A neoadjuvant therapy compatible prognostic staging for resected pancreatic ductal adenocarcinoma.

OBJECTIVE: To improve prediction, the AJCC staging system was revised to be consistent with upfront surgery (UFS) and neoadjuvant therapy (NAT) for PDAC. BACKGROUND: The AJCC staging system was designed for patients who have had UFS for PDAC, and it has limited predictive power for patients receiving NAT. METHODS: We examined 146 PDAC patients who had resection after NAT and 1771 who had UFS at Changhai Hospital between 2012 and 2021. The clinicopathological factors were identified using Cox proportional regression analysis, and the Neoadjuvant Therapy Compatible Prognostic (NATCP) staging was developed based on these variables. Validation was carried out in the prospective NAT cohort and the SEER database. The staging approach was compared to the AJCC staging system regarding predictive accuracy. RESULTS: The NAT cohort's multivariate analysis showed that tumor differentiation and the number of positive lymph nodes independently predicted OS. The NATCP staging simplified the AJCC stages, added tumor differentiation, and restaged the disease based on the Kaplan-Meier curve survival differences. The median OS for NATCP stages IA, IB, II, and III was 31.7 months, 25.0 months, and 15.8 months in the NAT cohort and 30.1 months, 22.8 months, 18.3 months, and 14.1 months in the UFS cohort. Compared to the AJCC staging method, the NATCP staging system performed better and was verified in the validation cohort. CONCLUSIONS: Regardless of the use of NAT, NATCP staging demonstrated greater predictive abilities than the existing AJCC staging approach for resected PDAC and may facilitate clinical decision-making based on accurate prediction of patients' OS.

Combined utility of Ki-67 index and tumor grade to stratify patients with pancreatic ductal adenocarcinoma who underwent upfront surgery.

OBJECTIVE: To investigate the prognostic prediction of a new indicator, combined by tumor grade and Ki-67, in patients with resected pancreatic ductal adenocarcinoma (PDAC). METHODS: Data were retrospectively collected from consecutive patients who underwent primary resection of pancreas from December 2012 to December 2017. Tumor grade and Ki-67 were reviewed from routine pathological reports. G-Ki67 was classified as three categories as I (G1/2 and Ki-67 < 40%), II (G1/2 and Ki-67 ≥ 40%), and III(G3/4 and all Ki-67). RESULTS: Cox regression analyses revealed that tumor stage (II vs. I: hazard ratio (HR), 3.781; 95% confidence index (CI), 2.844-5.025; P < 0.001; III vs. I: HR, 7.476; 95% CI, 5.481-10.20; P < 0.001) and G-Ki67 (II vs. I: HR, 1.299; 95% CI, 1.038-1.624; P = 0.022; III vs. I: HR, 1.942; 95% CI, 1.477-2.554; P < 0.001) were independent prognostic factors in the developing cohort. The result was rectified in the validation cohort. In subgroups analysis, G-Ki67 (II vs. I: HR, 1.866 ; 95% CI, 1.045-3.334; P = 0.035; III vs. I: HR, 2.333 ; 95% CI, 1.156-4.705; P = 0.018) also had a high differentiation for survival prediction. CONCLUSION: Our findings indicate that three-categories of G-Ki67 in resectable PDAC according to the routine pathological descriptions provided additional prognostic information complementary to the TNM staging system.

Impact of previous upper/lower abdominal surgery on pancreatic surgical outcomes and complications: a propensity score matching study.

PURPOSE: Pancreatic surgery is a complex operation that has been associated with severe intraoperative and postoperative complications, especially in patients with previous abdominal surgery (PAS). Our study aimed to assess the impact of PAS on pancreatic surgery. METHODS: A total of 1430 patients who underwent pancreatic surgery were included in this retrospective study and classified into the following 3 groups: previous upper abdominal surgery (PUAS) (n = 135); previous lower abdominal surgery (PLAS) (n = 161), and no history of abdominal surgery (non-PAS) (n = 1134). Using propensity score matching (PSM), patients were matched to one another at a 1:1:1 ratio with balanced baseline characteristics. Intraoperative factors, surgical complications, hospital costs, and postoperative hospitalization were collected and compared. RESULTS: A longer operative duration was observed in the PUAS group compared to the non-PAS group (187.54 vs. 150.50 min, p = 0.016). The intraoperative blood loss in the PUAS group was significantly higher (193.68 vs. 150.51 and 156.81 mL, p < 0.05), while the intraoperative plasma transfusion volume was higher in PLAS patients than in non-PAS patients (183.8 vs. 102.7 mL, p = 0.008). Intra-abdominal adhesions in PUAS patients were most severe, and non-PAS patients exhibited significantly lower intra-abdominal adhesion grading (p < 0.001). No significant differences were observed in postoperative complications, postoperative histopathology, postoperative hospitalization, or hospital cost. CONCLUSION: PAS has no significant influences on surgical outcomes, and pancreatic surgery is relatively safe in this patient population. A patient history of PAS may prolong operation duration and increase intraoperative blood loss but has no impact on postoperative complications and does not increase the economic burden.

Comparison of 4- and 4 plus-courses S-1 administration as adjuvant chemotherapy for pancreatic ductal adenocarcinoma.

PURPOSE: The study aimed to investigate the potential benefit of more than 4 courses of S1 adjuvant chemotherapy for patients with pancreatic ductal adenocarcinoma (PDAC) after surgery. METHOD: Data were retrospectively collected from consecutive patients who underwent S-1 adjuvant chemotherapy following curative pancreatectomy between January 2016 and December 2018. Four-courses and > 4 courses cohorts were compared for overall survival (OS) as a primary outcome, and relapse-free survival (RFS) and adverse event incidence as secondary outcomes. RESULTS: Four-courses and > 4 courses cohorts comprised 99 patients and 64 ones, respectively. TNM stage (stage II vs. I: HR, 2.125; 95% CI, 1.164-4.213; P = 0.015), duration of S-1 administration (4 vs. > 4 courses: HR, 3.113; 95% CI, 1.531-6.327; P = 0.002) and tumor grade (G3 vs. G1/2: HR, 3.887; 95% CI, 1.922-7.861; P < 0.001) were independent prognostic factors. Under the condition of patients' survival time beyond 8 months, the OS of patients in > 4 courses cohort was significantly prolonged compared with that of 4 courses cohort (4 vs. > 4 courses: HR, 2.284; 95% CI, 1.197-4.358; P = 0.012), especially for patients in TNM stageII (4 vs. > 4 courses: HR, 2.906; 95% CI, 1.275-6.623; P = 0.011).RFS and adverse events incidence did not signifcantly difer between both cohorts. CONCLUSION: Prolonged duration of S-1 intake is beneficial to prognosis of patients with PDAC resection.

Modified artery-first approach for distal pancreatectomy with celiac axis resection.

BACKGROUND: The superior mesenteric artery-first approach has been proved superior in pancreatoduodenectomy compared with the standard procedure. It is unclear whether similar benefits could be obtained in distal pancreatectomy with celiac axis resection. METHODS: Perioperative and survival outcomes of patients who underwent distal pancreatectomy with celiac axis resection with the modified artery-first approach or traditional approach between January 2012 and September 2021 were compared. RESULTS: The entire cohort comprised 106 patients (modified artery-first approach, n = 35; traditional approach, n = 71). The most common complication was postoperative pancreatic fistula (n = 18, 17.0 per cent), followed by ischaemic complications (n = 17, 16.0 per cent) and surgical site infection (n = 15, 14.0 per cent). Intraoperative blood loss (400 versus 600 ml, P = 0.017) and intraoperative transfusion rate (8.6 versus 29.6 per cent, P = 0.015) were lower in the modified artery-first approach group compared with the traditional approach group. A higher number of harvested lymph nodes (18 versus 13, P = 0.030) and R0 resection rate (88.6 versus 70.4 per cent, P = 0.038) and a lower incidence of ischaemic complications (5.7 versus 21.1 per cent, P = 0.042) was observed in the modified artery-first approach group compared with the traditional approach group. In multivariable analysis, the modified artery-first approach (OR 0.006, 95 per cent c.i., 0 to 0.447; P = 0.020) was protective against ischaemic complications. CONCLUSIONS: Compared with the traditional approach, the modified artery-first approach was associated with lower blood loss and fewer ischaemic complications, and a higher number of harvested lymph nodes and R0 resection rate. Thus, it might improve the safety, staging and prognosis of distal pancreatectomy with celiac axis resection for pancreatic cancer.

Negative p53 Expression Confers Worse Prognosis in Patients With Resected Pancreatic Ductal Adenocarcinoma: Research Focused on Reinterpretation of Immunohistochemical Staining.

OBJECTIVE: The aim of the study is to reinterpret the prognostic prediction of p53 expression categories in pancreatic ductal adenocarcinoma with exploration of the relationship between TP53 mutation genotype and p53 expression pattern. METHODS: Data were retrospectively collected from consecutive patients who underwent primary pancreatic resection. Complete loss of function of TP53 is defined as nonsense and frameshift mutations. A tissue microarray was used to evaluate p53 expression by immunohistochemistry and was categorized as regulated, high, or negative. RESULTS: The κ coefficient for agreement between p53 expression and TP53 was 0.761. Cox regression analyses revealed that p53 expression (high vs regulated: hazard ratio [HR], 2.225; P < 0.001; negative vs regulated: HR, 2.788; P < 0.001), tumor-node-metastasis stage (II vs I: HR, 3.471; P < 0.001; III vs I: HR, 6.834; P < 0.001), and tumor grade (G3/4 vs G1/2: HR, 1.958; P < 0.001) were independent prognostic factors in developing cohort and validation cohort. In subgroups of stage I, II, and III, compared with regulated expression, the patients with negative expression had a worse prognosis in both cohorts (P < 0.05). CONCLUSIONS: Our findings indicate that 3-tier p53 expression in resectable pancreatic ductal adenocarcinoma provided independent prognostic information complementary to the tumor-node-metastasis staging system and facilitated patient stratification for personalized therapy.

Systemic therapy and perioperative management improve the prognosis of pancreatic ductal adenocarcinoma: A retrospective cohort study of 2000 consecutive cases.

OBJECTIVE: This study aimed to explore patterns of the treatment strategies of pancreatic ductal adenocarcinoma based on 2000 consecutive cases of a prospective database since 2012 to obtain new insights for future directions. METHODS: Among 2000 patients enrolled in this study, 210 patients were excluded, and 710, 521, and 559 patients were treated between 2012 and 2015 (group 1), between 2016 and 2017 (group 2), and between 2018 and 2019 (group 3), respectively. Patient clinicopathologic and biological factors, and perioperative outcomes were used to assess the prognostic factors. RESULTS: The median survival for all patients with pancreatic ductal adenocarcinoma was 21.7 months (1-year survival, 75.0%; 2-year survival, 43.7%; 5-year survival, 19.7%). Group 3 had a better survival outcome than groups 1 and 2 (median survival time: 23 versus 20.5 and 21.1 months). The proportion of patients younger than 65 gradually increased over time, as did the use of systemic chemotherapy and postoperative adjuvant radiotherapy. The tendency for early diagnosis (lower CA19-9 and CEA levels, smaller size, and earlier N stage), use of chemotherapy and radiotherapy, early recovery (lesser hospital stay and Clavien-Dindo grade <3), absence of abdominal pain, younger age, length of operation ≤3 h, and pathological factors (absence of lymphovascular invasion, peripancreatic fat infiltration and neural invasion, higher differentiation) were related to patients' survival. Multivariable analysis for prognosis revealed that tumor biological factors (increased preoperative serum CA19-9 level, tumor size, tumor differentiation, N stage, and presence of lymphovascular invasion and neural invasion), chemotherapy, radiotherapy, abdomen pain, operation period, length of stay, and length of operation correlated with patients' survival. CONCLUSIONS: Systemic therapy, including chemotherapy and radiotherapy, has gradually improved the prognosis after operative resection for pancreatic ductal adenocarcinoma. Neoadjuvant therapy is also beneficial to improve the prognosis to a certain extent. The enhanced recovery after surgery (ERAS) policies and the specific assessment of postoperative pancreatic fistula (POPF) risk may be related to reduced hospital stays and the reduction of serious complications. These advancements show that the concept of systemic therapy has been accepted and actively applied by Chinese medical institutions.

Nomogram for the Prediction of High-Grade Dysplasia and Invasive Carcinoma in Patients With Intraductal Papillary Mucinous Neoplasms of the Pancreas Based on Variables of Noninvasive Examination.

Intraductal papillary mucinous neoplasms (IPMNs) are a heterogeneous group of neoplasms and represent the most common identifiable precursor lesions of pancreatic cancer. Clinical decision-making of the risk for malignant disease, including high-grade dysplasia and invasive carcinoma, is challenging. Moreover, discordance on the indication for resection exists between the contemporary guidelines. Furthermore, most of the current nomogram models for predicting malignant disease depend on endoscopic ultrasonography to evaluate the precise size of mural nodules. Thus, this study aimed to propose a model to predict malignant disease using variables from a noninvasive examination. We evaluated patients who underwent resection of pathologically confirmed IPMNs between November 2010 and December 2018 and had preoperative clinical data available for review. Based on binary multivariable logistic regression analysis, we devised a nomogram model to predict malignant IPMNs. The area under the receiver operating characteristics curve (AUC) was used to evaluate the discrimination power of the model. Of the 333 patients who underwent resection of IPMNs, 198 (59.5%) had benign and 135 (40.5%) had malignant IPMNs. Multivariable logistic regression analysis showed that cyst size, cyst location, cyst wall enhancement, multicystic lesion, diameter of main pancreatic duct, neutrophil-to-lymphocyte ratio, serum carbohydrate antigen 19-9, and carcinoembryonic antigen were significantly associated with malignancy. The nomogram, constructed based on these variables, showed excellent discrimination power with an AUC of 0.859 (95% CI: 0.818-0.900, P < 0.001). In conclusion, we have developed a nomogram consisting of a combination of cross-sectional imaging features and blood markers, variables that can readily be obtained by noninvasive examinations during the surveillance period, which can distinguish benign from malignant IPMNs. Nevertheless, external validation is warranted.

The Landscape of Genetic Alterations Stratified Prognosis in Oriental Pancreatic Cancer Patients.

BACKGROUND: Pancreatic cancer is a life-threatening malignant disease with significant diversity among geographic regions and races leading to distinct carcinogenesis and prognosis. Previous studies mainly focused on Western patients, while the genomic landscape of Oriental patients, especially Chinese, remained less investigated. METHODS: A total of 408 pancreatic cancer patients were enrolled. A panel containing 436 cancer-related genes was used to detect genetic alterations in tumor samples. RESULTS: We profiled the genomic alteration landscape of pancreatic duct adenocarcinoma (PDAC), intraductal papillary mucinous neoplasm (IPMN), periampullary carcinoma (PVC), and solid-pseudopapillary tumor (SPT). Comparison with a public database revealed specific gene mutations in Oriental PDAC patients including higher mutation rates of DNA damage repair-related genes. Analysis of mutational signatures showed potential heterogenous carcinogenic factors caused by diabetes mellitus. KRAS mutation, especially KRAS G12D mutation, was associated with poor survival, while patients not harboring the 17 significant copy number variations (CNVs) had a better prognosis. We further identified multiple correlations between clinicopathologic variables and genetic mutations, as well as CNVs. Finally, by network-based stratification, three classes of PDAC patients were robustly clustered. Among these, class 1 (characterized by the Fanconi anemia pathway) achieved the best outcome, while class 2 (involved in the platinum drug resistance pathway) suffered from the worst prognosis. CONCLUSIONS: In this study, we reported for the first time the genetic alteration landscape of Oriental PDAC patients identifying many Oriental-specific alterations. The relationship between genetic alterations and clinicopathological factors as well as prognosis demonstrated important genomic impact on tumor biology. This study will help to optimize clinical treatment of Oriental PDAC patients and improve their survival.

[The rules of acupoint selection of acupuncture for dry eye].

The rules of acupoint selection of acupuncture for dry eye in recent 10 years were summarized to provide reference for clinical treatment. The clinical researches regarding acupuncture for dry eye published from May 5, 2007 to December 1, 2017 were searched in CNKI, WANFANG and VIP database. The acupoint and meridian used and application frequency were analyzed to summarize the rules of acupoint selection. Totally, 52 related clinical papers were collected, involving 60 acupoints, 14 meridians and 5 extra point. The total frequency of acupoints was 541, which were mainly related with the bladder meridian, stomach meridian and gallbladder meridian. In conclusion, the rules of acupoint selection of acupuncture for dry eye highlighted meridians circulation, acupoint combination, and syndrome differentiation.

[Xerophthalmia of qi and yin deficiency treated with jinhuobu needling technique].

OBJECTIVE: To explore the differences in the clinical therapeutic effects on xerophthalmia of qi and yin deficiency between the jinhuobu needling technique (the combined reinforcing technique to induce warm sensation) and the reinforcing needing technique achieved by rotating needle. METHODS: A total of 54 patients of xerophthalmia were randomized into an observation group (28 cases) and a control group (26 cases). In both of the groups, the main acupoints included Cuanzu (BL 2), Sizhukong (TE 23), Taiyang (EX-HN 5) and Fengchi (GB 20); the combined acupoints were Danzhong (CV 17), Sanyinjiao (SP 6), Taixi (KI 3) and Taichong (LR 3). In the observation group, the jinhuobu needling technique was used and in the control group, the reinforcing needing technique achieved by rotating needle was adopted. The treatment was given once every day. 10 treatments made one course and 2 courses were required. Before and after treatment, the score of eye symptoms, tear secretion and the breakup time of tear film were observed in the two groups. The clinical therapeutic effects were compared between the two groups after treatment and in 4-week follow-up after treatment separately. RESULTS: After treatment, the total effective rate was 92.9% (26/28) in the observation group and was 80.8% (21/26) in the control group, without significant difference in comparison (P>0.05). In 4-week follow-up after treatment, the total effective rate was 85.7% (24/28) in the observation group and was 61.5% (16/26) in the control group, indicating the significant difference in comparison (P<0.05). After treatment, the differences were significant in the score of eye symptoms, tear secretion and the breakup time of tear film as compared with those before treatment in the two groups (all P<0.01). After treatment, the improvements of the score of eye symptoms, tear secretion and the breakup time of tear film in the observation group were better remarkably than those in the control group, indicating the significant differences (all P<0.05). CONCLUSION: The jinhuobu needling technique achieves the significant therapeutic effects on xerophthalmia of qi and yin deficiency and the recurrence rate of the disease is low.