Analysis of the Mechanical Characteristics of Human Pancreas through Indentation: Preliminary In Vitro Results on Surgical Samples

: Pancreatic surgery is extremely challenging and demands an extended learning curve to be executed with a low incidence of post-operative complications. The soft consistency of the human pancreas poses a primary challenge for pancreatic surgeons. This study aimed to analyze the preliminary mechanical characteristics of the human pancreas to develop a realistic synthetic phantom for surgical simulations in the near future. Pancreatic specimens, comprehensive of the pancreatic parenchyma and main pancreatic duct, were collected during pancreatic resections and analyzed through nano-bio-indentation (BioindenterTM UNHT3 Bio, Anton Paar GmbH, Graz, Austria) to measure the elastic modulus. Comparisons were made between slow and fast loading rates, immediate and post-freezing analyses, and multipoint indentations. The results demonstrated that a slow loading rate (30 μN/min), immediate analysis, and multipoint measurements are crucial for obtaining accurate values of the elastic modulus of the human pancreas (1.40 ± 0.47 kPa). In particular, the study revealed that analysis after freezing could impact the outcomes of the indentation. Moreover, the study suggested that both the pancreatic parenchyma and the main pancreatic duct should be analyzed to achieve a more precise and comprehensive definition of the. mechanical features of the pancreas. These preliminary findings represent the initial steps toward defining the consistency and mechanical characteristics of human pancreatic tissue with the goal of creating a realistic synthetic phantom

The Role of Pathological Method and Clearance Definition for the Evaluation of Margin Status after Pancreatoduodenectomy for Periampullary Cancer. Results of a Multicenter Prospective Randomized Trial

Simple SummaryThere is no clear evidence on the most effective method of pathological analysis and clearance definition (0 vs. 1 mm) to define R1 resection after pancreatoduodenectomy (PD). However, several studies showed that the R1 resection is a poor prognostic factor in patients that have undergone PDs for periampullary cancers. In this randomized clinical trial, specimens were randomized with two pathological methods, the Leeds Pathology Protocol (LEEPP) or the conventional method adopted before the study. The 1 mm clearance is the most effective factor in determining R1 rate after PD but only when adopting the LEEP, the R1 resection represents a significant prognostic factor.Background: There is extreme heterogeneity in the available literature on the determination of R1 resection rate after pancreatoduodenectomy (PD); consequently, its prognostic role is still debated. The aims of this multicenter randomized study were to evaluate the effect of sampling and clearance definition in determining R1 rate after PD for periampullary cancer and to assess the prognostic role of R1 resection. Methods: PD specimens were randomized to Leeds Pathology Protocol (LEEPP) (group A) or the conventional method adopted before the study (group B). R1 rate was determined by adopting 0- and 1-mm clearance; the association between R1, local recurrence (LR) and overall survival (OS) was also evaluated. Results. One-hundred-sixty-eight PD specimens were included. With 0 mm clearance, R1 rate was 26.2% and 20.2% for groups A and B, respectively; with 1 mm, R1 rate was 60.7% and 57.1%, respectively (p > 0.05). Only in group A was R1 found to be a significant prognostic factor: at 0 mm, median OS was 36 and 20 months for R0 and R1, respectively, while at 1 mm, median OS was not reached and 30 months. At multivariate analysis, R1 resection was found to be a significant prognostic factor independent of clearance definition only in the case of the adoption of LEEPP. Conclusions. The 1 mm clearance is the most effective factor in determining the R1 rate after PD. However, the pathological method is crucial to accurately evaluate its prognostic role: only R1 resections obtained with the adoption of LEEPP seem to significantly affect prognosis

External validation of three lymph node ratio-based nomograms predicting survival using an international cohort of patients with resected pancreatic head ductal adenocarcinoma.

INTRODUCTION Lymph node ratio (LNR) is an important prognostic factor of survival in patients with pancreatic ductal adenocarcinoma (PDAC). This study aimed to validate three LNR-based nomograms using an international cohort. MATERIALS AND METHODS Consecutive PDAC patients who underwent upfront pancreatoduodenectomy from six centers (Europe/USA) were collected (2000-2017). Patients with metastases, R2 resection, missing LNR data, and who died within 90 postoperative days were excluded. The updated Amsterdam nomogram, the nomogram by Pu et al., and the nomogram by Li et al. were selected. For the validation, calibration, discrimination capacity, and clinical utility were assessed. RESULTS After exclusion of 176 patients, 1'113 patients were included. Median overall survival (OS) of the cohort was 23 months (95% CI: 21-25). For the three nomograms, Kaplan-Meier curves showed significant OS diminution with increasing scores (p < 0.01). All nomograms showed good calibration (non-significant Hosmer-Lemeshow tests). For the Amsterdam nomogram, area under the ROC curve (AUROC) for 3-year OS was 0.64 and 0.67 for 5-year OS. Sensitivity and specificity for 3-year OS prediction were 65% and 59%. Regarding the nomogram by Pu et al., AUROC for 3- and 5-year OS were 0.66 and 0.70. Sensitivity and specificity for 3-year OS prediction were 68% and 53%. For the Li nomogram, AUROC for 3- and 5-year OS were 0.67 and 0.71, while sensitivity and specificity for 3-year OS prediction were 63% and 60%. CONCLUSION The three nomograms were validated using an international cohort. Those nomograms can be used in clinical practice to evaluate survival after pancreatoduodenectomy for PDAC

Effects of Reactive Oxygen Species on Mitochondrial Content and Integrity of Human Anastomotic Colorectal Dehiscence: A Preliminary DNA Study

BACKGROUND: Anastomotic dehiscence is one of the most severe complications of colorectal surgery. Gaining insight into the molecular mechanisms responsible for the development of anastomotic dehiscence following colorectal surgery is important for the reduction of postoperative complications. OBJECTIVE: Based on the close relationship between surgical stress and oxidative stress, the present study aimed to determine whether a correlation exists between increased levels of reactive oxygen species and colorectal anastomotic dehiscence. METHODS: Patients who underwent surgical resection for colorectal cancer were divided into three groups: patients with anastomotic dehiscence (group 1); patients without dehiscence who underwent neoadjuvant radiochemotherapy (group 2); and patients without anastomotic dehiscence who did not undergo neoadjuvant radiochemotherapy (group 3). Quantitative polymerase chain reaction and real-time polymerase chain reaction assays were performed to measure nuclear DNA and mitochondrial DNA (mtDNA) content, and possible oxidative damage to nonmalignant colon and rectal tissues adjacent to the anastomoses. RESULTS: mtDNA content was reduced in the colon tissue of patients in groups 1 and 2. Rectal mtDNA was found to be more damaged than colonic mtDNAs in all groups. The 4977 bp common deletion was observed in the mtDNA of tissues from both the colon and rectum of all patients. DISCUSSION: Patients in groups 1 and 2 were more similar to one another than to group 3, probably due to higher levels of reactive oxygen species in the mitochondria; the greater damage found in the rectum suggests that dehiscence originates primarily from the rectal area. CONCLUSIONS: The present study of mtDNA analyses of normal human colon and rectal tissues from patients with colorectal cancer is among the first of its kind

Integrating metabolic profiling of pancreatic juice with transcriptomic analysis of pancreatic cancer tissue identifies distinct clinical subgroups

IntroductionMetabolic reprogramming is a hallmark feature of pancreatic ductal adenocarcinoma (PDAC). A pancreatic juice (PJ) metabolic signature has been reported to be prognostic of oncological outcome for PDAC. Integration of PJ profiling with transcriptomic and spatial characterization of the tumor microenvironment would help in identifying PDACs with peculiar vulnerabilities.MethodsWe performed a transcriptomic analysis of 26 PDAC samples grouped into 3 metabolic clusters (M_CL) according to their PJ metabolic profile. We analyzed molecular subtypes and transcriptional differences. Validation was performed by multidimensional imaging on tumor slides.ResultsPancreatic juice metabolic profiling was associated with PDAC transcriptomic molecular subtypes (p=0.004). Tumors identified as M_CL1 exhibited a non-squamous molecular phenotype and demonstrated longer survival. Enrichment analysis revealed the upregulation of immune genes and pathways in M_CL1 samples compared to M_CL2, the group with worse prognosis, a difference confirmed by immunofluorescence on tissue slides. Enrichment analysis of 39 immune signatures by xCell confirmed decreased immune signatures in M_CL2 compared to M_CL1 and allowed a stratification of patients associated with longer survival.DiscussionPJ metabolic fingerprints reflect PDAC molecular subtypes and the immune microenvironment, confirming PJ as a promising source of biomarkers for personalized therapy

Body composition parameters, immunonutritional indexes, and surgical outcome of pancreatic cancer patients resected after neoadjuvant therapy: A retrospective, multicenter analysis

Background and aims: Body composition parameters and immunonutritional indexes provide useful information on the nutritional and inflammatory status of patients. We sought to investigate whether they predict the postoperative outcome in patients with pancreatic cancer (PC) who received neoadjuvant therapy (NAT) and then pancreaticoduodenectomy. Methods: Data from locally advanced PC patients who underwent NAT followed by pancreaticoduodenectomy between January 2012 and December 2019 in four high-volume institutions were collected retrospectively. Only patients with two available CT scans (before and after NAT) and immunonutritional indexes (before surgery) available were included. Body composition was assessed and immunonutritional indexes collected were: VAT, SAT, SMI, SMA, PLR, NLR, LMR, and PNI. The postoperative outcomes evaluated were overall morbidity (any complication occurring), major complications (Clavien-Dindo ≥ 3), and length of stay. Results: One hundred twenty-one patients met the inclusion criteria and constituted the study population. The median age at the diagnosis was 64 years (IQR16), and the median BMI was 24 kg/m2 (IQR 4.1). The median time between the two CT-scan examined was 188 days (IQR 48). Skeletal muscle index (SMI) decreased after NAT, with a median delta of −7.8 cm2/m2 (p &lt; 0.05). Major complications occurred more frequently in patients with a lower pre-NAT SMI (p = 0.035) and in those who gained in subcutaneous adipose tissue (SAT) compartment during NAT (p = 0.043). Patients with a gain in SMI experienced fewer major postoperative complications (p = 0.002). The presence of Low muscle mass after NAT was associated with a longer hospital stay [Beta 5.1, 95%CI (1.5, 8.7), p = 0.006]. An increase in SMI from 35 to 40 cm2/m2 was a protective factor with respect to overall postoperative complications [OR 0.43, 95% (CI 0.21, 0.86), p &lt; 0.001]. None of the immunonutritional indexes investigated predicted the postoperative outcome. Conclusion: Body composition changes during NAT are associated with surgical outcome in PC patients who receive pancreaticoduodenectomy after NAT. An increase in SMI during NAT should be favored to ameliorate the postoperative outcome. Immunonutritional indexes did not show to be capable of predicting the surgical outcome