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1.
Colorectal Dis ; 26(2): 281-289, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38131642

RESUMEN

AIM: Local excision (LE) in selected cases after neoadjuvant radiochemotherapy (RCT) for locally advanced rectal cancer in clinically complete or major responders has been recently reported as an alternative to standard radical resection. Completion total mesorectal excision (cTME) is generally performed when high-risk pathological features are found in LE surgical specimens. The aim of this study was to evaluate the incidence of residual tumour and lymph node metastases after cTME in patients previously treated by RCT + LE. The secondary aims were to quantify the rate of postoperative morbidity and mortality and to evaluate the long-term oncological outcome of this group of patients. METHODS: All patients treated from 2007 to 2020 by LE for locally advanced rectal cancer with a clinically complete or major response to RCT who had a subsequent cTME for high-risk pathological factors (ypT >1 and/or TRG >2 and/or positive margins) were included in this multicentre retrospective study. Pathological data, postoperative short-term morbidity (classified according to Clavien-Dindo) and mortality and oncological long-term outcome after cTME were recorded in a database. Statistical analysis was performed using Wizard for iOS version 1.9.31. RESULTS: A total of 47 patients were included in the study. The rate of R0 resection was 95.7%, and a sphincter-saving procedure was performed in 37 patients (78.7%), with a protective stoma rate of 78.4%. In 28 cases (59.6%), it was possible to perform a minimally invasive approach. A residual tumour (pT and/or pN) on cTME specimens was found in 21 cases (44.7%). The rate of lymph node metastases was 12.8%. The overall short-term (within 30 days) postoperative morbidity was 34%, but grade >2 postoperative complications occurred in only nine patients (19.1%), with a reoperation rate of 6.4%. No short-term postoperative deaths occurred. At a median follow-up of 57 months (range: 21-174), the long-term stoma-free rate was 70.2%, and the actuarial 5-year overall survival (OS), disease-free survival (DFS) and local control (LC) were 86.7%, 88.9% and 95.7%, respectively. CONCLUSION: When patients exhibit high-risk pathological factors after RCT + LE, cTME should be suggested due to the high risk of residual tumour or lymph node involvement (44.7%). The results after cTME in terms of the rate of R0 resection, sphincter-saving procedure, postoperative morbidity and mortality and long-term oncological outcome seem to be acceptable and do not represent a contraindication to use LE as a first-step treatment in patients with major or complete clinical response after RCT.


Asunto(s)
Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Terapia Neoadyuvante/efectos adversos , Metástasis Linfática , Neoplasia Residual/tratamiento farmacológico , Neoplasia Residual/etiología , Neoplasia Residual/patología , Resultado del Tratamiento , Neoplasias del Recto/cirugía , Neoplasias del Recto/tratamiento farmacológico , Quimioradioterapia , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias
2.
Langenbecks Arch Surg ; 409(1): 71, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38393349

RESUMEN

PURPOSE: Anomalies of the right hepatic artery (RHA) may represent an additional challenge in pancreatoduodenectomy (PD). The aim of this study is to assess the potential impact of variations in hepatic arterial anatomy on perioperative outcomes. METHODS: PDs performed for periampullary malignancies between 2017 and 2022 were retrospectively enrolled and subdivided in two groups: modal pattern of vascularization (MPV) and anomalous pattern of vascularization (APV). A propensity score matching (PSM) analysis was conducted to homogenize the two study populations. The two groups were then compared in terms of perioperative outcomes and pathological findings. RESULTS: Thirty-eight patients (16.3%) out of 232 presented a vascular anomaly: an accessory RHA in 7 cases (3%), a replaced RHA in 26 cases (11.2%), and a replaced HA in 5 cases (2.1%). After PSM, 76 MPV patients were compared to the 38 APV patients. The incidence rate of postoperative complications was comparable between the two study populations (p=0.2). Similarly, no difference was detected in terms of histopathological data, including margin status. No difference was noted in terms of intraoperative hemorrhage and vascular resection. CONCLUSION: When PDs are performed in high-volume centers, the presence of an APV of the RHA does not relate to a significant impact on perioperative complications. Moreover, no influence was noted on histopathological findings.


Asunto(s)
Neoplasias Duodenales , Arteria Hepática , Humanos , Arteria Hepática/cirugía , Estudios Retrospectivos , Centros de Atención Terciaria , Pancreaticoduodenectomía , Neoplasias Duodenales/cirugía
3.
Langenbecks Arch Surg ; 409(1): 184, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38862717

RESUMEN

PURPOSE: Post-operative pancreatic fistula (POPF) remains the main complication after distal pancreatectomy (DP). The aim of this study is to evaluate the potential benefit of different durations of progressive stapler closure on POPF rate and severity after DP. METHODS: Patients who underwent DP between 2016 and 2023 were retrospectively enrolled and divided into two groups according to the duration of the stapler closure: those who underwent a progressive compression for < 10 min and those for ≥ 10 min. RESULTS: Among 155 DPs, 83 (53.5%) patients underwent pre-firing compression for < 10 min and 72 (46.5%) for ≥ 10 min. As a whole, 101 (65.1%) developed POPF. A lower incidence rate was found in case of ≥ 10 min compression (34-47.2%) compared to < 10 min compression (67- 80.7%) (p = 0.001). When only clinically relevant (CR) POPFs were considered, a prolonged pre-firing compression led to a lower rate (15-20.8%) than the < 10 min cohort (32-38.6%; p = 0.02). At the multivariate analysis, a compression time of at least 10 min was confirmed as a protective factor for both POPF (OR: 5.47, 95% CI: 2.16-13.87; p = 0.04) and CR-POPF (OR: 2.5, 95% CI: 1.19-5.45; p = 0.04) development. In case of a thick pancreatic gland, a prolonged pancreatic compression for at least 10 min was significantly associated to a lower rate of CR-POPF compared to < 10 min (p = 0.04). CONCLUSION: A prolonged pre-firing pancreatic compression for at least 10 min seems to significantly reduce the risk of CR-POPF development. Moreover, significant advantages are documented in case of a thick pancreatic gland.


Asunto(s)
Pancreatectomía , Fístula Pancreática , Complicaciones Posoperatorias , Grapado Quirúrgico , Humanos , Fístula Pancreática/prevención & control , Fístula Pancreática/etiología , Pancreatectomía/efectos adversos , Pancreatectomía/métodos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Grapado Quirúrgico/métodos , Engrapadoras Quirúrgicas , Adulto , Factores de Tiempo , Neoplasias Pancreáticas/cirugía
4.
Int J Mol Sci ; 25(11)2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38892122

RESUMEN

Pancreatic islet isolation is critical for type 2 diabetes research. Although -omics approaches have shed light on islet molecular profiles, inconsistencies persist; on the other hand, functional studies are essential, but they require reliable and standardized isolation methods. Here, we propose a simplified protocol applied to very small-sized samples collected from partially pancreatectomized living donors. Islet isolation was performed by digesting tissue specimens collected during surgery within a collagenase P solution, followed by a Lympholyte density gradient separation; finally, functional assays and staining with dithizone were carried out. Isolated pancreatic islets exhibited functional responses to glucose and arginine stimulation mirroring donors' metabolic profiles, with insulin secretion significantly decreasing in diabetic islets compared to non-diabetic islets; conversely, proinsulin secretion showed an increasing trend from non-diabetic to diabetic islets. This novel islet isolation method from living patients undergoing partial pancreatectomy offers a valuable opportunity for targeted study of islet physiology, with the primary advantage of being time-effective and successfully preserving islet viability and functionality. It enables the generation of islet preparations that closely reflect donors' clinical profiles, simplifying the isolation process and eliminating the need for a Ricordi chamber. Thus, this method holds promises for advancing our understanding of diabetes and for new personalized pharmacological approaches.


Asunto(s)
Separación Celular , Islotes Pancreáticos , Humanos , Islotes Pancreáticos/metabolismo , Islotes Pancreáticos/citología , Separación Celular/métodos , Donadores Vivos , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Insulina/metabolismo , Glucosa/metabolismo , Secreción de Insulina
5.
Int J Mol Sci ; 24(7)2023 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-37047843

RESUMEN

Dysfunction of the complex cerebral networks underlying wakefulness and awareness is responsible for Disorders of Consciousness (DoC). Traumatic Brain Injury (TBI) is a common cause of DoC, and it is responsible for a multi-dimensional pathological cascade that affects the proper functioning of the brainstem and brain consciousness pathways. Iron (Fe), Zinc (Zn), and Copper (Cu) have a role in the neurophysiology of both the ascending reticular activating system, a multi-neurotransmitter network located in the brainstem that is crucial for consciousness, and several brain regions. We aimed to summarize the role of these essential metals in TBI and its possible link with consciousness alterations. We found that TBI alters many neuronal molecular mechanisms involving essential metals, causing neurodegeneration, neural apoptosis, synaptic dysfunction, oxidative stress, and inflammation. This final pattern resembles that described for Alzheimer's disease (AD) and other neurological and psychiatric diseases. Furthermore, we found that amantadine, zolpidem, and transcranial direct current stimulation (tDCS)-the most used treatments for DoC recovery-seem to have an effect on essential metals-related pathways and that Zn might be a promising new therapeutic approach. This review summarizes the neurophysiology of essential metals in the brain structures of consciousness and focuses on the mechanisms underlying their imbalance following TBI, suggesting their possible role in DoC. The scenario supports further studies aimed at getting a deeper insight into metals' role in DoC, in order to evaluate metal-based drugs, such as metal complexes and metal chelating agents, as potential therapeutic options.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Estimulación Transcraneal de Corriente Directa , Humanos , Trastornos de la Conciencia/etiología , Metales , Estado de Conciencia/fisiología , Zinc
6.
Int J Mol Sci ; 24(7)2023 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-37047347

RESUMEN

Alzheimer's disease (AD) is a type of dementia whose cause is incompletely defined. Copper (Cu) involvement in AD etiology was confirmed by a meta-analysis on about 6000 participants, showing that Cu levels were decreased in AD brain specimens, while Cu and non-bound ceruloplasmin Cu (non-Cp Cu) levels were increased in serum/plasma samples. Non-Cp Cu was advocated as a stratification add-on biomarker of a Cu subtype of AD (CuAD subtype). To further circumstantiate this concept, we evaluated non-Cp Cu reliability in classifying subtypes of AD based on the characterization of the cognitive profile. The stratification of the AD patients into normal AD (non-Cp Cu ≤ 1.6 µmol/L) and CuAD (non-Cp Cu > 1.6 µmol/L) showed a significant difference in executive function outcomes, even though patients did not differ in disease duration and severity. Among the Cu-AD patients, a 76-year-old woman showed significantly abnormal levels in the Cu panel and underwent whole exome sequencing. The CuAD patient was detected with possessing the homozygous (c.1486T > C; p.(Ter496Argext*19) stop-loss variant in the RGS7 gene (MIM*602517), which encodes for Regulator of G Protein Signaling 7. Non-Cp Cu as an add-on test in the AD diagnostic pathway can provide relevant information about the underlying pathological processes in subtypes of AD and suggest specific therapeutic options.


Asunto(s)
Enfermedad de Alzheimer , Proteínas RGS , Femenino , Humanos , Anciano , Cobre/metabolismo , Ceruloplasmina/genética , Ceruloplasmina/metabolismo , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Reproducibilidad de los Resultados , Cognición , Proteínas RGS/metabolismo
7.
HPB (Oxford) ; 25(3): 363-373, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36764909

RESUMEN

BACKGROUND: Post-pancreatectomy acute pancreatitis (PPAP) is an increasingly described complication after pancreatic resection. No uniform definition criteria were present in the literature until the recent proposal of the International Study Group of Pancreatic Surgery (ISGPS). Aim of this study is to evaluate the clinical significance of the novel ISGPS definition of PPAP. METHODS: Patients who underwent pancreatoduodenectomy (PD) between 2006 and 2022 were enrolled. PPAP was defined and graded according to the ISGPS criteria. RESULTS: Among 520 PDs, 120 (23%)patients developed post-operative hyperamylasemia (POH), while PPAP occurred in 63(12.1%) cases. PPAP occurrence related to a higher rate of more severe complications (48-76.1%vs118-25.8%; p < 0.0001), delayed gastric emptying (DGE) (27-42.9%vd114-24.9%; p = 0.003) and post-operative pancreatic fistula (POPF) (57-90.5%vs186-40.8%; p < 0.0001). When stratified for PPAP severity, grade B and C patients more frequently developed major complications (p < 0.0001), POPF (p < 0.0001), DGE (p = 0.02) and post-operative hemorrhage (p < 0.0001) as compared to POH. At the multivariable analysis, soft pancreatic texture (p = 0.01)and a Wirsung diameter ≤3 mm (p = 0.01) were recognized as prognostic factors for PPAP onset, while a pancreatic duct ≤3 mm was the only feature significantly influencing a more severe course of PPAP (p = 0.01). CONCLUSION: The ISGPS classification is confirmed as a valuable method for a uniform definition and clinical course evaluation. Further studies in a prospective manner are still needed for a further confirmation.


Asunto(s)
Pancreaticoduodenectomía , Pancreatitis , Humanos , Pancreaticoduodenectomía/efectos adversos , Estudios Prospectivos , Enfermedad Aguda , Pancreatitis/complicaciones , Factores de Riesgo , Fístula Pancreática/etiología , Complicaciones Posoperatorias
8.
Int J Colorectal Dis ; 37(12): 2501-2510, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36385574

RESUMEN

PURPOSE: Circular staplers for colorectal anastomoses significantly ameliorated post-operative outcomes after rectal resection. The more recent three-row technology was conceived to improve anastomotic resistance and, thus, lower the incidence of anastomotic complications. The aim of this study was to evaluate potential advantages of three-row circular staplers (Three-CS) on anastomotic leakage (AL), stenosis (AS), and hemorrhage (AH) rates after rectal resection as compared to two-row circular staplers (Two-CS). METHODS: All rectal resections for rectal cancer between 2016 and 2021 were retrospectively included. Patients were classified according to the circular stapler employed in Two-CS and Three-CS cohorts. AL, AS, and AH rates were compared between the two populations. Additionally, the prognostic role of the type of circular stapler on AL onset was evaluated. RESULTS: Three-hundred and seventy-five patients underwent a rectal resection with an end-to-end anastomosis during the study period: 197 constituted the Two-CS group and 178 the Three-CS cohort. AL rate was 6.7%, significantly higher in the Two-CS group (19-9.6%) as compared to the Three-CS cohort (6-3.4%) (p = 0.01). No difference was noted in terms of AL severity. Although not statistically significant, a lower incidence rate of AL was evidenced even in the subset of patients with low rectal cancers (4.5% vs 12.5% in the two-row cohort; p = 0.33). At the multivariate analysis, Two-CS was a negative prognostic factor for AL onset (OR: 2.63; p = 0.03). No difference was noted between the two groups in terms of AS and AH. CONCLUSION: Three-row CSs significantly decrease the rate of AL after rectal resection. Further multicenter controlled trials are still needed to confirm the advantages of three-row CSs on anastomotic complications.


Asunto(s)
Proctectomía , Neoplasias del Recto , Humanos , Estudios Retrospectivos , Anastomosis Quirúrgica/efectos adversos , Proctectomía/efectos adversos , Recto/cirugía , Fuga Anastomótica/cirugía , Neoplasias del Recto/cirugía , Neoplasias del Recto/complicaciones
9.
Hepatobiliary Pancreat Dis Int ; 14(4): 443-5, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26256091

RESUMEN

The shortage of organs and the increasing median age of deceased donors for orthotopic liver transplantation stimulate transplant centres to accept grafts that otherwise would have been discarded due to severe vascular abnormalities. We encountered a donor with two arterial aneurysms and a left accessory hepatic artery: an arterial aneurysm of the common hepatic artery and a left accessory hepatic artery arising from a second aneurysm of the left gastric artery (Michels type V). A complex reconstruction was created to transplant the liver. Multiple arterial anastomosis was made and the hepatic inflow of the transplanted liver restored. Although the procedure increased the risk of hepatic artery thrombosis, one more organ supposed to be discarded was saved.


Asunto(s)
Aneurisma/complicaciones , Arteria Hepática/cirugía , Cirrosis Hepática Alcohólica/cirugía , Trasplante de Hígado/métodos , Donantes de Tejidos , Malformaciones Vasculares/complicaciones , Procedimientos Quirúrgicos Vasculares , Anciano , Anastomosis Quirúrgica , Aneurisma/diagnóstico , Selección de Donante , Femenino , Arteria Hepática/anomalías , Arteria Hepática/diagnóstico por imagen , Humanos , Cirrosis Hepática Alcohólica/diagnóstico , Trasplante de Hígado/efectos adversos , Masculino , Tomografía Computarizada Multidetector , Factores de Riesgo , Resultado del Tratamiento , Malformaciones Vasculares/diagnóstico
10.
Minerva Surg ; 79(4): 470-480, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38953759

RESUMEN

Locally advanced extraperitoneal rectal cancer represents a significant clinical challenge, and currently, the standard treatment is based on neoadjuvant chemoradiation therapy (CRT) followed by radical surgical resection with total mesorectal excision (TME). In the last 30 years, its management has undergone significant changes due to the improvement of complementary radio- and chemotherapy treatments, the improvement of minimally invasive surgical approaches and the diffusion of organ-sparing approaches, such as nonoperative management, commonly called "watch and wait" (NOM) and local excision (LE), in highly selected patients who achieve a major or complete response to neoadjuvant CRT. This review aimed to critically examine the efficacy and oncological safety of NOM and LE compared to those of standard TME in rectal cancer patients after neoadjuvant CRT. Both the pros and cons of these approaches were strictly analyzed, providing a comprehensive and critical overview of these novel management strategies for rectal cancer.


Asunto(s)
Terapia Neoadyuvante , Neoplasias del Recto , Neoplasias del Recto/terapia , Neoplasias del Recto/radioterapia , Humanos , Espera Vigilante , Quimioradioterapia , Resultado del Tratamiento , Quimioradioterapia Adyuvante
11.
J Trace Elem Med Biol ; 82: 127370, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38159434

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide and a public health problem. Several clinical studies have shown that copper (Cu) is involved in carcinogenesis, possibly via cuproptosis, a new form of programmed cell death, but the conclusions from published reports are inconsistent. This study aimed at evaluating the potential of Cu dysregulation as a CRC susceptibility factor. METHODS: In this systematic review and meta-analysis, we searched Cochrane Library, EBSCOhost, EMBASE, ProQuest, PubMed/MEDLINE, Scopus, and Web of Science for studies reporting serum Cu concentrations in CRC patients and controls from articles published till June 2023. The studies included reported measurements of serum/plasma/blood Cu levels. Meta-analyses were performed as well as study quality, heterogeneity, and small study effects were assessed. Based on a random effects model, summary standardized mean differences (SMDs) and the corresponding 95% confidence intervals (95% CIs) were applied to compare the levels of Cu between CRC patients and controls. RESULTS: 26 studies with a pooled total of9628 participants and 2578 CRC cases were included. The pooled SMD was equal to 0.85 (95% CIs -0.44; 2.14) showing that the CRC patients had higher mean Cu levels than the control subjects, but the difference was not significant (p = 0.185) and the heterogeneity was very high, I2 = 97.9% (95% CIs: 97.5-98.3%; p < 0.001). CONCLUSION: The pooled results were inconclusive, likely due to discordant results and inaccuracy in reporting data of some studies; further research is needed to establish whether Cu dysregulation might contribute to the CRC risk and whether it might reflect different CRC grades.


Asunto(s)
Neoplasias Colorrectales , Cobre , Humanos
12.
Front Oncol ; 14: 1343596, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38912067

RESUMEN

Introduction: Gastric cancer (GC) is the fourth leading cause of cancer-related death worldwide with limited therapeutic options. The aim of this study was to analyze the value of adding surgery to the first-line treatment in patients with oligometastatic GC (OGC). Methods: This retrospective study included patients with OGC who underwent induction chemotherapy followed by surgery of both primary tumor and synchronous metastasis between April 2012 and April 2022. Endpoints were overall survival (OS) and relapse-free survival (RFS) analyzed by the Kaplan-Meier method. Prognostic factors were assessed with the Cox model. Results: Data from 39 patients were collected. All cases were referred to our multidisciplinary tumor board (MTB) to evaluate the feasibility of radical surgery. After a median follow-up of 33.6 months (mo.), median OS was 26.6 mo. (95% CI 23.8-29.4) and median RFS was 10.6 mo. (95% CI 6.3-14.8). Pathologic response according to the Mandard criteria (TRG 1-3, not reached versus 20.5 mo. for TRG 4-5; HR 0.23, p=0.019), PS ECOG ≤ 1 (26.7 mo. for PS ≤ 1 versus 11.2 mo. for PS >1; HR 0.3, p=0.022) and a low metastatic burden (26.7 mo. for single site versus 12.9 mo. for ≥2 sites; HR 0.34, p=0.039) were related to good prognosis. No major intraoperative complications nor surgery-related deaths occurred in our series. Discussion: A sequential strategy of preoperative chemotherapy and radical surgical excision of both primary tumor and metastases was demonstrated to significantly improve OS and RFS. Multidisciplinary evaluation is mandatory to identify patients who could benefit from this strategy.

13.
J Trace Elem Med Biol ; 84: 127429, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38493666

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is a growing public health problem. Several clinical studies have shown a potentially protective effect of selenium (Se), but the reports are inconsistent. The objective of the study was to examine the evidence for relation between serum/tissue Se status and CRC. METHOD AND MATERIALS: In this Systematic Review and Meta-Analysis, we searched Cochrane Library, EBSCOhost, EMBASE, ProQuest, PubMed/MEDLINE, Scopus, and Web of Science for studies reporting serum/plasma/whole blood/tissue Se concentrations in CRC patients and controls for articles published till August 2023. Meta-analysis was performed, and study quality, heterogeneity, and small study effects were assessed. Based on a random effects model, summary mean differences in serum levels of Se between CRC patients and healthy controls, and Se levels between malignant and matched non-malignant tissue specimens were assessed. RESULTS: After initial screening, a total of 24 studies (18 serum and 6 tissue studies) with a pooled total of 2640 participants were included in the meta-analysis. CRC patients had significantly lower serum Se levels than healthy controls, being the difference between the two equal to 3.73 µg/dl (95% CI: 6.85-0.61). However, the heterogeneity was very high, I2= 99% (p < 0.01). Our meta-analysis showed higher Se levels in CRC cancerous specimens than in matched healthy colon tissue: the increase was equal to 0.07 µg/g wet tissue weight (95% CI: 0.06-0.09; p= 0.02). CONCLUSIONS: CRC patients have lower serum and higher colon cancerous tissue Se levels. Some factors, such as Se levels in different tumor grades of CRC need to be further considered for a more conclusive association between Se levels and risk of CRC.


Asunto(s)
Neoplasias Colorrectales , Selenio , Selenio/sangre , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/patología , Humanos
14.
Eur J Intern Med ; 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38871564

RESUMEN

AIMS: Chronic pancreatitis (CP) is - along with acute pancreatitis - the most frequent cause of diabetes of the exocrine pancreas (DEP). Although insulin deficiency is widely accepted as the major feature of DEP, it is still unclear whether diabetes associated with CP is characterized by additional or different functional defects of the insulin secretory machinery. To identify possible functional defects specifically induced by CP, we performed a cross-sectional study in individuals with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and diabetes mellitus (DM) comparing patients with and without CP (CP vs. NCP). METHODS: We administered an oral glucose tolerance test (OGTT) to all participants and, according to their glucose tolerance, classified them as NGT, IGT and DM. Insulin sensitivity and beta-cell functional parameters were derived from OGTT, hyperglycemic clamp and hyperinsulinemic euglycemic clamp. RESULTS: Studying 146 subjects, we found that beta-cell function and insulin secretion were significantly lower in CP compared to NCP patients. However, when we classified the subjects according to OGTT-derived glucose tolerance, we found no differences in beta-cell function or in insulin sensitivity between CP and NCP with the same glucose tolerance status. Of note, we found that arginine-stimulated insulin secretion is reduced only in subjects with CP and DM compared to NCP subjects with DM. CONCLUSIONS: Patients with CP had no specific alterations in insulin secretion and beta-cell function. However, in patients diagnosed with diabetes, we found a lower arginine-stimulated insulin secretion, a marker of reduced functional mass.

15.
Nat Commun ; 15(1): 2764, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38553466

RESUMEN

The existing Intraductal Papillary Mucinous Neoplasm (IPMN) risk stratification relies on clinical and histological factors, resulting in inaccuracies and leading to suboptimal treatment. This is due to the lack of appropriate molecular markers that can guide patients toward the best therapeutic options. Here, we assess and confirm subtype-specific markers for IPMN across two independent cohorts of patients using two Spatial Transcriptomics (ST) technologies. Specifically, we identify HOXB3 and ZNF117 as markers for Low-Grade Dysplasia, SPDEF and gastric neck cell markers in borderline cases, and NKX6-2 and gastric isthmus cell markers in High-Grade-Dysplasia Gastric IPMN, highlighting the role of TNFα and MYC activation in IPMN progression and the role of NKX6-2 in the specific Gastric IPMN progression. In conclusion, our work provides a step forward in understanding the gene expression landscapes of IPMN and the critical transcriptional networks related to PDAC progression.


Asunto(s)
Adenocarcinoma Mucinoso , Carcinoma Ductal Pancreático , Neoplasias Intraductales Pancreáticas , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Neoplasias Intraductales Pancreáticas/genética , Adenocarcinoma Mucinoso/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Hiperplasia , Proteínas de Homeodominio/genética
16.
J Clin Med ; 12(23)2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-38068281

RESUMEN

The creation of a protective stoma is considered a valid life-saving tool, significantly reducing the effects of anastomotic leakage in terms of related morbidity, mortality, and reoperation rate. The aim of this study was to evaluate the impact of a protective loop ileostomy in terms of short- and long-term postoperative morbidity, quantifying the stoma-related complications arising after stoma creation and stoma closure and the risk of permanent stoma. From January 2009 to January 2020, 149 patients with rectal cancer treated by anterior resection and protective ileostomy were enrolled in the study. A total of 113 (75.84%) patients were preoperatively treated with neoadjuvant radiochemotherapy. A clinically relevant anastomotic leak occurred in two patients (1.34%). The postoperative stoma complication rate was 6%. According to the Clavien classification, the stoma-related complication grade was I in seven patients (4.7%) and II in two patients (1.3%). A late stoma-related parastomal hernia occurred in one patient (0.67%). In 129 patients (86.57%), it was possible to close the stoma. Postoperative complications of stoma closure occurred in 12 patients (9.3%). The stoma closure complication grade was I in seven cases (5.43%), II in two cases (1.55%), and ≥3 in three cases (2.33%). Incisional hernia was the only late complication recorded in seven cases (5.42%). The permanent stoma rate was 13.43%. A protective ileostomy has a nonnegligible complication rate, but the rate of severe complications is low. Every effort should be made to clearly identify patients in whom the risk of anastomotic leakage justifies the stoma.

17.
Biol Trace Elem Res ; 2023 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-37938458

RESUMEN

The emergence of conflicting reports on the natural occurrence of Alzheimer's disease (AD) in non-human primates has prompted research on the comparison of the role of diet-associated changes in gene expression between humans and non-human primates. This article analyzes the effects of different human and chimpanzee diets and their link with apolipoproteins, lipid, and iron (Fe) metabolism, starting from available data, to find out any gap in the existing knowledge. By using a system biology approach, we have re-analyzed the liver and brain RNA seq data of mice fed with either human or chimpanzee diet for 2 weeks to look for genetic differences that may explain the differences in AD occurrence between those two classes. In liver samples of mice fed with the chimpanzee diet in comparison to the human diet, apolipoprotein A-1, ceruloplasmin, and 10 other genes were upregulated while 21 genes were downregulated. However, brain apolipoprotein E4 gene expression was not changed upon diet. Genetic, structural, and functional differences in apolipoprotein E protein, along with differences in Fe metabolisms and a longer lifespan of humans during evolution may account for the observed disparity.

18.
Cancers (Basel) ; 15(9)2023 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-37174063

RESUMEN

Esophagogastric junction (EGJ) carcinoma represents a specific site of disease, given the opportunities for multimodal clinical care and management and the possibilities of combined treatments. It encompasses various clinical subgroups of disease that are heterogeneous and deserve different treatments; therefore, the guidelines have progressively evolved over time, considering the evidence provided by clinical trials. The aim of this narrative review was to summarize the main evidence, which orientates the current guidelines, and to collect the main ongoing studies to address existing gray areas.

19.
Front Med (Lausanne) ; 10: 1189740, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37663653

RESUMEN

Introduction: Gastric cancer (GC) is an aggressive and clinically heterogeneous tumor, and better risk stratification of lymph node metastasis (LNM) could lead to personalized treatments. The role of radiomics in the prediction of nodal involvement in GC has not yet been systematically assessed. This study aims to assess the role of radiomics in the prediction of LNM in GC. Methods: A PubMed/MEDLINE systematic review was conducted to assess the role of radiomics in LNM. The inclusion criteria were as follows: i. original articles, ii. articles on radiomics, and iii. articles on LNM prediction in GC. All articles were selected and analyzed by a multidisciplinary board of two radiation oncologists and one surgeon, under the supervision of one radiation oncologist, one surgeon, and one medical oncologist. Results: A total of 171 studies were obtained using the search strategy mentioned on PubMed. After the complete selection process, a total of 20 papers were considered eligible for the analysis of the results. Radiomics methods were applied in GC to assess the LNM risk. The number of patients, imaging modalities, type of predictive models, number of radiomics features, TRIPOD classification, and performances of the models were reported. Conclusions: Radiomics seems to be a promising approach for evaluating the risk of LNM in GC. Further and larger studies are required to evaluate the clinical impact of the inclusion of radiomics in a comprehensive decision support system (DSS) for GC.

20.
Front Surg ; 10: 1119557, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36874464

RESUMEN

Background: The introduction of multidisciplinary tumor boards (MDTBs) for the diagnostic and therapeutic pathway of several oncological disease significantly ameliorated patients' outcomes. However, only few evidences are currently present on the potential impact of the MDTB on pancreatic cancer (PC) management. Aim of this study is to report how MDTB may influence PC diagnosis and treatment, with particular focus on PC resectability assessment and the correspondence between MDTB definition of resectability and intraoperative findings. Methods: All patients with a proven or suspected diagnosis of PC discussed at the MDTB between 2018 and 2020 were included in the study. An evaluation of diagnosis, tumor response to oncological/radiation therapy and resectability before and after the MDTB was conducted. Moreover, a comparison between the MDTB resectability assessment and the intraoperative findings was performed. Results: A total of 487 cases were included in the analysis: 228 (46.8%) for diagnosis evaluation, 75 (15.4%) for tumor response assessment after/during medical treatment, 184 (37.8%) for PC resectability assessment. As a whole, MDTB led to a change in treatment management in 89 cases (18.3%): 31/228 (13.6%) in the diagnosis group, 13/75 (17.3%) in the assessment of treatment response cohort and 45/184 (24.4%) in the PC resectability evaluation group. As a whole, 129 patients were given indication to surgery. Surgical resection was accomplished in 121 patients (93.7%), with a concordance rate of resectability between MDTB discussion and intraoperative findings of 91.5%. Concordance rate was 99% for resectable lesions and 64.3% for borderline PCs. Conclusions: MDTB discussion consistently influences PC management, with significant variations in terms of diagnosis, tumor response assessment and resectability. In this last regard, MDTB discussion plays a key role, as demonstrated by the high concordance rate between MDTB resectability definition and intraoperative findings.

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