DNA methylation classifier to diagnose pancreatic ductal adenocarcinoma metastases from different anatomical sites.

Background: We have recently constructed a DNA methylation classifier that can discriminate between pancreatic ductal adenocarcinoma (PAAD) liver metastasis and intrahepatic cholangiocarcinoma (iCCA) with high accuracy (PAAD-iCCA-Classifier). PAAD is one of the leading causes of cancer of unknown primary and diagnosis is based on exclusion of other malignancies. Therefore, our focus was to investigate whether the PAAD-iCCA-Classifier can be used to diagnose PAAD metastases from other sites.

Placental growth factor promotes neural invasion and predicts disease prognosis in resectable pancreatic cancer.

Background: Surgery represents the only curative treatment option for pancreatic ductal adenocarcinoma (PDAC), but recurrence in more than 85% of patients limits the success of curative-intent tumor resection. Neural invasion (NI), particularly the spread of tumor cells along nerves into extratumoral regions of the pancreas, constitutes a well-recognized risk factor for recurrence. Hence, monitoring and therapeutic targeting of NI offer the potential to stratify recurrence risk and improve recurrence-free survival.

Surgical Strategies for Combined Hepatocellular-Cholangiocarcinoma (cHCC-CC).

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a tumor entity presenting features of hepatocellular and cholangiocellular epithelial differentiation. Due to the likeness between cHCC-CC, HCC and CC, accurate pretherapeutical diagnosis is challenging and advanced stages are prevalent. Radical oncological surgery is the only curative therapeutical option in patients with cHCC-CC.

Regional hyperthermia with cisplatin added to gemcitabine versus gemcitabine in patients with resected pancreatic ductal adenocarcinoma: The HEAT randomised clinical trial.

Background: Regional hyperthermia (RHT) with cisplatin added to gemcitabine showed efficacy in gemcitabine-pre-treated patients with advanced pancreatic ductal adenocarcinoma. We conducted a randomised clinical trial to investigate RHT with cisplatin added to gemcitabine (GPH) compared with gemcitabine (G) in the adjuvant setting of resected pancreatic ductal adenocarcinoma.

Methods: This randomised, multicentre, open-label trial randomly assigned patients to either GPH (gemcitabine 1000 mg/m on day 1, 15 and cisplatin 25 mg/m with RHT on day 2, 3 and 15,16) or to G (gemcitabine 1000 mg/m on day 1,8,15), four-weekly over six cycles.

Inhibition of Vascular Endothelial Growth Factor Protects against the Development of Oxaliplatin-Induced Sinusoidal Obstruction Syndrome in Wild-Type but Not in CD39-Null Mice.

(1) : Sinusoidal obstruction syndrome (SOS) after oxaliplatin-based chemotherapy is associated with unfavorable outcomes after partial hepatectomy for colorectal liver metastases (CLM). Bevacizumab, a monoclonal antibody against (VEGF), may prevent SOS development. We investigated the impact of VEGF-inhibition on the development of SOS in a murine model.

Current status of robotic surgery for hepato-pancreato-biliary malignancies.

Introduction: Robotic surgery is an emerging aspect of gastrointestinal surgery. Hepato-pancreato-biliary surgery is currently being explored for a broad spectrum of indications, entities, and postoperative outcomes. Noninferiority and financial aspects are the focus of studies.

Progranulin mediates immune evasion of pancreatic ductal adenocarcinoma through regulation of MHCI expression.

Immune evasion is indispensable for cancer initiation and progression, although its underlying mechanisms in pancreatic ductal adenocarcinoma (PDAC) are not fully known. Here, we characterize the function of tumor-derived PGRN in promoting immune evasion in primary PDAC. Tumor- but not macrophage-derived PGRN is associated with poor overall survival in PDAC.

The challenge to differentiate between sarcoma or adrenal carcinoma-an observational study.

Background: Adrenal sarcomas are rare malignant tumors with structural and clinical similarities to sarcomatoid adrenocortical carcinoma. Preoperative diagnosis of tumors of the adrenal gland can be challenging and often misleading thus detaining patients from appropriate oncological strategies.

Objective: This analysis of a case series evaluated the predictive capability of the primary clinical diagnosis in case of malignancies of the adrenal gland.

Development and validity evidence of an objective structured assessment of technical skills score for minimally invasive linear-stapled, hand-sewn intestinal anastomoses: the A-OSATS score.

Introduction: The aim of this study was to develop a reliable objective structured assessment of technical skills (OSATS) score for linear-stapled, hand-sewn closure of enterotomy intestinal anastomoses (A-OSATS).

Materials And Methods: The Delphi methodology was used to create a traditional and weighted A-OSATS score highlighting the more important steps for patient outcomes according to an international expert consensus. Minimally invasive novices, intermediates, and experts were asked to perform a minimally invasive linear-stapled intestinal anastomosis with hand-sewn closure of the enterotomy in a live animal model either laparoscopically or robot-assisted.

Role of extracellular matrix structural components and tissue mechanics in the development of postoperative pancreatic fistula.

Radical resection remains the only curative treatment option in pancreatic cancer. Postoperative pancreatic fistulas (POPF) occur in up to 30% of patients leading to prolonged hospital-stay, increased cost of care and morbidity and mortality. Mechanical properties of the pancreas are associated with POPF.

Cancer Associated Fibroblasts Derived from Pancreatic Adenocarcinoma and Their Role in Cell Migration.

Background/aim: Pancreatic ductal adenocarcinoma (PDAC) shows poor survival and early systemic dissemination. Cancer associated fibroblasts (CAFs) enhance migration and invasion of cancer cells. We aimed to investigate the role of CAFs in cell migration and their underlying paracrine effects.

Mucin-1 Protein Is a Prognostic Marker for Pancreatic Ductal Adenocarcinoma: Results From the CONKO-001 Study.

Background: The Mucin-family protein, MUC1, impacts on carcinogenesis and tumor invasion. We evaluated the impact of MUC1 expression on outcome in a cohort of 158 patients with resected pancreatic ductal adenocarcinomas (PDAC) in the CONKO-001 study (adjuvant gemcitabine [gem] . observation [obs]).

[Surgical treatment of distal cholangiocarcinoma].

Distal cholangiocarcinoma accounts for about 20% of bile duct cancers, representing the third most common tumor entity among periampullary cancers, along with adenocarcinoma of the pancreas and carcinomas of the papilla of Vater. Precise diagnostics of tumor localization and exact knowledge of tumor-specific growth patterns are crucial for successful surgery. When planning the surgical procedure, the differential diagnosis of central bile duct cancer (Bismuth type I) or middle bile duct carcinoma must be considered.

Minimally Invasive Open Ivor-Lewis Esophagectomy for Esophageal Cancer or Cancer of the Gastroesophageal Junction: Comparison of Postoperative Outcomes and Long-term Survival Using Propensity Score Matching Analysis.

Background/aim: Esophagectomy is crucial for achieving long-term survival in patients with esophageal cancer, while being associated with a significant risk of complications. Aiming to reduce invasiveness and morbidity, total minimal-invasive esophagectomy (MIE) has been gradually implemented worldwide. The aim of the study was to compare MIE to open Ivor-Lewis esophagectomy (OE) for esophageal cancer or cancer of the gastroesophageal junction (GEJ), in terms of postoperative and oncological outcomes.

Development of a Novel Dorsal Incision Only Invagination Type Pancreatogastrostomy (Charité-PG) Following Open Pancreaticoduodenectomy-A Single Centre Experience.

The implementation of a pancreatico-enteric anastomosis following open single stage pancreaticoduodenectomy (PD) is still associated with the most threatening complications in modern pancreatic surgery, such as postoperative pancreatic fistula (POPF), postpancreatectomy haemorrhage (PPH), delayed gastric emptying (DGE), intraabdominal abscesses and related mortality. With this study, we introduce Charité-PG, a new dorsal incision only invagination type pancreatogastrostomy (dioPG) for the restoration of the pancreatic remnant following PD, and compare it to a PG requiring ventral gastrotomy (vgPG). A total of 49 consecutive patients, who underwent reconstruction via dioPG, and 92 consecutive patients, who underwent restoration via vgPG, were identified from our prospective database and further reviewed for perioperative parameters, complication rates, mortality and follow-up.

Impact of completeness of adjuvant gemcitabine, relapse pattern, and subsequent therapy on outcome of patients with resected pancreatic ductal adenocarcinoma - A pooled analysis of CONKO-001, CONKO-005, and CONKO-006 trials.

Background: Pancreatic ductal adenocarcinoma (PDAC) represents one of the most fatal malignancies worldwide. It is suggested that survival in PDAC depends, among other things, on pattern of disease recurrence.

Patients And Methods: We performed a pooled analysis of the adjuvant therapy studies CONKO-001, CONKO-005, and CONKO-006, including a total of 912 patients with regard to prognostic factors in patients with recurrent disease.

Postoperative single-sequence (PoSSe) MRI: imaging work-up for CT-guided or endoscopic drainage indication of collections after hepatopancreaticobiliary surgery.

Purpose: Fluid collections due to anastomotic leakage are a common complication after hepatopancreaticobiliary (HPB) surgery and are usually treated with drainage. We conducted a study to evaluate imaging work-up with a postoperative single-sequence (PoSSe) MRI for the detection of collections and indication of drainage.

Material And Methods: Forty-six patients who developed signs of leakage (fever, pain, laboratory findings) after HPB surgery were prospectively enrolled.

Identification and validation of a multivariable prediction model based on blood plasma and serum metabolomics for the distinction of chronic pancreatitis subjects from non-pancreas disease control subjects.

Objective: Chronic pancreatitis (CP) is a fibroinflammatory syndrome leading to organ dysfunction, chronic pain, an increased risk for pancreatic cancer and considerable morbidity. Due to a lack of specific biomarkers, diagnosis is based on symptoms and specific but insensitive imaging features, preventing an early diagnosis and appropriate management.

Design: We conducted a type 3 study for multivariable prediction for individual prognosis according to the TRIPOD guidelines.

Notch Signaling Pathway in Pancreatobiliary Tumors.

The Notch signaling pathway plays an important role both in the development of the ductal systems of the pancreas and the bile ducts as well as in cancer development and progression. The aim of this study was to examine the expression of central proteins of the Notch signaling pathway in pancreatobiliary tumors and its influence on patient survival. We compared the receptors (Notch1, Notch4), activating splicing factors (ADAM17), and target genes (HES1) of the Notch pathway and progenitor cell markers with relevance for the Notch signaling pathway (CD44, MSI1) between pancreatic adenocarcinomas (PDAC, = 14), intrahepatic cholangiocarcinoma (iCC, = 24), and extrahepatic cholangiocarcinoma (eCC, = 22) cholangiocarcinomas via immunohistochemistry and ImageJ software-assisted analysis.

Induction Chemotherapy for Primarily Unresectable Locally Advanced Pancreatic Adenocarcinoma-Who Will Benefit from a Secondary Resection?

An increasing number of patients (pts) with locally advanced pancreatic cancer (LAPC) are treated with an intensive neoadjuvant therapy to obtain a secondary curative resection. Only a certain number of patients benefit from this intention. The aim of this investigation was to identify prognostic factors which may predict a benefit for secondary resection.

Implementation of Robotic Assistance in Pancreatic Surgery: Experiences from the First 101 Consecutive Cases.

Robotic assisted minimally invasive surgery has been implemented to overcome typical limitations of conventional laparoscopy such as lack of angulation, especially during creation of biliary and pancreatic anastomoses. With this retrospective analysis, we provide our experience with the first 101 consecutive robotic pancreatic resection performed at our center. Distal pancreatectomies (RDP, N = 44), total pancreatectomies (RTP, N = 3) and pancreaticoduodenectomies (RPD, N = 54) were included.

Nab-paclitaxel plus gemcitabine versus nab-paclitaxel plus gemcitabine followed by FOLFIRINOX induction chemotherapy in locally advanced pancreatic cancer (NEOLAP-AIO-PAK-0113): a multicentre, randomised, phase 2 trial.

Background: The optimal preoperative treatment for locally advanced pancreatic cancer is unknown. We aimed to compare the efficacy and safety of nab-paclitaxel plus gemcitabine with nab-paclitaxel plus gemcitabine followed by fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) as multidrug induction chemotherapy regimens in locally advanced pancreatic cancer.

Methods: In this open-label, multicentre, randomised phase 2 study, done at 28 centres in Germany, eligible patients were adults (aged 18-75 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1 and histologically or cytologically confirmed, treatment-naive locally advanced pancreatic adenocarcinoma, as determined by local multidisciplinary team review.

The ILLS Laparoscopic Liver Surgery Fellow Skills Curriculum.

Introduction: Laparoscopy is becoming the standard approach in liver surgery. As the degree of difficulty varies greatly from core skills to advanced procedures, strategies for teaching young surgeons need to be reconsidered. We here aimed to design a skills curriculum for LLR.

Tomoelastography for Measurement of Tumor Volume Related to Tissue Stiffness in Pancreatic Ductal Adenocarcinomas.

Objectives: Estimations of tumor volume and boundary in pancreatic ductal adenocarcinoma (PDAC) are crucial for surgery planning. The aim of the study is to evaluate tomoelastography for detection of PDAC and quantification of PDAC volume based on tissue stiffness.

Materials And Methods: From March 2018 to December 2019, a total of 102 participants (30 healthy participants and 72 patients with histologically proven PDAC) were prospectively enrolled in a multicenter study.