Outcomes in intraductal papillary mucinous neoplasm-derived pancreatic cancer differ from PanIN-derived pancreatic cancer.

BACKGROUND AND AIM: Intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) management is generally extrapolated from pancreatic intraepithelial neoplasia (PanIN)-derived PDAC guidelines. However, these are biologically divergent, and heterogeneity further exists between tubular and colloid subtypes. METHODS: Consecutive upfront surgery patients with PanIN-derived and IPMN-derived PDAC were retrospectively identified from international centers (2000-2019). One-to-one propensity score matching for clinicopathologic factors generated three cohorts: IPMN-derived versus PanIN-derived PDAC, tubular IPMN-derived versus PanIN-derived PDAC, and tubular versus colloid IPMN-derived PDAC. Overall survival (OS) was compared using Kaplan-Meier and log-rank tests. Multivariable Cox regression determined corresponding hazard ratios (HR) and 95% confidence intervals (95% CI). RESULTS: The median OS (mOS) in 2350 PanIN-derived and 700 IPMN-derived PDAC patients was 23.0 and 43.1 months (P < 0.001), respectively. PanIN-derived PDAC had worse T-stage, CA19-9, grade, and nodal status. Tubular subtype had worse T-stage, CA19-9, grade, nodal status, and R1 margins, with a mOS of 33.7 versus 94.1 months (P < 0.001) in colloid. Matched (n = 495), PanIN-derived and IPMN-derived PDAC had mOSs of 30.6 and 42.8 months (P < 0.001), respectively. In matched (n = 341) PanIN-derived and tubular IPMN-derived PDAC, mOS remained poorer (27.7 vs 37.4, P < 0.001). Matched tubular and colloid cancers (n = 112) had similar OS (P = 0.55). On multivariable Cox regression, PanIN-derived PDAC was associated with worse OS than IPMN-derived (HR: 1.66, 95% CI: 1.44-1.90) and tubular IPMN-derived (HR: 1.53, 95% CI: 1.32-1.77) PDAC. Colloid and tubular subtype was not associated with OS (P = 0.16). CONCLUSIONS: PanIN-derived PDAC has worse survival than IPMN-derived PDAC supporting distinct outcomes. Although more indolent, colloid IPMN-derived PDAC has similar survival to tubular after risk adjustment.

Comparison of clinical/histological outcomes according to puncture sites in endoscopic ultrasound-guided fine needle biopsy for large pancreatic masses: Multicenter randomized prospective pilot study.

OBJECTIVES: There are no recommendations regarding the optimal puncture site in endoscopic ultrasound-guided fine needle biopsy (EUS-FNB). This multicenter randomized prospective study compared the diagnostic accuracy and histological findings according to the sampling site for pancreatic masses larger than 3 cm. METHODS: Consecutive patients with pancreatic masses larger than 3 cm indicated for EUS-FNB were included in the study. Patients were randomly assigned to two groups for the initial puncture site (central vs. peripheral sampling of the masses). A minimum of four passes were performed, alternating between the center and the periphery. The primary outcome was diagnostic accuracy. RESULTS: A total of 100 patients were equally divided into the central group and the peripheral group. The final diagnosis revealed malignancy in 95 patients (pancreatic cancer [n = 89], neuroendocrine tumor [n = 4], lymphoma [n = 1], metastatic carcinoma [n = 1]), and benign conditions in five patients (chronic pancreatitis [n = 4], autoimmune pancreatitis [n = 1]). There was no significant difference in diagnostic accuracy between the puncture sites. However, combining samples from both areas resulted in higher diagnostic accuracy (97.0%) compared to either area alone, with corresponding values of 88.0% for the center (P = 0.02) and 85.0% for the periphery (P = 0.006). CONCLUSIONS: Both central sampling and peripheral sampling showed equivalent diagnostic accuracy in detecting malignancy. However, combining samples from both areas generated superior diagnostic yield compared to using either sampling site alone. For pancreatic masses larger than 3 cm, it is advisable to consider sampling from various areas of the masses to maximize the diagnostic yield.

Late Presentation of Recurrent Solid Pseudopapillary Pancreatic Neoplasm With Liver Metastases During Pregnancy.

Our case highlights a rare instance of recurrent metastatic solid pseudopapillary epithelial neoplasms of the pancreas, emerging 8 years after radical pancreatic resection-an extended interval surpassing the reported average. Managing solid pseudopapillary epithelial neoplasm during pregnancy is uniquely challenging, given the increase in the expression of progesterone receptors during the intrapartum period, leading to tumor growth. Although surgical resection remains the primary approach, systemic chemotherapy, radiation therapy, and liver transplant are other considerations. The absence of consensus guidelines for recurrence monitoring emphasizes the need for vigilant, long-term surveillance extending beyond the conventional 5-year mark.

Prognostic impact of aberrant right hepatic artery involvement in patients with pancreatic cancer: A multicenter retrospective cohort study.

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the prognostic value of aberrant right hepatic artery (A-RHA) involvement in patients with pancreatic cancer (PC). METHODS: This study enrolled 474 patients who underwent upfront pancreatectomy or neoadjuvant treatment for resectable (R) or borderline resectable (BR) PC from four institutions. The patients were divided into three groups: A-RHA involvement group (n = 12), patients who had sole A-RHA involvement without major arterial involvement; BR-A group (n = 104), patients who had major arterial involvement; R/BR-PV group (n = 358), others. RESULTS: All patients in the A-RHA involvement group underwent margin-negative resection. The median overall survival of the entire cohort in the A-RHA involvement, R/BR-PV, and BR-A groups was 41.2, 33.5, and 25.2 months, respectively. Although survival in the R/BR-PV group was significantly more favorable than that in the BR-A group (p = 0.0003), no significant difference was observed between the A-RHA involvement group and the R/BR-PV (p = 0.7332) and BR-A (p = 0.1485) groups. CONCLUSIONS: The prognosis of patients with PC and sole A-RHA involvement was comparable to that of patients with R/BR-PV.

Association between pancreatic adenocarcinoma risk and concentration of organochlorine pesticides in adipose tissue and urine: A targeted-screening analysis case-control study (PESTIPAC).

BACKGROUND: Knowledge about environmental pancreatic adenocarcinoma (PA) risk factors, including pesticide exposure, remains limited. Organochlorine (OC) accumulates in adipose tissue and can help reflect long-term exposure. PATIENTS AND METHODS: Age and body mass index (BMI) of patients with PA were matched with those undergoing a surgery for a benign disease on age and BMI (1:1). Targeted analyses screened 345 pesticides and metabolites, including 29 OC, in adipose tissue and urine samples. The primary aim was to investigate the association between organochlorine concentrations in visceral fat or urine, and PA. Adjusted conditional logistic regressions were carried out accounting for multiple testing. RESULTS: Trans-nonachlor (odds ratio [OR] = 1.325, 95% confidence interval [CI] [1.108-1.586]), cis-nonachlor (OR = 15.433, 95% CI [2.733-87.136]), Mirex (OR = 2.853, 95% CI [1.213-6.713]) and 4,4 DDE (OR = 1.019, 95% CI [1.005-1.034]) in fat and a greater number of positive samples (OR = 1.758 95% CI [1.11-2.997]) were significantly associated with higher odds of PA. In contrast, as awaited, urine samples did not yield any statistically significant associations for all tested pesticides. CONCLUSION: Some OCs were associated with higher odds of PA. The underlying mechanisms of pancreatic aggression need to be investigated to refine these findings. TRIAL REGISTRATION: Clinicaltrials.gov NCT04429490.

The Initial Journey of Patients with Metastatic Pancreatic Cancer (PaCTO Project): A Nationwide Survey among Portuguese Specialist Physicians.

Introduction: We aimed to characterize the initial healthcare journey of metastatic pancreatic ductal adenocarcinoma (mPDAC) patients in Portugal, including healthcare provision and factors affecting therapeutic decisions, namely BRCA mutations testing. Methods: This is a descriptive cross-sectional, web-based survey using a convenience sampling approach. Portuguese oncologists and pathologists that routinely work with mPDAC patients from the different geographical regions and settings were invited to participate in the study via email (December 2020). Descriptive statistical analyses were performed, with categorical variables reported as absolute and relative frequencies, and continuous variables with non-normal distribution as median and interquartile range (IQR) (Stata v.15.0). Results: Seventy physicians participated in the study (43 oncologists, 27 pathologists). According to the responses, a median of 28 patients per center (IQR 12-70) was diagnosed with PDAC in the previous year; 22 of them referring (IQR 8-70) to mPDAC. The pointed median time from patients' first hospital admission until disease diagnosis/staging is between 2 and 4 weeks. Endoscopic ultrasound with fine-needle biopsy is available in most hospitals (86%). Around 50% of physicians request BRCA testing; the assessment of additional biomarkers besides BRCA is requested by 40% of professionals. Half of them stated that BRCA testing should be requested earlier-upon histological diagnosis, especially because the median time for results is of 4.0 weeks (IQR 4-8). PARP inhibitors such as olaparib, when available, would be the therapy of choice for most oncologists (71%) if no disease' progression occurs after 4 months. Treatments' selection is usually grounded on clinical criteria (e.g., performance status, liver function). Around 45% of patients use FOLFIRINOX/mFOLFIRINOX as the first-line therapy. Gemcitabine + nab-paclitaxel is used by 35% of patients as the second-line therapy. Conclusions: Physicians in Portugal support the increasing role of patient-tailored treatments in mPDAC, whose selection should be grounded on tumoral subtyping and molecular profiling. Further efforts to develop multidisciplinary teams, standardized clinical practice, and optimize the implementation of new target therapies are needed.

Introdução: Este estudo teve como objetivo caracterizar o percurso inicial dos doentes com adenocarcinoma ductal pancreático metastático (ACDPm) em Portugal, incluindo a prestação de cuidados de saúde e determinação de fatores que afetam as decisões terapêuticas, nomeadamente o teste de mutações BRCA. Métodos: Trata-se de um estudo descritivo transversal (web-based) usando uma abordagem de amostragem por conveniência. Médicos oncologistas e anatomopatologistas portugueses dedicados ao ACDPm e de diferentes regiões geográficas e instituições foram convidados a participar do estudo por email (Dez-2020). Foram realizadas análises estatísticas descritivas, com variáveis categóricas relatadas como frequências absolutas e relativas, e variáveis contínuas com distribuição não-normal como mediana e intervalo interquartil (IIQ) (Stata v.15.0). Resultados: Setenta médicos participaram do estudo (43 oncologistas, 27 patologistas). De acordo com as respostas, uma mediana de 28 doentes por centro (IIQ 12­70) foi diagnosticada com ACDP no ano anterior; 22 deles (IIQ 8­70) referentes a ACDPm. O tempo médio desde a primeira admissão hospitalar dos doentes até o diagnóstico/estadiamento da doença foi entre 2­4 semanas. A ultrassonografia endoscópica com biópsia por agulha fina é realizada pela maioria dos hospitais (86%). Aproximadamente 50% dos médicos referem solicitar o teste BRCA; a avaliação de biomarcadores adicionais além do BRCA é solicitada por 40% dos profissionais. Metade dos médicos assume que o teste BRCA deveria ser solicitado mais precocemente ­ durante o diagnóstico histológico, principalmente porque o tempo médio para obtenção do resultado é de 4,0 semanas (IIQ 4­8). Os inibidores PARP, como o olaparibe, quando disponíveis, seriam a terapia de escolha para a maioria dos oncologistas (71%) caso não haja progressão da doença após quatro meses. A seleção dos tratamentos é usualmente baseada em critérios clínicos (por exemplo, performance status, função hepática). Em cerca de 45% dos doentes é utilizado FOLFIRINOX/mFOLFIRINOX como terapia de primeira linha. Um esquema com Gemcitabina + nab-paclitaxel é usado em 35% dos doentes como terapia de segunda linha. Conclusões: Os médicos em Portugal apoiam o papel crescente do tratamento individualizado no ACDPm, cuja seleção deve ser baseada na subtipagem tumoral e no perfil molecular. São necessários mais esforços para capacitar as equipas multidisciplinares, desenvolver práticas clínicas padronizadas e otimizar a implementação de novas terapias-alvo.

Survival after vascular resections in patients with borderline resectable or locally advanced pancreatic head cancer: A systematic review.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors, and the most common cause of cancer-related deaths. In the past, vascular infiltration of the tumor rendered the disease unresectable. However, today, venous or arterial involvement of a PDAC is classified as borderline resectable (BR) or locally advanced (LA) disease. Pancreaticoduodenectomy (PD) with vascular resections is a promising intervention intended for complete resection of BR- and LA-PDAC. This study aims to assess the overall survival of patients undergoing PD with vascular resections, compared to those without. A PubMed search was conducted for cohort studies that included patients with BR- or LA-PDAC treated with vascular resections. The retrieved publications were screened following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist. The study protocol was registered at the International Prospective Register for Systematic Reviews (PROSPERO). Sixteen cohort studies were included in our systematic review. Fourteen of them included patients undergoing PD with venous-only resections for PDAC. The 5-year overall survival rates ranged from 8.0% to 22.2% for vascular resection patients, and 4.0% to 24.3% for standard PD patients. Three cohorts included patients with PDAC and arterial and/or venous involvement who were treated with arterial resections. Their median overall survival ranged from 13.7 to 17.0 months, similar to that of patients who did not undergo vascular resections. PD with vascular resections in patients with BR- and LA-PDAC could lead to similar overall survival to that after standard PD.

Early postoperative fever as a predictor of pancreatic fistula after pancreaticoduodenectomy: a single-center retrospective observational study.

BACKGROUND: The connection between early postoperative fever and clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy remains unclear. This study aimed to investigate this association and assess the predictive value of early postoperative fever for CR-POPF. METHODS: This retrospective observational study included adult patients who underwent pancreaticoduodenectomy at a tertiary teaching hospital between 2007 and 2019. Patients were categorized into those with early postoperative fever (≥ 38 °C in the first 48 h after surgery) and those without early postoperative fever groups. Weighted logistic regression analysis using stabilized inverse probability of treatment weighting (sIPTW) and multivariable logistic analysis were performed. The c-statistics of the receiver operating characteristic curves were calculated to evaluate the impact on the predictive power of adding early postoperative fever to previously identified predictors of CR-POPF. RESULTS: Of the 1997 patients analyzed, 909 (45.1%) developed early postoperative fever. The overall incidence of CR-POPF among all the patients was 14.3%, with an incidence of 19.5% in the early postoperative fever group and 9.9% in the group without early postoperative fever. Early postoperative fever was significantly associated with a higher risk of CR-POPF after sIPTW (adjusted odds ratio [OR], 1.73; 95% confidence interval [CI], 1.34-2.22; P < 0.001) and multivariable logistic regression analysis (adjusted OR, 1.88; 95% CI, 1.42-2.49; P < 0.001). The c-statistics for the models with and without early postoperative fever were 0.76 (95% CI, 0.73-0.79) and 0.75 (95% CI, 0.72-0.78), respectively, showing a significant difference between the two (difference, 0.02; 95% CI, 0.00-0.03; DeLong's test, P = 0.005). CONCLUSIONS: Early postoperative fever is a significant but not highly discriminative predictor of CR-POPF after pancreaticoduodenectomy. However, its widespread occurrence limits its applicability as a predictive marker.

The impact of myosteatosis on postoperative outcomes and survival of patients undergoing pancreatoduodenectomy for suspected/confirmed malignancy.

Backgrounds/Aims: While the effects of myosteatosis are emerging, the evidence for its use as a predictor of outcomes in patients undergoing pancreatoduodenectomy (PD) still needs to be established. The study aims to evaluate the effect of myosteatosis on the short- and long-term outcomes of PD. Methods: We analyzed the effect of myosteatosis on the short- and long-term outcomes of patients who underwent PD between July 2006 and May 2013. Myosteatosis was measured retrospectively from preoperative computed tomography (CT) at the L3 vertebra level, and dichotomized as a binary exposure variable as < 38.5 Hounsfield unit (HU) for males, and < 36.1 HU for females. Results: A total of 214 patient (median age 62 years, range: 41-80 years) CTs were analyzed for myosteatosis. Overall, 120/214 (56.1%) patients were classed as having myosteatosis. Both groups had similar comorbidity profiles. The presence of myosteatosis was not shown to increase the rate of any short- or long-term complication. However, pancreatic leak (29.8% vs. 13.3%; p = 0.006) and postoperative bleeding (13.8% vs. 5.0%; p = 0.034) were higher in the non-myosteatosis group. The median intensive care (2 days) and hospital stay (12 days) were the same in both groups. The 30-day mortality (myosteatosis: 3.3% vs. non-myosteatosis: 3.2%; p = 0.95), and 5-year overall survival (myosteatosis: 26.7% vs. non-myosteatosis: 31.9%; p = 0.5), were similar in both groups. Conclusions: We have found no evidence supporting myosteatosis affecting either the short-term or long-term outcomes of patients undergoing PD for suspected/confirmed malignant tumors.

Comparing clinical and genomic features based on the tumor location in patients with resected pancreatic cancer.

BACKGROUND: Pancreatic cancer is anatomically divided into pancreatic head and body/tail cancers, and some studies have reported differences in prognosis. However, whether this discrepancy is induced from the difference of tumor biology is hotly debated. Therefore, we aimed to evaluate the differences in clinical outcomes and tumor biology depending on the tumor location. METHODS: In this retrospective cohort study, we identified 800 patients with pancreatic ductal adenocarcinoma who had undergone upfront curative-intent surgery. Cox regression analysis was performed to explore the prognostic impact of the tumor location. Among them, 153 patients with sufficient tumor tissue and blood samples who provided informed consent for next-generation sequencing were selected as the cohort for genomic analysis. RESULTS: Out of the 800 patients, 500 (62.5%) had pancreatic head cancer, and 300 (37.5%) had body/tail cancer. Tumor location in the body/tail of the pancreas was not identified as a significant predictor of survival outcomes compared to that in the head in multivariate analysis (hazard ratio, 0.94; 95% confidence interval, 0.77-1.14; P = 0.511). Additionally, in the genomic analyses of 153 patients, there were no significant differences in mutational landscapes, distribution of subtypes based on transcriptomic profiling, and estimated infiltration levels of various immune cells between pancreatic head and body/tail cancers. CONCLUSIONS: We could not find differences in prognosis and tumor biology depending on tumor location in pancreatic ductal adenocarcinoma. Discrepancies in prognosis may represent a combination of lead time, selection bias, and clinical differences, including the surgical burden between tumor sites.

CTNNB1 exon 3 mutations in metastatic solid pseudopapillary neoplasm of the pancreas.

BACKGROUND AND OBJECTIVES: Solid pseudopapillary neoplasm (SPN) of the pancreas demonstrates an indolent disease course; however, some patients present with a "malignant" phenotype, including distant metastases resistant to chemotherapy. This analysis identifies molecular drivers of metastatic SPN using the world's largest clinicogenomics database. METHODS: The American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange was queried for primary and metastatic SPN samples. Sample-level genomic alterations were compared. A pan-pancreatic cancer analysis assessed relevant mutations among all metastatic pancreatic malignancies. RESULTS: Among 28 SPN samples identified (n = 17 primary, n = 11 metastatic), the most commonly mutated gene was CTNNB1, (24/28 samples; 85.7%). Most mutations were missense (21/24; 87.5%) or in-frame deletions (3/24; 12.5%). The most common CTNNB1 mutations in primary SPN were exon 3 S37F/C missense mutations (6/16 profiled patients, 37.5%), contrasting exon 3 D32N/Y/H missense mutations in metastatic samples (6/11 profiled patients, 54.5%). Metastatic SPN had higher rates of CTNNB1 mutations than metastases from pancreatic ductal adenocarcinoma (72.7% vs. 1.1%; q < 0.0001), pancreatic neuroendocrine tumor (72.7% vs. 2.5%; q < 0.0001), and pancreatic acinar cell carcinoma (72.7% vs. 11.5%; q = 0.0254). CONCLUSIONS: Missense mutations along exon 3 of CTNNB1 predominate metastatic SPN, differentiating these patients from those with metastases from analogous pancreatic malignancies.

Significant Association of PD-L1 With CD44 Expression and Patient Survival: Avenues for Immunotherapy and Cancer Stem Cells Downregulation in Pancreatic Cancers.

Background: Pancreatic cancers are known for their aggressive nature. This aggressiveness may be attributed to the presence of cancer stem cells (CSCs), which promote relapse, metastasis, and resistance to chemotherapy. Targeting CSCs is essential to reverse this aggressiveness in pancreatic malignancies. Literature highlights the association of PD-L1 expression with CSCs in various cancers, suggesting immunotherapy as a promising therapeutic approach. This study is aimed at investigating the potential of immunotherapy in pancreatic cancers by examining its association with selected CSC marker expression. Method: A retrospective cohort study was conducted involving 56 patients with confirmed diagnoses of pancreatic cancers at Aga Khan University Hospital from January 2015 to October 2022. After exclusions, based on refusal to provide consent or incomplete follow-up data, 38 patients were enrolled in the study. Immunohistochemistry was performed on formalin-fixed paraffin-embedded (FFPE) tumor tissue samples to assess the expression of CSC markers (CD133, CD44, and L1CAM) and immune checkpoint inhibitor marker (PD-L1). Statistical analysis was employed to determine associations between marker expression, clinical factors, and overall survival. Results: The study revealed that 86.8% of pancreatic cancer cases exhibited positive PD-L1 expression. Moreover, a significant association of PD-L1 expression was observed with the presence of CD44 protein (p = 0.030), as well as with the overall survival of patients (p = 0.023). Conclusion: Our findings show a significant association of PD-L1 with CD44 marker expression as well as patient survival. This research shows the potential to serve as the foundation for investigating the efficacy of immunotherapy in reducing CD44-expressing CSCs in pancreatic cancer, potentially enhancing patient outcomes.

Pancreas Fine Needle Aspiration: Current and Future Impact on Patient Care.

Pancreatic lesions can be solid or cystic and comprise a wide range of benign, premalignant, and malignant entities. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the current primary sampling method for the preoperative diagnosis of pancreatic lesions. Optimal handling of cytology/small tissue specimens is critical to ensure that the often-scant diagnostic material is appropriately utilized for ancillary and/or molecular studies when appropriate. Ultimately, evaluation of EUS-FNA cytology and small biopsy material can provide accurate and timely diagnoses to guide patient management and triage them to surveillance or surgical intervention.

Liquid-based cytology features of pancreatic acinar cell carcinoma: comparison with other non-ductal neoplasms of the pancreas.

BACKGROUND: Acinar cell carcinoma (ACC) is a rare malignant epithelial neoplasm, which shares many cytomorphological features with other non-ductal pancreatic neoplasms such as pancreatic neuroendocrine neoplasm (PanNEN) and solid-pseudopapillary neoplasm (SPN). Due to the relative rarity of these tumors, pathologists are less familiar with the cytological features, especially on liquid-based cytology (LBC) which has been relatively recently introduced for endoscopic ultrasound-guided fine needle aspiration specimens. METHODS: We evaluated the detailed cytological features of 15 histologically confirmed ACC (7 conventional smears [CS], 8 LBC), and compared them with the LBC features of SPN (n = 9) and PanNEN (n = 9). RESULTS: Compared with CS, LBCs of ACC demonstrated significantly less bloody background. All ACCs demonstrated prominent nucleoli and macronucleoli on LBC. On comparison with the LBC features of SPN and PanNEN, most ACCs demonstrated a necrotic background with apoptotic debris while PanNEN and SPN did not show these features. Acinar structures were predominantly observed in ACC, while frequent pseudopapillary structures were seen only in SPN. Prominent nucleoli and macronucleoli were only seen in ACC. CONCLUSIONS: ACC had characteristic cytological features that could be observed on LBC preparations, such as high cellularity, necrotic/apoptotic background, nuclear tangles, acinar arrangement of cells, and macronucleoli. These findings also help distinguish ACC from PanNEN and SPN on LBC. It is important to be familiar with these features, as an accurate diagnosis on endoscopic ultrasound-guided fine needle aspiration cytology would have impact on the management of the patient.

Clinical course of pancreas cancer diagnosed after spleen-preserving distal pancreatectomy with borderline lesion: two case reports.

Distal pancreatectomy with splenectomy is considered the standard operation for pancreas tail and body cancer. However, splenectomy may be option for benign or low-grade malignant tumors including mucinous cystadenoma and intraductal papillary mucinous neoplasm. If spleen-preserving distal pancreatectomy (SPDP) with borderline lesion is performed and pancreas cancer is diagnosed on postoperative pathologic finding, if it is R0 resection, the necessity of additional splenectomy remains questionable. The authors would like report two clinical cases diagnosed as pancreatic cancer on postoperative pathology after SPDP and under observation without additional splenectomy.

Pancreatoduodenectomy with colon-last approach for advanced pancreatic head cancer.

PURPOSE: Margin-negative surgery is very important in surgical oncology. Considering margin-negative pancreatectomy is known to be essential for cure of the pancreatic cancer, pancreatoduodenectomy with combined venous vascular or arterial resection can be a potential option for margin-negative resection, especially, in era of neoadjuvant treatment with potent systemic chemotherapy. To the contrary, special attention was not paid on combined colonic resection during PD. In this article, safe surgical technique for PD with combined colonic resection is introduced, under the name of PD with "colon-last" approach. METHODS: At Severance Hospital (Yonsei University College of Medicine, Seoul, Republic of Korea), between 2014 and 2021, a total of six patients underwent PD with "colon-last" approach. The surgical technique and surgical outcome are reviewed. RESULTS: All patients recovered without major complications (Clavien-Dindo classification grade ≥ III) after surgery, and most of them recovered after conservative treatment with postoperative pancreatic fistula biochemical leak. None of the patients were readmitted. Only the first and second cases represent cancer-related mortality, and the other patients are still alive and are being followed up. CONCLUSION: It is hoped that the present technique, PD with colon-last approach, could be helpful enhance the procedural safety in treating advanced cancer requiring PD with combined colon resection. However, its technical safety and oncologic role should be validated by many pancreatic surgeons' collaborative studies in the near future.

An international Multi-Institutional validation of T1 Sub-staging of intraductal papillary mucinous neoplasm-derived pancreatic cancer.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) is resected at smaller sizes compared to its biologically distinct counterpart, pancreatic intraepithelial neoplasia (PanIN)-derived PDAC. Thus, experts proposed T1 sub-staging for IPMN-derived PDAC. However, this has never been validated. METHODS: Consecutive upfront surgery patients with IPMN-derived PDAC from five international high-volume centers were classified by the proposed T1 sub-staging classification (T1a ≤ 0.5, T1b > 0.5 and ≤1.0, and T1c >1.0 and ≤2.0 cm) using the invasive component size. Kaplan-Meier and log-rank tests were utilized to compare overall survival (OS). A multivariable Cox-regression was used to determine hazard ratios (HR) with confidence intervals (95%CI). RESULTS: Among 747 patients, 69 (9.2%), 50 (6.7%), 99 (13.0%), and 531 patients (71.1%), comprised the T1a, T1b, T1c, and T2-4 subgroups, respectively. Increasing T-stage was associated with elevated CA19-9, poorer grade, nodal positivity, R1-margin, and tubular subtype. Median OS for T1a, T1b, T1c, and T2-4 were 159.0 (95%CI:126.0-NR), 128.8 (98.3-NR), 77.6 (48.3-108.2), and 31.4 (27.5-37.7) months, respectively (p < .001). OS decreased with increasing T-stage for all pairwise comparisons (all p < .05). After risk-adjustment, age > 65, elevated CA19-9, T1b [HR : 2.55 (1.22-5.32)], T1c [HR : 3.04 (1.60-5.76)], and T2-4 [HR : 3.41 (1.89-6.17)] compared to T1a, nodal positivity, R1-margin, and no adjuvant chemotherapy were associated with worse OS. Disease recurrence was more common in T2-4 tumors (56.4%) compared to T1a (18.2%), T1b (23.9%), and T1c (36.1%, p < .001). CONCLUSION: T1 sub-staging of IPMN-derived PDAC is valid and has significant prognostic value. Advancing T1 sub-stage is associated with worse histopathology, survival, and recurrence. T1 sub-staging is recommended for future guidelines.

In Silico Identification of Dysregulated miRNAs Targeting KRAS Gene in Pancreatic Cancer.

Pancreatic cancer (PC) is highly lethal, with KRAS mutations in up to 95% of cases. miRNAs inversely correlate with KRAS expression, indicating potential as biomarkers. This study identified miRNAs targeting KRAS and their impact on PC characteristics using in silico methods. dbDEMC identified dysregulated miRNAs in PC; TargetScan, miRDB, and PolymiRTS 3.0 identified miRNAs specific for the KRAS gene; and OncomiR evaluated the association of miRNAs with clinical characteristics and survival in PC. The correlation between miRNAs and KRAS was analysed using ENCORI/starBase. A total of 210 deregulated miRNAs were identified in PC (116 overexpressed and 94 underexpressed). In total, 16 of them were involved in the regulation of KRAS expression and 9 of these (hsa-miR-222-3p, hsa-miR-30a-5p, hsa-miR-30b-5p, hsa-miR-30e-5p, hsa-miR-377-3p, hsa-miR-495-3p, hsa-miR-654-3p, hsa-miR-877-5p and hsa-miR-885-5p) were associated with the clinical characteristics of the PC. Specifically, the overexpression of hsa-miR-30a-5p was associated with PC mortality, and hsa-miR-30b-5p, hsa-miR-377-3p, hsa-miR-495-3p, and hsa-miR-885-5p were associated with survival. Correlation analysis revealed that the expression of 10 miRNAs is correlated with KRAS expression. The dysregulated miRNAs identified in PC may regulate KRAS and some are associated with clinically relevant features, highlighting their potential as biomarkers and therapeutic targets in PC treatment. However, experimental validation is required for confirmation.

Emerging role of local treatment in the era of advanced systemic treatment in pancreatic cancer with liver metastasis: A systematic review and meta-analysis.

BACKGROUND: Approximately 50% of pancreatic cancer cases are diagnosed with distant metastases, commonly in the liver, leading to poor prognosis. With modern chemotherapy regimens extending patient survival and stabilizing metastasis, there has been a rise in the use of local treatments. However, the effectiveness for local treatment remains unclear. METHODS: PubMed, Embase, and Cochrane databases were searched for studies reporting the survival outcomes of pancreatic cancer cases with isolated synchronous or metachronous liver metastases who underwent curative-intent local treatment. Hazard ratios were combined using a random-effects model. RESULTS: The full texts of 102 studies were screened, and 14 retrospective studies were included in the meta-analysis. Among patients with synchronous liver metastases, overall survival was significantly better in those who underwent curative-intent local treatment than in those who did not (hazard ratio [HR]: 0.35, 95% confidence interval [CI]: 0.24-0.52). Among patients with metachronous liver metastases, overall survival was also significantly better in those who underwent curative-intent local treatment than in those who did not (HR 0.37, 95% CI: 0.19-0.73). CONCLUSIONS: Curative-intent local treatment may be a feasible option for highly selected pancreatic cancer cases with liver metastases. However, the optimal strategy for local treatments should be explored in future studies.

Evaluating surgeon communication of pancreatic cancer prognosis using the VitalTalk ADAPT framework.

BACKGROUND AND OBJECTIVES: Few data exist to guide optimal communication practices for surgical oncologists. VitalTalk, an evidence-based communication skills training model for clinicians, offers the five-step ADAPT tool for discussing prognosis. This study aimed to characterize surgeon communication of pancreatic cancer prognosis using VitalTalk's ADAPT framework. METHODS: Contemporaneous audio recordings from 12 initial surgeon-patient encounters for borderline resectable pancreatic cancer were transcribed. Directed qualitative content analysis based on ADAPT (Ask, Discover, Anticipate, Provide, and Track) was used to deductively code transcripts. RESULTS: All encounters contained at least one ADAPT step while only one (8%) incorporated four or five steps. Surgeons provided prognostic information (Provide) in all but one encounter (92%); most was qualitative and clustered into themes: serious illness, surgical candidacy, prognostic ambiguity, and cancer recurrence. Surgeons elicited understanding (Ask), requested information preferences (Discover), anticipated ambivalence (Anticipate), and responded to emotion (Track) in a minority of encounters (25%-42%); of 15 patient emotional cues, six were not addressed by surgeons. CONCLUSIONS: During an initial encounter for pancreatic cancer, surgeons focus heavily on providing information but omit critical prognostic communication steps. Future studies are needed to investigate if surgeon training in palliative care-based communication is feasible and impacts patient-perceived quality of communication.