Enhancement pattern of the pancreatic parenchyma predicts postpancreatectomy acute pancreatitis after pancreaticoduodenectomy.

OBJECTIVES: To assess the association between the enhancement pattern of the pancreatic parenchyma on preoperative multiphasic contrast-enhanced computed tomography (CECT) and the occurrence of postpancreatectomy acute pancreatitis (PPAP) after pancreaticoduodenectomy (PD). METHODS: A total of 513 patients who underwent PD were retrospective enrolled. The CT attenuation values of the nonenhanced (N), arterial (A), portal venous (P), and late (L) phases in the pancreatic parenchyma were measured on preoperative multiphasic CECT. The enhancement pattern was quantized by the CT attenuation value ratios in each phase. Receiver operating characteristic (ROC) curve analyses were computed to evaluate predictive performance. Regression analyses were used to identify independent risk factors for PPAP. RESULTS: PPAP developed in 102 patients (19.9%) and was associated with increased morbidity and a worse postoperative course. The A/P ratio, P/L ratio, and A/L ratio were significantly higher in the PPAP group. On the ROC analysis, the A/L ratio and A/P ratio both performed well in predicting PPAP (A/L: AUC = 0.7579; A/P: AUC = 0.7497). On multivariate analyses, the A/L ratio > 1.29 (OR 4.30 95% CI: 2.62-7.06, p < 0.001) and A/P ratio > 1.13 (OR 5.02 95% CI: 2.98-8.45, p < 0.001) were both independent risk factors of PPAP in each model. CONCLUSIONS: The enhancement pattern of the pancreatic parenchyma on multiphasic preoperative CECT is a good predictor of the occurrence of PPAP after PD, which could help clinicians identify high-risk patients or enable selective enhance recovery protocols. CLINICAL RELEVANCE STATEMENT: Preoperative identification of patients at high risk for postpancreatectomy acute pancreatitis by enhancement patterns of the pancreatic parenchyma allows surgeons to tailor their perioperative management and take precautions. KEY POINTS: PPAP is associated with increased risk of postoperative complications and a worse postoperative course. A rapid-decrease enhancement pattern of the pancreatic parenchyma is related to the occurrence of PPAP. The A/L and A/P ratios were both independent risk factors of PPAP in each multivariate model.

TP53 missense mutation reveals gain-of-function properties in small-sized KRAS transformed pancreatic ductal adenocarcinoma.

BACKGROUND: Although the molecular features of pancreatic ductal adenocarcinoma (PDAC) have been well described, the impact of detailed gene mutation subtypes on disease progression remained unclear. This study aimed to evaluate the impact of different TP53 mutation subtypes on clinical characteristics and outcomes of patients with PDAC. METHODS: We included 639 patients treated with PDAC in Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine between Jan 2019 and Jun 2021. The genomic alterations of PDAC were analyzed, and the association of TP53 mutation subtypes and other core gene pathway alterations with patients' clinical characteristics were evaluated by Chi-squared test, Kaplan-Meier method and Cox regression model. RESULTS: TP53 missense mutation was significantly associated with poor differentiation in KRASmut PDAC (50.7% vs. 36.1%, P = 0.001). In small-sized (≤ 2 cm) KRASmut tumors, significantly higher LNs involvement (54.8% vs. 23.5%, P = 0.010) and distal metastic rate (20.5% vs. 2.9%, P = 0.030) were observed in those with TP53 missense mutation instead of truncating mutation. Compared with TP53 truncating mutation, missense mutation was significantly associated with reduced DFS (6.6 [5.6-7.6] vs. 9.2 [5.2-13.3] months, HR 0.368 [0.200-0.677], P = 0.005) and OS (9.6 [8.0-11.1] vs. 18.3 [6.7-30.0] months, HR 0.457 [0.248-0.842], P = 0.012) in patients who failed to receive chemotherapy, while higher OS (24.2 [20.8-27.7] vs. 23.8 [19.0-28.5] months, HR 1.461 [1.005-2.124], P = 0.047) was observed in TP53missense cases after chemotherapy. CONCLUSIONS: TP53 missense mutation was associated with poor tumor differentiation, and revealed gain-of-function properties in small-sized KRAS transformed PDAC. Nonetheless, it was not associated with insensitivity to chemotherapy, highlighting the neoadjuvant therapy before surgery as the potential optimized strategy for the treatment of a subset of patients.

Serum lipase on postoperative day one is a strong predictor of clinically relevant pancreatic fistula after pancreaticoduodenectomy: A retrospective cohort.

BACKGROUND: Increased postoperative serum amylase has been recently reported to be associated with increased postoperative morbidity, but studies on postoperative serum lipase are limited. The aim of this study was to evaluate the value of postoperative serum lipase in predicting clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD). METHOD: A retrospective analysis was performed on 212 patients who underwent PD from September 2018 and March 2021, focusing on the association between postoperative day (POD) 1 serum lipase and CR-POPF. RESULTS: Overall, 108 (50.9%) patients had elevated serum lipase levels (>68 U/L) on POD 1. Patients with elevated serum lipase exhibited a significantly higher incidence of CR-POPF (37.0% vs. 6.7%, p < 0.001). Receiver operating characteristic (ROC) analyses showed improved diagnostic accuracy for POD 1 serum lipase compared with POD 1 serum amylase in predicting CR-POPF (AUC: 0.801 vs. 0.745, p = 0.029). Elevated serum lipase on POD 1 and elevated serum CRP on POD 3 were identified as independent predictors of CR-POPF. A simple early postoperative model, consisting of POD 1 serum lipase levels and POD 3 serum CRP levels, showed good discrimination (AUC 0.76, 95% CI 0.69-0.83) to identify the onset of CR-POPF. CONCLUSION: Serum lipase on POD 1 outperformed serum amylase on POD 1 in predicting CR-POPF after PD. The combination of POD 1 serum lipase and POD 3 serum CRP provides a reliable predicting model for CR-POPF.

Original study: The rescue staging for pancreatic ductal adenocarcinoma with inadequate examined lymph nodes.

BACKGROUND: In previous studies, it's recommended that the lymph node involvement should be evaluated with enough examined lymph nodes (eLNs) in the 8th American Joint Committee on Cancer (AJCC) staging system for pancreatic cancer. This study aims to put forward a rescue staging system for pancreatic ductal adenocarcinoma (PDAC) patients with inadequate eLNs after pancreatoduodenectomy (PD). METHOD: 11,224 PDAC patients undergoing PD in The Surveillance, Epidemiology, and End Results (SEER) database were included. Another Ruijin Pancreatic Disease Center (RJPDC) database consisted of 821 patients was utilized for external validation. RESULTS: The proportions of patients with eLNs≥15 were 44.7% and 32.8% in SEER and RJPDC database separately. The rescue staging system was put forward relying on LNR (HR = 1.83, 95% CI 1.74-1.92, P < 0.001) for N staging of eLNs<15 population and pLNs for the rest. The TNM modalities were also rearranged in the rescue system for better survival coordination. The C-index of rescue staging system was 0.638 while that of AJCC 8th staging system was 0.613 in SEER database. Similar phenomena were observed in RJPDC database. Kaplan-Meier analyses revealed reliable internal coherences (SEER: Ib: P = 0.26; IIa: P = 0.063; IIb: P = 0.53; IIIa: P = 0.11. RJPDC: Ib: P = 0.32; IIa: P = 0.66; IIb: P = 0.76; IIIa: P = 0.66) and significant staging efficiency (SEER: P < 0.001; RJPDC: P = 0.002). CONCLUSION: A rescue staging system was put forward regardless of the eLNs number. And the novel system manifested better predictive capacity than 8th AJCC staging system.

Predictive factors for postoperative pancreatitis after pancreaticoduodenectomy: A single-center retrospective analysis of 1465 patients.

BACKGROUND: Postoperative acute pancreatitis (POAP) after pancreaticoduodenectomy (PD) has been recently recognized as an independent complication that is associated with undesirable postoperative outcomes and often precedes other complications, yet predictive factors attributable to POAP after PD remain elusive. METHODS: The data from 1465 consecutive patients who underwent laparotomy or minimally invasive robotic PD from March 2010 to December 2018 were retrospectively reviewed. POAP was defined as an elevation of the serum amylase levels above the institution's normal upper limit (100 U/L) on postoperative day (POD) 1. Univariate and multivariate analyses were performed to investigate the predictive factors for POAP after PD and the association between POAP and clinically relevant postoperative pancreatic fistulas (CR-POPFs). RESULTS: Among the 1465 patients, 411 (28%) underwent minimally invasive robotic surgeries, and the overall POAP and CR-POPFs rates were 770 (53%) and 277 (19%), respectively. The female sex (OR 1.76), a normal bilirubin level (OR 1.55), the robotic surgery (OR 1.36), a main pancreatic duct (MPD) ≤3 mm (OR 5.69) and a high-risk nonadenocarcinoma pathology (cystic disease: OR 4.33; pNETs: OR 4.34; others: OR 2.74) were considered independent risk factors for POAP. A nondilated MPD was a predominant predictor for POAP, with 72.2% sensitivity and 71.8% specificity. POAP was also an independent predictive factor for CR-POPFs (OR 3.48). CONCLUSION: A nondilated MPD, a high-risk pathology, the female sex, a normal bilirubin level and the robotic surgery were independent predictive factors for POAP after PD. Prevention and early treatment strategy changes can be made based on these preoperative predictive factors.

[The Efficacy of 17 Cases of Pancreaticoduodenectomy Combined with Vascular Resection and Reconstruction by Using Robotic Operation System (with Video)].

OBJECTIVE: To explore the clinical efficacy of pancreaticoduodenectomy (PD) combined with vascular resection and reconstruction under robotic surgery system in the treatment of borderline resectable pancreatic cancer. METHODS: The clinical data of 17 patients with borderline resectable pancreatic cancer who underwent PD combined with vascular resection and reconstruction (see the Video 1 in Supplemental Contents, http://ykxb.scu.edu.cn/article/doi/10.12182/20200760202) under robotic surgery system between August 2011 and September 2018 was analyzed retrospectively. RESULTS: There were 4 cases required conversion because of serious tumor invasion and soft pancreas texture, the other 13 cases were successfully completed. 16 cases (94%) achieved margin-negative resection (R0 resection), 14 cases combined with vein resection, and 3 cases combined with arterial resection. The mean operation time was (401±170) min, the mean blood loss was (647±345) mL, the mean postoperative length of hospital stay was (20±8) d. There was no perioperative death. Postoperative pathology findings and follow-up outcomes were as follows: 1 patient was diagnosed as intraductal papillary mucinous neoplasm (IPMN) and 1 patient was diagnosed as pancreatic neuroendocrine tumors (PNET) (Grade 1), 8 patients with pancreatic ductal adenocarcinoma (PDAC). 1 patient with pancreatic neuroendocrine carcinoma (PNEC) died because of tumor recurrence and metastasis during the follow-up period, the median (Min-Max) survival time was 12 (8-26) months. 5 patients with PDAC and 1 patient with malignant IPMN were currently in the follow-up period. CONCLUSION: It is safe and feasible to perform RPD with vascular resection and reconstruction. The patient's condition should be fully evaluated before surgery to select the most appropriate treatment.

Perineural invasion is related to p38 mitogen-activated protein kinase pathway activation and promotes tumor growth and chemoresistance in pancreatic cancer.

Metastasis is a key component of cancer progression and is strongly associated with poor prognosis. Perineural invasion is thought to be related to pain, tumor recurrence, and other conditions. However, the exact molecular mechanism is unclear. This study was conducted to identify the key components and signaling pathways involved in the perineural invasion of pancreatic cancer and alterations in the phenotype after the interaction between the dorsal root ganglion (DRG) and pancreatic cancer cells. The results indicated that the p38 mitogen-activated protein kinase signaling pathway was activated after coculture of the DRG and pancreatic cancer cells and lead to the promotion of cell growth and chemoresistance.

Should a standard lymphadenectomy include the No. 9 lymph nodes for body and tail pancreatic ductal adenocarcinoma?

OBJECTIVES: This study aimed to use a retrospective data base to investigate whether a standard lymphadenectomy during distal pancreatectomy should include the No. 9 lymph nodes (LNs) for resectable pancreatic ductal adenocarcinoma (PDAC) located in the body and tail of the pancreas. METHODS: Data from 169 patients undergoing curative distal pancreatectomy for PDAC between Jan 1, 2013 and Dec 31, 2016 were collected. According to the tumor location, patients were divided into three groups: pancreatic neck tumor, pancreatic body and tail tumor with margin-to-bifurcation-distance (MTBD) ≤ 2.5 cm and pancreatic body and tail tumor with MTBD > 2.5 cm. The metastatic rate of the No. 9 LNs was compared among the 3 groups. The survival outcomes were analyzed. RESULTS: The involvement rate for No. 9 LNs was 20.7% (6/29) for pancreatic neck tumors, 17.6% (15/85) for body and tail tumors with MTBD ≤ 2.5 cm and 1.8% (1/55) for MTBD > 2.5 cm. The No. 9 LNs were significantly more frequently involved in neck or body and tail tumors with MTBD ≤2.5 cm than with the cases with MTBD >2.5 cm (OR 0.082, P = 0.016). No. 9 LN involvement was not associated with worse survival compared with survival associated with involvement of other LNs (P = 0.780). CONCLUSIONS: For PDAC located in the neck or in the body and tail of the pancreas with MTBD ≤ 2.5 cm, the involvement rate for No. 9 LNs is high. Standard lymphadenectomy should include the No. 9 LNs.

Resection of pancreatic metastatic renal cell carcinoma: experience and long-term survival outcome from a large center in China.

PURPOSE: This study aimed to determine the outcome of pancreatic metastatic renal cell carcinoma (PmRCC) after treatment and share the relevent results. METHODS: In total, 13 patients with PmRCC were diagnosed and treated in our institution from December 2013 to October 2017. We retrospectively reviewed the records and analyzed the patient demographics, perioperative outcomes, and overall survival. Simultaneously, our experience including treatment and misdiagnosis was shared. RESULTS: The median time between nephrectomy and reoperation for pancreatic recurrence was 11 years (range 1-20 years). Four patients had multiple tumors and nine patients had solitary tumor. Five patients accepted distal pancreatectomy, and five patients underwent pancreaticoduodenectomy. One patient underwent total pancreatectomy, one patient underwent duodenum-preserving pancreatic head resection plus distal pancreatectomy, and one patient underwent exploratory laparotomy and gastrointestinal bypass due to widespread metastasis with clear obstructive symptoms. The misdiagnosis rate of preoperative diagnosis at our center was 69.2% (9/13). The median follow-up duration was 26 months (range 7-53 months, until June 2018). By the end of follow-up, 12 patients were alive and one patient died of gastrointestinal bleeding within 1 month after surgery. CONCLUSIONS: PmRCCs are uncommon, but pancreatic metastasectomy has a relatively good prognosis and may, therefore, be a good therapeutic choice for patients with PmRCCs. Because PmRCC occurs long after the primary tumor resection, long-term follow-up is necessary. Besides, detailed medical history and specific manifestation in imaging features could contribute to avoiding misdiagnosis.

MicroRNA-300 promotes apoptosis and inhibits proliferation, migration, invasion and epithelial-mesenchymal transition via the Wnt/ß-catenin signaling pathway by targeting CUL4B in pancreatic cancer cells.

The study aims to verify the hypothesis that up-regulation of microRNA-300 (miR-300) targeting CUL4B promotes apoptosis and suppresses proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells by regulating the Wnt/ß-catenin signaling pathway. Pancreatic cancer tissues and adjacent tissues were collected from 110 pancreatic cancer patients. Expression of miR-300, CUL4B, Wnt, ß-catenin, E-cadherin, N-cadherin, Snail, GSK-3ß, and CyclinD1 were detected using qRT-PCR and Western blot. CFPAC-1, Capan-1, and PANC-1 were classified into blank, negative control (NC), miR-300 mimics, miR-300 inhibitors, siRNA-CUL4B, and miR-300 inhibitors + siRNA-CUL4B groups. The proliferation, migration, invasion abilities, the cell cycle distribution, and apoptosis rates were measured in CCK-8 and Transwell assays. Pancreatic cancer tissues showed increased CUL4B expression but decreased miR-300 expression. When miR-300 was lowly expressed, CUL4B was upregulated which in-turn activated the Wnt/ß-catenin pathway to protect the ß-catenin expression and thus induce EMT. When miR-300 was highly expressed, CUL4B was downregulated which in-turn inhibited the Wnt/ß-catenin pathway to prevent EMT. Weakened cell migration and invasion abilities and enhanced apoptosis were observed in the CUL4B group. The miR-300 inhibitors group exhibited an evident increase in growth rate accompanied the largest tumor volume. Smaller tumor volume and slower growth rate were observed in the miR-300 mimics and siRNA-CUL4B group. Our study concludes that lowly expressed miR-300 may contribute to highly expressed CUL4B activating the Wnt/ß-catenin signaling pathway and further stimulating EMT, thus promoting proliferation and migration but suppressing apoptosis of pancreatic cancer cells.

Long noncoding RNA NORAD, a novel competing endogenous RNA, enhances the hypoxia-induced epithelial-mesenchymal transition to promote metastasis in pancreatic cancer.

BACKGROUND: Pancreatic cancer, one of the top two most fatal cancers, is characterized by a desmoplastic reaction that creates a dense microenvironment, promoting hypoxia and inducing the epithelial-to-mesenchymal transition (EMT) to facilitate invasion and metastasis. Recent evidence indicates that the long noncoding RNA NORAD may be a potential oncogenic gene and that this lncRNA is significantly upregulated during hypoxia. However, the overall biological role and clinical significance of NORAD remains largely unknown. METHODS: NORAD expression was measured in 33 paired cancerous and noncancerous tissue samples by real-time PCR. The effects of NORAD on pancreatic cancer cells were studied by overexpression and knockdown in vitro. Insights into the mechanism of competitive endogenous RNAs (ceRNAs) were gained from bioinformatics analyses and luciferase assays. In vivo, metastatic potential was identified using an orthotopic model of PDAC and quantified using bioluminescent signals. Alterations in RhoA expression and EMT levels were identified and verified by immunohistochemistry and Western blotting. RESULTS: NORAD is highly expressed in pancreatic cancer tissues and upregulated in hypoxic conditions. NORAD upregulation is correlated with shorter overall survival in pancreatic cancer patients. Furthermore, NORAD overexpression promoted the migration and invasion of pancreatic carcinoma cells, while NORAD depletion inhibited EMT and metastasis in vitro and in vivo. In particular, NORAD may function as a ceRNA to regulate the expression of the small GTP binding protein RhoA through competition for hsa-miR-125a-3p, thereby promoting EMT. CONCLUSIONS: Elevated expression of NORAD in pancreatic cancer tissues is linked to poor prognosis and may confer a malignant phenotype upon tumor cells. NORAD may function as a ceRNA to regulate the expression of the small GTP binding protein RhoA through competition for hsa-miR-125a-3p. This finding may contribute to a better understanding of the role played by lncRNAs in hypoxia-induced EMT and provide a potential novel diagnostic and therapeutic target for pancreatic cancer.

Robot-assisted laparoscopic versus open middle pancreatectomy: short-term results of a randomized controlled trial.

OBJECTIVE: This first prospective randomized controlled trial was performed to compare short-term outcomes of robot-assisted laparoscopic middle pancreatectomy (RA-MP) with open middle pancreatectomy (OMP). BACKGROUND: RA-MP is a novel minimally invasive surgical technique for benign or borderline tumors in the pancreatic neck or body. Its short-term effectiveness and safety remain unknown, compared to OMP. METHODS: Patients eligible for MP from August 2011 to November 2015 were randomized into the RA-MP or OMP group. The primary endpoint was length of hospital stay (LOS). Secondary endpoints were intraoperative parameters, and postoperative and recovery variables. RESULTS: A total of 100 patients were included into the study to analyze primary and secondary endpoints. Demographic characteristics and pathological parameters were similar in both groups. Furthermore, LOS was significantly shorter (15.6 vs. 21.7 days, P = 0.002), median operative time was reduced (160 vs. 193 min, P = 0.002), median blood loss was lower (50 vs. 200 mL, P < 0.001), rate of clinical postoperative pancreatic fistula (POPF) was lower (18 vs. 36.0 %, P = 0.043), nutritional status recovery was better, off-bed return to activity was expedited (3.1 vs. 4.6 days, P < 0.001), and resumption of bowel movement was faster (3.5 vs. 5.0 days, P < 0.001) in the RA-MP group, compared to the OMP group. CONCLUSION: RA-MP was associated with significantly shorter LOS, reduced operative time, blood loss and clinical POPF rate, and expedited postoperative recovery, compared to OMP.

Robot-Assisted Middle Pancreatectomy for Elderly Patients: Our Initial Experience.

BACKGROUND: The aim of this study was to evaluate the indications, safety, feasibility, and short- and long-term outcomes for elderly patients who underwent robot-assisted middle pancreatectomies (MPs). MATERIAL AND METHODS: Ten patients (≥60 years) underwent robot-assisted middle pancreatectomies from 2012 to 2015. The perioperative data, including tumor size, operating time, rate of postoperative pancreatic fistula (POPF), postoperative morbidity, and other parameters, were analyzed. We collected and analyzed the follow-up information. RESULTS: The mean age of patients was 64.30 years (range, 60-73 years). The average tumor size was 2.61 cm. The 10 cases were all benign or low-grade malignant lesions. The mean operating time was 175.00 min. The mean blood loss was 113.00 ml with no blood transfusion needed. Postoperative fistulas developed in 5 patients; there were 2 Grade A fistulas and 3 grade B fistulas. There were 3 patients who underwent postoperative complications, including 2 Grade 1 or 2 complications and 1 Grade 3 complication. No reoperation and postoperative mortality occurred. The mean hospital stay was 19.91 days. After a median follow-up of 23 months, new onset of diabetes mellitus developed in 1 patient and none suffered from deterioration of previously diagnosed diabetes or exocrine insufficiency, and no tumor recurrence happened. CONCLUSIONS: Robot-assisted middle pancreatectomy was safe and feasible for elderly people. It had low risk of exocrine or endocrine dysfunction and benefited patients' long-term outcomes. Incidence of POPF was relatively high but we could prevent it from resulting in bad outcomes by scientific perioperative care and systemic treatment.

The prevalence of osteoarthritis of the atlanto-odontoid joint in adults using multidetector computed tomography.

BACKGROUND: The prevalence of osteoarthritis of the atlanto-odontoid joint has been reported by radiology, autopsy, and conventional computed tomography (CT), but the prevalence has not yet been assessed by multidetector computed tomography (MDCT). PURPOSE: To reveal the prevalence of osteoarthritis of the atlanto-odontoid joint and to analyze the inter-relationships among gender, age, and osteoarthritis with MDCT in adults. MATERIAL AND METHODS: First, a series of 700 selected domestic patients aged >18 years undergoing an upper cervical MDCT scan were divided equally into seven age groups. Second, using the postprocessing technique of multiplanar reconstruction, osteoarthritis of the atlanto-odontoid joint was viewed from any direction and classified into four grades, which were normal, mild, moderate, and severe. Lastly, the incidence of the different grades of osteoarthritis was assessed, and the reproducibility was tested. RESULTS: There was no significant difference between gender and osteoarthritis of atlanto-odontoid joint (P > 0.05). The rate of osteoarthritis was 16% in the age group 18-25 years, 23% in the age group 25-30 years, 33% in the age group 30-40 years, 54% in the age group 40-50 years, 70% in the age group 50-60 years, 87% in the age group 60-70 years, and 93% in the age group >70 years. Mild osteoarthritis appeared at the earliest at age 19.6 years, moderate osteoarthritis in at earliest at age 24.2 years, and severe osteoarthritis at the earliest at age 48.5 years. The inter-observer reliability was excellent (k = 0.86). CONCLUSION: Osteoarthritis of the atlanto-odontoid joint could be detected by MDCT in a young adult. It increased rapidly with increasing age on MDCT.

BHLHE40 Inhibits Ferroptosis in Pancreatic Cancer Cells via Upregulating SREBF1.

Pancreatic cancer (PCa) is one of the most fatal human malignancies. The enhanced infiltration of stromal tissue into the PCa tumor microenvironment limits the identification of key tumor-specific transcription factors and epigenomic abnormalities in malignant epithelial cells. Integrated transcriptome and epigenetic multiomics analyses of the paired PCa organoids indicate that the basic helix-loop-helix transcription factor 40 (BHLHE40) is significantly upregulated in tumor samples. Increased chromatin accessibility at the promoter region and enhanced mTOR pathway activity contribute to the elevated expression of BHLHE40. Integrated analysis of chromatin immunoprecipitation-seq, RNA-seq, and high-throughput chromosome conformation capture data, together with chromosome conformation capture assays, indicate that BHLHE40 not only regulates sterol regulatory element-binding factor 1 (SREBF1) transcription as a classic transcription factor but also links the enhancer and promoter regions of SREBF1. It is found that the BHLHE40-SREBF1-stearoyl-CoA desaturase axis protects PCa cells from ferroptosis, resulting in the reduced accumulation of lipid peroxidation. Moreover, fatostatin, an SREBF1 inhibitor, significantly suppresses the growth of PCa tumors with high expressions of BHLHE40. This study highlights the important roles of BHLHE40-mediated lipid peroxidation in inducing ferroptosis in PCa cells and provides a novel mechanism underlying SREBF1 overexpression in PCa.

Middle-preserving pancreatectomy: report of two cases and review of the literature.

BACKGROUND: Middle-preserving pancreatectomy (MPP) is a parenchyma-sparing surgical procedure which has recently been sporadically reported for the treatment of multicentric periampullary-pancreatic lesions. However, a comprehensive recognition of this procedure has not been clearly elucidated. CASE PRESENTATION: We herein report two patients undergoing MPP due to synchronous multicentric pancreatic neoplasm. Patient one was a 24-year-old woman with a multicentric solid pseudopapillary neoplasm (SPN) and patient two was a 36-year-old woman with a multicentric serous cystic neoplasm (SCN). Simultaneous atypical pancreaticoduodenectomy and atypical left pancreatectomy were performed in patient one; simultaneous standard pancreaticoduodenectomy and atypical left pancreatectomy with spleen preservation were performed in patient two. Approximately 6 cm and 5 cm segments of the middle portion of the pancreas were preserved, respectively. At follow-up at 36 months and 6 months respectively, patient one had developed diabetes and malabsorption requiring dietary control, exercise and pancreatic enzyme supplement whereas patient two showed normal fasting blood glucose without diarrhea. Both patients were disease-free and in good nutritional condition. We reviewed twenty cases of MPP that were previously reported in the literature. Patient characteristics, surgical techniques and short- and long-term outcomes were analyzed. CONCLUSION: MPP is mainly beneficial for multicentric noninvasive periampullary-pancreatic lesions. However, for multicentric periampullary-pancreatic lesions involving even primary invasive cancers, as long as the invasive cancers affect only one side of the pancreas (proximal or distal), MPP could serve as a rational choice in well-selected patients.

Specific human leukocyte antigen class I genotypes predict prognosis in resected pancreatic adenocarcinoma: a retrospective cohort study.

BACKGROUND: Patients with resected pancreatic adenocarcinoma (PAAD) often experience short-term relapse and dismal survival, suggesting an urgent need to develop predictive and/or prognostic biomarkers for these populations. Given the potential associations of the human leukocyte antigen class I ( HLA -I) genotype with oncogenic mutational profile and immunotherapy efficacy, we aimed to assess whether differential HLA -I genotype could predict the postoperative outcomes in resected PAAD patients. MATERIALS AND METHODS: HLA -I ( A , B , and C ) genotyping and somatic variants of 608 Chinese PAAD patients were determined by targeted next-generation sequencing of matched blood cells and tumor tissues. HLA - A / B alleles were classified with the available definition of 12 supertypes. The Kaplan-Meier curves of disease-free survival (DFS) and multivariable Cox proportional-hazards regression analyses were performed to determine the survival difference in 226 selected patients with radical resection. Early-stage (I-II) patients constituted the majority (82%, 185/226) and some stage I-II individuals with high-quality tumor samples were analyzed by RNA-sequencing to examine immunophenotypes. RESULTS: Patients with HLA-A02 + B62 + B44 - had significantly shorter DFS (median, 239 vs. 410 days; hazard ratio=1.65, P =0.0189) than patients without this genotype. Notably, stage I-II patients carrying HLA-A02 + B62 + B44 - had sharply shorter DFS than those without HLA-A02 + B62 + B44 - (median, 237 vs. 427 days; hazard ratio=1.85, P =0.007). Multivariate analysis revealed that HLA-A02 + B62 + B44 - was associated with significantly inferior DFS ( P =0.014) in stage I-II patients but not in stage III patients. Mechanistically, HLA-A02 + B62 + B44 - patients were associated with a high rate of KRAS G12D and TP53 mutations, lower HLA-A expression, and less inflamed T-cell infiltration. CONCLUSION: The current results suggest that a specific combination of germline HLA-A02/B62/B44 supertype, HLA-A02 + B62 + B44 - , was a potential predictor for DFS in early-stage PAAD patients after surgery.

Solid-pseudopapillary tumor of the pancreas: clinical features, pathological characteristics, and origin.

OBJECTIVE: [corrected] To study clinically pathological features and origin of solid-pseudopapillary tumor of pancreas (SPT). PATIENTS AND METHODS: Clinical and pathological data of 82 cases with SPT were retrospectively studied. SAS6.12 statistics package was used for analysis. P < 0.05 was regarded as statistically significant difference. RESULTS: The SPT patients included 70 females and 12 males, with a median age of 31 years old. The mean tumor size was 6.71 ± 4.42 cm. Vascular or organs was invaded in nine cases. The clinical and pathological characteristics show no significant difference between male and female patients. In the non-encapsulate group (22 cases), the tumor was larger (P = 0.0015), exogenous growth pattern (P = 0.0194), and would probably involve major vascular or organs (P = 1.697E-06). The typical features of SPT include pseudopapillary pattern with fibro vascular stalks by uniform poorly cohesive polygonal cells. The tumor cell expresses a variety of immune markers in heterogeneity. Under electron microscope, there are some electron dense granules, about 8-1.2 µm in diameter, with membrane similar to the zymogen granules in SPT cell cytoplasm. CONCLUSIONS: SPT with incomplete capsule often presents malignant behaviors. SPT shows multi-heterogeneity, which is caused by the disorder in the development of pancreatic stem cell.

Sintering Bonding of SiC Particulate Reinforced Aluminum Metal Matrix Composites by Using Cu Nanoparticles and Liquid Ga in Air.

SiC particulate reinforced aluminum metal matrix composites (SiCp/Al MMCs) are characterized by controllable thermal expansion, high thermal conductivity and lightness. These properties, in fact, define the new promotional material in areas and industries such as the aerospace, automotive and electrocommunication industries. However, the poor weldability of this material becomes its key problem for large-scale applications. Sintering bonding technology was developed to join SiCp/Al MMCs. Cu nanoparticles and liquid Ga were employed as self-fluxing filler metal in air under joining temperatures ranging from 400 °C to 500 °C, with soaking time of 2 h and pressure of 3 MPa. The mechanical properties, microstructure and gas tightness of the joint were investigated. The microstructure analysis demonstrated that the joint was achieved by metallurgical bonding at contact interface, and the sintered layer was composed of polycrystals. The distribution of Ga was quite homogenous in both of sintered layer and joint area. The maximum level of joint shear strength of 56.2 MPa has been obtained at bonding temperature of 450 °C. The specimens sintering bonded in temperature range of 440 °C to 460 °C had qualified gas tightness during the service, which can remain 10-10 Pa·m3/s.

LncRNA SNHG7 Regulates Mesenchymal Stem Cell Through the Notch1/Jagged1/Hes-1 Signaling Pathway and Influences Folfirinox Resistance in Pancreatic Cancer.

Pancreatic cancer (PC) is one of the deadliest gastrointestinal cancers, accounting for the fourth highest number of cancer-related fatalities. Increasing data suggests that mesenchymal stem cells (MSCs) might influence the drug resistance of GC cells in the tumor microenvironment and play essential roles in drug resistance development. However, the precise underlying process remains a mystery. The purpose of this study was to look at the control of MSC-induced SNHG7 in pancreatic cancer. In vitro and in vivo sphere formation, colony formation, and flow cytometry investigations revealed the stemness and Folfirinox resistance in pancreatic cancer cells. To confirm the direct connections between SNHG7 and other related targets, RNA pulldown and immunoprecipitation tests were performed. MSC co-culture enhanced the stemness and Folfirinox resistance in pancreatic cancer cells according to the findings. MSC co-culture increased SNHG7 expression in pancreatic cancer cells, contributing to the stemness and Folfirinox resistance. We demonstrated that Notch1 interacted with SNHG7 and could reverse the facilitative effect of SNHG7 on the stemness and Folfirinox resistance in pancreatic cancer cells. Finally, our findings showed that MSCs increased SNHG7 expression in pancreatic cancer cells, promoting the stemness and Folfirinox resistance via the Notch1/Jagged1/Hes-1 signaling pathway. These findings could provide a novel approach and therapeutic target for pancreatic cancer patients.