Prognostic Factors and Clinical Characteristics of Duodenal Adenocarcinoma With Survival: A Retrospective Study

BackgroundTo evaluate the clinical risk factors that influence the overall survival in patients with duodenal adenocarcinoma (DA) after tumor resection.MethodsThis study retrospectively analyzed 188 patients who underwent tumor resection for DA between January 2005 and June 2020 at Xiangyang Central Hospital.ResultsThe median survival of the patients who underwent resectional operation was 54 months, longer than of those who underwent palliative surgery (20.8 months) (2,916.17; 95% CI, 916.3−9,280.5; p < 0.001). Survival of non-ampullary duodenal carcinoma patients (50.3 months; 95% CI, 39.7−61.8) was similar to that of ampullary duodenal carcinoma patients (59.3 months; 95% CI, 38.6−66.7) but was significantly better than that of papillary adenocarcinoma patients (38.9 months; 95% CI, 29.8−54.8; p = 0.386). Those with intestinal-type ductal adenocarcinomas had a longer median overall survival than those with the gastric type (61.8 vs. 46.7 months; p < 0.01) or pancreatic type (32.2 months; p < 0.001). Clinical DA samples had significantly diverse expressions of ATG12, IRS2, and IGF2. Higher expressions of the ATG12 and IRS2 proteins were significantly correlated with worse survival. Multivariate Cox regression analysis revealed that lymph node metastasis (hazard ratio (HR), 6.44; 95% CI, 3.68−11.27; p < 0.0001), margin status (HR, 4.94; 95% CI, 2.85−8.54; p < 0.0001), and high expression of ATG12 (HR, 1.89; 95% CI, 1.17−3.06; p = 0.0099) were independent prognostic factors negatively associated with survival in patients undergoing curative resection. There was no survival difference between the groups with ampullary, non-ampullary, and papillary adenocarcinomas treated with adjuvant chemotherapy (p = 0.973).ConclusionGastric/pancreatic type, high expression of ATG12, lymph node metastases, and margin status were negative prognosticators of survival in patients with DAs than in those with tumor anatomical location. Curative resection is the best treatment option for appropriate patients.

P-P43 Lymph Node Negative Duodenal Adenocarcinoma Is Associated with Long-term Patient Survival following Pancreaticoduodenal Resection

Background Duodenal adenocarcinoma (DA) is a rare gastrointestinal malignancy. Due to the low incidence of DA there is limited data reporting patient outcomes following radical pancreatic resection. Large retrospective single and multi-centre studies suggest that lymph node metastasis is an important factor for long-term patient survival following resection. The management of DA has tended to favour aggressive surgical resection with pancreaticoduodenectomy (PD), although a morbidity of up to 50% has been reported, mostly related to post-operative pancreatic fistulas. We assessed the disease-free (DFS) and overall survival (OS) in patients undergoing pancreaticoduodenectomy for DA in our institution. Methods We retrospectively analysed all patients undergoing pancreatic resection for DA at our institution between January 2009 – March 2020 inclusive. All DAs were cytologically or histologically proven prior to surgical resection following imaging review in a Hepato-pancreaticobiliary multidisciplinary team meeting. Patients underwent a Whipple’s with distal gastrectomy or pylorus preserving pancreaticoduodenectomy (PPPD) based on tumour size and location. Statistical analysis was performed by a Mann-Whitney U test using a p-value significance of 0.05 (SPSS, IBM, USA). DFS and OS curves were presented by Kaplan- Meier survival curves. Results 19 patients underwent pancreatic resection at our institution for DA during the study period. 12 patients underwent Whipple’s with distal gastrectomy and 9 patients underwent PPPD. The overall postoperative morbidity and mortality was 37% and 5% respectively. R0 resection was achieved in 18 patients (95%). 9 patients (47%) had no nodal involvement. Median follow up was 31 months (range 1-108 months). Median DFS was 17 months but was significantly higher in patients with no nodal metastasis [p < 0.001]. Median OS was 9.5 months for the whole cohort but was significantly higher in the patients with no nodal vs nodal metastasis (60 vs 17.5 months respectively) p < 0.003]. Conclusions DA can be resected by PD or segmental resection. PD is favoured due to improved resection margins and overall increased patient survival, despite an increased morbidity. Our series reports comparable morbidity and mortality to the published literature for DA resected by PD. This study reports a 95% R0 resection rate for DA with a 3- and 5-year survival of 50% and 30% respectively. DFS was found to be significantly higher in patients with no nodal disease, despite predominant T4 disease. This series has identified that lymph node metastasis is one of the most important prognostic determinants of long-term patient survival. Program permission yes

Rational Design 2-Hydroxypropylphosphonium Salts as Cancer Cell Mitochondria-Targeted Vectors: Synthesis, Structure, and Biological Properties

It has been shown for a wide range of epoxy compounds that their interaction with triphenylphosphonium triflate occurs with a high chemoselectivity and leads to the formation of (2-hydroxypropyl)triphenylphosphonium triflates 3 substituted in the 3-position with an alkoxy, alkylcarboxyl group, or halogen, which were isolated in a high yield. Using the methodology for the disclosure of epichlorohydrin with alcohols in the presence of boron trifluoride etherate, followed by the substitution of iodine for chlorine and treatment with triphenylphosphine, 2-hydroxypropyltriphenylphosphonium iodides 4 were also obtained. The molecular and supramolecular structure of the obtained phosphonium salts was established, and their high antitumor activity was revealed in relation to duodenal adenocarcinoma. The formation of liposomal systems based on phosphonium salt 3 and L-α-phosphatidylcholine (PC) was employed for improving the bioavailability and reducing the toxicity. They were produced by the thin film rehydration method and exhibited cytotoxic properties. This rational design of phosphonium salts 3 and 4 has promising potential of new vectors for targeted delivery into mitochondria of tumor cells.

Microsatellite Instability Analysis and Its Prognostic Value in Invasive Nonampullary Duodenal Adenocarcinoma

Purpose: Nonampullary duodenal adenocarcinoma is a rare disease. Although several prognostic factors have been reported for this disease, they remain controversial due to their rarity. In this study, we retrospectively analyzed 54 cases of invasive nonampullary duodenal adenocarcinoma, focusing on the microsatellite instability phenotype, PD-L1 expression, and prognostic factors. Methods: Expression of the PD-L1 protein and cell differentiation markers in tumors was detected by immunohistochemistry. Microsatellite markers (NR-21, NR-22, NR-24, BAT-25 and BAT-26) were amplified for MSI assessment by PCR.Results: The incidence of microsatellite instability in invasive nonampullary duodenal adenocarcinoma was 35.2%. No significant correlation between the microsatellite instability phenotype and clinicopathological factors was observed. Positive expression of PD-L1 by immune cells was common in advanced-stage disease (P=0.054), and positive expression of PD-L1 in cancer cells correlated significantly with the histologically undifferentiated type (P=0.016). Kaplan-Meier survival analysis demonstrated a significantly better overall survival in patients with microsatellite instability (P=0.013) and at early-stage disease (P=0.000) than in those with microsatellite stability or at late tumor stages. Univariate and multivariate analyses showed that microsatellite instability (hazard ratio [HR]: 0.282, 95% confidence interval [CI]: 0.106-0.751, p=0.011) and early tumor stage (stage Ⅰ-Ⅱ) (hazard ratio [HR]: 8.81, 95% confidence interval [CI]: 2.545-30.500, p=0.001) were independent better prognostic factors of overall survival. Conclusions: Microsatellite instability and early tumor stage (stage Ⅰ-Ⅱ) were independent better prognostic factors of overall survival. A high proportion of microsatellite instability phenotypes and positive PD-L1 expression may be helpful for identifying immune checkpoint inhibitors as a novel therapeutic strategy.