Prevalence and spectrum of germline pathogenic variants in cancer susceptibility genes among mexican patients with exocrine pancreatic cancer.

BACKGROUND: Although universal germline genetic testing is recommended for patients with exocrine pancreatic cancer (PC), access to genetic testing remains limited in low- and middle-income countries. This study aims to narrow the gap in our understanding of the spectrum of germline pathogenic and likely pathogenic variants (PVs) in cancer susceptibility genes in the Mexican population. METHODS: The landscape of PVs in cancer susceptibility genes was identified by next-generation sequencing multigene panel assays among patients with PC who were enrolled in the Clinical Cancer Genomics Community Research Network prospective registry in Mexico City. RESULTS: From August 2019 to April 2023, 137 patients underwent genetic testing. The median age at diagnosis was 60 years (range 36-85), 58.4 % were women, and 38.7 % were metastatic at diagnosis. The frequency of germline PVs was 16 % (n = 22): ATM 36.4 % (n = 8), CDKN2A/p16INK4A 27.3 % (n = 6), BRCA2 9.1 % (n = 2), PALB2 9.1 % (n = 2), CHEK2 9.1 % (n = 2), TP53 4.5 % (n = 1), and NF1 4.5 % (n = 1). Additionally, 2 carriers of monoallelic germline variants in MUTYH were identified. No significant differences were observed between carriers and non-carriers in terms of family history of pancreatic cancer. CONCLUSIONS: We identified a significant frequency of actionable germline PVs in Mexicans with PC, wherein the majority were in a broad spectrum of genes associated with the homologous recombination DNA repair mechanism. Most pancreatic cancer associated PVs were detected in non-BRCA genes, so our findings support the recommendation of multigene panel testing for genetic cancer risk assessment of Mexican individuals with PC.

Clear cell sarcoma of the pancreas, an unusual cancer with unusual metastatic site or unusual primary site?

Clear cell sarcoma (CCS) is a type of malignant tumor that can arise from tendons and aponeuroses. This malignant proliferation of cells with melanocytic lineage normally occurs in young patients, and it is normally identified in extremities. However, different sites including gastrointestinal organs are also described. Due difficulties in the molecular and histopathology evaluation, the diagnosis is often confused with malignant melanoma. Most cases are treated with surgical resection, but overall, the prognosis is poor. In this editorial, we will discuss a very interesting case of CCS identified in the pancreas. We will discuss the literature and controversies in the management of this type of cancer. Furthermore, we will address molecular strategies to be incorporated in those cases to better understand the primary location of the tumor. Finally, future perspectives of the field and new strategies of treatment will be described.

Concomitant or antecedent intraductal papillary mucinous neoplasm is not a prognostic factor in resected pancreatic cancer.

Background: Intraductal papillary mucinous neoplasm (IPMN)-associated pancreatic cancer is becoming a common subtype of pancreatic cancer found in resected specimens. The prognostic of this subtype is still under evaluation. The study aims to evaluate the prognosis of IPMN-associated pancreatic adenocarcinoma compared to the conventional pancreatic adenocarcinoma. Methods: In this study, patients with resected pancreatic neoplasms and IPMN treated at Hospital Israelita Albert Einstein, from January 2016 to December 2020, were analyzed. Overall survival (OS) was estimated using the Kaplan-Meier method, and correlations between the variables of interest and the disease specific OS was assessed by multivariate analysis. Results: Of 187 patients undergoing resection for pancreatic adenocarcinoma or IPMN, 125 (67%) had pancreatic adenocarcinoma, 33 (18%) had IPMN-associated pancreatic adenocarcinoma, and 29 (16%) had IPMN. Resected IPMN was associated with long-term OS for most of the patients. Similar OS was identified in this study in upfront resected pancreatic cancer associated or not with IPMN. No statistical differences in median OS were identified between resected pancreatic adenocarcinoma and IPMN-associated pancreatic adenocarcinoma (48 vs. 44 months, P=0.44). Size of the tumor [hazard ratio (HR), 1.33], resected stage III (HR, 1.31), perineural invasion (HR, 1.58), lymphovascular invasion (HR, 1.44), positive lymph nodes (HR, 1.34), and neoadjuvant treatment (HR, 1.70) were associated with worse outcomes. Conclusions: Our findings confirm that resected pancreatic cancer has a poor prognosis and IPMN-associated pancreatic adenocarcinoma has the same prognosis as a conventional pancreatic adenocarcinoma. More than half of the cases of IPMN-associated adenocarcinoma already had positive lymph nodes. The impact of neoadjuvant treatment in this group of patients should be investigated in larger cohorts.

Prevalence of germline variants in Brazilian pancreatic carcinoma patients.

We evaluated the prevalence of pathogenic/likely pathogenic germline variants (PGV) in Brazilian pancreatic adenocarcinoma (PC) patients, that represent a multiethnic population, in a cross-sectional study. We included 192 PC patients unselected for family history of cancer. We evaluated a panel of 113 cancer genes, through genomic DNA sequencing and 46 ancestry-informative markers, through multiplex PCR. The median age was 61 years; 63.5% of the patients presented disease clinical stages III or IV; 8.3% reported personal history of cancer; 4.7% and 16.1% reported first-degree relatives with PC or breast and/or prostate cancer, respectively. Although the main ancestry was European, there was considerable genetic composition admixture. Twelve patients (6.25%) were PGV carriers in PC predisposition genes (ATM, BRCA1, BRCA2, CDKN2A, MSH2, PALB2) and another 25 (13.0%) were PGV carriers in genes with a limited association or not previously associated with PC (ACD, BLM, BRIP1, CHEK2, ERCC4, FANCA, FANCE, FANCM, GALNT12, MITF, MRE11, MUTYH, POLE, RAD51B, RAD51C, RECQL4, SDHA, TERF2IP). The most frequently affected genes were CHEK2, ATM and FANC. In tumor samples from PGV carriers in ACD, BRIP1, MRE11, POLE, SDHA, TERF2IP, which were examined through exome sequencing, the main single base substitutions (SBS) mutational signature was SBS1+5+18, probably associated with age, tobacco smoking and reactive oxygen species. SBS3 associated with homologous repair deficiency was also represented, but on a lower scale. There was no difference in the frequency of PGV carriers between: (a) patients with or without first-degree relatives with cancer; and (b) patients with admixed ancestry versus those with predominantly European ancestry. Furthermore, there was no difference in overall survival between PGV carriers and non-carriers. Therefore, genetic testing should be offered to all Brazilian pancreatic cancer patients, regardless of their ancestry. Genes with limited or previously unrecognized associations with pancreatic cancer should be further investigated to clarify their role in cancer risk.

New Smoothened ligands based on the purine scaffold as potential agents for treating pancreatic cancer.

Aberrant activation of the Hedgehog (Hh) signalling pathway has been associated with the development and progression of pancreatic cancer. For this reason, blockade of Hh pathway by inhibitors targeting the G protein-coupled receptor Smoothened (SMO) has been considered as a therapeutic target for the treatment of this cancer. In our previous work, we obtained a new SMO ligand based on a purine scaffold (compound I), which showed interesting antitumor activity in several cancer cell lines. In this work, we report the design and synthesis of 17 new purine derivatives, some of which showed high cytotoxic effect on Mia-PaCa-2 (Hh-dependent pancreatic cancer cell lines) and low toxicity on non-neoplastic HEK-293 cells compared with gemcitabine, such as 8f, 8g and 8h (IC50 = 4.56, 4.11 and 3.08 µM, respectively). Two of these purines also showed their ability to bind to SMO through NanoBRET assays (pKi = 5.17 for 8f and 5.01 for 8h), with higher affinities to compound I (pKi = 1.51). In addition, docking studies provided insight the purine substitution pattern is related to the affinity on SMO. Finally, studies of Hh inhibition for selected purines, using a transcriptional functional assay based on luciferase activity in NIH3T3 Shh-Light II cells, demonstrated that 8g reduced GLI activity with a IC50 = 6.4 µM as well as diminished the expression of Hh target genes in two specific Hh-dependent cell models, Med1 cells and Ptch1-/- mouse embryonic fibroblasts. Therefore, our results provide a platform for the design of SMO ligands that could be potential selective cytotoxic agents for the treatment of pancreatic cancer.

The role of AMPK in pancreatic cancer: from carcinogenesis to treatment.

Pancreatic cancer has doubled over the previous two decades. Routine therapies are becoming incredibly resistant and failing to compensate for the burden caused by this aggressive neoplasm. As genetic susceptibility has always been a highlighted concern for this disease, identifying the molecular pathways involved in the survival and function of pancreatic cancer cells provides insight into its variant etiologies, one of which is the role of AMPK. This regulating factor of cell metabolism is crucial in the homeostasis and growth of the cell. Herein, we review the possible role of AMPK in pancreatic cancer while considering its leading effects on glycolysis and autophagy. Then, we assess the probable therapeutic agents that have resulted from the suggested pathways. Studying the underlying genetic changes in pancreatic cancer provides a chance to detect and treat patients suffering from advanced stages of the disease, and those who have given up their hope on conventional therapies can gain an opportunity to combat this cancer.

Duodenopancreatectomía cefálica con resección vascular laparoscópica / Laparoscopic cephalic pancreaticoduodenectomy with laparoscopic vascular resection

RESUMEN Antecedentes: la duodenopancreatectomía cefálica (DPC) con resección vascular venosa está indicada para el tratamiento del adenocarcinoma ductal y de tumores neuroendocrinos de páncreas, tanto por laparoscopia como por laparotomía. Objetivo: describir los resultados de una serie de pacientes operados de DPC con resección vascular venosa y comparar la morbimortalidad entre los abordados por laparoscopia y por laparotomía. Material y métodos: se realizó un estudio observacional, comparativo, retrospectivo de pacientes con DPC con resección vascular entre enero de 2022 y agosto de 2023. El abordaje laparoscópico fue determinado en menores de 80 años, invasión venosa tumoral igual a 180° o menor en la tomografía, buen performance status, y no haber realizado tratamiento neoadyuvante. Resultados: fueron realizadas 23 DPC con resección vascular venosa: 11 por laparoscopia y 12 por laparotomía. Las 11 realizadas por laparoscopia fueron resecciones laterales, y, en los 12 abordados por laparotomía, se realizó resección total de vena porta en 5 y en el resto, resección lateral. El tiempo de "clampeo" (pinzamiento) portal y la necesidad de transfusiones fue similar en ambos grupos. El estudio patológico reveló R0 en el 78,2% de los pacientes e invasión venosa en el 40.9%. La morbilidad con laparoscopia y con laparotomía consistió, respectivamente, en: fístula pancreática en 7 (4 y 3), vaciamiento gástrico retardado en 4 (1 y 4), fístula biliar en uno (1 y 0), neumonía en dos (1 y 1) e infección de herida en uno (0 y 1). La mortalidad fue de 8,6% por el fallecimiento de dos pacientes, uno en cada grupo. Conclusión: de acuerdo con los criterios empleados, la morbimortalidad de la DPC con resección vascular fue similar por laparoscopia y por laparotomía.

ABSTRACT Background: Cephalic pancreaticoduodenectomy (CPD) with venous resection is indicated for the treatment of ductal adenocarcinoma and neuroendocrine tumors of the pancreas, either through laparoscopy or laparotomy. Objective: The aim of this study was to describe the results of a series of patients undergoing CPD with venous vascular resection and compare morbidity and mortality between the laparoscopic approach and open surgery. Material and methods: We conducted a retrospective, comparative and observational study of patients who underwent CPD with venous vascular resection between January 2022 and July 2023. Criteria for laparoscopic surgery were age < 80 years, interface between tumor and vein of 180° of the circumference of the vessel wall or less on computed tomography, good performance status, and no previous neoadjuvant treatment. Results: A total of 23 CPD procedures with venous vascular resection were performed: 11 by laparoscopy and 12 by laparotomy. The 11 laparoscopic procedures were lateral resections, and in the 12 patients approached by laparotomy, 5 were total portal vein resections and 7 were lateral resections. Portal vein clamping time and need for transfusion was similar in both groups. The pathological examination reported R0 resections in 78.2% and venous invasion in 40.9%. The complications associated with laparoscopy and laparotomy were pancreatic fistula in 4 and 3 patients, respectively, delayed gastric emptying in 1 and 4 patients, respectively, biliary fistula in 1 and 0 patients, respectively, aspiration pneumonia i 1 and 1 patients, respectively and surgical site infection in 0 and 1 patients, respectively. Mortality was 8.6% (n =2), one in each group. Conclusion: According to the criteria used, the morbidity and mortality of CPD with vascular resection were similar for laparoscopy and laparotomy.

Early diagnosis of pancreatic cancer: Shedding light on an unresolved challenge.

Diagnosing early-stage pancreatic cancer (PC) remains a clinical challenge. Hence, studying novel imaging aspects that could enhance the diagnostic accuracy of malignant pancreatic precursor lesions is imperative. This article aims to underscore the promising role of emerging imaging aspects that may facilitate the earlier diagnosis of PC, thereby improving its management and prognosis.

Rutinosides-derived from Sarocladium strictum 6-O-α-rhamnosyl-ß-glucosidase show enhanced anti-tumoral activity in pancreatic cancer cells.

BACKGROUND: Low targeting efficacy and high toxicity continue to be challenges in Oncology. A promising strategy is the glycosylation of chemotherapeutic agents to improve their pharmacodynamics and anti-tumoral activity. Herein, we provide evidence of a novel approach using diglycosidases from fungi of the Hypocreales order to obtain novel rutinose-conjugates therapeutic agents with enhanced anti-tumoral capacity. RESULTS: Screening for diglycosidase activity in twenty-eight strains of the genetically related genera Acremonium and Sarocladium identified 6-O-α-rhamnosyl-ß-glucosidase (αRßG) of Sarocladium strictum DMic 093557 as candidate enzyme for our studies. Biochemically characterization shows that αRßG has the ability to transglycosylate bulky OH-acceptors, including bioactive compounds. Interestingly, rutinoside-derivatives of phloroglucinol (PR) resorcinol (RR) and 4-methylumbelliferone (4MUR) displayed higher growth inhibitory activity on pancreatic cancer cells than the respective aglycones without significant affecting normal pancreatic epithelial cells. PR exhibited the highest efficacy with an IC50 of 0.89 mM, followed by RR with an IC50 of 1.67 mM, and 4MUR with an IC50 of 2.4 mM, whereas the respective aglycones displayed higher IC50 values: 4.69 mM for phloroglucinol, 5.90 mM for resorcinol, and 4.8 mM for 4-methylumbelliferone. Further, glycoconjugates significantly sensitized pancreatic cancer cells to the standard of care chemotherapy agent gemcitabine. CONCLUSIONS: αRßG from S. strictum transglycosylate-based approach to synthesize rutinosides represents a suitable option to enhance the anti-proliferative effect of bioactive compounds. This finding opens up new possibilities for developing more effective therapies for pancreatic cancer and other solid malignancies.

New avenues for the treatment of immunotherapy-resistant pancreatic cancer.

Pancreatic cancer (PC) is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases worldwide. However, due to its complexity, it ranks 7th in the list of the most lethal cancers worldwide. The pathogenesis of PC involves several complex processes, including familial genetic factors associated with risk factors such as obesity, diabetes mellitus, chronic pancreatitis, and smoking. Mutations in genes such as KRAS, TP53, and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and, consequently, cancer. In this context, some therapies are used for PC, one of which is immunotherapy, which is extremely promising in various other types of cancer but has shown little response in the treatment of PC due to various resistance mechanisms that contribute to a drop in immunotherapy efficiency. It is therefore clear that the tumor microenvironment (TME) has a huge impact on the resistance process, since cellular and non-cellular elements create an immunosuppressive environment, characterized by a dense desmoplastic stroma with cancer-associated fibroblasts, pancreatic stellate cells, extracellular matrix, and immunosuppressive cells. Linked to this are genetic mutations in TP53 and immunosuppressive factors that act on T cells, resulting in a shortage of CD8+ T cells and limited expression of activation markers such as interferon-gamma. In this way, finding new strategies that make it possible to manipulate resistance mechanisms is necessary. Thus, techniques such as the use of TME modulators that block receptors and stromal molecules that generate resistance, the use of genetic manipulation in specific regions, such as microRNAs, the modulation of extrinsic and intrinsic factors associated with T cells, and, above all, therapeutic models that combine these modulation techniques constitute the promising future of PC therapy. Thus, this study aims to elucidate the main mechanisms of resistance to immunotherapy in PC and new ways of manipulating this process, resulting in a more efficient therapy for cancer patients and, consequently, a reduction in the lethality of this aggressive cancer.

Calix[6]arene dismantles extracellular vesicle biogenesis and metalloproteinases that support pancreatic cancer hallmarks.

Many challenges are faced in pancreatic cancer treatment due to late diagnosis and poor prognosis because of high recurrence and metastasis. Extracellular vesicles (EVs) and matrix metalloproteinases (MMPs), besides acting in intercellular communication, are key players in the cancer cell plasticity responsible for initiating metastasis. Therefore, these entities provide valuable targets for the development of better treatments. In this context, this study aimed to evaluate the potential of calix[6]arene to disturb the release of EVs and the activity of MMPs in pancreatic cancer cells. We found a correlation between the endocytic-associated mediators and the prognosis of pancreatic cancer patients. We observed a more active EV machinery in the pancreatic cancer cell line PANC-1, which was reduced three-fold by treatment with calix[6]arene at subtoxic concentration (5 µM; p ã€ˆ0,001). We observed the modulation of 186 microRNAs (164 miRNAs upregulated and 22 miRNAs downregulated) upon calix[6]arene treatment. Interestingly, some of them as miR-4443 and miR-3909, regulates genes HIF1A e KIF13A that are well known to play a role in transport of vesicles. Furthermore, Calix[6]arene downmodulated matrix metalloproteinases (MMPs) -2 and - 9 and disturbed the viability of pancreatic organoids which recapitulate the cellular heterogeneity, structure, and functions of primary tissues. Our findings shed new insights on calix[6]arene's antitumor mechanism, including its intracellular effects on vesicle production and trafficking, as well as MMP activity, which may harm the tumor microenvironment and contribute to a reduction in cancer cell dissemination, which is one of the challenges associated with high mortality in pancreatic cancer.

Chronological pattern of venous thromboembolism (VTE) occurrence impacts in survival of pancreatic ductal adenocarcinoma (PDAC).

BACKGROUND: Limited data exist on the prognostic significance of the chronology of VTE in patients with PDAC. METHODS: Medical data and survival characteristics of patients treated for PDAC from 2019 to 2021 were retrospectively reviewed. Early VTE was defined as occurring within the three months of PDAC diagnosis. RESULTS: 197 patients were included, 54 (27.4%) developed a VTE. Early appearance of VTE was associated with worse prognosis: median overall survival (mOS) VTE < 3 months 8.5 months (HR 1.65, 95% CI 1.11-2.46; p = 0.014), mOS VTE > 3 months 12.8 months (HR 0.78, 95% CI 0.39-1.54; p = 0.5) and mOS patients without VTE 11.4 months (95% CI 10.1-15.4). There was no significant association between the patient's VTE risk according to the Khorana risk score (KRS) (chi2 test p-value = 0.9). CONCLUSION: Early VTE is a prognostic factor in PDAC, which may identify a more aggressive subtype.

A meta-analysis on the efficacy of endoscopic ultrasonography for treatment of pancreatic cancer.

OBJECTIVE: This study aimed to systematically evaluate the efficacy and safety of Endoscopic Ultrasonography (EUS) for the treatment of pancreatic cancer. METHODS: The PubMed, Embase, Web of Science, and Google Scholar databases were searched from the inception of the databases to June 2022. RevMan 5.3.0 software was utilized for data analysis. In total, 13 self-descriptive studies, which enrolled 382 patients, were finally included. RESULTS: It was revealed that EUS for the treatment of pancreatic cancer exhibited a lower incidence of adverse reactions (Relative Risk Ration [RR = 0.23], 95 % Confidence interval [95 % CI 0.23-0.23]), a higher success rate (RR = 0.90, 95 % CI 0.90-0.90), and a low failure rate (RR = 0.06, 95 % CI 0.06-0.06). Moreover, EUS-guided Celiac Plexus Neurolysis (EUS-CPN) not only significantly relieved pancreatic cancer patients' pain (RR = 0.83, 95 % CI 0.83-0.83), but also significantly eliminated pain in some patients (RR = 0.09, 95 % CI 0.09-0.09). The effects of EUS on pancreatic cancer treatment were satisfactory, and few adverse reactions were found. CONCLUSION: Owing to the restricted sample size in this meta-analysis, primarily consisting of descriptive studies, it was imperative to conduct more rigorously designed, multi-center, long-term follow-up, larger sample, and Randomized Controlled Trials (RCTs) to validate the findings.

Deep Learning Techniques to Characterize the RPS28P7 Pseudogene and the Metazoa-SRP Gene as Drug Potential Targets in Pancreatic Cancer Patients.

The molecular explanation about why some pancreatic cancer (PaCa) patients die early and others die later is poorly understood. This study aimed to discover potential novel markers and drug targets that could be useful to stratify and extend expected survival in prospective early-death patients. We deployed a deep learning algorithm and analyzed the gene copy number, gene expression, and protein expression data of death versus alive PaCa patients from the GDC cohort. The genes with higher relative amplification (copy number >4 times in the dead compared with the alive group) were EWSR1, FLT3, GPC3, HIF1A, HLF, and MEN1. The most highly up-regulated genes (>8.5-fold change) in the death group were RPL30, RPL37, RPS28P7, RPS11, Metazoa_SRP, CAPNS1, FN1, H3-3B, LCN2, and OAZ1. None of their corresponding proteins were up or down-regulated in the death group. The mRNA of the RPS28P7 pseudogene could act as ceRNA sponging the miRNA that was originally directed to the parental gene RPS28. We propose RPS28P7 mRNA as the most druggable target that can be modulated with small molecules or the RNA technology approach. These markers could be added as criteria to patient stratification in future PaCa drug trials, but further validation in the target populations is encouraged.

Update on the management of older patients with pancreatic adenocarcinoma: a perspective from medical oncology.

In the context of pancreatic cancer, surgical intervention is typically recommended for localized tumours, whereas chemotherapy is the preferred approach in the advanced and/or metastatic setting. However, pancreatic cancer is closely linked to ageing, with an average diagnosis at 72 years. Paradoxically, despite its increased occurrence among older individuals, this population is often underrepresented in clinical studies, complicating the decision-making process. Age alone should not determine the therapeutic strategy but, given the high comorbidity and mortality of this disease, a comprehensive geriatric assessment (CGA) is necessary to define the best treatment, prevent toxicity, and optimize older patient care. In this review, a group of experts from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica, SEOM), the Spanish Cooperative Group for the Treatment of Digestive Tumours (Grupo Español de Tratamiento de los Tumores Digestivos, TTD), and the Multidisciplinary Spanish Group of Digestive Cancer (Grupo Español Multidisciplinar en Cáncer Digestivo, GEMCAD) have assessed the available scientific evidence and propose a series of recommendations on the management and treatment of the older population with pancreatic cancer.

Exploring the logic and conducting a comprehensive evaluation of AdipoRon-based adiponectin replacement therapy against hormone-related cancers-a systematic review.

The potential benefits of adiponectin replacement therapy extend to numerous human diseases, with current research showing particular interest in its effectiveness against specific cancer forms, especially hormone-related. However, limitations in the pharmacological use of the intact protein have led to a focus on alternative options. AdipoRon is an extensively studied non-peptidic drug candidate for adiponectin replacement therapy. While researchers have explored the efficacy and therapeutic applications of AdipoRon in various disease conditions, their effects against cancer models advanced more, with no review regarding AdipoRon's efficacy against hormone-related cancers being published. The present systematic review aims to fill this gap. Preclinical evidence was compiled from PubMed, EMBASE, COCHRANE, and Google Scholar following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the manuscript's quality assessment was conducted using the Joanna Briggs Institute (JBI) Checklist Critical Appraisal Tool for Systematic Reviews' Quality. The included nine studies incorporated various cell and animal models of the pancreas, gynaecological system, and osteosarcoma cancers. AdipoRon demonstrated effectiveness against pancreatic cancer by activating p44/42 MAPK, mitochondrial dysfunction, and AMPK-mediated inhibition of ACC1. In gynaecological cancers, it exhibited promising anticancer effects through the activation of AMPK, potential inhibition of mTOR, and modulation of the SET1B/BOD1/AdipoR1 signaling cascade. Against osteosarcoma, AdipoRon worked by perturbing ERK1/2 signaling and reducing p70S6K phosphorylation. AdipoRon shows promise in preclinical studies, but human trials are crucial for clinical safety and effectiveness. Caution is needed due to potential off-target effects, especially in cancer therapy with multi-target approaches. Structural biology and computational methods can help predict these effects.

Three-month life expectancy as inclusion criterion for clinical trials in advanced pancreatic cancer: is it really a valid tool for patient selection?

PURPOSE: To analyze the 3-month life expectancy rate in pancreatic cancer (PC) patients treated within prospective trials from the German AIO study group. PATIENTS AND METHODS: A pooled analysis was conducted for patients with advanced PC that were treated within five phase II/III studies conducted between 1997 and 2017 (Gem/Cis, Ro96, RC57, ACCEPT, RASH). The primary goal for the current report was to identify the actual 3-month survival rate, a standard inclusion criterion in oncology trials. RESULTS: Overall, 912 patients were included, 83% had metastatic and 17% locally advanced PC; the estimated median overall survival (OS) was 7.1 months. Twenty-one percent of the participants survived < 3 months, with a range from 26% in RC57 to 15% in RASH. Significant predictors for not reaching 3-month OS were > 1 previous treatment line (p < 0.001) and performance status (p < 0.001). CONCLUSIONS: Despite the definition of a life expectancy of > 3 months as a standard inclusion criterion in clinical trials for advanced PC, a significant proportion of study patients does not survive > 3 months. TRIAL REGISTRATION NUMBERS: NCT00440167 (AIO-PK0104), NCT01729481 (RASH), NCT01728818 (ACCEPT).

A meta-analysis on the efficacy of endoscopic ultrasonography for treatment of pancreatic cancer

Abstract Objective: This study aimed to systematically evaluate the efficacy and safety of Endoscopic Ultrasonography (EUS) for the treatment of pancreatic cancer. Methods: The PubMed, Embase, Web of Science, and Google Scholar databases were searched from the inception of the databases to June 2022. RevMan 5.3.0 software was utilized for data analysis. In total, 13 self-descriptive studies, which enrolled 382 patients, were finally included. Results It was revealed that EUS for the treatment of pancreatic cancer exhibited a lower incidence of adverse reactions (Relative Risk Ration [RR = 0.23], 95 % Confidence interval [95 % CI 0.23-0.23]), a higher success rate (RR = 0.90, 95 % CI 0.90-0.90), and a low failure rate (RR = 0.06, 95 % CI 0.06-0.06). Moreover, EUS-guided Celiac Plexus Neurolysis (EUS-CPN) not only significantly relieved pancreatic cancer patients' pain (RR = 0.83, 95 % CI 0.83-0.83), but also significantly eliminated pain in some patients (RR = 0.09, 95 % CI 0.09-0.09). The effects of EUS on pancreatic cancer treatment were satisfactory, and few adverse reactions were found. Conclusion: Owing to the restricted sample size in this meta-analysis, primarily consisting of descriptive studies, it was imperative to conduct more rigorously designed, multi-center, long-term follow-up, larger sample, and Randomized Controlled Trials (RCTs) to validate the findings.

Factores asociados a mayor sobrevida en pacientes con cáncer de páncreas tratados mediante pancreatoduodenectomía. Estudio de casos y controles

Introducción: El cáncer de páncreas (CP) tiene un pronóstico ominoso a pesar de los avances en técnica quirúrgica y en los cuidados peri/postoperatorios. Nuestro objetivo fue identificar factores asociados a mayor sobrevida en pacientes con CP tratados mediante pancreatoduodenectomía (PD). Material y Método: Estudio de casos y controles de pacientes con CP tratados mediante PD en el Hospital Clínico de la Universidad Católica entre 2002-2015. Se definió como caso al paciente con sobrevida ≥ 3 años y como control a aquel con sobrevida inferior a ese plazo. Se comparó entre casos y controles datos biodemográficos, clínicos, histopatológicos, de morbilidad y mortalidad mediante regresión logística. Resultados: Se analizaron 70 pacientes, con una edad media de 62 ± 11 años; 40 (57%) mujeres. Hubo morbilidad en 26 enfermos (37,1%); Clavien-Dindo ≥ Illa en 8 (11,4%). La mediana (rango) de días de hospitalización fue 12 (7-84). La sobrevida actuarial a 1, 3 y 5 años fue 77%, 32% y 22% respectivamente. Se identificaron 21 casos (30%) y 49 controles (70%). En el análisis univariable, la resección R0, los ganglios regionales negativos, la ausencia de infiltración perineural, los estadios más precoces (IA, IB y IIA) y la ausencia de diabetes mellitus (DM2) al momento del diagnóstico, fueron variables asociadas a sobrevida ≥ 3 años (p 100 U/mL) y los tratamientos complementarios no se asociaron a diferencias significativas en sobrevida. En el análisis multivariable, se identificó la ausencia de DM2 (OR ajustado: 12; IC95% 1,7-84,3), la ausencia de infiltración perineural (OR ajustado: 7; IC95% 1,3-36,3) y los estadios precoces IA, IB y IIA (OR ajustado: 10,3; IC95% 2,1-49,1) como los factores independientes asociados a sobrevida mayor a 3 años. Conclusión: Los pacientes no diabéticos, con etapas precoces del CP sin infiltración perineural, resecados R0 mediante PD pueden obtener una sobrevida mayor a 3 años.

Introduction: Pancreatic cancer (PC) remains one of the most lethal malignancies, despite developments in surgical and non-surgical therapies. Significant improvements in long-term survival have not been achieved. Only radical surgical resection has obtained a moderate extension in survival. We aim to identify factors associated with longer survival in patients with PC treated by pancreatoduodenectomy (PD). Material and Method: We designed a case-control study of patients with PC treated by PD in our center between 2002-2015. We compare patients who survived ≥ 3 years (case) with those not achieving it (control). Bio-demographic, clinical, histopathological, morbidity and mortality data were compared between cases and controls using logistic regression. Results: Seventy patients were analyzed; mean age 62 ± 11 years; 40 (57%) women. Morbidity was found in 26 patients (37.1%); Clavien-Dindo ≥ Illa in 8 (11.4%). The median (range) of hospitalization days was 12 (7-84). The actuarial 1, 3, and 5 years survival was 77%, 32%, and 22%, respectively, for the entire series. Twenty-one cases (30%), and 49 controls (70%) were identified. In the univariate analysis, R0 resection, negative regional lymph nodes, the absence of perineural infiltration, the earliest stages (IA, IB, and IIA) and the absence of diabetes mellitus (DM) at time of diagnosis were variables associated with survival ≥ 3 years (p 100 U / mL), and neo/adjuvant treatments, did not significantly show differences in survival. In the multivariate analysis, no DM at diagnosis (adjusted OR: 12; 95% CI 1.7 - 84.3), no perineural infiltration (adjusted OR: 7; 95% CI 1.3 - 36.3) and early stages IA, IB, and IIA (adjusted OR: 10.3; 95% CI 2.1 - 49.1) were identified as independent factors associated with survival > 3 years. Conclusion: Nondiabetic patients with early stages PC without perineural infiltration, resected R0 by PD can achieve survival over 3 years.