pancreatic ductal adenocarcinoma

胰腺导管腺癌
  • 文章类型: Case Reports
    本报告详细介绍了一例胰腺癌肝转移,对个性化免疫疗法表现出积极的免疫反应。我们的研究涉及使用内部生物信息学管道鉴定新抗原及其相应的免疫原性肽。该过程包括通过实体瘤组织的DNA/RNA测序和血液活检来鉴定体细胞突变。然后采用计算预测技术来鉴定新的表位,然后设计和制造患者特异性免疫肽。结合标准治疗化疗,患者接受了一系列每周5次的初始注射,然后在2个月和5个月后进行2次强化注射。将肽在Montanide中乳化,并用纳武单抗和咪喹莫特调节注射部位。肽免疫和化疗的组合方案导致在初免和加强应用后CA19-9肿瘤标志物水平的显著下降。随后的MRI评估显示,在免疫开始后几个月,肝转移的大小减小。重要的是,患者显示并改善了总生存期,并报告了生活质量的改善,但未出现明显的治疗相关不良反应.该病例强调了个性化基于肽的免疫作为辅助治疗晚期胰腺癌的潜在益处。在肿瘤标志物减少方面展示了有希望的结果,肿瘤缩小,增强患者的幸福感。
    This report details a case of pancreatic cancer with liver metastasis that exhibited a positive immune response to personalized immunization therapy. Our study involved the identification of neoantigens and their corresponding immunogenic peptides using an in-house bioinformatic pipeline. This process included the identification of somatic mutations through DNA/RNA sequencing of solid tumor tissue and blood liquid biopsy. Computational prediction techniques were then employed to identify novel epitopes, followed by the design and manufacture of patient-specific immunization peptides. In combination with standard-of-care chemotherapy, the patient received a sequence of 5 biweekly prime injections followed by 2 boost injections 2 and 5 months later. The peptides were emulsified in Montanide and the injection-site was conditioned with nivolumab and imiquimod. The combined regimen of peptide immunization and chemotherapy resulted in a notable decline in CA19-9 tumor marker levels following both prime and boost applications. Subsequent MRI assessments revealed a reduction in the size of liver metastases several months post-immunization initiation. Importantly, the patient showed and improved overall survival and reported an improved quality of life without experiencing significant treatment-related adverse effects. This case underscores the potential benefits of personalized peptide-based immunization as an adjunctive therapy in the treatment of advanced pancreatic cancer, showcasing promising outcomes in tumor marker reduction, tumor shrinkage, and enhanced patient well-being.
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  • 文章类型: Case Reports
    胰腺导管腺癌(PDAC)与不良预后相关,复发率>70%,即使在可切除的情况下。复发性PDAC的治疗策略包括全身化疗,吉西他滨(GEM)单药治疗历来是标准治疗。本研究描述了患有PDAC和术后肝转移的患者在GEM单一疗法后维持临床完全缓解(cCR)>7年的情况。一名63岁的上腹痛妇女被诊断为可切除的PDAC,并接受了胰十二指肠切除术。患者接受GEM+S-1辅助化疗6个月。术后15个月检测到多发性肝转移,患者仅接受GEM治疗。12次循环后,计算机断层扫描显示cCR和GEM单药治疗在15个周期后停止.患者在首次复发后>7年没有复发的体征或症状。此外,本研究分析了四名患者的PDAC切除标本,包括这个案子,检测hENT1蛋白在肿瘤组织中的表达水平。hENT1是跨膜蛋白,其充当核苷转运蛋白,并且是GEM摄取进入人细胞的主要介质。在目前的情况下,hENT1染色在中心区表现出低频和弱阳性,而在癌症侵袭性前部的几乎所有细胞膜中都观察到强烈的阳性反应。位置,强度,hENT1染色的频率因病例而异。总之,GEM的疗效可以在治疗前通过评估hENT1表达来预测。
    Pancreatic ductal adenocarcinoma (PDAC) is associated with a poor prognosis, and it has a recurrence rate of >70%, even in resectable cases. The treatment strategy for recurrent PDAC involves systemic chemotherapy, with gemcitabine (GEM) monotherapy historically serving as the standard of care. The present study describes the case of a patient with PDAC and postoperative liver metastases that maintained clinical complete remission (cCR) for >7 years following GEM monotherapy. A 63-year-old woman with upper abdominal pain was diagnosed with resectable PDAC and underwent pancreaticoduodenectomy. The patient was treated with GEM + S-1 as adjuvant chemotherapy for 6 months. Multiple liver metastases were detected 15 months post-operation and the patient was administered GEM alone. After 12 cycles, computed tomography showed cCR and GEM monotherapy was discontinued after 15 cycles. The patient has had no signs or symptoms of recurrence >7 years after the first recurrence. In addition, the present study analyzed PDAC resection specimens from four patients, including this case, to determine the expression levels of hENT1 protein in the tumor tissues. hENT1 is a transmembrane protein that acts as a nucleoside transporter and is a major mediator of GEM uptake into human cells. In the present case, hENT1 staining exhibited low frequency and weak positivity in the central region, whereas a strong positive reaction was observed in nearly all cell membranes at the invasive front of the cancer. The location, intensity, and frequency of hENT1 staining varied among cases. In conclusion, the efficacy of GEM may be predicted prior to treatment by evaluating hENT1 expression.
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  • 文章类型: Case Reports
    4年前,在腹腔镜胰腺远端切除术和胰腺导管腺癌的脾切除术的背景下,对一名76岁妇女的上腹痛进行了调查。成像显示,孤立的32毫米氟代脱氧葡萄糖狂热病变同时接触前腹壁和胃的较大曲率。免疫组织化学和细针活检证实了与转移性胰腺癌一致的表型。进行了腹腔镜切除肿块和部分胃切除术以清除边缘。组织病理学显示低分化胰腺导管腺癌,患者接受吉西他滨/卡培他滨辅助治疗,术后过程简单。本文介绍了一例胰腺导管腺癌孤立性腹壁复发的罕见病例。通过手术切除和辅助化疗成功治疗。
    A 76-year-old woman was investigated for epigastric pain on a background of a laparoscopic distal pancreatectomy and splenectomy for pancreatic ductal adenocarcinoma 4 years prior. Imaging revealed an isolated 32 mm fluorodeoxyglucose avid lesion contacting both the anterior abdominal wall and greater curvature of the stomach. Immunohistochemistry and fine needle biopsy confirmed a phenotype consistent with metastatic pancreatic adenocarcinoma. Laparoscopic excision of the mass and partial gastrectomy for clearance of margins was performed. Histopathology demonstrated a poorly differentiated pancreatic ductal adenocarcinoma, and the patient received adjuvant gemcitabine/capecitabine following an uncomplicated postoperative course. This article presents a rare case of isolated abdominal wall recurrence of pancreatic ductal adenocarcinoma, which was successfully treated with surgical resection and adjuvant chemotherapy.
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  • 文章类型: Case Reports
    背景:在此,我们报告了一例极为罕见的胰腺腺癌与肠母细胞分化(AED),一种未被认识的组织学亚型。此外,肿瘤与神经内分泌癌(NEC)混合,这也是胰腺中一种罕见的恶性肿瘤。
    方法:患者是一名老年男性,偶然诊断为35毫米大小的胰头肿瘤,并接受了胰十二指肠切除术。组织病理学,肿瘤由四种不同类型组成:传统导管腺癌,AED,NEC,和鳞状细胞癌。有趣的是,p53过表达和Rb表达的丧失,这是NEC的特征发现,在所有组件中都观察到。手术后他接受了辅助化疗,然而,他在手术后14个月死于与沐浴相关的心脏骤停。
    结论:在胃中,AED,类似胎儿肠道上皮的癌,是一种罕见但确定的亚型,被认为是肝样癌(HAC)的相关实体。然而,胃AED和HAC在一定程度上不同。与胃相反,胃外AED,包括胰腺AED,非常罕见,其生物学特征尚不清楚。混合瘤与NEC是一个复杂的现象,但偶尔会在胃外AED中报告。混合AED-NEC的组织发生可以通过确定p53和Rb状态来解决。
    结论:由于其稀有和新颖的性质,胃外AED与HAC的认识不足或混淆。需要进一步的研究和建立胃外AED分类。
    BACKGROUND: Herein we report a case of an extremely rare pancreatic adenocarcinoma with enteroblastic differentiation (AED), an underrecognized histological subtype. Moreover, the tumor was mixed with a neuroendocrine carcinoma (NEC), which is also a rare malignancy in the pancreas.
    METHODS: The patient was an elderly male who was incidentally diagnosed with a 35 mm-sized pancreatic head tumor and underwent pancreatoduodenectomy. Histopathologically, the tumor was composed of four different types: conventional ductal adenocarcinoma, AED, NEC, and squamous cell carcinoma. Interestingly, p53 overexpression and loss of Rb expression, which are characteristic findings of NEC, were observed in all components. He had been received adjuvant chemotherapy after the surgery, however, he died of bath-related cardiac arrest 14 months after surgery.
    CONCLUSIONS: In the stomach, AED, a carcinoma resembling fetal gut epithelium, is a rare but established subtype and is considered a related entity of hepatoid carcinoma (HAC). However, gastric AED and HAC differ to some extent. In contrast to the stomach, extragastric AED, including pancreatic AED, is extremely rare, and its biological features are unclear. A mixed tumor with NEC is a complex phenomenon, but it is occasionally reported in extragastric AED. The histogenesis of mixed AED-NEC can be resolved by determining p53 and Rb status.
    CONCLUSIONS: Owing to their rare and novel nature, extragastric AED is under-recognized or confused with HAC. Further studies and the establishment of an extragastric AED classification are required.
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  • 文章类型: Case Reports
    肝脏通常由从腹腔干分支出来的肝动脉供血。偶尔,替换的肝总动脉(RCHA),从肠系膜上动脉(SMA)出现,可以在1.5-4.0%的病例中供应肝脏。计算机断层扫描(CT)血管造影是识别动脉异常的高度准确的方法,在手术之前可能不会被发现,导致意想不到的并发症。
    一名53岁的男性表现出食欲下降的症状,减肥,呕吐,改变巩膜,尿液,和凳子的颜色,接受了对比增强CT扫描,显示胆道扩张和胰腺异常,导致胰十二指肠切除术.在手术过程中,我们注意到来自SMA的罕见动脉发现-CHA.确诊胰腺癌。患者在手术后一周出院,没有任何问题,强调围手术期护理进展。
    作者\'研究的重点是在2017年至2023年之间报告的8例病例中相同肝动脉异常的检测条件。在其中两个尸体中,通过常规尸检发现了异常。在三种情况下,这种变异是在手术前发现的,但在另外三个病例中,直到手术后才发现。在作者的情况下,由于多种原因,异常在手术前仍未发现.
    本研究强调了彻底的术前评估以掌握血管变异对更好的患者护理的重要性。此外,在我们的案例中值得注意的观察是,外科医生发现了扩张的肝血管,促使进一步调查这一异常现象。
    UNASSIGNED: It is common for the liver to be supplied blood by a hepatic artery branching off the coeliac trunk. Occasionally, a replaced common hepatic artery (RCHA), emerges from the superior mesenteric artery (SMA), can supply the liver in 1.5-4.0% of cases. Computed tomography (CT) angiography is a highly accurate method for identifying arterial anomalies, which may remain undetected until the time of surgery, leading to unexpected complications.
    UNASSIGNED: A 53-year-old male exhibiting symptoms of decreased appetite, weight loss, vomiting, and altered sclera, urine, and stool colour, underwent a contrast-enhanced CT scan revealing biliary tract dilatation and pancreatic abnormalities, leading to a pancreaticoduodenectomy. During the surgery, an uncommon arterial finding-CHA from SMA-was noted. Pancreatic cancer was confirmed. The patient was discharged a week post-surgery without issues, emphasizing perioperative care progress.
    UNASSIGNED: The authors\' study focused on the detection conditions of the same hepatic artery anomaly in eight cases reported between 2017 and 2023. In two of them the anomaly was discovered in cadaver by routine autopsy. In three cases, this variation was identified before the surgery, but in three other cases it wasn\'t detected until the surgical procedure. In the authors\' case, due to multiple reasons, the anomaly remained undetectable until the surgery.
    UNASSIGNED: This study underscores the importance of thorough preoperative evaluation to grasp vascular variations for better patient care. Also, a noteworthy observation in our case is that the surgeon identified an expanded hepatic vessel, prompting further investigation into this anomaly.
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  • 文章类型: Case Reports
    血清碳水化合物抗原19-9(CA19-9)用于胰腺导管腺癌(PDAC)切除患者的复发监测。该报告描述了男性PDAC幸存者中CA19-9增加与前列腺增生的关系。男性PDAC幸存者中原因不明的CA19-9升高可能归因于良性前列腺疾病。
    Serum carbohydrate antigen 19-9 (CA19-9) is used for recurrence surveillance in patients with resected pancreatic ductal adenocarcinoma (PDAC). This report describes the association of increasing CA19-9 in a male PDAC survivor with presence of prostatic hyperplasia. Unexplained elevation of CA19-9 in male PDAC survivors might be attributable to benign prostatic conditions.
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  • 文章类型: Case Reports
    背景:转移性胰腺导管腺癌(PDAC)是一种致死性恶性肿瘤,生存数据令人沮丧。免疫治疗是许多癌症类型的一种有前途的方法,但由于其免疫抑制性肿瘤微环境,在晚期PDAC中取得了较差的疗效。我们描述了一例用pembrolizumab有效治疗的转移性PDAC病例。
    方法:我们报告了一例67岁女性,患有不可切除的局部晚期PDAC,接受吉西他滨+nab-紫杉醇治疗,然后接受放疗+卡培他滨。九个月时,在肝门水平观察到胰腺肿瘤进展,并出现新的肺结节,提示第二次原发性,经左肺活检证实。然后用pembrolizumab开始全身免疫疗法,一种针对程序性细胞死亡蛋白1的免疫检查点抑制剂,涵盖两种肿瘤类型。患者表现出在整个治疗过程中维持的完全代谢反应。自免疫疗法开始以来,患者在5.6年仍无疾病。
    结论:这些结果表明,放化疗后给予派姆单抗对转移性PDAC患者具有有益作用。据我们所知,这是首例报道的转移性PDAC和转移性肺癌患者在pembrolizumab治疗后未进行治愈性手术后表现出如此持久的完全缓解.需要进一步的研究来确定识别PDAC患者最有可能从这种免疫疗法中受益的生物标志物。
    BACKGROUND: Metastatic pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with dispiriting survival data. Immunotherapy is a promising approach to many cancer types, but achieves poor outcomes in advanced PDAC due to its immunosuppressive tumor microenvironment. We describe a case of metastatic PDAC effectively treated with pembrolizumab.
    METHODS: We report the case of a 67-year-old woman with unresectable locally advanced PDAC, treated with gemcitabine plus nab-paclitaxel followed by radiotherapy plus capecitabine. At nine months, pancreatic tumor progression was observed at the level of the hepatic hilum with the appearance of a new pulmonary nodule suggestive of a second primary, confirmed by left lung biopsy. Systemic immunotherapy was then initiated with pembrolizumab, an immune checkpoint inhibitor targeting programmed cell death protein-1 that covers the two tumor types. The patient showed a complete metabolic response that was maintained throughout the treatment. The patient continues to be disease-free at 5.6 years since the start of immunotherapy.
    CONCLUSIONS: These results suggest that the administration of pembrolizumab after chemoradiotherapy has a beneficial effect in patients with metastatic PDAC. To our knowledge, this is the first reported case of a patient with metastatic PDAC and metastatic lung cancer showing such a long-lasting complete response after pembrolizumab treatment without curative surgery. Further studies are required to determine biomarkers that identify PDAC patients most likely to benefit from this immunotherapy.
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  • 文章类型: Case Reports
    对于临床医生来说,探索不确定的胆道狭窄(IBS)的性质仍然是一个具有挑战性的问题。经过彻底的术前评估,约有20%的胆道狭窄仍未确定。
    这里,我们介绍了2例不确定的胆道狭窄患者,其横断面成像和内镜检查无诊断性。患者最终行剖腹探查术,确诊为恶性肿瘤。我们还回顾了最近有关IBS评估的文献报道。
    鉴于大多数胆道狭窄都是恶性肿瘤,术前区分良恶性是选择最佳治疗方案的关键。因此,密切跟进,多学科讨论,对于一些困难的诊断病例,需要及时的手术探查。
    UNASSIGNED: It is still a challenging problem for clinicians to explore the nature of the indeterminate biliary strictures (IBSs). Approximately 20% of biliary strictures remain undetermined after a thorough preoperative assessment.
    UNASSIGNED: Here, we present two cases of indeterminate biliary strictures patients, whose cross- sectional imaging and endoscopic examination were nondiagnostic. The patients underwent exploratory laparotomy finally and were confirmed as malignancy. We also reviewed the recent reports in literatures regarding the evaluation of IBSs.
    UNASSIGNED: Given the majority of the biliary strictures are malignancy, preoperative differentiation between benign and malignant is critical for choosing the best therapeutic regimen. Thus, close follow-up, multiple multidisciplinary discussion, and prompt surgical exploration are necessary for some difficult diagnostic cases.
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  • 文章类型: Case Reports
    背景:胰腺导管腺癌(PDAC)是一种高度致命的疾病,有效治疗有限,尤其是在一线化疗后。人表皮生长因子受体2(HER-2)免疫组织化学(IHC)阳性与PDAC中更具侵略性的临床行为和较短的总生存期相关。
    方法:我们介绍了1例多发性转移性PDAC,IHC错配修复有效,但HER-2IHC弱阳性诊断,一线nab-紫杉醇联合吉西他滨和PD-1抑制剂治疗后肿瘤没有消退。RC48(HER2-抗体-药物偶联物)的新型联合治疗PRaG3.0,放射治疗,PD-1抑制剂,然后应用粒细胞-巨噬细胞集落刺激因子和白细胞介素-2作为二线治疗,患者确认部分缓解良好,无进展生存期为6.5个月,总生存期为14.2个月.她在任何时候都没有出现任何2级或以上的治疗相关不良事件。在包含放疗的PRaG3.0治疗的前两个激活周期中,外周CD8Temra和CD4Temra的百分比增加,但在不包含放疗的维持周期中降低至基线。
    结论:PRaG3.0可能是HER2阳性转移性PDAC患者的一种新策略,这些患者以前的一线方法甚至PD-1免疫治疗均失败,但在前瞻性试验中需要更多数据。
    BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease with limited effective treatment especially after first-line chemotherapy. The human epidermal growth factor receptor 2 (HER-2) immunohistochemistry (IHC) positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.
    METHODS: We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn\'t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment. A novel combination therapy PRaG 3.0 of RC48 (HER2-antibody-drug conjugate), radiotherapy, PD-1 inhibitor, granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month. She had not developed any grade 2 or above treatment-related adverse events at any point. Percentage of peripheral CD8+Temra and CD4+Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.
    CONCLUSIONS: PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.
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  • 文章类型: Case Reports
    自身免疫性胰腺炎(AIP)被认为是一种预后良好的疾病,对类固醇反应良好,但胰腺导管腺癌(PDAC)在AIP中的并发症是一种罕见的疾病。我们报告了一例被形成肿瘤的1型AIP包裹的PDAC。
    病人,一位65岁的女性,在腹部超声检查中发现CA19-9水平高,胰腺肿块直径为30mm。对比增强的计算机断层扫描显示,胰腺尾部有40毫米的肿块,内部有27毫米的寡肿块。从这些体检中,这个肿瘤被诊断为PDAC,有结肠侵入的证据.作为PDAC的治愈性切除,进行了远端胰腺切除术,脾切除术和联合结肠切除术。组织病理学检查显示侵袭性PDAC被IgG4阳性浆细胞浸润包围。基于这些发现,诊断为位于胰尾的PDAC被1型AIP包裹。术后进展顺利,患者在术后第15天出院。术后给予S-1辅助化疗6个月,术后2年无复发。
    目前,AIP诱导PDAC的机制有两种:(1)慢性炎症引起的致癌刺激和(2)AIP引起的副肿瘤综合征。需要进一步研究AIP与胰腺癌之间的关系,应进行随访,同时注意并发症的可能性。
    UNASSIGNED: Autoimmune pancreatitis (AIP) is recognized as a disease with a good prognosis that responds well to steroids, but the complication of pancreatic ductal adenocarcinoma (PDAC) in AIP is a rare condition. We report a case of PDAC encapsulated by tumor-forming type 1 AIP.
    UNASSIGNED: The patient, a 65-year-old female, was found to have high CA19-9 levels and a pancreatic mass with a diameter of 30 mm on abdominal ultrasonography. Contrast-enhanced computed tomography revealed a 40-mm mass in the tail of the pancreas that had a 27-mm oligemic mass inside it. From these work-up examinations, this tumor was diagnosed as PDAC, with evidence of colonic invasion. As curative resection for PDAC, a distal pancreatectomy with splenectomy and combined colon resection were performed. Histopathological examination showed invasive PDAC surrounded by IgG4-positive plasma cell infiltration. Based on these findings, a diagnosis was made of PDAC located in the pancreatic tail capsulized by type 1 AIP. The postoperative course was uneventful, and the patient was discharged on postoperative day 15. She underwent postoperative adjuvant chemotherapy with S-1 for 6 months, and no recurrence was noted for 2 years after operation.
    UNASSIGNED: Currently, there are two hypothetical mechanisms of PDAC induction by AIP: (1) carcinogenic stimulation due to chronic inflammation and (2) paraneoplastic syndrome caused by AIP. Further study of the relationship between AIP and pancreatic cancer is needed, and follow-up should be conducted while keeping in mind the possibility of complications.
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