Tumor engraftment in patient-derived xenografts of pancreatic ductal adenocarcinoma is associated with adverse clinicopathological features and poor survival

Patient-derived xenograft (PDX) tumors are powerful tools to study cancer biology. However, the ability of PDX tumors to model the biological and histological diversity of pancreatic ductal adenocarcinoma (PDAC) is not well known. In this study, we subcutaneously implanted 133 primary and metastatic PDAC tumors into immunodeficient mice. Fifty-seven tumors were successfully engrafted and even after extensive passaging, the histology of poorly-, moderately-, and well-differentiated tumors was maintained in the PDX models. Moreover, the fibroblast and collagen contents in the stroma of patient tumors were recapitulated in the corresponding PDX models. Analysis of the clinicopathological features of patients revealed xenograft tumor engraftment was associated with lymphovascular invasion (P = 0.001) and worse recurrence-free (median, 7 vs. 16 months, log-rank P = 0.047) and overall survival (median, 13 vs. 21 months, log-rank P = 0.038). Among successful engraftments, median time of growth required for reimplantation into new mice was 151 days. Reflective of the inherent biological diversity between PDX tumors with rapid (<151 days) and slow growth, differences in their growth were maintained during extensive passaging. Rapid growth was additionally associated with lymph node metastasis (P = 0.022). The association of lymphovascular invasion and lymph node metastasis with PDX formation and rapid growth may reflect an underlying biological mechanism that allows these tumors to adapt and grow in a new environment. While the ability of PDX tumors to mimic the cellular and non-cellular features of the parental tumor stroma provides a valuable model to study the interaction of PDAC cells with the tumor microenvironment, the association of successful engraftment with adverse clinicopathological features suggests PDX models over represent more aggressive forms of this disease

Surgical treatment of stage IV gastric cancer: is it worthwhile?

Aim: To analyze clinical features and survival outcomes of patients with surgically-treated stage IV gastric cancer, in order to evaluate the suitability of surgery in these patients.Methods: We performed a systematic literature search using PubMed, MEDLINE, and Embase on October 9th, 2017. Survival outcomes data were collected.Results: The original search returned 2434 papers. Thirty-nine studies were included in the final review, of which 26 evaluated liver metastasis resection, four pulmonary metastasis resections and nine palliative gastrectomies. In total 933 patients underwent hepatectomy for liver metastasis from gastric cancer and median survival rates were 73%, 37% and 27% at 1-, 3- and 5-year respectively, with a median overall survival of 22 months (9-52 months). Data regarding resection of lung metastases were scarce and extremely heterogeneous. In total 1115 patients underwent palliative gastrectomy and median overall survival of patients was 12 months (8-53 months). In the only randomized controlled trial, no survival benefit of additional gastrectomy over chemotherapy alone was found, in contrast with the retrospective studies.Conclusion: Survival benefit of surgery in advanced gastric cancer is still unclear. Surgery may play an important role in highly selected patients. However, further randomized controlled trials are necessary to clarify the actual impact of surgery in these patients

Risk of misdiagnosis and overtreatment in patients with main pancreatic duct dilatation and suspected combined/main-duct intraductal papillary mucinous neoplasms

Segmental/diffuse dilatation of the main pancreatic duct (MPD) is the typical feature of combined/main-duct intraductal papillary mucinous neoplasms (CMD-IPMNs). MPD dilation in IPMNs may be also expression of mucus hypersecretion/obstructive chronic pancreatitis (OCP). The aim of this study was to evaluate the presence and extension of MPD involvement by tumor/OCP and assess the risk of overtreatment

Effective operating room (OR) utilization by performing low-complex surgical procedures during the 2020 corona pandemic

Purpose!#!The SARS-CoV-2 pandemic has almost stopped all elective surgical treatment throughout the world. As operating room (OR) capacities are reduced everywhere to ensure availability of intensive care capacities, especially low-complex surgical procedures are often postponed. These include totally implantable central-venous access ports which are important for the oncologic treatment of cancer patients.!##!Methods!#!In our study, we investigated the potential of an outpatient surgical centre (OSC) in terms of workflow effectiveness compared to the central operating room complex (COR) of a university hospital using low-complex surgical procedures as an example. Data of 524 consecutive patients who received a Port-a-cath procedure (422 implantations (80.5%) and 102 explantations (19.5%)) in our department between February 2019 and February 2020 were evaluated.!##!Results!#!A total of 277 patients were operated in outpatient surgical centre (OSC), and 247 patients received the procedure in the central OR (COR) complex. Grade II and III complications according to the Clavien-Dindo classification occurred in 5.2% (OSC) and 7.3% (COR) of patients. Incision-to-suture time was significantly quicker in the OSC group (36 vs. 42 min., p &amp;lt; 0.032). Total OR time (01:08 vs. 01:20 h) and preparation-to-incision time were also shorter in the OSC group (12 vs. 17 min., p &amp;lt; 0.002).!##!Conclusion!#!In order to ensure effective OR utilization especially in times of the corona pandemic, the use of smaller decentralized OR units, e.g., outpatient surgical centres, for performing low-complex surgical cases is beneficial. Our study revealed shorter total OR and preparation-to-incision times

SUVmax after (18)fluoro-deoxyglucose positron emission tomography/computed tomography: A tool to define treatment strategies in pancreatic cancer

(18)fluoro-deoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) might be a useful tool in the management of pancreatic ductal adenocarcinoma (PDAC)

Arterial Resection for Pancreatic Cancer: Feasibility and Current Standing in a High-Volume Center

Background:. Arterial resection (AR) during pancreatectomy for curative R0 resection of pancreatic ductal adenocarcinoma (PDAC) remains a controversial procedure with high morbidity. Objective:. To investigate the feasibility and oncological outcomes of pancreatectomy combined with AR at a high-volume center for pancreatic surgery. Methods:. We retrospectively analyzed our experience in PDAC patients, who underwent pancreatic resection with AR and/or venous resection (VR) between 2007 and 2021. Results:. In total 259 PDAC patients with borderline resectable (n = 138) or locally advanced (n = 121) PDAC underwent vascular resection during tumor resection. From these, 23 patients had AR (n = 4 due to intraoperative injury, n = 19 due to suspected arterial infiltration). However, 12 out of 23 patients (52.2%) underwent simultaneous VR including 1 case with intraoperative arterial injury. In comparison, 11 patients (47.8%) underwent AR only including 3 intraoperative arterial injury patients. Although the operation time and bleeding rate of patients with AR were respectively longer and higher than in VR, no significant difference was detected in postoperative complications between VR and AR (P = 0.11). The final histopathological findings of PDAC patients were similar, including M stage, regional lymph node metastases, and R0 margin resection. The mortality of the entire cohort was 6.2% (16/259), with a tendency to increase mortality in the AR cohort, yet without statistical significance (VR: 5% vs AR: 21.1%; P = 0.05). Although 19 (82.6%) patients had PDAC in the final histopathology, only 6 were confirmed to have infiltrated arteria. The microscopic distribution of PDAC in these infiltrated arterial walls on hematoxylin-eosin staining was classified into 3 patterns. Strikingly, the perivascular nerves frequently exhibited perineural invasion. Conclusions:. AR can be performed in high-volume centers for pancreatic surgery with an acceptable morbidity, which is comparable to that of VR. However, the likelihood of arterial infiltration seems to be rather overestimated, and as such, AR might be avoidable or replaced by less invasive techniques such as divestment during PDAC surgery

Reappraisal of a 2-Cm Cut-Off Size for the Management of Cystic Pancreatic Neuroendocrine Neoplasms: A Multicenter International Study

MINI: The characteristics of cystic pancreatic neuroendocrine neoplasms (cPanNENs) are largely unknown, and their clinical management remains unclear; specifically, an observational strategy for asymptomatic cPanNENs 642\u200acm has been proposed by recent guidelines, but evidence is scarce and limited to single institutional series. In this international cohort study of 263 resected cPanNENs from 16 institutions worldwide, a preoperative size &gt;2\u200acm was independently associated with aggressive behavior both in the whole cohort and in the subset of asymptomatic patients; notably, only 1 of 61 asymptomatic cPanNENs 642\u200acm was aggressive. Based on these results, a watch-and-wait policy for sporadic asymptomatic cPanNENs 642\u200acm seems justified and safe

Implications of Perineural Invasion on Disease Recurrence and Survival After Pancreatectomy for Pancreatic Head Ductal Adenocarcinoma

OBJECTIVE: To describe PNI and to evaluate its impact on disease-free (DFS) and overall survival (OS) in patients with resected pancreatic ductal adenocarcinoma (PDAC).SUMMARY OF BACKGROUND DATA: Although PNI is a prognostic factor for survival in many GI cancers, there is limited knowledge regarding its impact on tumor recurrence, especially in "early stage disease" (PDAC 6420\u200amm, R0/N0 PDAC).METHODS: This multicenter retrospective study included patients undergoing PDAC resection between 2009 and 2014. The association of PNI with DFS and OS was analyzed using Cox proportional-hazards models.RESULTS: PNI was found in 87% of 778 patients included in the study, with lower rates in PDAC 6420\u200amm (78.7%) and in R0/N0 tumors (70.6%). PNI rate did not differ between patients who underwent neoadjuvant therapy and upfront surgery (88% vs 84%, P = 0.08). Although not significant at multivariate analysis (P = 0.07), patients with PNI had worse DFS at univariate analysis (median DFS: 20 vs 15 months, P &lt; 0.01). PNI was the only independent predictor of DFS in R0/N0 tumors (hazard ratio [HR]: 2.2) and in PDAC 6420\u200amm (HR: 1.8). PNI was an independent predictor of OS in the entire cohort (27 vs 50 months, P = 0.01), together with G3 tumors, pN1 status, carbohydrate antigen (CA) 19.9 &gt;37 and pain.CONCLUSIONS: PNI represents a major determinant of tumor recurrence and patients' survival in pancreatic cancer. The role of PNI is particularly relevant in early stages, supporting the hypothesis that invasion of nerves by cancer cells has a driving role in pancreatic cancer progression