Palliative bypass surgery for patients with advanced pancreatic adenocarcinoma: experience from a tertiary center
- 作者列表："Niv Pencovich","Lior Orbach","Yonatan Lessing","Amit Elazar","Sophie Barnes","Phillip Berman","Arye Blachar","Ido Nachmany","Boaz Sagie
Abstract Background As advances in oncological treatment continue to prolong the survival of patients with non-resectable pancreatic ductal adenocarcinoma (PDAC), decision-making regarding palliative surgical bypass in patients with a heavy disease burden turns challenging. Here we present the results of a pancreatic surgery referral center. Methods Patients that underwent palliative gastrojejunostomy and/or hepaticojejunostomy for advanced, non-resectable PDAC between January 2010 and November 2018 were retrospectively assessed. All patients were taken to a purely palliative surgery with no curative intent. The postoperative course as well as short and long-term outcomes was evaluated in relation to preoperative parameters. Results Forty-two patients (19 females) underwent palliative bypass. Thirty-one underwent only gastrojejunostomy (22 laparoscopic) and 11 underwent both gastrojejunostomy and hepaticojejunostomy (all by an open approach). Although 34 patients (80.9%) were able to return temporarily to oral intake during the index admission, 15 (35.7%) suffered from a major postoperative complication. Seven patients (16.6%) died from surgery and another seven within the following month. Nine patients (21.4%) never left the hospital following the surgery. Mean length of hospital stay was 18 ± 17 days (range 3–88 days). Mean overall survival was 172.8 ± 179.2 and median survival was 94.5 days. Age, preoperative hypoalbuminemia, sarcopenia, and disseminated disease were associated with palliation failure, defined as inability to regain oral intake, leave the hospital, or early mortality. Conclusions Although palliative gastrojejunostomy and hepaticojejunostomy may be beneficial for specific patients, severe postoperative morbidity and high mortality rates are still common. Patient selection remains crucial for achieving acceptable outcomes.
文摘背景随着肿瘤治疗的进展不断延长不可切除的胰腺导管腺癌 (PDAC) 患者的生存期,疾病负担较重的患者姑息性手术旁路的决策变得具有挑战性。这里我们介绍胰腺手术转诊中心的结果。方法回顾性评估 2010年1月至 2018年11月因晚期不可切除的 PDAC 行姑息性胃空肠吻合术和/或肝管空肠吻合术的患者。所有患者均接受单纯姑息性手术，无治疗意图。根据术前参数评估术后病程以及短期和长期结局。结果 42 例患者 (19 例女性) 行姑息性旁路术。31 例仅行胃空肠吻合术 (22 例腹腔镜)，11 例同时行胃空肠吻合术和肝管空肠吻合术 (均采用开放入路)。虽然 34 例患者 (80.9%) 在索引入院期间能够暂时恢复口服摄入，但 15 例 (35.7%) 发生了术后主要并发症。7 例患者 (16.6%) 死于手术，另有 7 例在随后的一个月内死亡。9 例患者 (21.4%) 手术后从未离开医院。平均住院时间为 18 ± 17 天 (范围 3-88 天)。平均总生存期为 172.8 ± 179.2，中位生存期为 94.5 天。年龄、术前低蛋白血症、肌肉减少症和播散性疾病与缓解失败相关，定义为无法恢复口服摄入、出院或早期死亡率。结论虽然姑息性胃空肠吻合术和肝管空肠吻合术可能对特定患者有益，但术后严重并发症和高死亡率仍然很常见。患者选择对于实现可接受的结果仍然至关重要。
METHODS::Pancreatic ductal adenocarcinoma (PDAC) is a disease of aging. The TP53 gene product regulates cell growth, aging, and cancer. To determine the important targets of TP53 in PDAC, we examined the expression of 440 proteins on a reverse phase protein array (RPPA) in PDAC-derived MIA-PaCa-2 cells which either had WT-TP53 or lacked WT-TP53. MIA-PaCa-2 cells have a TP53 mutation as well as mutant KRAS and represent a good in vitro model to study PDAC. RPPA analysis demonstrated expression of tumor promoting proteins in cells that lacked WT-TP53; and this feature could be reversed significantly when the cells were transfected with vector encoding WT-TP53 or treated with berberine or a modified berberine (BBR). Expression of miR-34a-associated signaling was elevated in cells expressing WT-TP53 compared to cells expressing mTP53. Results from in vivo studies using human PDAC specimens confirmed the in vitro results as the expression of miR-34a and associated signaling was significantly decreased in PDAC specimens compared to non-cancerous tissues. This study determined SERPINE1 as a miR-34a target with relevance to the biology of PDAC. Thus, we have identified a key target (SERPINE1) of the TP53/miR-34a axis that may serve as a potential biomarker for early detection of pancreatic cancer.
METHODS::Background: SLC6A14 (ATB0,+), a Na+/Cl-coupled transporter for neutral/cationic amino acids, is overexpressed in many cancers; It has been investigated as a target for improved liposomal drug delivery to treat liver cancer.Research design and methods: Here we explored the mechanism of ATB0,+-mediated entry of such liposomes. As ATB0,+ is highly-expressed in pancreatic cancer, we also examined the therapeutic utility of ATB0,+-targeted liposomal drug delivery to treat this cancer.Results: The uptake of lysine-conjugated liposomes (LYS-LPs) was greater in ATB0,+-positive MCF7 cells. The uptake process consisted of two steps: binding and internalization. The binding of LYS-LPs to MCF7 cells was higher than that of bare liposomes, and the process was dependent on Na+ and Cl-, and inhibitable by ATB0,+ substrates or blocker. In contrast, the internalization step was independent of lysine. The cellular entry of LYS-LPs facilitated by ATB0,+ occurred via endocytosis with transient endosomal degradation of ATB0,+ protein with subsequent recovery. Moreover, LYS-LPs also enhanced the uptake and cytotoxicity of gemcitabine in these cells in an ATB0,+-dependent manner.Conclusions: We conclude that ATB0,+ could be exploited for targeted drug delivery in the form of lysine-conjugated liposomes and that the approach represents a novel strategy for enhanced pancreatic cancer therapy.
METHODS:PURPOSE:Pre-operative prediction of histological response to neoadjuvant therapy aids decisions regarding surgical management of borderline resectable pancreatic cancer (BRPC). We elucidate correlation between pre-/post-treatment whole-tumor apparent diffusion coefficient (ADC) value and rate of tumor cell destruction. We newly verify whether post-treatment ADC value at the site of vascular contact predicts R0 resectability of BRPC. METHODS:We prospectively reviewed 28 patients with BRPC who underwent diffusion-weighted magnetic resonance imaging before neoadjuvant chemotherapy and surgery. Correlation between the percentage of tumor cell destruction and various parameters was analyzed. Strong parameters were assessed for their ability to predict therapeutic histological response and R0 resectability. RESULTS:Pre-/post-treatment whole-tumor ADC value correlated with tumor cell destruction rate by all parameters (R = 0.630/0.714, P 50% was determined at 1.40 × 10-3 mm2/s. It predicts histological response with 100% sensitivity, 81% specificity, and 89% accuracy. It predicts R0 with 88% sensitivity, 70% specificity, and 75% accuracy. CONCLUSIONS:Post-treatment whole-tumor ADC value may be a predictor of R0 resectability in patients with BRPC. Tumor cell destruction rate is indicated by the difference between pre-/post-treatment ADC values. This difference is strongly affected by the pre-treatment ADC value. The cutoff value of ADC at the site of vascular contact could not discriminate R0 resectability.