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BACKGROUND: Sarcopenia, defined as a loss of skeletal muscle mass and quality, is found in 30-65% of patients with pancreatic ductal adenocarcinoma (PDAC) at diagnosis, and is a poor prognostic factor. However, it is yet to be evaluated why sarcopenia is associated with poor prognosis. Therefore, this study elucidated the tumor characteristics of PDAC with sarcopenia, including driver gene alterations and tumor microenvironment. PATIENTS AND METHODS: We retrospectively analyzed 162 patients with PDAC who underwent pancreatic surgery between 2008 and 2017. We defined sarcopenia by measuring the skeletal muscle mass at the L3 level using preoperative computed tomography images and evaluated driver gene alteration (KRAS, TP53, CDKN2A/p16, and SMAD4) and tumor immune (CD4+, CD8+, and FOXP3+) and fibrosis status (stromal collagen). RESULTS: In localized-stage PDAC (stage ≤ IIa), overall survival (OS) and recurrence-free survival were significantly shorter in the sarcopenia group than in the non-sarcopenia group (2-year OS 89.7% versus 59.1%, P = 0.03; 2-year RFS 74.9% versus 50.0%, P = 0.02). Multivariate analysis revealed that sarcopenia was an independent poor prognostic factor in localized-stage PDAC. Additionally, tumor-infiltrating CD8+ T cells in the sarcopenia group were significantly less than in the non-sarcopenia group (P = 0.02). However, no difference was observed in driver gene alteration and fib.rotic status. These findings were not observed in advanced-stage PDAC (stage ≥ IIb). CONCLUSIONS: Sarcopenia was associated with a worse prognosis and decreased tumor-infiltrating CD8+ T cells in localized-stage PDAC. Sarcopenia may worsen a patient's prognosis by suppressing local tumor immunity.
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Linfócitos T CD8-Positivos , Carcinoma Ductal Pancreático , Linfócitos do Interstício Tumoral , Músculo Esquelético , Neoplasias Pancreáticas , Sarcopenia , Sarcopenia/diagnóstico por imagem , Sarcopenia/etiologia , Prognóstico , Carcinoma Ductal Pancreático/complicações , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/imunologia , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/imunologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos T CD8-Positivos/imunologia , Estadiamento de Neoplasias , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologiaRESUMO
BACKGROUND AND AIM: Endoscopic ultrasonography (EUS) findings of the pancreatic parenchyma, such as hyperechoic foci/stranding and lobularity, may be associated with the severity of chronic pancreatitis (CP). However, the correlation between parenchymal EUS findings and histology remains unclear. We designed a large-scale retrospective study analyzing over 200 surgical specimens to elucidate the association between parenchymal EUS findings and histological features. METHODS: Clinical data of 221 patients with pancreatobiliary tumors who underwent preoperative EUS and pancreatic surgery between January 2010 and November 2020 were reviewed to investigate the association between parenchymal EUS findings and histological features at the pancreatic body. None of these patients met the definition of CP. RESULTS: Of the 221 patients, 87 (39.4%), 89 (40.2%), and 45 (20.4%) had normal EUS findings, hyperechoic foci/stranding without lobularity, and hyperechoic foci/stranding with lobularity, respectively. In the multivariate analyses, parenchymal EUS findings significantly correlated with histological CP findings of fibrosis, inflammation, and atrophy (hyperechoic foci/stranding without lobularity vs hyperechoic foci/stranding with lobularity, odds ratio [95% confidence interval]: 4.1 [2.2-7.9] vs 31.3 [9.3-105.6], Ptrend < 0.001; 3.9 [1.9-8.2] vs 21.8 [8.0-59.4], Ptrend < 0.001; and 4.0 [2.0-7.8] vs 22.9 [7.0-74.5], Ptrend < 0.001, respectively). Further, a trend toward higher histological grade was observed in the following order: normal findings, hyperechoic foci/stranding without lobularity, and hyperechoic foci/stranding with lobularity. CONCLUSIONS: Endoscopic ultrasonography findings of the pancreatic parenchyma may be associated with the histological conditions in CP, such as pancreatic fibrosis, inflammation, and atrophy. Lobularity reflects more severe histological conditions than does hyperechoic foci/stranding.
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Endossonografia , Pancreatite Crônica , Humanos , Estudos Retrospectivos , Pancreatite Crônica/patologia , Inflamação , FibroseRESUMO
BACKGROUND: A step-up approach is recommended as a new treatment algorithm for pancreatic fluid collections (PFCs). However, determining which patients with PFCs require a step-up approach after endoscopic ultrasound-guided transmural drainage (EUS-TD) is unclear. If the need for a step-up approach could be predicted, it could be performed early for relevant patients. We aimed to identify PFC-related predictive factors for a step-up approach after EUS-TD. METHODS: This retrospective cohort study included consecutive patients who had undergone EUS-TD for PFCs from January 2008 to May 2020. Multivariable logistic regression analyses were performed to investigate PFC factors related to requiring a step-up approach. A step-up approach was performed for patients who did not respond clinically to EUS-TD. RESULTS: We enrolled 81 patients, of whom 25 (30.9%) required a step-up approach. In multivariate logistic regression analysis, the pre-EUS-TD number of PFC-occupied regions ≥ 3 (multivariate odds ratio [OR] 16.2, 95% confidence interval [CI] 2.68-97.6, P = 0.002), the post-EUS-TD PFC-remaining percentage ≥ 35% (multivariate OR 19.9, 95% CI 2.91-136.1, P = 0.002), and a positive sponge sign, which is a distinctive computed tomography finding in the early stage after EUS-TD (multivariate OR 6.26, 95% CI 1.33-29.3, P = 0.020), were independent predictive factors associated with requiring a step-up approach for PFCs. CONCLUSION: Pre-EUS-TD PFC-occupied regions, post-EUS-TD PFC-remaining percentage, and a positive sponge sign were predictors of the need for a step-up approach. Patients with PFC with these findings should be offered a step-up approach whereas conservative treatment is recommended for patients without these findings. CLINICAL REGISTRATION NUMBER: UMIN 000030898.
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Pancreatopatias , Humanos , Estudos Retrospectivos , Endossonografia/métodos , Tomografia Computadorizada por Raios X , Drenagem/métodos , Stents , Ultrassonografia de Intervenção/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) concomitant with intraductal papillary mucinous neoplasm (IPMN) is defined as PDAC occurring apart from IPMN. This study comprehensively investigated the molecular biologic characteristics of PDAC concomitant with IPMN in major genetic alterations, tumor microenvironment, and prognosis by contrast with those of conventional PDAC. METHODS: The study retrospectively reviewed the data of 158 surgically resected PDAC patients. The driver gene alteration status (KRAS, TP53, CDKN2A, SMAD4, and GNAS) together with the immune and fibrotic status in tumor was evaluated. The prognosis of PDAC concomitant with IPMN and that of conventional PDAC also were compared. RESULTS: No statistically significant difference was found between PDAC concomitant with IPMN and conventional PDAC in the alteration frequency analysis of the major driver genes and the immune and fibrotic status in the tumor microenvironment. Overall survival and disease-free survival between patients who had PDAC concomitant with IPMN and those who had conventional PDAC did not show statistically significant differences in propensity-matched subjects. Furthermore, the co-existence of IPMN was not a poor prognostic factor in the multivariable-adjusted Cox proportional hazards model (hazard ratio, 0.95; 95 % confidence interval, 0.51-1.78). CONCLUSIONS: In this study, PDAC concomitant with IPMN had tumor characteristics similar to those of conventional PDAC in terms of the major driver gene alterations, tumor microenvironment, and prognosis.
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Adenocarcinoma Mucinoso , Adenocarcinoma Papilar , Produtos Biológicos , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Papilar/patologia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos , Microambiente Tumoral/genética , Neoplasias PancreáticasRESUMO
BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is associated with acute pancreatitis (AP) in some cases, however its causes have not been fully elucidated. We investigated the association of the incidence of AP with epithelial subtypes and pancreatic volume in IPMN. METHODS: This retrospective study included 182 consecutive surgically resected IPMN patients between January 2000 and December 2018. The relationship between the incidence of AP and epithelial subtypes of IPMN and pancreatic volume was investigated. Epithelial subtypes of IPMN were classified into gastric (G type: N = 116), intestinal (I type: N = 49), pancreatobiliary (PB type: N = 14), and oncocytic types (O type: N = 3). Pancreatic volume of the contrast-enhanced computed tomography scan was measured using Ziostation2 software. Histological pancreatic parenchymal atrophy was also evaluated. RESULTS: AP occurred more frequently in I-types (I-type vs. G-type, 22.4% [11/49] vs 3.4% [4/116], P = 0.003) and PB-types (PB type vs. G-type, 35.7% [5/14] vs. 3.4% [4/116], P = 0.007) in comparison with G-types, which constituted the majority of the resected IPMNs. AP occurred more frequently in I-type patients with high pancreatic volumes (I-type with high pancreatic volume vs. I-type with low pancreatic volume, 37.0% [10/27] vs. 4.7% [1/21], P = 0.02). However, histological atrophy did not show an additional influence on the association between the incidence of AP and epithelial subtypes. The elevation of serum pancreatic enzymes was not significantly related to epithelial subtypes. CONCLUSION: Epithelial subtypes and the degree of pancreatic volume may be closely associated with the incidence of AP in IPMN.
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Carcinoma Ductal Pancreático/complicações , Carcinoma Ductal Pancreático/diagnóstico por imagem , Pâncreas/diagnóstico por imagem , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/diagnóstico por imagem , Pancreatite/diagnóstico por imagem , Pancreatite/etiologia , Adenocarcinoma Mucinoso , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/patologia , Meios de Contraste , Epitélio/diagnóstico por imagem , Epitélio/patologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pâncreas/enzimologia , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Pancreatite/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Video 1Pancreatic cannulation via the uneven method.
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OBJECTIVES: Aging is associated with a high prevalence of pancreatic cysts and intraductal papillary mucinous neoplasms (IPMNs). Metabolic syndrome (MS) may increase the risk of neoplasms, including those that develop in the pancreas. However, the influence of factors associated with MS on the development of IPMN remains unclear. METHODS: A total of 9363 patients who underwent abdominal ultrasound examinations between April 2012 and May 2013 were included in this study. Multivariate logistic regression analysis was performed to identify factors associated with the presence of IPMN by age. RESULTS: Pancreatic cysts were detected in 198 of 9363 patients, of whom 129 were found to have IPMNs. The presence of IPMN significantly correlated with age (10-year increments; odds ratio, 2.73; 95% CI, 2.28-3.29; P < 0.001). High body mass index, history of smoking, hyperlipidemia, hypertension, and MS were associated with a higher prevalence of IPMN with advancing age. In multivariate analysis, the presence of IPMN was more frequent in elderly patients with MS (odds ratio, 3.14; 95% CI, 3.14-6.72; P = 0.003). CONCLUSIONS: The present study suggests that the incidence of IPMN increases with age and is accelerated in the presence of MS.
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Adenocarcinoma Mucinoso , Carcinoma Ductal Pancreático , Síndrome Metabólica , Cisto Pancreático , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Humanos , Idoso , Carcinoma Ductal Pancreático/epidemiologia , Síndrome Metabólica/epidemiologia , Adenocarcinoma Mucinoso/epidemiologia , Adenocarcinoma Mucinoso/metabolismo , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/metabolismo , Pâncreas/metabolismo , Estudos RetrospectivosRESUMO
BACKGROUND: Recent evidence suggests that the presence of microbiome within human pancreatic ductal adenocarcinoma (PDAC) tissue potentially influences cancer progression and prognosis. However, the significance of tumor-resident microbiome remains unclear. We aimed to elucidate the impact of intratumoral bacteria on the pathophysiology and prognosis of human PDAC. METHODS: The presence of intratumoral bacteria was assessed in 162 surgically resected PDACs using quantitative polymerase chain reaction (qPCR) and in situ hybridization (ISH) targeting 16S rRNA. The intratumoral microbiome was explored by 16S metagenome sequencing using DNA extracted from formalin-fixed paraffin-embedded tissues. The profile of intratumoral bacteria was compared with clinical information, pathological findings including tumor-infiltrating T cells, tumor-associated macrophage, fibrosis, and alterations in four main driver genes (KRAS, TP53, CDKN2A/p16, SMAD4) in tumor genomes. RESULTS: The presence of intratumoral bacteria was confirmed in 52 tumors (32%) using both qPCR and ISH. The 16S metagenome sequencing revealed characteristic bacterial profiles within these tumors, including phyla such as Proteobacteria and Firmicutes. Comparison of bacterial profiles between cases with good and poor prognosis revealed a significant positive correlation between a shorter survival time and the presence of anaerobic bacteria such as Bacteroides, Lactobacillus, and Peptoniphilus. The abundance of these bacteria was correlated with a decrease in the number of tumor-infiltrating T cells positive for CD4, CD8, and CD45RO. CONCLUSIONS: Intratumoral infection of anaerobic bacteria such as Bacteroides, Lactobacillus, and Peptoniphilus is correlated with the suppressed anti-PDAC immunity and poor prognosis.
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Carcinoma Ductal Pancreático , Microbiota , Neoplasias Pancreáticas , Humanos , RNA Ribossômico 16S , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , PrognósticoRESUMO
BACKGROUND: Focal parenchymal atrophy and main pancreatic duct (MPD) dilatation have been identified as early signs of pancreatic ductal adenocarcinoma. However, limited evidence exists regarding their temporal progression due to previous study limitations with restricted case numbers. OBJECTIVE: To ascertain a more precise frequency assessment of suspicious pancreatic ductal adenocarcinoma findings as well as delineate the temporal progression of them. METHODS: A multicenter retrospective study was conducted on patients diagnosed with pancreatic ductal adenocarcinoma between 2015 and 2021. We included patients who had undergone at least one computed tomography (CT) scan ≥6 months before diagnosing pancreatic ductal adenocarcinoma. The temporal progression of suspicious pancreatic ductal adenocarcinoma findings on CT was investigated. RESULTS: Out of 1832 patients diagnosed with pancreatic ductal adenocarcinoma, 320 had a previous CT before their diagnosis. Suspicious pancreatic ductal adenocarcinoma findings were detected in 153 cases (47.8%), with focal parenchymal atrophy (26.6%) being the most common followed by MPD dilatation (11.3%). Focal parenchymal atrophy was the earliest detectable sign among all suspicious findings and became visible on average 2.7 years before diagnosis, and the next most common, MPD dilatation, 1.1 years before diagnosis. Other findings, such as retention cysts, were less frequent and appeared around 1 year before diagnosis. Focal parenchymal atrophy followed by MPD dilatation was observed in 10 patients but not in reverse order. Focal parenchymal atrophy was more frequently detected in the pancreatic body/tail. No significant relationship was found between the pathological pancreatic ductal adenocarcinoma differentiation or tumor stage and the time course of the CT findings. All cases of focal parenchymal atrophy progressed just prior to diagnosis, and the atrophic area was occupied by tumor at diagnosis. Main pancreatic duct dilatation continued to progress until diagnosis. CONCLUSION: This large-scale study revealed that the temporal progression of focal parenchymal atrophy is the earliest detectable sign indicating pancreatic ductal adenocarcinoma. These results provide crucial insights for early pancreatic ductal adenocarcinoma detection.
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Atrofia , Carcinoma Ductal Pancreático , Progressão da Doença , Ductos Pancreáticos , Neoplasias Pancreáticas , Tomografia Computadorizada por Raios X , Humanos , Estudos Retrospectivos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/diagnóstico , Masculino , Feminino , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/patologia , Pessoa de Meia-Idade , Idoso , Ductos Pancreáticos/diagnóstico por imagem , Ductos Pancreáticos/patologia , Fatores de Tempo , Detecção Precoce de Câncer/métodos , Dilatação Patológica/diagnóstico por imagem , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Adulto , Idoso de 80 Anos ou maisRESUMO
A 75-year-old Japanese woman visited a hospital with a stomachache. The patient was diagnosed with localized mild acute pancreatitis. Blood tests revealed elevated serum IgG4 levels. Contrast-enhanced computed tomography showed a hypovascular mass, 3 cm in size, in the pancreatic body with dilation of the upstream duct. Additionally, it showed another tumorous lesion of 10 mm in size in the anterior wall of the stomach, and endoscopic examination confirmed a submucosal tumor (SMT) sized 10 mm in the anterior wall of the stomach. Endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) of the pancreas revealed an adenocarcinoma concomitant with marked IgG4-positive cell infiltration. Hence, distal pancreatectomy with local gastrectomy was performed, and the final diagnosis was concluded as pancreatic ductal adenocarcinoma (PDAC) complicated by IgG4-related diseases (IgG4-RD) in the pancreas and stomach. IgG4-RD of the digestive tract is exceedingly rare. The correlation between PDAC and autoimmune pancreatitis or malignancy and IgG4-RD is controversial. However, the clinical course and histopathological examination, in this case, provide valuable suggestive findings for further discussion.
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Adenocarcinoma , Doenças Autoimunes , Carcinoma Ductal Pancreático , Doença Relacionada a Imunoglobulina G4 , Neoplasias Pancreáticas , Pancreatite , Feminino , Humanos , Idoso , Doença Relacionada a Imunoglobulina G4/complicações , Doença Relacionada a Imunoglobulina G4/diagnóstico , Pancreatite/complicações , Pancreatite/diagnóstico , Doença Aguda , Pâncreas/patologia , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Carcinoma Ductal Pancreático/complicações , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/diagnóstico , Estômago/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirurgia , Imunoglobulina G , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , Neoplasias PancreáticasRESUMO
When the etiology of pancreatitis cannot be determined despite sufficient investigation, recurrence and progression to chronic pancreatitis often involve genetic mutations. Herein, we describe a case of recurrent pancreatitis with the IVS3+2T>C mutation in the serine protease inhibitor Kazal type 1 (SPINK1) gene that progressed to chronic pancreatitis in only 3 years. A 35-year-old man was referred to our hospital, where he was diagnosed with mild pancreatitis and was treated conservatively. However, the patient experienced recurrent episodes of pancreatitis, which progressed to become chronic pancreatitis with a pancreatic calcification 1 year later. After 3 years, the patient developed pancreatic duct stenosis and required a pancreatic duct stent placement. Regarding the cause of chronic pancreatitis, alcohol abuse was ruled out based on history taking. Considering the course of treatment, autoimmune pancreatitis and obstructive pancreatitis, such as pancreatic divisum, were also ruled out. Finally, a germline genetic test was performed to determine the etiology of pancreatitis, which revealed the IVS3+2T>C mutation in SPINK1. This case shows the importance of genetic testing in patients with idiopathic pancreatitis to determine their etiology and is a rare incident that can report the progression of the disease from acute to chronic pancreatitis.
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BACKGROUND: Tertiary lymphoid structure (TLS) reflects an intense immune response against cancer, which correlates with favorable patient survival. However, the association of TLS with tumor-infiltrating lymphocytes (TILs) and clinical outcomes has not been investigated comprehensively in pancreatic ductal adenocarcinoma (PDAC). METHODS: We utilized an integrative molecular pathological epidemiology database on 162 cases with resected PDAC, and examined TLS in relation to levels of TILs, patient survival, and treatment response. In whole-section slides, we assessed the formation of TLS and conducted immunohistochemistry for tumor-infiltrating T cells (CD4, CD8, CD45RO, and FOXP3). As confounding factors, we assessed alterations of four main driver genes (KRAS, TP53, CDKN2A [p16], and SMAD4) using next-generation sequencing and immunohistochemistry, and tumor CD274 (PD-L1) expression assessed by immunohistochemistry. RESULTS: TLSs were found in 112 patients with PDAC (69.1%). TLS was associated with high levels of CD4+ TILs (multivariable odds ratio [OR], 3.50; 95% confidence interval [CI] 1.65-7.80; P = 0.0002), CD8+ TILs (multivariable OR, 11.0; 95% CI 4.57-29.7, P < 0.0001) and CD45RO+ TILs (multivariable OR, 2.65; 95% CI 1.25-5.80, P = 0.01), but not with levels of FOXP3+ TILs. TLS was associated with longer pancreatic cancer-specific survival (multivariable hazard ratio, 0.37; 95% CI 0.25-0.56, P < 0.0001) and favorable outcomes of adjuvant S-1-treatment. TLS was not associated with driver gene alterations but tumor CD274 negative expression. CONCLUSIONS: Our comprehensive data supports the surrogacy of TLS for vigorous anti-tumor immune response characterized by high levels of helper and cytotoxic T cells and their prognostic role.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Estruturas Linfoides Terciárias , Humanos , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Estruturas Linfoides Terciárias/metabolismo , Estruturas Linfoides Terciárias/patologia , Carcinoma Ductal Pancreático/genética , Prognóstico , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Neoplasias PancreáticasRESUMO
BACKGROUND: Abundant collagen deposition is a hallmark of pancreatic ductal adenocarcinomas (PDACs). This study clarified the interactive relationship between tumor-stromal collagen, molecular and immune characteristics, and tumor pr ogression in human PDAC. METHODS: We performed a comprehensive examination using an integrative molecular pathological epidemiology database on 169 cases with resected PDAC . The amount of tumor-stromal collagen was quantified through digital imaging analysis for Elastica van Gieson-stained whole-section tumor slides. We analyzed the association of tumor-stromal collagen with gene alterations (KRAS, TP53, CDKN2A/p16, and SMAD4), immune parameters (CD4+ tumor-infiltrating lymphocytes [TILs], CD8+ TILs, FOXP3+ TILs, and tertiary lymphoid structures), and patient prognosis. RESULTS: Low amounts of tumor-stromal collagen were associated with poor differentiation (multivariable OR = 3.82, 95%CI = 1.41-12.2, P = 0.008) and CDKN2A/p16 alteration (OR [95%CI] = 2.06 [1.08-4.02], P = 0.03). Tumors with low collagen levels had shorter overall survival (HR [95%CI] = 2.38 [1.59-3.56], P < 0.0001). In the S-1 and gemcitabine (GEM) treatment groups, low tumor-stromal collagen was linked to poor prognosis of patients with PDAC (S-1 group: multivariable HR [95%CI] = 2.76 [1.36-5.79], P = 0.005; GEM group: multivariate HR [95%CI] = 2.91 [1.34-6.71], P = 0.007). Additionally, low amounts of tumor-stromal collagen were also linked to low levels of CD4+ TILs (P = 0.046), CD8+ TILs (P = 0.09), and tertiary lymphoid structures (P = 0.001). CONCLUSIONS: Tumor-stromal collagen deposition may play a crucial role in modulating tumor-immune microenvironment and determining response to adjuvant chemotherapy and patient survival outcomes.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Estruturas Linfoides Terciárias , Humanos , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Prognóstico , Linfócitos do Interstício Tumoral/patologia , Colágeno , Microambiente Tumoral , Neoplasias PancreáticasRESUMO
Pancreatic cancer primarily arises from microscopic precancerous lesions, such as pancreatic intraepithelial neoplasia (PanIN) and acinar-to-ductal metaplasia (ADM). However, no established method exists for predicting pancreatic precancerous conditions. Endoscopic ultrasonography (EUS) can detect changes in pancreatic parenchymal histology, including fibrosis. This study aimed to elucidate the relationship between pancreatic parenchymal EUS findings and microscopic precancerous lesions. We retrospectively analyzed 114 patients with pancreatobiliary tumors resected between 2010 and 2020 and evaluated the association between pancreatic parenchymal EUS findings and the number of PanIN, ADM, and pancreatic duct gland (PDG). Of the 114 patients, 33 (29.0%), 55 (48.2%), and 26 (22.8%) had normal EUS findings, hyperechoic foci/stranding without lobularity, and hyperechoic foci/stranding with lobularity, respectively. Multivariate analyses revealed that abnormal EUS findings were significantly associated with the frequency of PanIN (hyperechoic foci/stranding without lobularity: OR [95% CI] = 2.7 [1.0-7.3], with lobularity: 6.5 [1.9-22.5], Ptrend = 0.01) and ADM (hyperechoic foci/stranding without lobularity: 3.1 [1.1-8.2], with lobularity: 9.7 [2.6-36.3], Ptrend = 0.003) but not with PDG (hyperechoic foci/stranding without lobularity: 2.2 [0.8-5.8], with lobularity: 3.2 [1.0-10.2], Ptrend = 0.12). We observed a trend toward a significantly higher number of precancerous lesions in the following order: normal findings, hyperechoic foci/stranding without lobularity, and hyperechoic foci/stranding with lobularity. Pancreatic parenchymal EUS findings were associated with the increased frequency of PanIN and ADM. Lobularity may help predict the increased number of precancerous lesions.
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Carcinoma in Situ , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Lesões Pré-Cancerosas , Humanos , Endossonografia/métodos , Estudos Retrospectivos , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Lesões Pré-Cancerosas/diagnóstico por imagem , Lesões Pré-Cancerosas/patologia , Carcinoma in Situ/patologia , Metaplasia/patologia , Carcinoma Ductal Pancreático/patologia , Neoplasias PancreáticasRESUMO
Endoscopic papillectomy for early ampullary tumors is considered a minimally invasive and useful alternative to pancreatoduodenectomy; however, its indications remain unclear. This study aimed to clarify the advantages of endoscopic papillectomy by investigating the clinical outcomes of patients who underwent endoscopic papillectomy or pancreatoduodenectomy for early ampullary tumors. Patients diagnosed with early ampullary tumors (adenoma, Tis, T1a) who underwent endoscopic papillectomy or pancreatoduodenectomy between June 2008 and October 2019 were included, and their clinical outcomes were analyzed. Seventy-four patients (34 patients with adenomas and 40 patients with adenocarcinomas) were divided into two groups, namely endoscopic papillectomy (n = 43) and pancreatoduodenectomy (n = 31). The estimated 5-year overall survival rate of all early ampullary tumors was 92%. Complete resection rate was significantly lower for endoscopic papillectomy patients versus pancreatoduodenectomy patients (48.8% vs. 100%; p < 0.001). Recurrence was more common in the endoscopic papillectomy group compared to the pancreatoduodenectomy group (16.3% vs. 3.2%; p = 0.128), but all recurrences were controllable by endoscopic treatment. The median length of hospital stay for the endoscopic papillectomy group was significantly shorter compared to the endoscopic papillectomy group (11 days vs. 42 days; p < 0.001). The Comprehensive Complication Index was significantly lower in the endoscopic papillectomy group compared to the pancreatoduodenectomy group (14.8 vs 22.6%; p = 0.002). Endoscopic papillectomy for early ampullary tumors is useful and may be an alternative treatment for pancreatoduodenectomy in selected cases.
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Adenoma , Ampola Hepatopancreática , Neoplasias do Ducto Colédoco , Neoplasias Duodenais , Neoplasias Pancreáticas , Adenoma/patologia , Ampola Hepatopancreática/patologia , Ampola Hepatopancreática/cirurgia , Neoplasias do Ducto Colédoco/patologia , Neoplasias Duodenais/patologia , Humanos , Neoplasias Pancreáticas/patologia , Pancreaticoduodenectomia/efeitos adversos , Estudos Retrospectivos , Esfinterotomia Endoscópica/efeitos adversos , Resultado do TratamentoRESUMO
A 78-year-old man who underwent right nephrectomy for renal cell carcinoma (RCC) 18 years ago visited our hospital complaining of abdominal pain. Imaging revealed that the pancreatic head tumor obstructed the Santorini duct. We suspected a pancreatic intraductal tumor, such as an intraductal tubulopapillary neoplasm or intraductal papillary mucinous neoplasm. Thus, the patient underwent subtotal stomach-preserving pancreaticoduodenectomy. Pathological findings confirmed the diagnosis of metastatic RCC. Herein, we report a case of pancreatic metastasis of an RCC that presented with a tumor in the pancreatic duct.
Assuntos
Carcinoma Ductal Pancreático , Carcinoma de Células Renais , Neoplasias Renais , Neoplasias Pancreáticas , Idoso , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/cirurgia , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Masculino , Ductos Pancreáticos/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgiaRESUMO
BACKGROUND: Hepatic portal venous gas (HPVG) generally indicates poor prognoses in patients with serious intestinal damage. Although surgical removal of the damaged portion is effective, some patients can recover with conservative treatments. AIM: To establish an optimal treatment strategy for HPVG, we attempted to generate computed tomography (CT)-based criteria for determining surgical indication, and explored reliable prognostic factors in non-surgical cases. METHODS: Thirty-four cases of HPVG (patients aged 34-99 years) were included. Necessity for surgery had been determined mainly by CT findings (i.e. free-air, embolism, lack of contrast enhancement of the intestinal wall, and intestinal pneumatosis). The clinical data, including treatment outcomes, were analyzed separately for the surgical cases and non-surgical cases. RESULTS: Laparotomy was performed in eight cases (surgical cases). Seven patients (87.5%) survived but one (12.5%) died. In each case, severe intestinal damage was confirmed during surgery, and the necrotic portion, if present, was removed. Non-occlusive mesenteric ischemia was the most common cause (n = 4). Twenty-six cases were treated conservatively (non-surgical cases). Surgical treatments had been required for twelve but were abandoned because of the patients' poor general conditions. Surprisingly, however, three (25%) of the twelve inoperable patients survived. The remaining 14 of the 26 cases were diagnosed originally as being sufficiently cured by conservative treatments, and only one patient (7%) died. Comparative analyses of the fatal (n = 10) and recovery (n = 16) cases revealed that ascites, peritoneal irritation signs, and shock were significantly more frequent in the fatal cases. The mortality was 90% if two or all of these three clinical findings were detected. CONCLUSION: HPVG related to intestinal necrosis requires surgery, and our CT-based criteria are probably useful to determine the surgical indication. In non-surgical cases, ascites, peritoneal irritation signs and shock were closely associated with poor prognoses, and are applicable as predictors of patients' prognoses.
Assuntos
Ascite/terapia , Embolia Aérea/terapia , Isquemia Mesentérica/terapia , Pneumatose Cistoide Intestinal/terapia , Veia Porta/cirurgia , Choque/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ascite/diagnóstico , Ascite/etiologia , Ascite/mortalidade , Tratamento Conservador/estatística & dados numéricos , Embolia Aérea/diagnóstico , Embolia Aérea/etiologia , Embolia Aérea/mortalidade , Feminino , Gases , Humanos , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/patologia , Mucosa Intestinal/cirurgia , Masculino , Isquemia Mesentérica/complicações , Isquemia Mesentérica/diagnóstico , Isquemia Mesentérica/mortalidade , Necrose/complicações , Necrose/diagnóstico , Necrose/mortalidade , Necrose/cirurgia , Pneumatose Cistoide Intestinal/diagnóstico , Pneumatose Cistoide Intestinal/etiologia , Pneumatose Cistoide Intestinal/mortalidade , Veia Porta/diagnóstico por imagem , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Choque/diagnóstico , Choque/etiologia , Choque/mortalidade , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
A 66-year-old Japanese man was referred to our hospital with multiple giant liver cysts. The cysts had already been detected as multiple 3-cm cysts with small nodules at another hospital 12 years prior to this presentation. The cysts were diagnosed as an intraductal papillary neoplasms of the bile duct (IPNB) occupying the right lobe of the liver. Extended right lobectomy was performed. Based on the pathological findings, the tumor was diagnosed to be an oncocytic-type IPNB with minimal invasion. This experience suggests that the progression of IPNBs occur relatively slowly. The present case might provide important information for understanding the natural history of IPNBs.
Assuntos
Adenocarcinoma Mucinoso , Neoplasias dos Ductos Biliares , Cistos , Idoso , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares , Ductos Biliares Intra-Hepáticos , Humanos , MasculinoRESUMO
BACKGROUND AND AIMS: Imaging tools for predicting pancreatic atrophy after steroid therapy in autoimmune pancreatitis (AIP) have not been established. As delayed equilibrium-phase contrast enhancement in computed tomography (CE-CT) may reflect interstitial fibrosis, we evaluated the ability of equilibrium-phase CT imaging for predicting pancreatic atrophy. METHODS: Forty-six steroid-treated AIP patients who underwent contrast-enhanced CT at our university hospital were included in this retrospective study. CT attenuation (Hounsfield units [HU]) values in noncontrast images (NC) and equilibrium-phase images (EP) and the differences in HU values between NC and EP images (SUB) were measured. Pancreatic volume was measured in CE-CT before (Volpre) and after (Volpost) steroid therapy. The volume reduction rate was calculated. The relationships of CT values with pancreatic atrophy, Volpost, volume reduction rate, and diabetes exacerbation were investigated. RESULTS: CT values in the EP and SUB images before steroid therapy were associated with pancreatic atrophy after steroid therapy (atrophy vs nonatrophy 114.5 ± 12.8 vs 99.5 ± 11.1, P = 0.0002; 70.9 ± 14.72 vs 57.2 ± 13.1, P = 0.003, respectively), but CT values in NC images were not (P = 0.42). CT values in EP and SUB images before steroid therapy were correlated with Volpost (EP images r = -0.70, P = 0.002; SUB images r = -0.68, P = 0.03) and volume reduction rate after steroid therapy (EP images: r = -0.55, P < 0.0001; SUB images r = -0.45, P = 0.002). Diabetes exacerbation was associated with higher EP and SUB values (P = 0.009 and P = 0.04, respectively). CONCLUSION: Equilibrium-phase contrast CT imaging may facilitate prediction of pancreatic atrophy after steroid therapy in AIP.