Daniel Perez

Beger and Frey Procedures for Treatment of Chronic Pancreatitis: Comparison of Outcomes at 16-Year Follow-Up

BACKGROUNDnChronic pancreatitis is a chronic inflammatory disorder characterized by progressive fibrosis of pancreatic tissue. The principal symptom is chronic pain resulting in reduced quality of life and inability to work. Short-term follow-up has shown that duodenum-preserving pancreatic head resections (DPPHRs) are superior in outcomes to pancreaticoduodenectomy. Therefore, these organ-sparing procedures have gained wide acceptance. This trial was conducted to compare patient outcomes 16 years after treatment for chronic pancreatitis by means of the Beger or the Frey procedure.nnnSTUDY DESIGNnSeventy-four patients suffering from chronic pancreatitis were randomly assigned to 2 treatment groups (Beger n = 38) and Frey (n = 36). The perioperative courses in the randomized controlled trial and the 8-year follow-up have been reported previously. All participating patients were contacted with a standardized, validated questionnaire to evaluate long-term survival, quality of life, pain, and exocrine and endocrine function.nnnRESULTSnNo significant differences between the 2 groups in terms of quality of life, pain control, or other somatic parameters were detected after a median of 16 years postoperatively. Mortality was comparable after Beger and Frey procedures at 39% vs 34%, respectively, with postoperative survivals of 13.0 ± 1.1 years and 13.3 ± 0.9 years, respectively (p = 0.660). No statistically significant differences were found in rates of endocrine insufficiency (Beger 87% vs Frey 86%; p = 0.953) or exocrine insufficiency (Beger 77% vs Frey 83%; p = 0.655).nnnCONCLUSIONSnDuodenum-preserving resections of the pancreatic head offered good and permanent pain relief and substantially increased quality of life in chronic pancreatitis. Overall, a 16-year long-term follow-up found comparable outcomes for the Beger and Frey procedures.

Cyclin D1 is a strong prognostic factor for survival in pancreatic cancer: Analysis of CD G870A polymorphism, FISH and immunohistochemistry

Cyclin D1 is an important regulator protein for the G1‐S cell cycle phase transition. The aim of this trial was to evaluate the impact of the CCND1 polymorphism G870A and corresponding protein expression and CCND1 amplification on the survival of the patients.

Expression of cancer testis antigens CT10 (MAGE-C2) and GAGE in gastrointestinal stromal tumors.

INTRODUCTIONnExpression of cancer testis antigens (CTAs) has been associated with prognosis in gastrointestinal stromal tumors (GIST) and other malignancies. CTAs are currently being investigated for cancer immunotherapy.nnnMATERIALS AND METHODSnWe analyzed two CTAs, CT10/MAGE-C2 and GAGE, in 51 GIST by immunohistochemistry and correlated it with established histopathological criteria for malignancy.nnnRESULTSnGAGE expression was found in 6/51 (12%) patients, whereas 5/51 (10%) patients expressed CT10/MAGE-C2. 7/51(14%) patients expressed at least one of both CTAs, in 4/51 (8%) patients both CTAs were positive. High-grade GIST are more likely to express GAGE (p = 0.002) and CT10/MAGE-C2 (p = 0.007) compared to less aggressive tumors. All patients with GAGE or CT10/MAGE-C2 expression had moderate- or high-risk of recurrence according to the established risk criteria. The presence of GAGE correlates with mitotic rate (p = 0.001) and tumor size (p = 0.02), but not with tumor location (p = 0.60). CT10/MAGE-C2 also significantly correlates with mitotic rate (p = 0.004) and tumor size (p = 0.002), whereas no correlation could be found with tumor location (p = 0.36).nnnDISCUSSIONnCT10/MAGE-C2 and GAGE should be explored together with other previously described CTAs as targets for immunotherapy of GIST in cases, which are refractory to conventional therapy.

Establishment of the First Well-differentiated Human Pancreatic Neuroendocrine Tumor Model

Clinical options for systemic therapy of neuroendocrine tumors (NET) are limited. Development of new drugs requires suitable representative in vitro and in vivo model systems. So far, the unavailability of a human model with a well-differentiated phenotype and typical growth characteristics has impaired preclinical research in NET. Herein, we establish and characterize a lymph node–derived cell line (NT-3) from a male patient with well-differentiated pancreatic NET. Neuroendocrine differentiation and tumor biology was compared with existing NET cell lines BON and QGP-1. In vivo growth was assessed in a xenograft mouse model. The neuroendocrine identity of NT-3 was verified by expression of multiple NET-specific markers, which were highly expressed in NT-3 compared with BON and QGP-1. In addition, NT-3 expressed and secreted insulin. Until now, this well-differentiated phenotype is stable since 58 passages. The proliferative labeling index, measured by Ki-67, of 14.6% ± 1.0% in NT-3 is akin to the original tumor (15%–20%), and was lower than in BON (80.6% ± 3.3%) and QGP-1 (82.6% ± 1.0%). NT-3 highly expressed somatostatin receptors (SSTRs: 1, 2, 3, and 5). Upon subcutaneous transplantation of NT-3 cells, recipient mice developed tumors with an efficient tumor take rate (94%) and growth rate (139% ± 13%) by 4 weeks. Importantly, morphology and neuroendocrine marker expression of xenograft tumors resembled the original human tumor. Implications: High expression of somatostatin receptors and a well-differentiated phenotype as well as a slow growth rate qualify the new cell line as a relevant model to study neuroendocrine tumor biology and to develop new tumor treatments. Mol Cancer Res; 16(3); 496–507. ©2018 AACR.

Evaluation of the germline single nucleotide polymorphism rs583522 in the TNFAIP3 gene as a prognostic marker in esophageal cancer

Most esophageal cancer patients die because of disease relapse, hence an accurate prognosis of disease relapse and survival is essential. Genetic variations in cancer patients may serve as important indicators. Three genotypes (GG, AG, and AA) are displayed by the single nucleotide polymorphism (SNP) rs583522, which maps to the TNFAIP3 gene on chromosome 6. Evaluation of the potential prognostic value of the TNFAIP3-SNP in esophageal cancer (EC) was the aim of this study. A total of 158 patients underwent complete surgical resection of the esophagus for EC. None of them received any neoadjuvant or adjuvant treatment. Peripheral blood was sampled, and genomic DNA was extracted from leukocytes before each operation. Clinicopathologic parameters, tumor cell dissemination in bone marrow, and clinical outcome were correlated with the TNFAIP3-SNP. A-allele carriers showed advanced tumor stages compared with those of homozygous G-allele carriers (P<0.001). Patients with an A-allele genotype (AA or AG) were significantly more likely to experience a relapse (P=0.003). Survival analysis (log-rank test) revealed a significant difference in overall survival between the three groups (P=0.039); however, none of the genotypes was identified as a disease stage-independent prognostic marker. In conclusion, TNFAIP3-SNP stratifies patients into different risk groups; however, it could not be identified as an independent prognostic marker.

HRG|[sol]|HER2|[sol]|HER3 signaling promotes AhR-mediated Memo-1 expression and migration in colorectal cancer

Colorectal cancer (CRC) is a complex disease with still unsatisfactory prognosis even in western societies, although substantial progress has been made in pre-screening programs, surgical techniques and targeted therapy options. Mediator of motility-1 (Memo-1) was previously recognized as an important effector of cell migration downstream of receptor tyrosine kinase signaling in breast cancer. This study identified Memo-1 as frequently overexpressed in CRC and established a close link between extracellular HER2 activation, AhR/ARNT transcriptional activity and Memo-1 expression. Dissection of the hMemo-1 gene promoter using reporter assays and chromatin IP techniques revealed recruitment of Aryl hydrocarbon receptor (AhR)/Aryl hydrocarbon receptor nuclear-translocator (ARNT) complex, which positively influenced Memo-1 expression in cancer cells. We found that Memo-1 depletion negatively influenced the cellular actin network and that its expression is required for HER2-mediated cell migration and invasion. Moreover, analyses of Memo-1 expression in primary CRC revealed correlation with clinical parameters that point to Memo-1 as a new prognostic factor of aggressive disease in CRC patients. Altogether, these observations demonstrate that Memo-1 is an important downstream regulator of HER2-driven CRC cell migration and invasion through connecting extracellular signals from membrane to the cytoskeletal actin network.

Robotic low anterior resection versus transanal total mesorectal excision in rectal cancer: A comparison of 115 cases

BACKGROUNDnRobotic low anterior resection (RLAR) and transanal total mesorectal excision (TaTME) are novel surgical techniques for resection of rectal cancer. To our knowledge, no data exist on direct comparison of these procedures in terms of oncological or functional parameters.nnnMETHODSn60 RLAR and 55 TaTME for rectal cancer were compared in respect to patient characteristics, clinicopathological parameters, intraoperative and perioperative results and anatomopathological outcome.nnnRESULTSn62 surgeries addressed tumors of the lower third (53.9%). No intergroup differences in terms of patient characteristics and clinicopathological parameters were observed. Operating time did not differ between groups (pxa0=xa00.312), nor did the perioperative complication rate (pxa0=xa00.176). Circumferential resection margin was wider in the RLAR than in the TaTME group (pxa0<xa00.001), while no differences were found in the remaining oncological parameters.nnnCONCLUSIONnOur study shows comparable results for RLAR and TaTME in rectal cancer treatment. Both procedures should be considered equally feasible for low rectal cancer cases and as an alternative to conventional anterior resections (open or laparoscopic). Furthermore, both techniques allow excellent oncological outcome especially in patients with anatomical limitations.

Minimally invasive surgery for colorectal cancer remains underutilized in Germany despite its nationwide application over the last decade

Minimally invasive surgery (MIS) has superior short-term outcomes than open surgery (OS) for colorectal cancer (CRC). However, a nationwide dataset has not been analysed to confirm these findings. We evaluated the distribution and outcomes of MIS for CRC from 2005 to 2015; all in-patients with CRC surgery procedure codes were identified from hospital data, which are entered into the nationwide diagnosis-related group database and forwarded anonymised to the Federal Bureau of Statistics. We determined absolute MIS, morbidity, and mortality rates for specific sub-categories, including procedure type. We identified 345,913 in-patient files. The MIS rate increased from 6.4% (nu2009=u20092366; 2005) to 28.5% (nu2009=u20098363; 2015), with the highest rates for sigmoid colon (38%) and rectal (39%) resections. The overall conversion rate was 14.4%, without noticeable improvement over time. International Classification of Disease codes related to postoperative complications were documented more frequently after OS than after MIS. OS was associated with a higher mortality rate (4.7%) than MIS (1.8%) (Pu2009<u20090.001), even after stratifying patients according to the resection site. Use of MIS remains low in Germany compared with that in other European countries. Underutilization of MIS has to be addressed in the future by promoting structured training programs and standardization of laparoscopic surgery.

Robotic cholecystectomy: first experience with the new Senhance robotic system

This retrospective study was performed to evaluate the safety and feasibility of the new Senhance robotic system (Transenterix) for robotic cholecystectomy. Our series is the first experience with cholecystectomies utilizing this new platform. From May 2017 to August 2017, 20 robotic cholecystectomies were performed using the Senhance robotic system. Patients were between 23xa0years and 78xa0years of age, eligible for a laparoscopic procedure with general anesthesia, with no life-threatening co-morbidities that limited the subjects’ life-expectancy to fewer than 12xa0months. A retrospective chart review was performed for a variety of pre-, peri- and postoperative data including, but not limited to patient demographics, intraoperative complications and postoperative complications. 9 male and 11 female patients were included in this study. Median age was 39.5xa0years (range 23–78); median BMI was 27.35xa0kg/m2 (range 22.8–48.3). Median docking time was 10xa0min (range 2–26), and median operative time was 71.5xa0min (range 34–197). Conversion to standard laparoscopy occurred in one case for lysis of extensive adhesions. There were no conversions to open technique. There were no intra- or post-operative complications noted. We report the first series of robotic cholecystectomies using the new Senhance system. Docking time and total operative time decreased significantly over the course of this series and did not plateau; console time did not change significantly. This study demonstrates the feasibility of utilizing this platform in performing minimally invasive cholecystectomies.