Role of phosphorylated Smad3 signal components in intraductal papillary mucinous neoplasm of pancreas

Background:Malignant intraductal papillary mucinous neoplasm(IPMN)has poor prognosis.The carcinogenesis of IPMN is not clear.The aim of this study was to clarify transitions in phosphorylated Smad3 signaling during IPMN carcinogenesis.Methods:By using immunohistochemistry,we examined the expression of pSmad3C and pSmad3L from 51 IPMN surgical specimens resected at our institution between 2010 and 2013.We also examined the expression of Ki-67,c-Myc and p-JNK.Results:The median immunostaining index of pSmad3C was 79.2%in low-grade dysplasia,74.9%in highgrade dysplasia,and 42.0%in invasive carcinoma(P<0.01),whereas that of pSmad3L was 3.4%,4.3%,and 42.4%,respectively(P<0.01).There was a negative relationship between the expression of pSmad3C and c-Myc(P<0.001,r=-0.615)and a positive relationship between the expression of pSmad3L and c-Myc(P<0.001,r=0.696).Negative relationship between the expression of pSmad3C and Ki-67(P<0.01,r=-0.610)and positive relationship between the expression of pSmad3L and Ki-67(P<0.01,r=0.731)were confirmed.p-JNK-positive cells were frequently observed among pSmad3L-positive cancer cells.The median of pSmad3L/pSmad3C ratio in the non-recurrence group and the recurrence group were 0.58(range,0.05–0.93),3.83(range,0.85–5.96),respectively(P=0.02).The median immunostaining index of c-Myc in the non-recurrence group and the recurrence group were 2.91(range,0–36.9)and 82.1(range,46.2–97.1),respectively(P=0.02).The median immunostaining index of Ki-67 in the non-recurrence group and the recurrence group were 12.9(range 5.7–30.8)and 90.9(range 52.9–98.5),respectively(P=0.02).Conclusions:pSmad3L was upregulated in malignant IPMN.pSmad3L/pSmad3C ratio may be a useful prognostic factor in IPMN.

初始不可切除胰腺导管腺癌转化手术的现状与展望

胰腺导管腺癌预后一直不佳，患者5年生存率〈5%，化疗领域的进展将不可切除胰腺导管腺癌中位生存时间延长。不可切除胰腺导管腺癌的治疗仍充满挑战，需多学科团队共同制订治疗方案。令人欣慰的是，近期研究结果显示：局部晚期和远处转移的胰腺导管腺癌对化疗良好的反应性及转化手术率的增高。近期几项研究结果显示：对初始不可切除胰腺导管腺癌行转化治疗后，外科手术可获得更高的切除率（20%-61%）、更高的R0切除率（27%-89%）和淋巴结阴性率（29%-86%），且多数研究中的手术死亡率和术后并发症发生率均在可控制范围内。不可切除胰腺导管腺癌患者行转化手术后中位生存时间可达24-56个月，显著优于无法行外科手术的患者。此外，关于最佳化疗方案的选择、残留肿瘤体积的测量、外科手术指征、最佳手术时间及切除范围仍是研究热点。对初始不可切除胰腺导管腺癌患者，转化手术治疗是目前改善其预后的重要方法，亦需多学科团队医师共同努力；临床尚需更多设计优良的临床研究确认转化治疗在不可切除胰腺导管腺癌中的应用价值。

Implementation of an educational program for pancreaticoduodenectomy in a university hospital: a retrospective observational study

Objective:No ideal training system exists for pancreaticoduodenectomy(PD).We developed an educational system that uses an objective structured assessment of technical skills.Methods:This retrospective observational study was conducted using the data of consecutive trainees and patients who underwent PD from 2007 to 2013 in Kansai Medical University Hospital.The total score on the task checklist(21 parameters)for measuring technical performance during PD by self assessment and instructor assessment was compared between junior(JN)and hepatobiliary pancreatic(HBP)trainees at a university hospital.Surgical outcomes of 303 PDs(2007-2013)were also compared among JN trainees,HBP trainees,and instructors,and the present position of the trainees was investigated.This study was approved by the institutional review board of Kansai Medical University on May 26,2020.Results:The self-assessment score on the task checklist was significantly higher for the HBP trainees than for the JN trainees on all parts of PD(P<.001).The discrepancy between self-assessment and instructor assessment improved in 3 JN trainees after experience with the first 5 PDs.Although total score curves rose to the right in the JN group,scores in the HBP group were stable,at 70 or higher,which correlated with the instructor assessment.The 90-day and 30-day mortality rates were 1.6%and 0.3%,respectively.Mortality and morbidity after PD did not differ between the JN and HBP trainees or between the instructors and the trainees.Four of 10 trainees became board-certified expert surgeons of the Japanese Society of Hepatobiliary Pancreatic Surgery.Conclusion:These results indicated good construct validity of the task checklist system.This program was safely and effectively implemented in terms of surgical outcomes and final outcomes of trainees becoming board-certified expert surgeons.

Conversion surgery in patients with initially unresectable pancreatic ductal adenocarcinoma: where do we stand in 2018?

Pancreatic ductal adenocarcinoma(PDAC)continues to have a dismal prognosis,with a 5-year survival rate of<5%.Most(70%-80%)patients are classified as unresectable(UR)disease.Recent progress in chemotherapeutic approaches has provided a high response rate and improved short-term survival.Recently,conversion surgery(CS),which is defined as an additional surgery during multimodal therapy in patients with initially UR-PDAC who respond favorably to anti-cancer treatments,has been successfully introduced as a novel treatment option for locally advanced(UR-LA)and metastatic(UR-M)PDAC.Several studies have demonstrated high resectability rates(UR-LA,20%-57%;UR-M,2%-24%),high margin-negative resection rates(27%-91%),and high negative lymph node rates(29%-83%)in patients who underwent CS.Most studies also demonstrated acceptable mortality and morbidity.Median survival time(MST)varied between 24.9 and 35.3 months for patients with UR-LA,19.5 and 64 months for UR-LA/M,and 26 and 56 months for UR-M,which is better than the MST of patients who did not undergo CS.The presence of M disease did not affect survival in patients who underwent CS.However,the actual clinical benefits of resection have not yet been fully investigated.There are still several issues to be resolved in this area.Therefore,sustained efforts to conduct appropriately designed clinical trials for confirming the efficacy of CS in the subset of patients with initially UR-PDAC are warranted.