Wang, Zhen

AbstractAutoimmune pancreatitis (AIP) is identified as a severe chronic immune‐related disorder in pancreas, including two subtypes. In this study, pancreatic lesions in patients diagnosed as either type 1 AIP or type 2 AIP are examined, and these patients’ peripheral blood at single‐cell level. Furthermore, flow cytometry, immunofluorescence, and functional assays are performed to verify the identified cell subtypes. In type 1 AIP, there is a notable increase in the amount of B cells and plasma cells, and IgG4+ plasma cells are key pathogenic cells of AIP. The differentiation path of naïve‐stage B cells into IgG4+ produced plasma cells is observed, and an increased amount of T helper cells and T follicular helper (Tfh) cells. This study also reveals that HIF‐1α, an activated transcriptional factor, can directly bind to promoter site of NAMPT, promoting higher levels of visfatin production in HIF1A+ classical monocytes. Pancreatic stellate cells can be activated by extracellular visfatin and promote the development of fibrotic response in pancreatic lesions across both AIP subtypes. The current findings shed light on the exploration of dynamic alterations in peripheral blood cells and cell subgroups in pancreatic lesions of AIP, while elucidating a pathogenic cell subset and potential fibrosis mechanism of AIP.

INTRODUCTION: The increasing prevalence of clarithromycin (CLA)-resistant Helicobacter pylori (H. pylori) strains poses a significant challenge in the management of H. pylori infections. This systematic review and meta-analysis investigates the diagnostic accuracy of polymerase chain reaction (PCR) in identifying CLA-resistant H. pylori strains in stool. METHODS: A comprehensive literature search was conducted using PubMed, Embase, and Cochrane databases from database inception to April 30, 2023. Eligible studies evaluated the effectiveness of PCR stool tests in detecting CLA-resistant H. pylori strains in adults (>18-year-old). Studies of pediatric populations, alternative methods to PCR or stool samples, and reference tests other than gastric biopsy were excluded. The bivariate random-effects model was used to pool diagnostic accuracy from the included studies. RESULTS: The analysis of 11 prospective diagnostic studies with a total of 866 patients showed a pooled sensitivity of 0.97 (95% CI: 0.9–0.99) and a pooled specificity of 0.98 (95% CI: 0.81–1.00). Subgroup analysis based on the used technique demonstrated consistent findings without notable variations. The diagnostic odds ratio was calculated at 1843.92 (95% CI: 134.28–25,321.3). The positive likelihood ratio was determined as 51.02 (95% CI: 4.61–564.5), while the negative likelihood ratio was found to be 0.03 (95% CI: 0.01–0.1). DISCUSSION: PCR testing for clarithromycin-resistant H. pylori was highly sensitive and specific across studies with proven reliability in clinical practice, particularly in outpatient settings. Their implementation offers cost-effectiveness and the potential for tailored treatment strategies, holding promise for improved patient outcomes.

Abstract Background Pancreatic cysts (PC) are increasingly detected through abdominal imaging, prompting exploration of alternatives such as endoscopic ultrasound-guided pancreatic cyst ablation (EUS-PCA) due to the risks and costs associated with surgery. This study conducts a systematic review and meta-analysis of EUS-PCA's short-term efficacy and complications for PC management. Methods A systematic review and meta-analysis were carried out on PubMed, Ovid, Cochrane, and TRIP electronic databases. The primary outcome was cyst resolution (partial and complete) and persistence on imaging 12 months after ablation. The secondary outcome was procedure-related adverse events. Results Eight studies were eligible for analysis. Complete cyst resolution on imaging 12 months after EUS ablation was 50% [95% CI 36, 63, I2 = 85.31%]. Partial cyst resolution was 27% [95% CI 15, 41, I2 = 87.07%], and cyst persistence was 17% [95% CI 11, 24, I2 = 62.11%]. The rate of complete resolution varied depending on the treatment agent (for ethanol 29% [95% CI 10, 53], lauromacrogol 51% [95% Cl 36, 67], ethanol and paclitaxel 63% [95% CI 48, 76], paclitaxel and gemcitabine 67% [95% CI 45, 83], ethanol, paclitaxel and gemcitabine 61% [95% CI 39, 80]). Post-procedure adverse events included abdominal pain in 4% [95% CI 0, 11], pancreatitis in 3% [95% CI 1, 5], and fever in 1% [95% CI 0, 3] of all patients. Conclusion The treatment of pancreatic cysts with EUS ablation results in acceptable levels of complete resolution, and low incidence of severe adverse events. The effectiveness of this treatment is further enhanced when chemoablative agents are employed.

Abstract Introduction: Incidence of secondary malignant neoplasm in patients with chronic lymphocytic leukemia (CLL) is already established. Genetic predisposition has been considered to be a possible contributory factor for the preponderance of second cancers in this population. In the present study, we examined the frequency, characteristics, and clinical outcomes of secondary malignancies in patients with CLL based on their Interphase fluorescence in situ hybridization (FISH) panel. Methods: We reviewed the medical records of consecutive patients with CLL observed or treated at Ellis Fischel Cancer Center during the period from 2007-2014. We collected demographic data, CLL Rai stage, treatment history, Interphase fluorescence in situ hybridization (FISH) panel results and the presence of a secondary malignancy (skin cancers, solid tumors and hematologic malignancy excluding CLL transformation).Our aim was to investigate the association between secondary malignancy and chromosomal abnormalities and other risk factors using Chi2test for categorical variables and Wilcoxon rank-sum test for continuous variables. Cox proportional hazard models and logistic regression models were used to evaluate risk factors of developing secondary malignancy and overall survival. Results: We identified 142 CLL patients who were either observed (n=62) or had a history of treatment (n=80) for CLL. 67% were male and 33% were female. 85% of patients were Caucasians, 10% African Americans, and 5% other. Familial CLL was present in 6% of cases. 51% of patients were non-smokers. 5% of patients had cancers preceding the diagnosis of CLL (non-melanoma skin cancers=3, melanoma=1, Hodgkin's lymphoma=1, Prostate=2). 28% of patients developed secondary malignancies after the diagnosis of CLL; among them non-melanoma skin cancers were the most common (78%), followed by cutaneous melanoma (9.5%) and papillary thyroid cancer (4.7%). Other malignancies included lung (2.3%), kidney (2.3%), prostate (2.3%) and ocular melanoma (2.3%). 12% patients had aggressive non-melanoma recurrent skin cancers that require multiple treatments along-with systemic therapy for progressive CLL. CLL-FISH panel at diagnosis was available in 98 patients. Among these patients,13q deletion was present in 45%. Within the 13q deletion group, secondary malignancy was noted in 50% during a median follow up of 7 years. All cases of papillary thyroid cancers were also present in 13q deletion. In contrast, 11q deletion was detected in 15% and trisomy 12 in 18% of patients with incidence of secondary malignancy 40% and 10%, respectively. No solid malignancy other than skin was identified in the 11q deletion and trisomy 12 groups. 17p deletion was present in 5% of cases and 60% of 17p deletion cases had secondary cancers (skin 80%). Normal FISH panel was present in 17% cases and 20% of normal FISH had secondary malignancy (solid 10%, skin 10%). The median overall survival time is 6 years for the entire cohort (IRQ: 3-9 years). Secondary malignancy was associated with worse overall survival (OS) (HR=0.57, 95% CI:0.33-0.98, p=0.04) compare to patients who did not have secondary malignancy. The risk of secondary malignancy is increased in patients with advanced age (OR=1.05, 95% CI:1.00-1.10, p=0.04) and in those who were treated with alkylating agent for CLL OR=6.62, 95% CI:2.08-21.03, p=0.001. However, there were no significant difference on risk of developing secondary malignancy based on specific chromosomal FISH result, Rai stage, smoking, family history and gender. Conclusion: Secondary malignancies are frequent in patients with detectable chromosome abnormality on FISH panel. However, the increased risk of secondary malignancy does not correlate with specific cytogenetic abnormality. Non melanoma skin cancers are exceedingly common in CLL patients and carries aggressive couse in progressive CLL patients. Larger studies are required to identify subtype of CLL based on integrated mutational and cytogenetic subgroup that are at increased risk of specific secondary malignancies. Disclosures No relevant conflicts of interest to declare.

e15779 Background: There is paucity of data regarding the best available second-line treatment following progression on gemcitabine-based regimens in metastatic pancreatic ductal adenocarcinoma (PDAC). While a Nanoliposomal formulation of irinotecan (MM398) is considered a standard of care, there is conflicting data relating to the use of oxaliplatin in this setting. We performed a meta-analysis to determine the effectiveness of adding oxaliplatin (OX) or various irinotecan (IRI) formulations to a fluoropyrimidine (FP) as a second-line in PDAC patients. Methods: We searched different databases, including PubMed, Embase and Cochrane, to identify randomized controlled trials comparing FP monotherapy to FP combination therapy that includes either oxaliplatin (FPOX) or various irinotecan formulations (FPIRI) in PDAC patients who progressed after first-line treatment. Secondary analyses were planned to assess the effectiveness of FPOX and FPIRI compared to FP. Outcomes of interest included overall survival (OS) and progression-free survival (PFS). The overall effect was pooled using the DerSimonian and Laird random effects models. Results: Five studies (2 with FPIRI and 3 with FPOX) with 895 patients were identified. Patients randomized to FPIRI/FPOX had a significantly improved PFS (HR = 0.74, CI 0.62 to 0.89) and a trend towards an improved OS compared to FP monotherapy (HR = 0.88, CI 0.65 to 1.19). When comparing FPIRI to FP, there was an improvement in both PFS (HR = 0.64, CI 0.47 to 0.87) and OS (HR = 0.70, CI 0.55 to 0.89) in patients treated with the combination. Conversely, FPOX showed only a modest improvement in PFS (HR = 0.81, CI 0.67, 0.97) with no improvement in OS (HR = 1.03, CI 0.64 to 1.67). Conclusions: Combination chemotherapy with oxaliplatin or various irinotecan formulations seem to improve PFS vs. single agent FP. FPIRI, but not FPOX seem to confer an OS advantage. Oxaliplatin with FP following gemcitabine failure may need further confirmatory studies to establish its role in refractory pancreas cancer.

BACKGROUNDThere are limited therapeutic options for treatment‐refractory pancreatic ductal adenocarcinoma (PDAC), with a paucity of data to support the best option after progression on gemcitabine‐based regimens. The authors performed a meta‐analysis to determine the effectiveness of adding oxaliplatin (OX) or various irinotecan formulations to a fluoropyrimidine (FP) after first‐line treatment progression in patients with PDAC.METHODSDifferent databases, including PubMed, EMBASE, and Cochrane, were searched to identify randomized controlled trials comparing FP monotherapy versus FP combination therapy that included either oxaliplatin (FPOX) or various irinotecan formulations (FPIRI) in patients with PDAC who progressed after first‐line treatment. Secondary analyses were planned to assess the effectiveness of FPOX and FPIRI compared with FP. Outcomes of interest included overall survival (OS) and progression‐free survival (PFS).RESULTSFive studies with 895 patients were identified. Patients randomized to receive FPIRI/FPOX had a significantly improved PFS and a trend toward improved OS compared with those who received FP monotherapy. When comparing FPIRI with FP, there was an improvement in both PFS (hazard ratio, 0.64; 95% confidence interval, 0.47‐0.87; P = .005) and OS (hazard ratio, 0.70; 95% confidence interval, 0.55‐0.89; P = .004) in patients who received the combination. Conversely, FPOX produced only a modest improvement in PFS with no improvement in OS.CONCLUSIONSCombination chemotherapy with OX or various IRI formulations appears to improve PFS compared with single‐agent FP. FPIRI, but not FPOX, appears to confer an OS advantage. The combination of FP with irinotecan formulations appears to be the appropriate next line of treatment upon progression after gemcitabine‐based chemotherapy regimens. Cancer 2017;123:4680‐4686. © 2017 American Cancer Society.