Clinical characteristics and treatment analysis of pancreatic acinar cell carcinoma: A single institutional comparison to pancreatic ductal adenocarcinoma

BackgroundPancreatic acinar cell carcinoma (PACC) is a rare malignancy that accounts for less than 1% of primary pancreatic neoplasms. Currently, the lack of large-scale clinical studies limits our understanding of PACC. The aim of this study was to investigate the clinical characteristics and prognosis of PACC.MethodsIn a retrospective analysis, 52 patients with PACC and 355 patients with pancreatic ductal adenocarcinoma (PDAC) who underwent surgical interventions were evaluated. Clinical characteristics and treatment outcomes were compared between the two groups.ResultsThe mean age was lower for patients with PACC than for those with PDAC (mean: 50.8 ± 10.9 versus 59.4 ± 10.9 years; p < 0.001). Except for alpha-fetoprotein (AFP), tumour markers were also lower in the PACC group than the PDAC group. In regard to tumour characteristics, maximum diameters of the primary tumour [median (range): 5.0 cm (1.0–18.2 cm) versus 3.5 cm (0.6–15.0 cm); p < 0.001] and hepatic metastatic lesions [6.7 cm (1.5–12.6 cm) versus 1.2 cm (0.3–3.3 cm); p < 0.001] were larger in patients with PACC than patients with PDAC, but vascular invasion [23.1% (12/52) versus 35.5% (126/355); p = 0.044] and perineural invasion [7.7% (4/52) versus 56.1% (199/355); p < 0.001] were more common in patents with PDAC than in patients with PACC. For treatment, radical resection was performed in 57.7% of patients with PACC, which increased the 5-year survival rate to 31.8%. In regard to prognosis, the 5-year survival rate was 21.4% for PACC and 9.7% for PDAC (p < 0.0001).ConclusionsPACC is more indolent than PDAC, which makes early diagnosis more difficult. Although the stage may be advanced at diagnosis, the overall survival (OS) of PACC is much better than that of PDAC, and the prognosis greatly improves after radical resection.     

胰腺腺泡细胞癌的CT表现

背景与目的：胰腺腺泡细胞癌(acinar cell carcinoma of the pancreas,ACCP)是一种罕见的胰腺恶性肿瘤,相关的影像学报道较少。该研究旨在探讨ACCP的CT表现。方法：收集自2011年1月-2014年1月经手术病理证实为ACCP的9例患者资料,回顾性分析其CT征象。结果：在9例ACCP患者中,肿块最大径均值为52 mm,肿瘤边缘不清的6例(66.7%),外生型生长者有6例(66.7%),强化程度低于正常胰腺组织者8例(88.9%),强化不均者6例(66.7%),累及血管者7例(77.8%),淋巴结转移者5例(55.6%),无出现肝转移病例,仅1例出现胰管扩张。结论：较大体积的乏血供胰腺肿块,内部异质性明显,呈外生型生长而无显著胰管扩张时,提示ACCP的可能。     

EGFR amplification induces sensitivity to antiEGFR therapy in pancreatic acinar cell carcinoma

Pancreatic acinar cell carcinoma (PACC) is a rare cancer. When the tumor is metastatic, few therapeutic options are available. Precision medicine using next-generation sequencing is defined by the administration of drugs based on the tumor genetic mutations. The usage of precision medicine for finding new therapeutic options for rare cancers is an emerging field. We have reported here the case of a patient bearing a multitreated metastatic PACC. This patient underwent somatic and constitutional exome analyses. The analyses revealed in the liver metastasis an amplification of the EGFR gene. Accordingly, the patient was treated with off-label usage of panitumumab. We observed rapid response with necrosis of the liver metastasis, while no efficacy was observed in the primary tumor. An exome analysis of the primary tumor revealed amplification of HER2 and MET with EGFR amplification. Such amplifications are known as a resistance mechanism to antiEGFR therapy. Our results suggest that exome analysis may be helpful to highlight targets in rare cancers, such as PACC. EGFR amplification in this pathology should be determined and could be used as a biomarker to propose antiEGFR therapy.     

High expression of DDR1 is associated with the poor prognosis in Chinese patients with pancreatic ductal adenocarcinoma

Background

Discoidin domain receptors 1 (DDR1), a subtype of DDRs, has been reported as a critical modulator of cellular morphogenesis, differentiation, migration and invasion.

Methods and results

In this study, we investigated the expression of DDR1 and its clinical association in Chinese patients with pancreatic ductal adenocarcinoma (PDAC). Across a cohort of 30 patients, we examined DDR1 expression in paired PDAC and corresponding adjacent non-tumor tissues by real-time quantitative PCR (RT-qPCR), or western blotting. DDR1 expression is significantly higher in PDAC, as compared to normal adjacent tissue, confirming results from the Oncomine databases. We validated DDR1 expression by immunohistochemistry across a non-overlapping cohort of 205 PDAC specimens. Kaplan-Meier survival curves indicate that increased expression of DDR1 is associated with a poor prognosis in PDAC patients (P = 0.013). Multivariate Cox regression analysis identified DDR1 expression, age, N classification and liver metastasis as independent prognostic factors in PDAC.

Conclusions

This study demonstrated that DDR1 can well serve as a novel prognostic biomarker in PDAC.     

胰腺导管腺癌免疫治疗研究现状和展望

胰腺导管腺癌(Pancreatic ductal adenocarcinoma,PDAC)是胰腺癌最常见的类型,预后极差。手术切除是目前唯一的根治手段,但多数患者就诊时已失去手术机会。免疫治疗作为一种新兴的治疗手段,在多种实体瘤和血液系统恶性肿瘤治疗中显现出乐观前景。然而,PDAC肿瘤抗原性低以及免疫抑制微环境等特征导致其免疫治疗困难重重。本文通过综述PDAC的肿瘤微环境组成特点和目前开展的新型免疫治疗策略,为PDAC的免疫治疗研究提供新思路。     

Oncologic outcomes of minimally invasive versus open distal pancreatectomy for pancreatic ductal adenocarcinoma: A systematic review and meta-analysis

In the absence of randomized trials, uncertainty regarding the oncologic efficacy of minimally invasive distal pancreatectomy (MIDP) remains. This systematic review aimed to compare oncologic outcomes after MIDP (laparoscopic or robot-assisted) and open distal pancreatectomy (ODP) in patients with pancreatic ductal adenocarcinoma (PDAC). Matched and non-matched studies were included. Pooled analyses were performed for pathology (e.g., microscopically radical (R0) resection and lymph node retrieval) and oncologic outcomes (e.g., overall survival). After screening 1760 studies, 21 studies with 11,246 patients were included. Overall survival (hazard ratio 0.86; 95% confidence interval (CI) 0.73 to 1.01; p = 0.06), R0 resection rate (odds ratio (OR) 1.24; 95%CI 0.97 to 1.58; p = 0.09) and use of adjuvant chemotherapy (OR 1.07; 95%CI 0.89 to 1.30; p = 0.46) were comparable for MIDP and ODP. The lymph node yield (weighted mean difference (WMD) −1.3 lymph nodes; 95%CI -2.46 to −0.15; p = 0.03) was lower after MIDP. Patients undergoing MIDP were more likely to have smaller tumors (WMD -0.46 cm; 95%CI -0.67 to −0.24; p < 0.001), less perineural (OR 0.48; 95%CI 0.33 to 0.70; p < 0.001) and less lymphovascular invasion (OR 0.53; 95%CI 0.38 to 0.74; p < 0.001) reflecting earlier staged disease as a result of treatment allocation bias. Based on these results we can conclude that in patients with PDAC, MIDP is associated with comparable survival, R0 resection, and use of adjuvant chemotherapy, but a lower lymph node yield, as compared to ODP. Due to treatment allocation bias and lower lymph node yield the oncologic efficacy of MIDP remains uncertain.     

Serum biomarkers for the differentiation of autoimmune pancreatitis from pancreatic ductal adenocarcinoma

Autoimmune pancreatitis(AIP), a chronic inflammation caused by the immune system attacking the pancreas, usually presents imaging and clinical features that overlap with those of pancreatic ductal adenocarcinoma(PDAC). Serum biomarkers, substances that quantitatively change in sera during disease development, are a promising non-invasive tool with high utility for differentiating between these diseases. In this way, the presence of AIP is currently suspected when serum concentrations of immunogl...     

合并第二原发雌激素相关肿瘤的肾细胞癌的临床特征：倾向评分匹配分析

背景与目的：随着肿瘤诊疗技术的进步,肿瘤患者的生存时间不断延长,第二原发肿瘤在临床上的报道也越来越多。探讨合并第二原发雌激素相关肿瘤的肾细胞癌（renal cell carcinoma,RCC）临床和病理学特征。方法：回顾性纳入2008年1月—2019年1月复旦大学附属肿瘤医院诊治的女性RCC患者520例,其中合并第二原发雌激素相关肿瘤39例,单一RCC 481例。本研究应用倾向评分匹配（propensity score matching,PSM）法对两类患者临床资料按1∶5进行匹配,比较两组患者临床病理学特点［年龄、体质量指数（body mass index,BMI）、肿瘤家族史、TNM分期、美国癌症联合会（American Joint Committee on Cancer,AJCC）临床分期等］。通过Kaplan-Meier法统计合并第二原发雌激素相关肿瘤RCC患者和单一RCC患者的预后情况。结果：经过倾向评分匹配后,合并第二原发雌激素相关肿瘤38例,单一RCC 185例。两组患者肿瘤家族史倾向评分匹配前差异有统计学意义（P=0.012）,匹配后,两组患者肿瘤家族史差异有统计学意义（P=0.042）。倾向评分匹配前两组患者总体生存情况差异有统计学意义（P=0.014）,倾向评分匹配后共纳入患者223例,所有患者都获得随访,随访时间为3~130个月,其中合并第二原发雌激素相关肿瘤组患者死亡8例,存活30例,中位生存时间为34.5个月,单一RCC组患者死亡57例,存活128例,中位生存时间为59.0个月。在随访时间内,合并第二原发雌激素相关肿瘤组的生存率均低于单一RCC组,两组总体生存情况相比较,差异有统计学意义（P=0.041）。结论：合并第二原发雌激素相关肿瘤的RCC并不少见,而肿瘤家族史可能使雌激素相关肿瘤患者再发RCC的风险升高。当合并第二原发雌激素相关肿瘤时,RCC患者的预后显著较单一RCC患者更差。     

pT but not pN stage of the 8th TNM classification significantly improves prognostication in pancreatic ductal adenocarcinoma

The UICC TNM (tumour-node-metastasis) staging system for pancreatic ductal adenocarcinoma (PDAC) has been a matter of debate over decades because survival prediction based on T stages was weak and unreliable. To improve staging, the recently published 8th TNM edition (2016) introduced a conceptually completely changed strictly size-based T staging system and a refined N stage for PDAC. To investigate the clinical value of the novel TNM classification, we compared the prognostic impact of pT and pN stage between the 7th and 8th edition in two well-characterised independent German PDAC cohorts from different decades, including a total number of 523 patients. Former UICC T staging (7th edition 2009) resulted in a clustering of pT3 cases (72% and 85% of cases per cohort, respectively) and failed to show significant prognostic differences between the four stages in one of the investigated cohorts (p = 0.074). Application of the novel size-based T stage system resulted in a more equal distribution of cases between the four T categories with a predominance of pT2 tumours (65% and 60% of cases). The novel pT staging algorithm showed greatly improved discriminative power with highly significant overall differences between the four pT stages in both investigated cohorts in univariate and multivariate analyses (p < 0.001, each). In contrast, no prognostic differences were observed between the recently introduced pN1 and pN2 categories in both cohorts (p = 0.970 and p = 0.061).pT stage of resected PDAC patients according to the novel UICC staging protocol (8th edition) significantly improves patient stratification, whereas introduction of an extended N stage protocol does not demonstrate high clinical relevance in our cohorts.     

The yield of staging laparoscopy for resectable and borderline resectable pancreatic cancer in the PREOPANC randomized controlled trial

BackgroundThe necessity of the staging laparoscopy in patients with pancreatic cancer is still debated. The objective of this study was to assess the yield of staging laparoscopy for detecting occult metastases in patients with resectable or borderline resectable pancreatic cancer.MethodThis was a post-hoc analysis of the randomized controlled PREOPANC trial in which patients with resectable or borderline resectable pancreatic cancer were randomized between preoperative chemoradiotherapy or immediate surgery. Patients assigned to preoperative treatment underwent a staging laparoscopy prior to preoperative treatment according to protocol, to avoid unnecessary chemoradiotherapy in patients with occult metastatic disease.ResultsOf the 246 included patients, 7 did not undergo surgery. A staging laparoscopy was performed in 133 patients (55.6%) and explorative laparotomy in 106 patients (44.4%). At staging laparoscopy, occult metastases were detected in 13 patients (9.8%); 12 liver metastases and 1 peritoneal metastasis. At direct explorative laparotomy, occult metastases were found in 9 patients (8.5%); 6 with liver metastases, 1 with peritoneal metastases, and 2 with metastases at multiple sites. One patient had peritoneal metastases at exploration after a negative staging laparoscopy. Patients with occult metastases were more likely to receive palliative chemotherapy if found with staging laparoscopy compared to laparotomy (76.9% vs. 30.0%, p = 0.040).ConclusionsStaging laparoscopy detected occult metastases in about 10% of patients with resectable or borderline resectable pancreatic cancer. These patients were more likely to receive palliative systemic chemotherapy compared to patients in whom occult metastases were detected with laparotomy. A staging laparoscopy is recommended before planned resection.     

系统免疫炎症指数与接受新辅助化疗胰腺导管腺癌患者预后的关系

目的 探讨新辅助化疗后系统免疫炎症指数（systemic immune-inflammation index,SII）对胰腺导管腺癌（pancreatic ductal adenocarcinoma,PDAC）预后评估的价值。方法 回顾性分析2013年1月至2016年12月在盘锦辽油宝石花医院行胰腺切除术的PDAC患者的临床资料。新辅助化疗后检测SII,依据ROC曲线确定SII最佳临界值（885）分为SII＞885组（n=37）和SII≤885组（n=58）,采用Cox回归评估SII与PDAC患者术后生存的关系。结果 SII与肿瘤大小、胆道引流、术前CA19-9水平有关（P<0.05）。SII≤885组的3年生存率高于SII＞885（43.1% vs 18.9%,P=0.015）。多因素Cox回归显示,肿瘤大小>3 cm（HR=1.367,95%CI：1.227～2.215,P=0.031）、CA19-9>37 IU/mL（HR=1.292,95%CI：1.132～1.931,P=0.011）及SII＞885（HR=1.451,95%CI：1.327～2.431,P=0.021）是影响PDAC患者术后生存的独立危险因素。结论 新辅助化疗后SII高的PDAC患者预后较差且SII＞885提示PDAC患者预后不良。     

MicroRNA-506 is up-regulated in the development of pancreatic ductal adenocarcinoma and is associated with attenuated disease progression

Background:MicroRNA?506 (miR?506) has been reported to function in several tumors as a tumor suppressor gene or oncogene. However, the expression and role of miR?506 in pancreatic ductal adenocarcinoma (PDAC) remains unclear. In this study, we aimed to evaluate the phenotype of miR?506 in PDAC. Methods:Using miRNA insitu hybridization, we examined the expression of miR?506 in 113 PDACs and 87 paired normal pancreatic tissues. We evaluated miR?506 expression in PDAC cells, normal pancreatic ducts, and acinus/islands, and we analyzed the associations between miR?506 expression and the clinicopathologic characteristics of PDAC patients. Results:miR?506 expression was higher in PDAC than in matched normal pancreatic ductal cells (P<0.001). On the other hand, the combined group of well and moderately differentiated PDACs showed higher levels of miR?506 than the poorly differentiated ones (P=0.023). Moreover, miR?506 expression was negatively associated with pathologic T category (P=0.004) and lymph node metastasis (P=0.033), suggesting that miR?506 might inhibit the progression of PDAC. Conclusions:Our results suggest that miR?506 either plays a role as an oncogene in the tumorigenesis and a tumor suppressor in the progression or serves as a house?keeping, tumor?suppressing miRNA, whose expression can be activated by oncogenic signals in early development to hinder the progression of PDAC.     

Presence of low-grade IPMN at the pancreatic transection margin does not have prognostic significance after resection of IPMN-associated pancreatic adenocarcinoma

IntroductionResection margin status is a well-established prognosticator in pancreatic cancer. The prognostic impact of IPMN dysplasia at the pancreatic transection margin in IPMN-associated carcinoma (IPMN-Ca) remains unclear, hence institutional practices on additional resections vary.MethodsPatients undergoing partial pancreatectomy or attempted partial pancreatectomy converted to total pancreatectomy for IPMN-Ca between 04/2002 and 12/2018 were identified. Final pathology of the definitive pancreatic transection margin was identified. The association between the presence of IPMN dysplasia at the margin and overall survival (OS) was assessed.ResultsOf 302 patients with IPMN-Ca, 181 (59.9%) patients received partial pancreatoduodenectomy, 61 (20.2%) distal pancreatectomy, and 60 (19.9%) were converted to total pancreatectomy. Median OS was 98.6 months in R0 (≥1 mm), 39.3 months in R1 (<1 mm), and 22.0 months in R1(direct) resected patients, respectively (p < 0.0001). No IPMN dysplasia at the definitive margin was present in 103 (34.1%), low-grade in 131 (43.4%), and high-grade/R1 in 8 (2.6%) patients. Low-grade dysplasia or total pancreatectomy were not associated with shorter OS compared to dysplasia-free margin across the entire cohort. Sensitivity analyses confirmed a lack of prognostic relevance of low-grade IPMN dysplasia at the pancreatic margin in R0 resected IPMN-Ca and in R0 resected UICC stage IA/IB IPMN-Ca.ConclusionsLow-grade IPMN at the transection margin is not associated with shorter overall survival after partial pancreatectomy for IPMN-Ca. Additional resections for low-grade dysplasia, up to total pancreatectomy do not result in a survival benefit and should be omitted. Due to limited sample size, high-grade dysplasia could not be analyzed.     

Complete circumferential lymphadenectomy around the superior mesenteric artery with preservation of nerve plexus reduces locoregional recurrence after pancreatoduodenectomy for resectable pancreatic ductal adenocarcinoma

BackgroundEvaluation of recurrence pattern and risk factors for recurrence are essential for good rates of survival after upfront pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC).MethodsThis retrospective study included 167 consecutive patients who underwent upfront PD for resectable PDAC between 2000 and 2018. Postoperative recurrences were classified into three patterns according to initial recurrence site: isolated locoregional, isolated distant, and simultaneous locoregional and distant recurrences.ResultsThis study found 114 patients who developed postoperative recurrence (68.3%), including 37 patients with isolated locoregional recurrence (32.5%), 67 patients with isolated distant recurrence (58.8%), and 10 patients with simultaneous locoregional and distant recurrences (6.0%). When locoregional recurrence was classified based on the location of recurrent lesions, locoregional recurrence most commonly occurred around the superior mesenteric artery (SMA) (70.2%), followed by around the hepatic artery (25.5%) and in the paraaortic region (14.9%). Multivariate analyses showed that complete circumferential lymphadenectomy around the SMA, including not only the right side, but also the left side, was an independent factor for reduction of locoregional recurrence (P = 0.019, odds ratio [OR]: 2.217). Lymph node metastasis was an independent risk factor for both locoregional (P < 0.001, OR: 3.686) and distant recurrences (P < 0.001, OR: 4.315). Non-completion of postoperative adjuvant therapy was a risk factor for distant recurrence (P < 0.001, OR: 3.748).ConclusionBased on our data, complete circumferential lymphadenectomy around the SMA might contribute to local control, and multidisciplinary treatment including neoadjuvant therapy might be needed for resectable PDAC with high risk for recurrence.     

The importance of quality-of-life management in patients with advanced pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis, and as such, a focus on quality of life is vital. This review will discuss various aspects of quality of life in patients with PDAC and their treatment. Pancreatic exocrine and endocrine insufficiency may result in issues related to nutrition, and pain and fatigue are other common symptoms, and may be managed with pharmaceutical or nonpharmaceutical methods. It has also been reported that low mood is a particular problem for patients with PDAC compared to patients with other cancers; however, the data supporting this is inconsistent. Data regarding improvements in quality of life in patients with PDAC receiving chemotherapy is also reviewed, which in some cases suggests a benefit to chemotherapy, particularly in the presence of a radiological response. Furthermore, the importance of early palliative care is discussed and the benefits reported including improved quality of life and mood, reduced aggressive interventions at the end of life and improved survival. Areas for future development may include increased use of quality of life as a trial outcome and the use of patient-reported outcomes to improve symptomatic care of patients, and particularly in those receiving active systemic treatment.     

miR-15a inhibits cell proliferation and epithelial to mesenchymal transition in pancreatic ductal adenocarcinoma by down-regulating Bmi-1 expression

Purposes

To investigate whether miR-15a inhibits cell proliferation and epithelial–mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC) via the down-regulation of B cell-specific moloney murine leukemia virus insertion site 1 (Bmi-1) expression.

Methods and Results

miR-15a and Bmi-1 expressions in normal pancreatic tissue and PDAC tissue were measured. The relationship between miR-15a and Bmi-1 expression was analyzed. We found that miR-15a suppressed the expression of Bmi-1 and PDAC cell proliferation; E-cadherin expression was visibly up-regulated after silencing Bmi-1 by transfecting miR-15a into PDAC cell line.

Conclusion

miR-15a inhibits cell proliferation and EMT in PDAC via the down-regulation of Bmi-1 expression.