胰腺癌的发病率逐年升高，其治疗策略受到业内高度关注。目前胰腺癌围术期药物治疗仍主要基于化疗，且日趋规范，但仍有诸多悬而未决、尚无定论的问题，亟需进一步探讨。随着国内外胰腺癌领域的研究及精准医学的发展，有望实现胰腺癌围术期治疗的精准化和个体化。
采用胶体金法对464例健康者进行粪便弹性蛋白酶-1(FE-1)测定，描述其分布特征，为应用FE-1测定胰腺外分泌功能提供临床数据支持。结果显示，FE-1浓度呈右偏态分布，且随年龄增长呈下降趋势。FE-1浓度与年龄和血糖相关，而与性别、体重指数、三酰甘油和胆固醇水平无关。
Objective:To evaluate the quality of life (QoL) of Chinese chronic pancreatitis (CP) patients based on the Chinese version of the pancreatitis quality of life Instrument (PANQOLI) and explore its impact factors.Methods:404 patients with CP admitted to the Department of Gastroenterology of the First Affiliated Hospital of Naval Medical University between September 2021 and January 2022 were enrolled. The Chinese version of PANQOLI was used for questionnaire survey on QoL of CP patients. Univariate analysis and multiple linear regression analysis were used to explore the impact factors for QoL of CP patients.Results:The total score of QoL of 404 Chinese CP patients was 28-94(72.47±13.61), which declined by 29.64% compared to the highest total score (103) in the Chinese version of PANQOLI. Score of physical function, role function, emotional function, and self-worth domain was 25.63±4.84, 13.86±2.78, 16.98±6.21 and 16.00±4.65, respectively. Compared to the highest scores (30, 25, 24 and 24), the scores of aforementioned four domains declined by 14.57%, 44.56%, 29.25% and 33.33%, respectively. Univariate analysis showed that sex, age, employment status, smoking, alcohol consumption, and frequency of pancreatitis recurrence were significantly associated with QoL of CP patients. Multiple linear regression analysis indicated that older age (coefficient=-0.127), unemployment status (coefficient=-0.106), smoking (coefficient=-0.176), and high frequency of pancreatitis recurrence (coefficient=-0.123) were independent factors for QoL of CP patients (all P value <0.05). Conclusions:The Chinese version of PANQOLI could be effectively applied to Chinese CP patients. Older age, unemployment, smoking, and pancreatitis attacks were risk factors for QoL of CP patients, indicating that the formulation of personalized intervention measures may help to improve QoL of CP patients.
疼痛是CP常见的首发症状，严重影响患者的生活质量。目前关于CP的疼痛临床评估仍较为局限。本文对CP疼痛的临床分型、疼痛发生率、影响因素、评估工具等进行综述，旨在为CP患者的疼痛诊治提供一定的理论依据。
胰管结石是慢性胰腺炎的主要并发症之一，随着内镜技术的发展，通过内镜治疗可以安全、有效地清除胰管结石，缓解临床症状，使患者避免外科手术治疗。目前内镜下治疗胰管结石的方法主要有体外冲击波碎石术联合内镜下逆行胰胆管造影取石、经胰管镜直视下碎石取石术，本文就这两种治疗方法及其研究进展进行综述。
Objective:To investigate the clinical diagnostic value of autotaxin(ATX) and its product lysophosphatidic acid(LPA) in patients with pancreatic cancer.Methods:Peripheral blood samples and related clinical data of 114 patients with pancreatic cancer (pancreatic cancer group) and 94 patients with benign pancreatic disease (benign pancreatic disease group) diagnosed in the Northern Theater General Hospital from January 2015 to May 2021 were collected, and peripheral blood of 120 healthy volunteers was used as control group. Patients′ gender, age, smoking history, history of alcohol consumption, family history of pancreatic cancer, tumor site and size, lymph node metastasis or not, peripheral nerve infiltration and the like were all recorded. Serum ATX, LPA and CA19-9 level was detected by ELISA. The receiver operating characteristic curve (ROC) of ATX alone, LPA alone and(or) combined with CA19-9 for the clinical diagnosis of pancreatic cancer was plotted, and the area under the curve (AUC) was calculated. Maximal Youden index method was used to determine the cutoff, and the sensitivity and specificity were calculated.Results:There were 54(47.3%) patients with high sugar diet and 60(52.6%) patients with smoking in pancreatic cancer group, which were higher than 15(16.1%) and 11(11.7%) in benign pancreatic disease group, and 24(20%) and 26(21.7%) in control group ( n=120). The serum ATX, LPA and CA19-9 of early and advanced pancreatic cancer [294.9(262, 1 455)ng/ml, 15.75(8.3, 92)μg/ml and 131.1(23, 289)U/ml; 422(312, 1 620)ng/ml, 24.6(9.5, 97.3)μg/ml and 217.4(32, 970)U/ml] were all greatly increased, and all the differences were statistically significant (all P value<0.05). The AUC values of serum ATX for early and advanced pancreatic cancer were 0.71 (95% CI 0.52-0.87) and 0.92 (95% CI 0.81-0.98), respectively; the Youden index was 0.57, the cutoff was 286 ng/ml, and the sensitivity was 65.3% and 89.6%, respectively; the specificity was 80%. The AUC values of LPA were 0.75 (95% CI 0.67-0.91) and 0.95 (95% CI 0.89-0.99); the Youden index was 0.48, the cutoff was 10.7 μg/ml, and the sensitivity was 80.7% and 95.7%, respectively; the specificity was 69.4%. The AUC values of CA19-9 were 0.82 (95% CI 0.71-0.85) and 0.86 (95% CI 0.78-0.93); the Youden index was 0.47, the cutoff was 57 U/ml, and the sensitivity was 77.3% and 82.3%, respectively; the specificity was 75.0%. Compared to control group and benign pancreatic disease group, the predictive efficiency of serum ATX+ CA19-9 and CA19-9+ ATX+ LPA for the diagnosis of early pancreatic cancer was significantly higher than that of CA19-9 alone, and the difference was statistically significant (all P value<0.05), while the predictive efficiency of serum ATX+ CA19-9 and CA19-9+ ATX+ LPA for the diagnosis of advanced pancreatic cancer was not significantly different from that of CA19-9 alone. Conclusions:The combined detection of serum LPA, ATX and CA19-9 can improve the diagnostic efficiency of early pancreatic cancer.
Objective:To analyze the characteristics of pancreatic metastatic tumors and evaluate the clinical value of endoscopic ultrasound-guided fine-needle aspiration or biopsy (EUS-FNA/B) in their diagnosis.Methods:A retrospective analysis was conducted on clinical, radiological, and pathological data of 11 cases with pancreatic metastatic tumors diagnosed by EUS-FNA/B at the First Affiliated Hospital of Naval Medical University between January 2011 and December 2020. Tumor size, number of lesions, time interval between diagnosis of metastatic lesions and primary tumors, radiological and EUS findings and pathological types were recorded, and success rate and diagnostic rate of EUS-FNA/B were analyzed.Results:The 11 patients with pancreatic metastatic tumors had an age range of 43 to 76 years, including 7 males and 4 females. Eight cases presented with symptoms of abdominal pain and poor appetite, 1 case had cervical lymph node enlargement, and 2 cases were detected during routine physical examination. Five cases had abnormal serum tumor markers. All patients had a confirmed history of primary tumors, and the median time interval between diagnosis of pancreatic metastatic lesions and primary tumors was 24 months (-1-124 months). Seven cases had solitary lesions, and 4 cases had multiple nodules under EUS. Eight cases were initially diagnosed clinically as pancreatic lesions or tumor, while 3 cases were considered as pancreatic metastatic tumor. All of 11 cases underwent EUS-FNA/B and were histologically confirmed as pancreatic metastatic tumors. The most common pathological type was lung small cell neuroendocrine cancer ( n=4), followed by renal cell carcinoma ( n=3), and esophageal squamous cell carcinoma ( n=1), pulmonary squamous cell carcinoma( n=1), malignant melanoma ( n=1), and gastric adenocarcinoma ( n=1). Conclusions:The pancreas is not a common target site for tumor metastasis.EUS-FNA/B is a relatively safe minimally invasive method for the diagnosis of pancreatic metastatic tumors.
胰管囊肿为腹侧胰管、背侧胰管局限性扩张，包括腹侧胰管末端局限性扩张及背侧胰管末端局限性扩张两种类型。本文报道1例老年男性患者在超声内镜下确诊腹侧胰管末端局限性扩张，供临床参考。
本研究探讨肠内营养添加ω-3多不饱和脂肪酸在儿童急性胰腺炎治疗中的作用。结果表明，在儿童急性胰腺炎治疗中使用添加ω-3多不饱和脂肪酸的早期肠内营养，能有效控制炎症，提高机体对炎症反应的耐受性，降低患儿机体早期炎症反应，缩短住院时间，降低住院费用。
检索国内外数据库中有关急性胰腺炎液体复苏管理的相关证据，获取文献1 630篇，通过筛选并对纳入文献进行评估，最终纳入12篇文献，包括指南6篇，临床决策1篇，专家共识1篇，系统评价4篇。通过对证据的提取整合，形成了液体复苏时机、补液原则、补液速度、液体选择、监测频率、液体复苏目标、液体复苏禁忌证、联合干预等8个类别。从中推荐了11条证据，其中8条A级推荐，3条B级推荐，为临床实施急性胰腺炎液体复苏提供参考。
本例胰腺炎合并假性囊肿继发假性动脉瘤诊断明确，通过影像学动态观察提示胃十二指肠动脉破裂，破入假性囊肿内，进而形成假性动脉瘤。本例影像学资料完整全面，较为准确的反映了其形成过程，为该病的早期诊断及早期治疗提供了有力的依据。
Objective:To observe the pathological changes of different intestinal parts and the changes of intestinal barrier function in mice with acute necrotizing pancreatitis (ANP) induced by sodium taurocholate.Methods:A total of 18 male C57BL/6 mice were randomly divided into sham operation group, ANP 24 h group and ANP 48 h group with 6 mice in each group. The ANP model was established by retrograde injection of 2 μl/g 5% sodium taurocholate into the pancreaticobiliary duct. The sham operation group only underwent intubation. The survival status was recorded. The pathology of pancreatic and intestinal tissues were observed using hematoxylin-eosin staining, and the pathological scores were evaluated. The activities of serum amylase and lipase were measured by automatic biochemistry analyzer. Serum D-lactate levels were detected by ELISA. The expression of tight-junction proteins ZO-1 and occludin in small intestinal tissue was detected by Western blotting.Results:The survival rates of sham operation group, ANP 24 h group and ANP 48 h group were 100%, 36.4% and 25.0%, respectively. The pancreatic pathological scores of sham operation group, ANP 24 h group and ANP 48 h group were (0.67±0.82), (10.58±0.64) and (8.81±1.55); the serum amylase activities were (479.14±86.42), (5998.72±2096.31) and (3055.43±2336.5)U/L; the serum lipase activities were (18.56±3.84), (558.20±559.65) and (112.58±94.91)U/L. The pancreatic pathological scores, serum amylase and lipase levels in ANP group were higher than those in sham operation group, and the increase in ANP 24 h group was more significant, and the difference was statistically significant (all P value <0.05). The upper small intestine pathological scores in different groups were (0.17±0.41), (2.11±1.41) and (1.61±0.80); The lower small intestine pathological scores were (0.17±0.41), (1.00±0.76) and (1.06±0.25); the colonic pathological scores were (0.33±0.52), (0.67±0.82) and (0.67±0.52), respectively. The serum D-lactic acid level was (388.92±126.30), (2159.11±386.12) and (307.69±141.18) μmol/L. The expression of ZO-1 was (0.87±0.08), (0.19±0.18) and (0.50±0.19); the expression of occludin was (0.98±0.04), (0.13±0.08) and (0.69±0.04). The pathological scores of upper and lower segments of small intestine in ANP 24 h group and ANP 48 h group were significantly higher than those in the sham operation group (all P value <0.05). There was no significant difference on colonic pathological score among the three groups. The serum D lactate level in the ANP 24 h group was significantly higher than that in the sham operation group ( P<0.05), but there was no significant difference between the ANP 48 h group and the sham operation group. The expression of ZO-1 and occludin was decreased in ANP group compared with that in the sham operation group ( P value <0.05). Conclusions:ANP mouse model was successfully induced by sodium taurocholate, and the intestinal pathological changes were mainly concentrated on the small intestine, especially upper part of small intestine. The dysfunction of intestinal barrier was significantly aggravated within 24 hours after modeling, and the intestinal barrier function gradually recovered after 48 hours.
Objective:To investigate the efficacy of neostigmine combined with raw rhubarb enema on severe acute pancreatitis (SAP) patients with intra-abdominal hypertension (IAH).Methods:The clinical data of 89 SAP patients, who were admitted and underwent continuous renal replacement treatment (CRRT) in intensive care unit (ICU) department of the First Affiliated Hospital of Hebei North University from January 2018 to June 2022, were retrospectively analyzed. Patients were divided into control group ( n=44) and experimental group ( n=45) according to the treatment mode. Raw rhubarb enema plus sodium sulfate topical application were administrated twice a day for 7 days in control group; besides the treatment above, intramuscular injection of neostigmine 0.5 mg twice a day for 7 days was given in experimental group. Intra-abdominal pressure was monitored, acute physiology and chronic health evaluation (APACHE)Ⅱ, kidney disease: improving global outcome stage (KDIGO), lung injury score (LIS) were recorded, and serum leukocyte, CRP, procalcitonin (PCT), IL-6, IL-8 and tumor necrosis factor (TNF)-ɑ level were examined before and after treatment in both groups. The primary endpoint was the amount change of intra-abdominal pressure within 24 hours, and secondary endpoints included increased fecal volume within 7 days after treatment, new abdominal compartment syndrome (ACS), new organ dysfunction, vascular complications, length of ICU stay, total length of stay, survival rate and treatment intervention and occurrence of complications within 6 months after the end of treatment. Results:Intra-abdominal pressure began to decrease at 9 hours after treatment both in control group and experimental group. Compared with that before treatment, the intra-abdominal pressure of the two groups decreased significantly after 7 days of treatment, and the decrease rate of the experimental group within 7 days was obviously higher than that of the control group, with statistical significance (all P values <0.05). Compared with those before treatment, APACHEⅡ, KDIGO and LIS in both groups were significantly decreased, but the decreases in experimental group were more remarkable than those in control group (all P values <0.05). After treatment, the serum WBC count and the levels of inflammatory factors CRP, PCT, IL-6, IL-8, TNF-ɑ in experimental group were obviously lower than those in control group with statistical significance (all P values <0.05). Compared with control group, the change of intra-abdominal pressure in experimental group was significantly increased after 24-hour treatment, and the fecal volume was also obviously increased on day 1, 2, 3, 5 and 7 after treatment (all P values <0.05). However, there were no significantly statistical differences on the severity of intra-abdominal pressure, new occurrence of ACS and organ failure, vascular complication, ICU hospitalization and total length of stay and survival rate between two groups. After 6-month follow-up, the recurrence of pancreatitis and its treatment intervention between two groups were not statistically significant. Conclusions:The adjuvant treatment of neostigmine could reduce intra-abdominal pressure, increase defecation volume in SAP patients and alleviate SAP condition, which might be related to reducing the release of inflammatory cytokines.
中性粒细胞活化和持续浸润是AP胰腺损伤和炎症反应的主要决定因素之一。本文阐述中性粒细胞在AP中的最新研究进展，聚焦中性粒细胞的活化、募集、浸润、迁移、逆向迁移及中性粒细胞胞外陷阱等在AP中的作用，为未来精准靶向中性粒细胞治疗AP的新策略提供理论依据。
作为恶性程度较高的消化道肿瘤之一，胰腺癌病情进展快、生存率低、死亡率高，这种现状与起病隐匿、治疗手段局限等多种因素相关。胰腺癌的靶向治疗是近年来研究的热点，而寻找一种有效且副作用小的靶向药物对改善胰腺癌预后至关重要。本文将围绕胰腺癌分子靶向治疗药物及靶点的研究现状作一综述。
Objective:To identify the risk factors and develop nomogram for idiopathic chronic pancreatitis (ICP) patients with common bile duct stricture (CBDS).Methods:The clinical data of 1 633 ICP patients admitted to the Department of Gastroenterology of First Affiliated Hospital of Naval Medical University from January 2000 to December 2013 were collected retrospectively and prospectively. The patients were classified into CBDS group ( n=259) and non-CBDS group ( n=1 374) according to whether CBDS occurred. The cumulative incidence of CBDS after the onset and diagnosis of ICP were calculated by Kaplan-Meier method. After excluding patients who had developed CBDS before/or at the diagnosis of ICP, the remaining patients were randomly divided into the training set and the validation set. The univariate and multivariate Cox proportional hazards regression analysis were used to establish a risk predicting nomogram for CBDS after ICP onset. Its clinical application value was evaluated through the consistency index (C index). Results:15.9%(259/1 633) of patients developed CBDS after the onset of ICP. The cumulative incidence of CBDS at 3, 5, and 10 years after the onset of ICP was 9.6% (95% CI 0.082-0.111), 11.2% (95% CI 0.097-0.129) and 16.2% (95% CI 0.142-0.184), respectively. 9.4%(143/1 517) of patients developed CBDS after the diagnosis of ICP. The cumulative incidence of CBDS at 3, 5, and 10 years after the diagnosis of ICP was 8.3% (95% CI 0.069-0.099), 8.9% (95% CI 0.074-0.105) and 13.3% (95% CI 0.110-0.162), respectively. Univariate analysis found that factors including gender, age at onset of ICP, age at diagnosis of ICP, being adolescents at onset of ICP, smoking history, alcohol intake, initial manifestations, pancreatic duct stones, fatty steatorrhea, main pancreatic duct (MPD) morphology and pain type were significantly different between CBDS group and non-CBDS group. Multivariate analysis showed that male ( HR 2.134, 95% CI 1.336-3.408), age at diagnosis of ICP ( HR 1.038, 95% CI 1.024-1.052), first manifestation (pancreatic abdominal pain) and main duct morphology (complex lesion) were identified as independent risk factors for CBDS in ICP patients. A nomogram for predicting CBDS after ICP diagnosis was established based on the above four variables. The nomogram had a C-index of 0.740 (95% CI 0.700-0.790) for internal validation in the training set and 0.650 (95% CI 0.570-0.730) for external validation in the validation set. Conclusions:The nomogram established in this study can evaluate the risk of developing CBDS in ICP patients, benefit the early diagnosis and timely intervention of CBDS in clinical practice, and prevent potential related complications.
回顾性分析214例SAP患者的资料，构建5种SAP并发急性呼吸窘迫综合征(ARDS)的机器学习预测模型，并筛选出最优模型。结果显示，5种机器学习模型中，极端梯度提升(XGBoost)为最优模型。XGBoost在测试集中的AUC值为0.851(95% CI 0.739~0.963)，灵敏度为0.840，特异度为0.793，阳性预测值为0.842，阴性预测值为0.743。最重要的4个预测变量为呼吸频率、血清淀粉酶、年龄和总蛋白。表明机器学习模型能够很好地预测SAP相关ARDS的发生，为临床早期识别高危患者提供了思路。
巨淀粉酶血症是一种因血清中淀粉酶与免疫球蛋白等分子结合或自身聚合而形成不能经肾排出大分子复合物，引起血淀粉酶持续升高的良性疾病。由于淀粉酶升高的特征易引起临床的误判，甚至导致一系列昂贵而无效的检查和治疗，因此及时确诊巨淀粉酶血症意义重大。本文对巨淀粉酶血症的诊断、常见伴发疾病、治疗等进行综述，以期增加对巨淀粉酶血症的认识。
Objective:To investigate the role of transforming growth factor β1 (TGF-β1) and matrix metalloproteinase (MMP)-2 in pancreatic tissue repair and reconstruction in rats with acute pancreatitis and its potential mechanism.Methods:114 male SD rats were randomly divided into normal control group (CON group) and acute edematous pancreatitis model group (AEP group), acute necrotic pancreatitis model group (ANP group), ANP control group and ANP intervention group. The rat AEP model was constructed by subcutaneous injection of caerulein, and the rat ANP model was prepared by intraperitoneal injection of L-arginine. The ANP intervention group and ANP control group were prepared by intraperitoneal injection of TGF-β1 inhibitor SB431542 or DMSO 30 min before, 24 h and 48 h after pancreatitis induction, respectively. Hydroxyproline content in pancreatic tissue was determined by hydroxyproline kit. The expression of TGF-β1, phosphorylated Smad3 (p-Smad3), type Ⅲ collagen and MMP-2 in pancreatic tissue was detected by immunohistochemical method. The activity of MMP-2 was determined by gelatin enzyme spectrometry. The expression levels of MMP-2 and p-Smad3 proteins in pancreatic tissue were detected by Western blot.Results:The hydroxyproline content in CON group was (61.71±8.56)μg/mg protein. The hydroxyproline content in AEP group reached the peak (116.72±8.53)μg/mg on the 3rd day. The peak value of hydroxyproline content in ANP group was (174.93±11.75)μg/mg on day 5. The peak value in ANP group was significantly higher than that in AEP group, and the peak value of hydroxyproline content in AEP group was significantly higher than that in CON group. The hydroxyproline content at day 3, 5 and 7 in the ANP intervention group was (108.07±10.48)μg/mg, (137.14±8.66)μg/mg and (112.35±13.16)μg/mg, respectively, and that at day 3, 5 and 7 in the ANP control group was (132.35±14.2)μg/mg, (175.43±13.75)μg/mg and (137.92±12.65)μg/mg, respectively. TGF-β1 immunohistochemical peak score in control group, AEP group and ANP group was (0.12±0.03), (1.96±0.21) and (3.00±0.28), respectively. p-Smad3 immunohistochemical peak score was (0.15±0.05), (2.05±0.20), and (3.05±0.24), while type Ⅲ collagen immunohistochemical peak score was (0.11±0.04), (1.56±0.15), and (3.10±0.17). MMP-2 immunohistochemical peak score was (0.05±0.03), (1.45±0.20), and (2.45±0.15), respectively. The immunohistochemical peak scores of TGF-β1, p-Smad3, type Ⅲ collagen and MMP-2 in ANP group were significantly higher than those in AEP group. The immunohistochemical peak scores of TGF-β1, p-Smad3, type Ⅲ collagen and MMP-2 in pancreatic tissue of ANP intervention group and ANP control group were (2.36±0.21), (2.25±0.22), (2.47±0.19), (2.00±0.10) and (3.02±0.21), (3.01±0.19), (3.05±0.24), (2.43±0.11), respectively, which in ANP intervention group was significantly lower than those in the ANP control group. The peak value of MMP-2 activity in pancreatic tissue of CON group, AEP group and ANP group was (10.85±1.73), (85.78±7.16) and (115.43±8.7), respectively, which in ANP group was significantly higher than that in AEP group, and in AEP group was significantly higher than that in CON group. In ANP intervention group and ANP control group 3 and 5 days after molding, the expression levels of MMP-2 protein in pancreas were 0.20±0.01, 1.19±0.02, 0.52±0.01, 1.54±0.05, respectively; p-Smad3 protein expression levels were 0.30±0.04, 0.66±0.11, 1.95±0.05, 1.30±0.01, respectively; and MMP-2 and p-Smad3 in ANP intervention group was significantly lower than those the ANP control group. All the differences among the groups above were statistically significant (all P value <0.001). Conclusions:TGF-β1 and MMP-2 play an important role in tissue remodeling and extracellular matrix deposition after acute pancreatitis inflammation.
卡波西型血管内皮瘤(KHE)是一种罕见的血管内皮细胞肿瘤，主要见于婴幼儿及儿童，多位于四肢浅表软组织，发生于深部软组织如胰腺者较为罕见，需与毛细血管瘤、胰腺母细胞瘤相鉴别。本文报道1例KHE合并卡梅现象的病例，以供临床参考。
