the German StuDoQ|Pancreas Registry.

Delayed gastric emptying (DGE) ranks as one of the most frequent complications in pancreatic surgery. It leads to increased costs for healthcare systems, lengthened hospital stays and reduced quality of life. Data about DGE after distal pancreatectomy (DP) are scarce. The StuDoQ|Pancreas registry of the German Society of General and Visceral Surgery provided data of patients who underwent distal pancreatectomy from 1 January 2014 to 31 December 2018. The retrospective evaluation included comprehensive data: 1688 patients were enrolled; DGE occurred 160 times (9.5%); grade "A" was reported for 98 (61.3%), grade "B" for 41 (25.6%) and grade "C" for 21 (13.1%) patients. In univariate analysis pancreatic fistulas were associated with higher frequencies of intraabdominal abscesses (9.1% vs. 2%, p > 0.001), postpancreatectomy haemorrhage (8.1% vs. 3.7%, >0.001) and DGE (14.5% vs. 6%, p < 0.001). According to multivariate analysis, "abscesses with invasive therapy" (p < 0.001), "other surgical complications" (p < 0.001), prolonged "stays in ICU" (p < 0.001), lengthened duration of surgery (p < 0.001) and conventional surgery (p = 0.007) were identified as independent risk factors for DGE. Perioperative and postoperative factors were identified as risk factors for DGE. Following research should examine this highly relevant topic in a prospective, register-based manner. As there is no causal therapy for DGE, its avoidance is of major importance.

Proposal of an algorithm for the management of rectally inserted foreign bodies: a surgical single-center experience with review of the literature.

BACKGROUND: Retained rectal foreign bodies (RFBs) are uncommon clinical findings. Although the management of RFBs is rarely reported in the literature, clinicians regularly face this issue. To date, there is no standardized management of RFBs. The aim of the present study was to evaluate our own data and subsequently develop a treatment algorithm. METHODS: All consecutive patients who presented between January 2006 and December 2019 with rectally inserted RFBs at the emergency department of the Klinikum Stuttgart, Germany, were retrospectively identified. Clinicopathologic features, management, complications, and outcomes were assessed. Based on this experience, a treatment algorithm was developed. RESULTS: A total of 69 presentations with rectally inserted RFBs were documented in 57 patients. In 23/69 cases (33.3%), the RFB was removed transanally by the emergency physician either digitally (n = 14) or with the help of a rigid rectoscope (n = 8) or a colonoscope (n = 1). In 46/69 cases (66.7%), the RFB was removed in the operation theater under general anesthesia with muscle relaxation. Among these, 11/46 patients (23.9%) underwent abdominal surgery, either for manual extraction of the RFB (n = 9) or to exclude a bowel perforation (n = 2). Surgical complications occurred in 3/11 patients. One patient with rectal perforation developed pelvic sepsis and underwent abdominoperineal extirpation in the further clinical course. CONCLUSION: The management of RFBs can be challenging and includes a wide range of options from removal without further intervention to abdominoperineal extirpation in cases of pelvic sepsis. Whenever possible, RFBs should obligatorily be managed in specialized colorectal centers following a clear treatment algorithm.

Impact of pylorus preservation on delayed gastric emptying after pancreaticoduodenectomy-analysis of 5,000 patients based on the German StuDoQ|Pancreas-Registry.

BACKGROUND: Delayed gastric emptying (DGE) is one of the most common complications after pancreatic head resection. It leads to increased length of hospital stay, high costs for healthcare systems and reduced quality of life. The primary aim of the study was to assess the impact of pylorus preservation, respectively resection on the occurrence of DGE in patients undergoing pancreaticoduodenectomy (PD). METHODS: All cases of pylorus-resecting PD (PRPD) and pylorus-preserving PD (PPPD) entered in the StuDoQ|Pancreas nationwide registry of the German Society of General and Visceral Surgery from 01/01/2014 until 31/12/2018 including demographics, surgical techniques, histopathological and perioperative data were retrospectively analyzed. This study was approved by the ethics committee of the Ruhr-University Bochum, Germany. RESULTS: Data of 5,080 patients were enrolled. PPPD was the method of choice (70.4%). Pylorus preservation had no impact on the occurrence of DGE (20.3% vs. 21.5%, P=0.33), but further risk factors could be identified. The comparison of PPPD and PRPD groups showed statistically significant differences in the surgical approach (primary open approach, 94.8% vs. 98.0%, P<0.001), duration of surgery (326.4 vs. 352.1 minutes, P<0.001), technique of pancreatic anastomosis (pancreaticojejunostomy vs. pancreaticojejunostomy), 78.6% vs. 85.2%, P<0.001). CONCLUSIONS: Patient factors, intraoperative factors, duration of surgery and postoperative factors (postoperative pancreatic fistula, biliary leakage and other surgical complications) were identified as risk factors for DGE. Future research should focus on register-based, prospective, randomised-controlled studies such as the currently recruiting "PyloResPres trial".

Resveratrol Is a Natural Inhibitor of Human Intestinal Mast Cell Activation and Phosphorylation of Mitochondrial ERK1/2 and STAT3.

Mast cells play a critical role as main effector cells in allergic and other inflammatory diseases. Usage of anti-inflammatory nutraceuticals could be of interest for affected patients. Resveratrol, a natural polyphenol found in red grapes, is known for its positive properties. Here, we analyzed the effects of resveratrol on FcεRI-mediated activation of mature human mast cells isolated from intestinal tissue (hiMC). Resveratrol inhibited degranulation and expression of cytokines and chemokines such as CXCL8, CCL2, CCL3, CCL4, and TNF-α in a dose-dependent manner. Further, resveratrol inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and signal transducer and activator of transcription (STAT) 3. ERK1/2 is known to be involved in cytokine expression of hiMC and to directly interact with STAT3. Mitochondrial STAT3 is phosphorylated by ERK1/2 and contributes to mast cell degranulation. We were able to isolate mitochondrial fractions from small hiMC numbers and could show that activation of mitochondrial STAT3 and ERK1/2 in hiMC was also inhibited by resveratrol. Our results indicate that resveratrol inhibits hiMC activation by inhibiting the phosphorylation of mitochondrial and nuclear ERK1/2 and STAT3, and it could be considered as an anti-inflammatory nutraceutical in the treatment of mast cell-associated diseases.

The transverse coloplasty pouch is technically easy and safe and improves functional outcomes after low rectal cancer resection-a single center experience with 397 patients.

BACKGROUND: Following resection for low rectal cancer, numerous patients suffer from frequent bowel movements, fecal urgency, and incontinence. Although there is good evidence that colonic J-pouch reconstruction, side-to-end anastomosis, or a transverse coloplasty pouch (TCP) improves functional outcome, many surgeons still prefer straight coloanal anastomosis because it is technically easier and lacks the risk of pouch-associated complications. The present single-center study aimed to evaluate the practicability of TCPs in routine clinical practice as well as pouch-related complications. METHOD: All consecutive patients who underwent low anterior rectal resection with restoration of bowel continuity for cancer during the period September 2008 to June 2018 were included. A TCP in combination with a diverting ileostomy was defined as the hospital standard. The feasibility and safety of TCPs were assessed in a retrospective single-center study. RESULTS: A total of 397 patients were included in the study. A total of 328/397 patients underwent TCP construction (82.6%). Two pouch-related surgical complications occurred (0.6%); one case of pouch-related stenosis and one case of sutural insufficiency. Overall, leakage of the coloanal anastomosis was reported in 14.1% of patients with a TCP and in 18.8% of patients without a pouch (p=0.252). Diverting ileostomy was applied in 378/397 patients (95.2%). The 30-day mortality was 0.25%. CONCLUSION: The present study is by far the largest single-center experience with TCP construction for low rectal cancer resection. The study shows that a TCP is technically applicable in the vast majority of cases (82.6%). Pouch-associated surgical complications are sporadic events. In our opinion, the TCP can be considered an alternative to J-pouch construction after low anterior rectal resection.

Preoperative versus pathological staging of rectal cancer-challenging the indication of neoadjuvant chemoradiotherapy.

BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) followed by surgery is recommended for patients with diagnosed rectal cancer UICC stage II/III. The present study aimed to evaluate the accuracy of preoperative staging with focus on tumor infiltration depth and lymph node status challenging the indication of neoadjuvant CRT. METHOD: All consecutive rectal cancer patients who underwent surgical resection without neoadjuvant CRT at the Klinikum Stuttgart, Germany, between January 2015 and December 2018, were included into the study. Clinicopathologic features focusing on preoperative tumor staging and histological outcome were assessed. RESULTS: A total of 100/162 patients (61.7%) underwent primary surgical rectal resection with curative intent. Among these patients, 54/100 had a correct preoperative T-staging, while 34 were overstaged and 12 understaged. With regard to the nodal status, 68 were accurately staged, while 28 were overstaged and 4 understaged. Only 4/40 perirectal lymph nodes of more than 5 mm in diameter in preoperative MRI histologically revealed to be metastasis. CONCLUSION: For patients without neoadjuvant CRT, a tendency to preoperative overstaging was observed. Lymph node size alone did not reliably predict metastasis. According to current guidelines, 21/62 (33.9%) of these patients would have been overtreated by using CRT. On the background of relevant side effects, complications, and the limited benefit of CRT on overall survival, we suggest that primary surgical resection should be recommended more liberally for stages II and III rectal cancer.

Gastrointestinal Complications After Pancreatoduodenectomy With Epidural vs Patient-Controlled Intravenous Analgesia: A Randomized Clinical Trial.

Importance: Morbidity is still high in pancreatic surgery, driven mainly by gastrointestinal complications such as pancreatic fistula. Perioperative thoracic epidural analgesia (EDA) and patient-controlled intravenous analgesia (PCIA) are frequently used for pain control after pancreatic surgery. Evidence from a post hoc analysis suggests that PCIA is associated with fewer gastrointestinal complications. Objective: To determine whether postoperative PCIA decreases the occurrence of gastrointestinal complications after pancreatic surgery compared with EDA. Design, Setting, and Participants: In this adaptive, pragmatic, international, multicenter, superiority randomized clinical trial conducted from June 30, 2015, to October 1, 2017, 371 patients at 9 European pancreatic surgery centers who were scheduled for elective pancreatoduodenectomy were randomized to receive PCIA (n = 185) or EDA (n = 186); 248 patients (124 in each group) were analyzed. Data were analyzed from February 22 to April 25, 2019, using modified intention to treat and per protocol. Interventions: Patients in the PCIA group received general anesthesia and postoperative PCIA with intravenous opioids with the help of a patient-controlled analgesia device. In the EDA group, patients received general anesthesia and intraoperative and postoperative EDA. Main Outcomes and Measures: The primary end point was a composite of pancreatic fistula, bile leakage, delayed gastric emptying, gastrointestinal bleeding, or postoperative ileus within 30 days after surgery. Secondary end points included 30-day mortality, other complications, postoperative pain levels, intraoperative or postoperative use of vasopressor therapy, and fluid substitution. Results: Among the 248 patients analyzed (147 men; mean [SD] age, 64.9 [10.7] years), the primary composite end point did not differ between the PCIA group (61 [49.2%]) and EDA group (57 [46.0%]) (odds ratio, 1.17; 95% CI, 0.71-1.95 P = .54). Neither individual components of the primary end point nor 30-day mortality, postoperative pain levels, or intraoperative and postoperative substitution of fluids differed significantly between groups. Patients receiving EDA gained more weight by postoperative day 4 than patients receiving PCIA (mean [SD], 4.6 [3.8] vs 3.4 [3.6] kg; P = .03) and received more vasopressors (46 [37.1%] vs 31 [25.0%]; P = .04). Failure of EDA occurred in 23 patients (18.5%). Conclusions and Relevance: This study found that the choice between PCIA and EDA for pain control after pancreatic surgery should not be based on concerns regarding gastrointestinal complications because the 2 procedures are comparable with regard to effectiveness and safety. However, EDA was associated with several shortcomings. Trial Registration: German Clinical Trials Register: DRKS00007784.

Indications for resection and perioperative outcomes of surgery for pancreatic neuroendocrine neoplasms in Germany: an analysis of the prospective DGAV StuDoQ|Pancreas registry.

PURPOSE: Pancreatic neuroendocrine neoplasms (pNENs) are rare, and their surgical management is complex. This study evaluated the current practice of pNEN surgery across Germany, including its adherence with guidelines and its perioperative outcomes. METHODS: Patients who underwent surgery for pNENs (April 2013-June 2017) were retrieved from the prospective StuDoQ|Pancreas registry of the German Society of General and Visceral Surgery and retrospectively analyzed. RESULTS: A total of 287 patients (53.7% male) with a mean age of 59.2 ± 14.2 years old underwent pancreatic resection for pNENs. Tumors were localized in the pancreatic head (40.4%), body (23%), or tail (36.6%). A total of 239 (83.3%) patients underwent formal resection with lymphadenectomy, 40 (14%) parenchyma-sparing resection, and 8 (2.8%) only exploration. Fifty (17.4%) patients underwent a minimally invasive approach. Among the 245 patients with complete pathological information, 42 (17.1%) had distant metastases, 78 (31.8%) had stage I tumors, 74 (30.2%) stage II, and 51 (20.8%) stage III. A total of 112 (45.7%) patients had G1 tumors, 101 (41.2%) G2, and 24 (9.8%) G3. Nodal involvement on imaging was an independent predictor of lymph node metastasis according to the multivariable analysis (odds ratio: 0.057; 95% confidence interval: 0.016-0.209; p < 0.01). R0 resection was reported in 240 (83.6%) patients. The 30- and 90-day mortality rates were 2.8% and 4.2%, respectively. CONCLUSION: In Germany the rate of potential curative resection for pNEN is high. However, formal pancreatic resection seems to be overrepresented, while minimally invasive resection is underrepresented.

Intraductal tubular papillary neoplasm (ITPN), a novel entity of pancreatic epithelial neoplasms and precursor of cancer: A case report and review of the literature.

BACKGROUND: Intraductal tubular papillary neoplasm (ITPN) displays a very rare subtype of epithelial neoplasms of the pancreas. ITPN is characterized by intraductal tubulopapillary growth and cellular dysplasia. In contrast to intraductal papillary neoplasm (IPMN) no overt epithelial mucin production is observed. To date, little is known about ITPN and particularly about pancreatic cancer arising in this tumor entity. CASE PRESENTATION: A 68-year-old male presented at our hospital with a distal bile duct occlusion suspicious for adenocarcinoma of the pancreatic head. Preoperative staging revealed no signs of distant metastasis. The patient was surgically explored and pylorus preserving duodenopancreatectomy was performed for a solid pancreatic head tumor. Final histopathology surprisingly revealed an ITPN with an associated invasive carcinoma pT3, pN0 (0/12), R0, G2. DISCUSSION: Patients with ITPN frequently present with jaundice suspicious for a bile duct stenosis or a malignant tumor of the pancreatic head. Although, it is possible to diagnose ITPN by endoscopic retrograde cholangiopancreaticography, many tumors are found not before histopathological examination. Differential diagnosis includes ductal adenocarcinoma of the pancreas, neuroendocrine tumors, IPMN, distal bile duct tumors, and solid pseudopapillary neoplasms. Using immunohistochemistry, other entities of pancreatic tumors can be ruled out. In case of R0 resection oncological prognosis is described to be more favorable when compared to regular ductal adenocarcinoma. CONCLUSION: ITPN displays a rare entity of pancreatic neoplasms. As shown in the present case report, there is a relevant potential of malignant transformation and therefore radical surgical resection and oncologic follow-up is warranted.

Nobiletin acts anti-inflammatory on murine IL-10-/- colitis and human intestinal fibroblasts.

PURPOSE: Inflammatory bowel disease (IBD) shows increasing prevalence over the last years. We propose that anti-inflammatory plant substances could be used as additional or alternative agents with good compliance in prevention and/or therapy of IBD and its complication intestinal fibrosis. We could recently show that the citrus flavonoid nobiletin acts anti-inflammatory on activation of intestinal mast cells. Here, we analysed the effects of nobiletin on inflammation and fibrosis in IL-10-/- colitis. METHODS: IL-10-/- and wild-type (WT) mice were orally treated with/without vehicle or nobiletin. Clinical symptoms of colitis and disease activity index (DAI) were assessed, and colon tissue was analysed for tissue damage, cellular infiltration, bowel wall thickness, mast cell number and degranulation, as well as collagen deposition as marker for fibrosis. Human intestinal fibroblasts (hiFB) were treated with nobiletin and the expression of collagen and pro-inflammatory cytokines was measured. RESULTS: Nobiletin treatment of IL-10-/- mice resulted in a reduction of clinical colitis symptoms and a longer survival time. In addition, histological scores of colitis were reduced compared to control groups. Mast cell number and degranulation was lower in nobiletin treated IL-10-/- mice, and correlated positively with DAI. As well, fibrotic marker of collagen deposition was reduced by nobiletin. In hiFB, the expression of collagen as well as of pro-inflammatory cytokines IL-6, TNF and CCL2 was down-regulated by nobiletin treatment. CONCLUSIONS: Nobiletin decreases inflammatory symptoms and markers in murine colitis as well as fibrotic collagen deposition and expression. Thus, nobiletin could be a potential new agent in therapy of chronic colitis.

Implementation of Current ENETS Guidelines for Surgery of Small (≤2 cm) Pancreatic Neuroendocrine Neoplasms in the German Surgical Community: An Analysis of the Prospective DGAV StuDoQ|Pancreas Registry.

BACKGROUND: ENETS guidelines recommend parenchyma-sparing procedures without formal lymphadenectomy, ideally with a minimally invasive laparoscopic approach for sporadic small pNENs (≤2 cm). Non-functioning (NF) small pNENs can also be observed. The aim of the study was to evaluate how these recommendations are implemented in the German surgical community. METHODS: Data from the prospective StuDoQ|Pancreas registry of the German Society of General and Visceral Surgery were analyzed regarding patient's demographics, tumor characteristics, surgical procedures, histology and perioperative outcomes. RESULTS: Eighty-four (29.2%) of 287 patients had sporadic pNENs ≤2 cm. Forty-three (51.2%) patients were male, and the mean age at diagnosis was 58.8 ± 15.6 years. Twenty-five (29.8%) pNENs were located in the pancreatic head. The diagnosis pNEN was preoperatively established in 53 (65%) of 84 patients. Sixty-two (73.8%) patients had formal pancreatic resections, including partial pancreaticoduodenectomy or total pancreatectomy (21.4%). Only 22 (26.2%) patients underwent parenchyma-sparing resections and 23 (27.4%) patients had minimally invasive procedures. A lymphadenectomy was performed in 63 (75.4%) patients, and lymph node metastases were diagnosed in 6 (7.2%) patients. Eighty-two (97.7%) patients had an R0 resection. Sixty (72%) tumors were classified G1, 24 (28%) tumors G2. Twenty-seven (32.2%) of 84 patients had postoperative relevant Clavien-Dindo grade ≥3 complications. Thirty- and 90-day mortalities were 2.4% and 3.6%. CONCLUSIONS: ENETS guidelines for surgery of small pNENs are yet not well accepted in the German surgical community, since the rate of formal resections with standard lymphadenectomy is high and the minimally invasive approach is underused. The attitude to operate small NF tumors seems to be rather aggressive.

Pylorus drainage procedures in thoracoabdominal esophagectomy - a single-center experience and review of the literature.

BACKGROUND: Pylorotomy and pyloroplasty in thoracoabdominal esophagectomy are routinely performed in many high-volume centers to prevent delayed gastric emptying (DGE) due to truncal vagotomy. Currently, controversy remains regarding the need for these practices. The present study aimed to determine the value and role of pyloric drainage procedures in esophagectomy with gastric replacement. METHODS: A retrospective review of prospectively collected data was performed for all consecutive patients who underwent thoracoabdominal resection of the esophagus between January 2009 and December 2016 at the Katharinenhospital in Stuttgart, Germany. Clinicopathologic features and surgical outcomes were evaluated with a focus on postoperative nutrition and gastric emptying. RESULTS: The study group included 170 patients who underwent thoracoabdominal esophageal resection with a gastric conduit using the Ivor Lewis approach. The median age of the patients was 64 years. Most patients were male (81%), and most suffered from adenocarcinoma of the esophagus (75%). The median hospital stay was 20 days, and the 30-day hospital death rate was 2.9%. According to the department standard, pylorotomy, pyloroplasty, or other pyloric drainage procedures were not performed in any of the patients. Overall, 28/170 patients showed clinical signs of DGE (16.5%). CONCLUSIONS: In the literature, the rate of DGE after thoracoabdominal esophagectomy is reported to be approximately 15%, even with the use of pyloric drainage procedures. This rate is comparable to that reported in the present series in which no pyloric drainage procedures were performed. Therefore, we believe that pyloric drainage procedures may be unwarranted in thoracoabdominal esophagectomy. However, future randomized trials are needed to ultimately confirm this supposition.

Resection of benign side-branch intraductal papillary mucinous neoplasm of the pancreas-is long term follow-up indicated?: A case report and review of the literature.

RATIONALE: Intraductal papillary mucinous neoplasms of the pancreas (IPMNs) are benign cystic tumors with a relevant risk of malignant transformation over time. Currently, follow-up after surgical resection of benign IPMNs remains controversial. PATIENT CONCERNS: This is a case report of a 68-year-old male who underwent pancreatic head resection for a multicystic side-branch IPMN with low-grade epithelial dysplasia in March 2009 at the Katharinenhospital Stuttgart, Germany. DIAGNOSES: During postoperative follow-up, a new solid, slightly hypodense lesion in the tail of the pancreas measuring 2.4 cm in diameter was diagnosed in July 2016. Preoperative staging revealed no signs of distant metastasis. INTERVENTION: Subsequently, the patient underwent pancreatic tail resection including splenectomy. Histology revealed IPMN-associated adenocarcinoma of the pancreas pT3, pN1 (2/24), M0, R0. OUTCOMES: Patients with IPMN bare a relatively high overall risk of developing pancreatic cancer. The 5-year incidence has been described to be as high as 6.9%. The current Consensus-Guidelines therefore recommend a structural life-time follow-up. In contrast, in 2015 the American Gastroenterological Association (AGA) explicitly states that follow-up is not recommended for resected benign IPMN. Currently, a general and international consensus is lacking. LESSONS: The presented case demonstrates that even more than 5 years following resection of benign IPMN, pancreatic cancer can occur in a separate location of the pancreatic gland. We believe that IPMNs can be considered as indicator lesions for pancreatic cancer. Patients with resected side-branch IPMN should therefore undergo long term follow-up.

Cinnamon reduces inflammatory response in intestinal fibroblasts in vitro and in colitis in vivo leading to decreased fibrosis.

SCOPE: Intestinal fibrosis, a complication of inflammatory bowel disease, is currently being addressed by surgery alone, with no adequate alternative therapy available for patients. We propose that anti-inflammatory plant substances like cinnamon extract (CE) or its main compound cinnamaldeyde (CA) could aid in therapy. We recently found CE reducing inflammation in murine colitis. Here, we analyzed effects of CE on fibrosis in IL-10-/- colitis. METHODS AND RESULTS: IL-10-/- and wild-type (WT) mice were orally treated with/without vehicle or CE. Colonic tissue was analyzed for collagen deposition and expression of matrix metalloproteinases (MMPs). Influence of CE or CA on expression and release of cytokines, and phosphorylation of IκB in LPS-activated fibroblasts was assessed. Fibrosis score and mRNA expression of MMPs were down-regulated in colonic tissue of CE-treated IL-10-/- mice. Fibroblasts treated with CE or CA showed reduced expression and release of IL-6, KC/C-X-C motif ligand (CXCL) 8, and C-C motif ligand (CCL) 2 in response to LPS-treatment. CE and CA appear to act via reducing phosphorylation of IκB. CONCLUSIONS: Cinnamon decreases fibrotic symptoms and markers in murine colitis, and expression of inflammatory and fibrotic markers in hiFB. Thus, CE and CA could be potential anti-fibrotic agents in chronic colitis.

Laparoscopic versus open distal pancreatectomy-a propensity score-matched analysis from the German StuDoQ|Pancreas registry.

PURPOSE: The aim of this study was to assess intraoperative, postoperative, and oncologic outcome in patients undergoing laparoscopic distal pancreatectomy (LDP) versus open distal pancreatectomy (ODP) for benign and malignant lesions of the pancreas. METHODS: Data from patients undergoing distal pancreatic resection were extracted from the StuDoQ|Pancreas registry of the German Society for General and Visceral Surgery. After propensity score case matching, groups of LDP and ODP were compared regarding demography, comorbidities, operative details, histopathology, and perioperative outcome. RESULTS: At the time of data extraction, the StuDoQ|Pancreas registry included over 3000 pancreatic resections from over 50 surgical departments in Germany. Data from 353 patients undergoing ODP (n = 254) or LDP (n = 99) from September 2013 to February 2016 at 29 institutions were included in the analysis. Baseline data showed a strong selection bias in LDP patients, which disappeared after 1:1 propensity score matching. A comparison of the matched groups disclosed a significantly longer operation time, higher rate of spleen preservation, more grade A pancreatic fistula, shorter hospital stay, and increased readmissions for LDP. In the small group of patients operated for pancreatic cancer, a lower lymph node yield with a lower lymph node ratio was apparent in LDP. CONCLUSIONS: LDP needed more time but potential advantages include increased spleen preservation and shorter hospital stay, as well as a trend for less transfusion, ventilation, and mortality. LDP for pancreatic cancer was performed rarely and will need critical evaluation in the future. Data from a prospective randomized registry trial is needed to confirm these results.

Duodenum-preserving pancreatic head resection: 10-year follow-up of a randomized controlled trial comparing the Beger procedure with the Berne modification.

BACKGROUND: Since the introduction of the duodenum-preserving pancreatic head resection for operative treatment of chronic pancreatitis, various modifications of the original Beger procedure have emerged. A randomized controlled trial comparing the Beger procedure and the Berne modification indicated that the latter is an equivalent alternative, but a comparison of the long-term results of both procedures has not yet been published. METHODS: Between December 2002 and January 2005, 65 patients were randomized intraoperatively to the Beger or the Berne procedure. For this 10-year follow-up, patients were contacted by phone and in writing to evaluate patient-relevant outcome parameters. Statistical analysis was made on an intention-to-treat basis. RESULTS: Median follow-up was 129 (111-137) months. Forty of 65 patients were available for follow-up; 11 of the original study cohort had died, and 14 were otherwise lost to follow-up. Quality of life, pain, occupational disability, exocrine and endocrine pancreatic function, endoscopic interventions, and redo operations were comparable in both groups. More than half of the patients were completely free of pain, and the majority in both groups judged that the index operation had improved their quality of life. CONCLUSION: Ten-year follow-up showed no differences in patient-relevant outcome parameters between the Beger and Berne procedures for treatment of chronic pancreatitis. Because short-term results have shown the Berne modification is superior in terms of operation time and duration of hospital stay, it should be preferred whenever possible, depending on the individual surgeon's expertise and the intraoperative findings.

The TICAP-Study (titanium clips for appendicular stump closure): A prospective multicentre observational study on appendicular stump closure with an innovative titanium clip.

BACKGROUND: To evaluate the effectiveness and safety of the DS Titanium Ligation Clip for appendicular stump closure in laparoscopic appendectomy. METHODS: Overall, 502 patients undergoing laparoscopic appendectomy were recruited for this observational multicentre study in nine study centres between October 2011 and July 2013. The clip was finally applied in 390 patients. Primary outcome variables were feasibility of the clip, intra-abdominal surgical site (abscesses, stump leakages) and superficial wound infections. Patients were followed 30 days after surgery. RESULTS: The clip was applicable in nearly 80 % of patients. Reasons for not applying the clip were mainly an inflamed caecum or a too large diameter of the appendix base. Superficial wound infections were found in nine (2.31 %), intra-abdominal abscesses in five (1.28 %), appendicular stump leak in one (0.26 %), and other adverse events in 22 (5.64 %) patients. In total, 12 (3.08 %) patients were re-admitted to hospital for treatment. Seven re-admissions were surgery-related; ten (2.56 %) patients had to be re-operated. One patient died during the course of the study due to persisting peritonitis (mortality 0.26 %). CONCLUSIONS: The results suggest that the DS Titanium Ligation Clip is a safe and effective option in securing the appendicular stump in laparoscopic appendectomy. The complication rates found with the use of the DS-Clip are comparable to the rates in the literature when other methods are used. TRIAL REGISTRATION: NCT01734837 .