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A Possible Role for TNF-α in Coordinating Inflammation and Angiogenesis in Chronic Liver Disease and Hepatocellular Carcinoma. TNF-α 在慢性肝病和肝细胞癌中协调炎症和血管生成的可能作用
Olfat Hammam, Ola Mahmoud, Manal Zahran, Azza Sayed, Rabab Salama, Karim Hosny, Ahmed Farghly

Background: Increasing evidence supports the hypothesis that chronic and persistent inflammation contributes to cancer development. However, the molecular mechanisms that lead to cancer in chronic inflammation and the role of angiogenesis in inflammation-associated cancer remain poorly understood.

Methods: NINETY PATIENTS WERE ENROLLED: 30 cases of CHC without cirrhosis, 28 cases of CHC with liver cirrhosis, and 32 cases of HCC and hepatitis C virus infection. Ten wedge liver biopsies, taken during laparoscopic cholecystectomy, served as normal controls. Serum TNF-α levels were measured using the ELISA technique; in situ hybridization and immunohistochemical studies were used to detect hepatic levels of messenger RNA (mRNA) transcripts and mature protein, respectively, for both TNF-α and VEGF.

Results: The highest hepatic expression of TNF-α was noticed in liver cirrhosis specimens compared to noncirrhotic CHC and HCC. Hepatic expression of VEGF and serum level of TNF-α revealed significant increases in the progression of the disease. Moreover, cases with higher grades of inflammation or stages of fibrosis showed significant increases in serum TNF-α and expression of TNF-α and VEGF. Expression of mRNA of both TNF-α and VEGF shows increasing expression with positive correlation to progression of viral hepatitis to cirrhosis with more positivity in cases developed HCC.

Conclusions: VEGF signaling could be one of the molecular signaling pathways involved in TNF-α induced angiogenesis which might pose an important link between inflammation and fibrosis in CHC and HCC development and progression. Moreover, serum inflammatory biomarkers can be used to monitor the disease progression.

背景:越来越多的证据支持慢性和持续性炎症导致癌症发展的假设。然而,人们对慢性炎症导致癌症的分子机制以及血管生成在炎症相关癌症中的作用仍然知之甚少:方法:共收治 90 例患者:30 例无肝硬化的 CHC,28 例伴有肝硬化的 CHC,32 例 HCC 和丙型肝炎病毒感染者。10例在腹腔镜胆囊切除术中采集的楔形肝活检组织作为正常对照组。采用 ELISA 技术检测血清 TNF-α 水平;采用原位杂交和免疫组化方法分别检测肝脏中 TNF-α 和 VEGF 的信使 RNA(mRNA)转录本和成熟蛋白水平:结果:与非肝硬化的 CHC 和 HCC 相比,肝硬化标本中 TNF-α 的肝脏表达量最高。肝脏中血管内皮生长因子的表达和血清中 TNF-α 的水平在疾病进展过程中显著升高。此外,炎症等级或纤维化阶段越高的病例,血清TNF-α以及TNF-α和血管内皮生长因子的表达量也越高。TNF-α和血管内皮生长因子的mRNA表达均呈上升趋势,与病毒性肝炎发展为肝硬化呈正相关,在发展为HCC的病例中阳性率更高:VEGF信号可能是TNF-α诱导血管生成的分子信号通路之一,这可能是CHC和HCC发展和进展过程中炎症和纤维化之间的重要联系。此外,血清炎症生物标志物还可用于监测疾病的进展。
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引用次数: 0
Upcoming articles. 即将到来的文章。
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引用次数: 0
Successful retreatment with chemoradiotherapy for local recurrence of pancreatic adenocarcinoma after neoadjuvant therapy and pancreaticoduodenectomy. 胰腺癌新辅助治疗及胰十二指肠切除术后局部复发的放化疗成功。
Minda A Gowarty, Bassem I Zaki, Michael J Tsapakos, Stuart R Gordon, Arief A Suriawinata, Gregory J Tsongalis, John E Sutton, J Marc Pipas
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引用次数: 0
Characteristics and outcomes of adenosquamous carcinoma of the pancreas. 胰腺腺鳞癌的特点和预后。
Christine G Simone, Tania Zuluaga Toro, Ellie Chan, Michael M Feely, Jose G Trevino, Thomas J George

Background: Adenosquamous carcinoma of the pancreas (ASCAP) is a rare histologic type of pancreatic carcinoma that constitutes 1% to 4% of all pancreatic exocrine malignancies. It has a clinical presentation similar to that of adenocarcinoma of the pancreas (ACP), but may have a worse overall prognosis, with most patients surviving for less than 2 years.

Methods: This was an institutional, retrospective, cohort analysis of 237 patients who underwent resection of pancreatic cancer with curative intent.

Results: Of the 237 cases examined, we identified 7 (2.9%) with histologically confirmed ASCAP. Demographics, comorbidities, risk factors, presenting symptoms, survival data, tumor characteristics, and types of treatment for each patient were included in the analysis. Risk factors for development of ASCAP were not conclusive. Although human papilloma virus (HPV) has been implicated in other squamous cell cancers, in our cohort, its involvement in ASCAP was 0%. Presurgical fine-needle aspiration failed to identify the invasive squamous cell component in all cases. In this cohort analysis, overall survival ranged from 3 to 25 months, with 2 patients surviving more than 20 months after surgical resection. With a median follow-up of 2.9 years, our data demonstrate a trend to worse median overall survival for ASCAP than for ACP (8.2 vs. 20.4 months; P = .23), with a limited number of long-term survivors.

Conclusions: Although recommended, adjuvant treatment was inconsistently provided for patients in this ASCAP cohort. Published data show variability in overall survival, but our findings support that surgical resection is one of the few options for control of this rare, poorly understood pancreatic malignancy. Further research is necessary to define risk factors and adjuvant and neoadjuvant treatments, to help improve patient outcomes.

背景:胰腺腺鳞癌(ASCAP)是一种罕见的胰腺组织学类型,占所有胰腺外分泌恶性肿瘤的1%至4%。它的临床表现与胰腺腺癌(ACP)相似,但总体预后可能更差,大多数患者存活时间不到2年。方法:对237例以治愈为目的行胰腺癌切除术的患者进行了制度性、回顾性、队列分析。结果:在237例病例中,我们发现7例(2.9%)有组织学证实的ASCAP。每位患者的人口统计学、合并症、危险因素、表现症状、生存数据、肿瘤特征和治疗类型均纳入分析。发展ASCAP的危险因素尚无定论。虽然人类乳头状瘤病毒(HPV)与其他鳞状细胞癌有关,但在我们的队列中,其与ASCAP的关系为0%。术前细针抽吸未能在所有病例中发现浸润性鳞状细胞成分。在本队列分析中,总生存期从3到25个月不等,其中2例患者在手术切除后存活超过20个月。中位随访时间为2.9年,我们的数据显示ASCAP患者的中位总生存期比ACP患者更差(8.2个月对20.4个月;P = .23),长期幸存者数量有限。结论:虽然推荐了辅助治疗,但ASCAP队列患者的辅助治疗并不一致。已发表的数据显示总体生存率存在差异,但我们的研究结果支持手术切除是控制这种罕见的,知之甚少的胰腺恶性肿瘤的少数选择之一。进一步的研究是必要的,以确定危险因素和辅助和新辅助治疗,以帮助改善患者的预后。
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引用次数: 0
A 40-year-old woman with locally advanced rectal cancer and a solitary liver metastasis. 一名40岁女性患有局部晚期直肠癌和单发肝转移。
Carla Hajj, Karyn Goodman, David Kelsen, Jinru Shia, Ali Shamseddine, Mohamed Naghy, Mustafa Sidani, Mohamed Eloubeidi, Fady Merhi, Fady Geara, Celina Ang, Leonard Saltz, Ghassan K Abou-Alfa
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引用次数: 0
An extremely rare case of pancreatic cancer presenting with leptomeningeal carcinomatosis and synchronous intraparenchymal brain metastasis. 摘要一例极为罕见的胰脏癌,表现为脑膜轻脑膜癌及脑实质内同步转移。
Rohit Rao, Santhosh K Sadashiv, Swapna Goday, Dulabh Monga
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引用次数: 0
Persistent racial disparities in survival among u.s. Adults with hepatocellular carcinoma after liver transplantation: the paradox of all-cause and cause-specific mortality. 美国成年肝细胞癌患者肝移植后生存的持续种族差异:全因死亡率和病因特异性死亡率的悖论。
Basile Njei, Ivo Ditah, Joseph K Lim
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引用次数: 0
Above-Label Doses of Octreotide-LAR in Patients With Metastatic Small Intestinal Carcinoid Tumors. 奥曲肽- lar在转移性小肠类癌患者中的应用
Jonathan Strosberg, Jill Weber, Max Feldman, Jamie Goldman, Khaldoun Almhanna, Larry Kvols

Background: Octreotide LAR is indicated for treatment of malignant carcinoid syndrome and has been studied at doses of 10 to 30 mg intramuscularly every 4 weeks. In clinical practice, higher doses are often prescribed for patients who experience refractory carcinoid syndrome (flushing and/or diarrhea) or tumor growth while on the maximum label-recommended dose.

Methods: We performed a retrospective, longitudinal review of octreotide LAR administration at a tertiary institution to determine the frequency of above-label dosing and outcomes.

Results: Three hundred thirty-eight patients were considered evaluable, among whom 100 (30%) underwent at least 1 increase in dose or frequency of octreotide-LAR above the standard label dose. The most common maximum doses were 40 mg every 4 weeks (n = 37 patients), 60 mg every 4 weeks (n = 34), and 30 mg every 3 weeks (n = 18). The indications for dose increase were worsening carcinoid syndrome (n = 60), radiographic progression (n = 33), and rising urine 5-HIAA (n = 6). Of the patients whose doses were increased for refractory carcinoid syndrome, 62% (n = 34) experienced improvement in diarrhea, and 56% (n = 28) experienced improvement in flushing.

Conclusions: In conclusion, octreotide LAR is commonly prescribed in doses or schedules above the recommended dose and frequency. Patients with refractory carcinoid syndrome appear to experience a clinical benefit from this change. Prospective data may be used to further evaluate this strategy.

背景:奥曲肽LAR适用于恶性类癌综合征的治疗,并研究了每4周10至30毫克肌肉注射剂量。在临床实践中,对于出现难治性类癌综合征(潮红和/或腹泻)或肿瘤生长的患者,在使用标签推荐的最大剂量时,通常会开出更高的剂量。方法:我们对一所高等院校的奥曲肽LAR给药进行了回顾性、纵向回顾,以确定超出标签的给药频率和结果。结果:338例患者被认为是可评估的,其中100例(30%)在标准标签剂量以上至少增加了一次奥曲肽- lar的剂量或频率。最常见的最大剂量为每4周40mg (n = 37例)、每4周60mg (n = 34)和每3周30mg (n = 18)。增加剂量的适应症为类癌综合征恶化(n = 60)、影像学进展(n = 33)和尿5-HIAA升高(n = 6)。在难治性类癌综合征增加剂量的患者中,62% (n = 34)的腹泻得到改善,56% (n = 28)的潮红得到改善。结论:综上所述,奥曲肽LAR的处方剂量或方案通常高于推荐剂量和频率。难治性类癌综合征患者似乎从这种改变中获得了临床益处。前瞻性数据可用于进一步评估这一策略。
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引用次数: 0
Upcoming articles. 即将到来的文章。
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引用次数: 0
Optimal chemotherapy dosing in a bilateral lower extremities amputee with metastatic pancreatic adenocarcinoma. 转移性胰腺腺癌双侧下肢截肢患者的最佳化疗剂量。
Dwight Owen, Eileen M O'Reilly, Celina Ang, Jennifer Ma, Richard K G Do, Ghassan K Abou-Alfa
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引用次数: 0
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Gastrointestinal cancer research : GCR
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