Severe hemorrhagic complications in acute necrotizing pancreatitis: a retrospective single-center study / 中华肝胆外科杂志

Objective:To study the clinical features in patients with acute necrotizing pancreatitis (ANP) complicated by hemorrhage, and to analyze the treatments and their outcomes.Methods:The clinical data of 44 ANP patients with hemorrhage managed at the Department of Pancreas Center, the First Affiliated Hospital of Nanjing Medical University from September 2015 to December 2020 were retrospectively analyzed. There were 34 males and 10 females, aged (48.9±12.2) years old. Clinical data were collected on the bleeding sites, bleeding interventions, and treatment outcomes. Follow-up visits were made by outpatients visits or telephone.Results:Of the 44 patients with bleeding, 8 had gastrointestinal bleeding, 31 had intra-abdominal bleeding, and the remaining 5 had mixed bleeding sites. The median interval from onset of ANP to development of hemorrhage was 30.5(20.8, 40.3) d. For the 13 patients with gastrointestinal bleeding and mixed sites of bleeding: 4 patients were successfully treated by endoscopically for upper gastrointestinal ulcers, 5 patients were successfully treated by endovascular embolization using digital subtraction angiography (DSA) to detect the sites of bleeding, and 4 patients were successfully treated by surgery. For the 31 patients with intra-abdominal hemorrhage: 24 underwent DSA. For the 7 patients who did not undergo DSA, 3 who were hemodynamically stable were treated conservatively, 2 underwent immediate open surgery to stop bleeding within 24 h after surgical debridement of infected pancreatic necrosis, 1 did not undergo DSA because the family members decided to abandon further treatment, and 1 died while preparing for DSA. For the 29 patients who underwent DSA, vascular abnormalities were found in 69.0%(20/29), with splenic artery hemorrhage being the most common. In the 44 patients with bleeding: 29.5%(13/44) were examined by endoscopy, and 4 were successfully stopped by endoscopic treatment; 65.9%(29/44) patients were examined by DSA, and 15 patients were successfully treated by intravascular embolization; 14 patients (31.9%) were treated by open surgery and 11 patients were successfully stopped. The mortality rate was 47.7%(21/44), of which 5 patients died from hemorrhagic shock complicated by multiple organ dysfunction syndrome (MODS) and 16 patients died from sepsis complicated by MODS. The mortality rate of 55.6%(20/36) in patients with intra-abdominal and mixed sites of bleeding was significantly higher than that of the 12.5%(1/8) in patients with gastrointestinal bleeding ( P=0.048). None of the 23 surviving patients developed recurrence of intra-abdominal and/or gastrointestinal bleeding on follow-up. Conclusion:Major bleeding commonly occurred about 1 month after ANP and it was associated with a higher in-hospital mortality rate. DSA, endoscopy, and open surgery were effective means to achieve hemostasis.

Development and application of data standards for real world studies of pancreatic diseases / 中华消化外科杂志

Pancreatic diseases is a kind of complex, high-risk gastrointestinal diseases. Pancreatic cancer is highly malignant and seriously endangers people′s health. Developing multi-center, large-scale real world research can better understand the incidence patterns and treatment outcomes of pancreatic diseases. Based on the multi-center and heterogeneous data, the authors for-mulate data standards for real world studies of pancreatic diseases, and build a database of pancreatic cancer, integrating and sharing data from multi-center sources, in order to fully explore the scientific research value of pancreatic cancer clinical information, and provide experience and reference for the construction of other real world research specific disease databases in the future.

Clinical value of lymph node dissection of No. 14cd during pancreaticoduodenectomy in patients with pancreatic head carcinoma / 中华外科杂志

Objectives: To evaluate the positive rate of left posterior lymph nodes of the superior mesenteric artery (14cd-LN) in patients undergoing pancreaticoduodenectomy for pancreatic head carcinoma,to analyze the impact of 14cd-LN dissection on lymph node staging and tumor TNM staging. Methods: The clinical and pathological data of 103 consecutive patients with pancreatic cancer who underwent pancreaticoduodenectomy at Pancreatic Center,the First Affiliated Hospital of Nanjing Medical University from January to December 2022 were analyzed,retrospectively. There were 69 males and 34 females,with an age(M (IQR))of 63.0 (14.0) years (range:48.0 to 86.0 years). The χ2 test and Fisher's exact probability method was used for comparison of the count data between the groups,respectively. The rank sum test was used for comparison of the measurement data between groups. Univariate and multivariate Logistic regression analyzes were used for the analysis of risk factors. Results: All 103 patients underwent pancreaticoduodenectomy successfully using the left-sided uncinate process and the artery first approach. Pathological examination showed pancreatic ductal adenocarcinoma in all cases. The location of the tumors was the pancreatic head in 40 cases,pancreatic head-uncinate in 45 cases,and pancreatic head-neck in 18 cases. Of the 103 patients,38 cases had moderately differentiated tumor and 65 cases had poorly differentiated tumor. The diameter of the lesions was 3.2 (0.8) cm (range:1.7 to 6.5 cm),the number of lymph nodes harvested was 25 (10) (range:11 to 53),and the number of positive lymph nodes was 1 (3) (range:0 to 40). The lymph node stage was stage N0 in 35 cases (34.0%),stage N1 in 43 cases (41.7%),and stage N2 in 25 cases (24.3%). TNM staging was stage ⅠA in 5 cases (4.9%),stage ⅠB in 19 cases (18.4%),stage ⅡA in 2 cases (1.9%),stage ⅡB in 38 cases (36.9%),stage Ⅲ in 38 cases (36.9%),and stage Ⅳ in 1 case (1.0%). In 103 patients with pancreatic head cancer,the overall positivity rate for 14cd-LN was 31.1% (32/103),and the positive rates for 14c-LN and 14d-LN were 21.4% (22/103) and 18.4% (19/103),respectively. 14cd-LN dissection increased the number of lymph nodes (P<0.01) and positive lymph nodes (P<0.01). As a result of the 14cd-LN dissection,the lymph node stage was changed in 6 patients,including 5 patients changed from N0 to N1 and 1 patient changed from N1 to N2. Similarly,the TNM stage was changed in 5 patients,including 2 patients changed from stage ⅠB to ⅡB,2 patients changed from stage ⅡA to ⅡB,and 1 patient changed from stage ⅡB to Ⅲ. Tumors located in the pancreatic head-uncinate (OR=3.43,95%CI:1.08 to 10.93,P=0.037) and the positivity of 7,8,9,12 LN (OR=5.45,95%CI:1.45 to 20.44,P=0.012) were independent risk factors for 14c-LN metastasis; while tumors with diameter >3 cm (OR=3.93,95%CI:1.08 to 14.33,P=0.038) and the positivity of 7,8,9,12 LN (OR=11.09,95%CI:2.69 to 45.80,P=0.001) were independent risk factors for 14d-LN metastasis. Conclusion: Due to its high positive rate in pancreatic head cancer,dissection of 14cd-LN during pancreaticoduodenectomy should be recommended,which can increase the number of lymph nodes harvested,provide a more accurate lymph node staging and TNM staging.

Astragali Radix-Curcumae Rhizoma combination inhibits proliferation, migration, and invasion of colon cancer HT-29 cells by regulating EMT / 中国中药杂志

This study aims to investigate the effect of Astragali Radix-Curcumae Rhizoma(AC) combination on the proliferation, migration, and invasion of colon cancer HT-29 cells based on epithelial-mesenchymal transition(EMT). HT-29 cells were respectively treated with 0, 3, 6 and 12 g·kg~(-1) AC-containing serum for 48 h. The survival and growth of cells were measured by thiazole blue(MTT) colorimetry, and the proliferation, migration, and invasion of cells were detected by 5-ethynyl-2'-deoxyuridine(EdU) test and Transwell assay. Cell apoptosis was examined by flow cytometry. The BALB/c nude mouse model of subcutaneous colon cancer xenograft was established, and then model mice were classified into blank control group, 6 g·kg~(-1) AC group, and 12 g·kg~(-1) AC group. The tumor weight and volume of mice were recorded, and the histopathological morphology of the tumor was observed based on hematoxylin-eosin(HE) staining. The expression of apoptosis-associated proteins B-cell lymphoma-2-associated X protein(Bax), cysteine-aspartic acid protease-3(caspase-3), and cleaved caspase-3, and EMT-associated proteins E-cadherin, MMP9, MMP2 and vimentin in HT-29 cells and mouse tumor tissues after the treatment of AC was determined by Western blot. The results showed that cell survival rate and the number of cells at proliferation stage decreased compared with those in the blank control group. The number of migrating and invading cells reduced and the number of apoptotic cells increased in the administration groups compared with those in the blank control group. As for the in vivo experiment, compared with the blank control group, the administration groups had small tumors with low mass and shrinkage of cells and karyopycnosis in the tumor tissue, indicating that the AC combination may improve EMT. In addition, the expression of Bcl2 and E-cadherin increased and the expression of Bax, caspase-3, cleaved caspase-3, MMP9, MMP2, and vimentin decreased in HT-29 cells and tumor tissues in each administration group. In summary, the AC combination can significantly inhibit the proliferation, invasion, migration, and EMT of HT-29 cells in vivo and in vitro and promote the apoptosis of colon cancer cells.

Clinical features and surgical treatment of abdominal unicentric Castleman's disease / 中华普通外科杂志

Objective:To summarize the clinical manifestations, diagnosis and surgical treatment of abdominal unicentric Castleman's disease.Methods:The clinical data of abdominal unicentric Castleman's disease cases admitted to the General Surgery Department of the First Affiliated Hospital,Nanjing Medical University from Jan 2009 to Dec 2019 was retrospectively analyzed.Results:A total of 18 patients were included with definite pathological diagnosis. The main complaint was abdominal pain and discomfort (50%, 6/12), dizziness and fatigue (25%, 3/12), multiple rash with oral ulcer (16.7%, 2/12) and weight loss (8.3%, 1/12). All patients received surgical resection. Postoperative pathology showed clear vascular type in 15 patients and plasma cell type in 3 patients. There were no major complications nor mortality.Conclusion:Abdominal unicentric Castleman's disease has diverse clinical manifestations, which was difficult for preoperative diagnosis, postoperative prognosis is satisfactory.

Clinical efficacy of pancreaticoduodenectomy for periampullary diseases: a report of 2 019 cases / 中华消化外科杂志

Objective:To investigate the clinical efficacy of pancreaticoduodenectomy (PD) for periampullary diseases.Methods:The retrospective cohort study was conducted. The clinico-pathological data of 2 019 patients with periampullary diseases who underwent PD in the First Affiliated Hospital of Nanjing Medical University from January 2016 to December 2020 were collected. There were 1 193 males and 826 females, aged 63(15) years. Observation indicators: (1) surgical situations; (2) postoperative conditions; (3) postoperative pathological examinations; (4) prognosis of patients with periampullary carcinoma. Regular follow-up was conducted by telephone interview and outpatient examination once every 3 months within the postoperative first year and once every 6 months thereafter to detect the survival of patients with periampullary carcinoma. The follow-up was up to December 2021. Measurement data with skewed distribution were represented as M(IQR) or M(range), and comparison between groups was analyzed using the rank sum test. Count data were described as absolute numbers and (or) percentages, and comparison between groups was analyzed by the chi-square test or Fisher exact probability. Kaplan-Meier method was used to draw survival curves and calculate survival rates, and Log-Rank test was used to conduct survival analysis. Results:(1) Surgical situations: of 2 019 patients, 1 116 cases were admitted from 2016-2018 and 903 cases were admitted from 2019-2020. There were 1 866 cases undergoing open PD and 153 cases undergoing laparoscopic or robot-assisted PD. There were 1 049 cases under-going standard PD and 970 cases undergoing pylorus-preserved PD. There were 215 cases combined with portal mesenteric vein resection, 3 cases combined with arterial resection. The operation time of 2 019 patients was 255(104)minutes and the volume of intraoperative blood loss was 250(200)mL. The intraoperative blood transfusion rate was 31.401%(623/1 984), with the blood transfusion data of 35 cases missing. The proportions of pylorus-preservation, combination with portal mesenteric vein resection, intraoperative blood transfusion were 585 cases(52.419%), 97cases(8.692%), 384 cases(34.941%) for patients admitted in 2016-2018, versus 385 cases(42.636%), 118 cases(13.068%), 239 cases(27.006%) for patients admitted in 2019-2020, showing significant differences between them ( χ2=19.14,10.05,14.33, P<0.05). (2) Postoperative conditions: the duration of postoperative hospital stay of 2 019 patients was 13 (10) days. One of 2 019 patients lacked the data of postopera-tive complications. The overall postoperative complication rate was 45.292%(914/2 018), of which the incidence rate of grade B or C pancreatic fistula was 23.439%(473/2 018), the rate of grade B or C hemorrhage was 8.127%(164/2 018), the rate of grade B or C delayed gastric emptying was 15.312%(309/2 018), the rate of biliary fistula was 2.428%(49/2 018) and the rate of abdominal infection was 12.884%(260/2 018). The reoperation rate of 2 019 patients was 1.932%(39/2 019), the in-hospital mortality was 0.644%(13/2 019), the postoperative 30-day mortality was 1.238%(25/2 019), and the postoperative 90-day mortality was 2.675%(54/2 019). There were 541 cases(48.477%) with overall postoperative complications, 109 cases(9.767%) with grade B or C hemorr-hage, 208 cases(18.638%) with grade B or C delayed gastric emptying , 172 cases(15.412%) with abdominal infection, 39 cases(3.495%) with postoperative 90-day mortality of 1 116 patients admitted in 2016-2018. The above indicators were 373 cases(41.353%), 55 cases(6.098%), 101 cases(11.197%), 88 cases(9.756%), 15 cases(1.661%) of 902 patients admitted in 2019-2020, respectively. There were significant differences in the above indicators between them( χ2=10.22, 9.00, 21.30, 14.22, 6.45 , P<0.05). The in-hospital mortality occurred to 11 patients(0.986%) of 1 116 patients admitted in 2016-2018 and to 2 cases(0.221%) of 903 patients admitted in 2019-2020, showing a significant difference between them ( P<0.05). (3) Postoperative pathological examinations. Disease area of 2 019 patients reported in postoperative pathological examinations: there were 1 346 cases(66.667%) with lesions in pancreas, including 1 023 cases of carcinoma (76.003%) and 323 cases(23.997%) of benign diseases or low potential malignancy. There were 250 cases(12.382%) with lesions in duodenal papilla, including 225 cases of carcinoma (90.000%) and 25 cases(10.000%) of benign diseases or low potential malignancy. There were 174 cases(8.618%) with lesions in bile duct, including 156 cases of carcinoma (89.655%) and 18 cases(10.345%) of benign diseases or low potential malignancy. There were 140 cases(6.934%) with lesions in ampulla, including 134 cases of carcinoma (95.714%) and 6 cases(4.286%) of benign diseases or low potential malignancy. There were 91 cases(4.507%) with lesions in duodenum, including 52 cases of carcinoma (57.143%) and 39 cases(42.857%) of benign diseases or low potential malignancy. There were 18 cases(0.892%) with carcinoma in other sites. Postoperative pathological examination showed carcinoma in 1 608 cases(79.643%), benign diseases or low potential malignancy in 411 cases(20.357%). The histological types of 1 608 patients with carcinoma included adenocarcinoma in 1 447 cases (89.988%), intra-ductal papillary mucinous carcinoma in 37 cases(2.301%), adenosquamous carcinoma in 35 cases(2.177%), adenocarcinoma with other cancerous components in 29 cases(1.803%), neuroendocrine carcinoma in 18 cases(1.119%), squamous carcinoma in 1 case (0.062%), and other histological malignancies in 41 cases(2.550%). The histological types of 411 patients with benign or low poten-tial malignancy included intraductal papillary mucinous neoplasm in 107 cases (26.034%), chronic or autoimmune inflammatory disease in 62 cases(15.085%), neuroendocrine tumor in 58 cases(14.112%), pancreatic serous cystadenoma in 52 cases(12.652%), pancreatic solid pseudopapillary tumor in 36 cases(8.759%), gastrointestinal stromal tumor in 29 cases(7.056%), villous ductal adenoma in 20 cases(4.866%), pancreatic mucinous cystadenoma in 2 cases(0.487%), pancreatic or duodenal trauma in 2 cases(0.487%) and other histological types in 43 cases(10.462%). (4) Prognosis of patients with periampullary carcinoma. Results of survival analysis of 1 590 patients with main locations of periampullary carcinoma showed that of 1 023 patients with pancreatic cancer, 969 cases were followed up for 3.0-69.6 months, with a median follow-up time of 30.9 months. The median overall survival time, 1-year, 3-year and 5-year survival rates of pancreatic cancer patients were 19.5 months [95% confidence interval ( CI) as 18.0-21.2 months], 74.28%, 29.22% and 17.92%. Of 225 patients with duodenal papillary cancer, 185 cases were followed up for 3.0-68.9 months, with a median follow-up time of 36.7 months. The median overall survival time, 1-year, 3-year and 5-year survival rates were unreached, 94.92%, 78.87% and 66.94%. Of 156 patients with distal bile duct cancer, 110 cases were followed up for 3.0-69.5 months, with a median follow-up time of 25.9 months. The median overall survival time, 1-year, 3-year and 5-year survival rates were 50.6 months (95% CI as 31.4 to not reached), 90.37%, 56.11% and 48.84%. Of 134 patients with ampullary cancer, 100 cases were followed up for 3.0-67.8 months, with a median follow-up time of 28.1 months. The median overall survival time, 1-year, 3-year and 5-year survival rates were 62.4 months (95% CI as 37.8 months to not reached), 90.57%, 64.98% and 62.22%. Of 52 patients with duodenal cancer, 38 cases were followed up for 3.0-69.5 months, with a median follow-up time of 26.2 months. The median overall survival time, 1-year, 3-year and 5-year survival rates were 52.0 months (95% CI as 30.6 months to not reached), 93.75%, 62.24% and 40.01%.There was a significant difference in overall survival after PD between patients with different locations of periampullary malignancies ( χ2=163.76, P<0.05). Conclusions:PD is safe and feasible in a high-volume pancreas center, but the incidence of overall postoperative complications remains high. With the increase of PD volume, the incidence of overall postoperative complications has significantly decreased. There is a significant difference in overall survival time after PD among patients with different locations of periampullary malignancies. The 5-year survival rate after PD for duodenal papillary cancer, ampullary cancer, duodenal cancer and distal bile duct cancer is relatively high, whereas for pancreatic cancer is low.

A novel surgical option for artery-involving pancreatic cancer: sub-adventitial divestment technique / 中华消化外科杂志

Radical resection remains as the key treatment to improve the prognosis of pancreatic cancer, and arterial invasion hinders radical resection for locally advanced lesions. More accurate assessment of resectability and selection of appropriate surgical techniques depend on better understanding of the anatomy, histology, and tumor biology of pancreatic cancer invasion to the artery. Traditional radiology assessment for artery involvement, based on the circumference of involved arteries, is not equivalent to pathological artery invasion. The depth of arterial invasion is more important than the circumference in evaluating resectability. Results of morphological observa-tion on arterial structure shows that both the feasibility of sub-adventitial divestment technique (SDT) and the necessity of arterial resection depend on whether the external elastic lamina of artery is invaded. The SDT can provide an opportunity for radical resection for pancreatic cancer with arterial invasion, while avoiding the high mortality and incidence of complications caused by arterial resection. A more precise assessment of tumor invasion depth and biological behavior will provide a more reliable basis for surgical decision for the treatment of locally advanced pancreatic cancer with arterial invasion.

Surgical robot: a tool or toy / 中华消化外科杂志

Laparoscopic surgery is a revolution in the fields of surgery in the 21st century. The concept of minimally invasive surgery has been widely accepted. Nowadays, the commercial robot-assisted laparoscopic instrument operating system, commonly known as "surgical robot", does not yet have the attributes of a real robot and still needs further optimization. We are still far from claiming that we are in the "surgical robot era". A new generation of surgical robots with more developed artificial intelligence and simulation functions are worth working on for. "Minimally invasive approach" does not necessarily mean "minimally invasive surgery". The real benefit of patients is the most important indicator for evaluating minimally invasive surgery. The essence of science is discovery but not technological fashion. In the face of rapid technological development, the Chinese surgeons should remain rational and enterprising.

Liuwei Dihuangtang Alleviates Myelin Injury in Anterior Cingulate Cortex and Depression-like Behaviors of Rats with Diabetes Mellitus and Depression via Promoting Autophagy and Regulating Microglial Phenotype / 中国实验方剂学杂志

ObjectiveTo observe the effect of Liuwei Dihuangtang （LWDHT） on depression-like behaviors of rats with diabetes mellitus and depression （DD） and explore its mechanism. MethodThe diabetes mellitus （DM） model was induced by the high-fat diet and tail vein injection of low-dose streptozotocin （STZ） in 50 male Sprague-Dawley rats of SPF grade. Then the DD model was induced by chronic unpredictable mild stress （CUMS） for 28 days in DM rats. Fifty DD rats were randomly divided into model group， fluoxetine group （10 mg·kg-1·d-1）， and low-， medium-， and high-dose LWDHT groups （3.375， 6.75， 13.5 g·kg-1·d-1）， with 10 rats in each group. Another 10 healthy rats were assigned into a control group and received normal saline by gavage. After four weeks of drug intervention， the forced swimming assay was carried out to assess the depression-like behaviors of rats. The expression levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， and interleukin-10 （IL-10） in the anterior cingulate cortex （ACC） were detected by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence was used to detect the expression of myelin basic protein （MBP） in ACC and the co-localization of ionized calcium-binding adapter molecule 1 （Iba1） with intracellular microtubule-associated protein 1 light chain 3 （LC3）. The protein expression levels of MBP， myelin proteolipid protein （PLP）， myelin oligodendrocyte glycoprotein （MOG）， Beclin-1， LC3， p62， and microglia （MG） phenotypic protein-related inducible nitric oxide synthase （iNOS）， and arginase 1 （Arg1） were detected by Western blot. ResultCompared with the control group， the model group showed shortened swimming time and prolonged immobility time （P<0.01）. Compared with the model group， the medium- and high-dose LWDHT groups showed reduced immobility time （P<0.05， P<0.01）. Compared with the control group， the model group showed decreased protein expression of MBP， PLP， and MOG in the ACC region （P<0.01）. Compared with the model group， the fluoxetine group and the medium- and high-dose LWDHT groups showed up-regulated protein expression of MBP， PLP， and MOG （P<0.05， P<0.01）. Compared with the control group， the model group showed decreased MBP fluorescence intensity in the ACC region （P<0.01）. Compared with the model group， the fluoxetine group and the medium- and high-dose LWDHT groups showed increased MBP fluorescence intensity in the ACC region （P<0.05， P<0.01）. Compared with the control group， the model group showed increased expression of iNOS （P<0.01） and slightly increased Arg1 protein expression. Compared with the model group， the medium- and high-dose LWDHT groups and the fluoxetine group showed down-regulated iNOS expression and up-regulated Arg1 protein expression （P<0.05， P<0.01）， but there was no significant difference between the fluoxetine group and the medium-，high-dose LWDHT groups. Compared with the control group， the model group showed increased expression levels of proinflammatory factors IL-1β and TNF-α in the ACC region （P<0.01） and slightly increased expression levels of anti-inflammatory factors IL-4 and IL-10. Compared with the model group， the fluoxetine group， and the medium- and high-dose LWDHT groups showed down-regulated expression of IL-1β and TNF-α （P<0.05， P<0.01） and up-regulated expression of IL-4 and IL-10 （P<0.05， P<0.01）. Compared with the control group， the model group showed reduced expression levels of Beclin-1 and LC3Ⅱ （P<0.01） and increased expression level of p62 （P<0.01）. Compared with the model group， the fluoxetine group and the medium- and high-dose LWDHT groups showed up-regulated Beclin-1 and LC3Ⅱ expression （P<0.01） and down-regulated p62 expression （P<0.01）. Compared with the control group， the model group showed decreased LC3+Iba1+ cells in the ACC region （P<0.01）. Compared with the model group， the fluoxetine group and the medium- and high-dose LWDHT groups showed increased LC3+Iba1+ cells （P<0.05， P<0.01）. ConclusionLWDHT can alleviate the depression-like behaviors in DD rats presumedly by promoting MG autophagy， regulating MG phenotypic changes， and increasing MG clearance of myelin sheath fragments. Meanwhile， MG phenotypic transformation also inhibits ACC inflammation in DD rats， improves the local microenvironment of oligodendrocyte proliferation and differentiation， and ultimately promotes the repair and remyelination of damaged myelin sheath.

Comparison of distal pancreatectomy with celiac axis resection and sub-adventitial divestment technique for locally advanced or borderline resectable pancreatic body cancer / 中华外科杂志

Objective: To compare the outcomes of modified Appleby procedure and sub-adventitial divestment technique for locally advanced or borderline resectable pancreatic body cancer. Methods: A total of consecutive 58 patients(33 males and 25 females) who were diagnosed as locally advanced or borderline resectable pancreatic body cancer and underwent distal pancreatectomy at Pancreas Center, First Affiliated Hospital of Nanjing Medical University between September 2013 and May 2019 were retrospectively reviewed. The age(M(IQR)) was 62(9)years(range: 43 to 79 years). Thirty-one patients underwent distal pancreatectomy with celiac axis resection (DP-CAR) and 27 patients underwent distal pancreatectomy with sub-adventitial divestment technique(SDT). Perioperative parameters and follow-up data of these patients were analyzed. Quantitative data were compared with Wilcoxon test while categorical variables were compared with χ2 test or Fisher's exact test. Survival results were estimated by the Kaplan-Meier survival method with a Log-rank test. Results: There were no differences in age,gender,body mass index,abdominal symptoms,comorbidity or preoperative serum CA19-9 between two groups(all P>0.05). Obvious preoperative weight loss was more common in the group of SDT(48.1%(13/27) vs. 19.4%(6/31),χ²=5.431,P=0.020). Longer operative time(310(123) minutes vs. 254(137)minutes, Z=2.277,P=0.023),higher rate of combined organ resection(41.9%(13/31) vs. 14.8%(4/27),χ²=5.123,P=0.041) and longer postoperative hospital stay(15(10) days vs. 11(5)days,Z=2.292,P=0.022) were observed in the group of DP-CAR. Moreover,rate of overall morbidities was also higher (71.0%(22/31) vs. 29.6%(8/27),χ2=9.876,P=0.003),implicated by clinically relevant postoperative pancreatic fistula(61.3%(19/31) vs. 29.6%(8/27),χ2=5.814,P=0.020) in the DP-CAR group. Tumor size of the DP-CAR group was bigger(4.9(1.5)cm vs. 4.0(1.2)cm,Z=2.343,P=0.019) but no difference was seen between the DP-CAR group and SDT group in R0+R1(<1 mm) resection rate (84.0%(21/25) vs. 90.0%(18/20),P=0.678) and LNR(12.0(23.0)% vs. 9.0(18.0)%,Z=1.238,P=0.216),as well as median disease free survival(11.7 months vs. 11.4 months,Z=0.019,P=0.892) and median overall survival(16.3 months vs. 13.7 months,Z=0.172,P=0.679). Conclusions: Both DP-CAR and distal pancreatectomy with SDT are relatively safe and feasible for locally advanced or borderline resectable pancreatic body cancer. Compared with arterial resection,SDT may contribute to lower rates of postoperative complications and shorter duration of hospitalization,but no significant benefit is seen in long-term survival.

Comparative clinical efficacy analysis of pancreatoduodenectomy for distal bile duct and pancreatic head cancer: a report of 1 005 cases / 中华外科杂志

Objective: To compare and analyze the clinical efficacy of pancreaticoduodenectomy for distal bile duct cancer and pancreatic head cancer. Methods: Clinical data of 1 005 patients who underwent pancreaticoduodenectomy and postoperative pathological examination confirmed the diagnosis of distal bile duct cancer and pancreatic head cancer at the Pancreas Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to December 2020 were analyzed retrospectively. There were 112 cases in the distal bile duct cancer group, 71 males and 41 females,with age (M(IQR)) of 65(15) years(range: 40 to 87 years); 893 cases in the pancreatic head cancer group, 534 males and 359 females,with age of 64(13)years(range: 16 to 91 years). The differences between clinicopathological characteristics and postoperative overall survival of the two groups were analyzed by χ2 test, Fisher's exact probability method, rank sum test or log-rank test, respectively. The difference in postoperative overall survival between the two groups was compared using Kaplan-Meier method after propensity score matching (1∶1). Results: Compared with the pancreatic head cancer group,the distal bile duct cancer group had shorter operative time (240.0(134.0) minutes vs. 261.0(97.0) minutes, Z=2.712, P=0.007),less proportion of combined venous resection (4.5% (5/112) vs. 19.4% (173/893), χ²=15.177,P<0.01),smaller tumor diameter (2.0(1.0) cm vs. 3.0(1.5) cm,Z=10.567,P<0.01),higher well/moderate differentiation ratio (51.4% (56/112) vs. 38.0% (337/893), χ²=7.328, P=0.007),fewer positive lymph nodes (0(1) vs. 1(3), Z=5.824, P<0.01),and higher R0 resection rate (77.7% (87/112) vs. 38.3%(342/893), χ²=64.399, P<0.01),but with a higher incidence of overall postoperative complications (50.0% (56/112) vs. 36.3% (324/892), χ²=7.913,P=0.005),postoperative pancreatic fistula (28.6% (32/112) vs. 13.9% (124/893), χ²=16.318,P<0.01),and postoperative abdominal infection (21.4% (24/112) vs. 8.6% (77/892), χ²=18.001,P<0.01). After propensity score matching, there was no statistical difference in postoperative overall survival time between patients in the distal bile duct cancer group and the pancreatic head cancer group (50.6 months vs. 35.1 months,Z=1.640,P=0.201),and multifactorial analysis showed that tumor site was not an independent risk factor affecting the prognosis of patients in both groups after matching (HR=0.73,95%CI:0.43 to 1.23,P=0.238). Conclusions: Patients with distal bile duct cancer are more likely to benefit from early diagnosis and surgical treatment than patients with pancreatic head cancer,but with a relative higher postoperative complication rates. The different tumor origin site is not an independent risk factor for prognosis of patients with distal bile duct cancer and pancreatic head cancer after propensity score matching.

Application value of TRIANGLE operation in radical resection of pancreatic cancer / 中华消化外科杂志

Objective:To investigate the application value of TRIANGLE operation in radical resection of pancreatic cancer.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 30 patients with pancreatic cancer who underwent TRIANGLE operation in the First Affiliated Hospital of Nanjing Medical University from March 2020 to July 2020 were collected. There were 18 females and 12 males, aged from 41 to 79 years, with a median age of 65 years. After assessment of the resectability and dissection of the hepatoduodenal ligament, the superior mesenteric artery, celiac axis, common hepatic artery, portal vein and superior mesenteric vein of patients were exposed. According to the location of tumor, patients were performed pancreaticoduodenectomy, distal pancreatectomy or total pancreatectomy combined with dissection of putatively tumor-infiltrated lymphatic and neural tissue from the triangular space. During the TRIANGLE operation, it required to at least finish the skeletonization of right semi-circumference of the superior mesenteric artery and celiac axis in cases of pancreatico-duodenectomy, whereas the left semi-circumference in cases of distal pancreatectomy. In principle, both of the superior mesenteric artery and celiac axis were circumferentially skeletonized for cases of total pancreatectomy. Lymphatic, neural and fibrous tissues between the superior mesenteric artery and the celiac artery were completely dissected in all patients. Observation indicators: (1) surgical conditions and postoperative histopathological examination; (2) postoperative recovery situations; (3) follow-up. Regular follow-up was conducted by telephone interview or outpatient examinations to understand tumor recurrence and metastasis of patients up to January 2021. Measurement data with skewed distribution were represented as M (range). Count data were described as absolute numbers or percentages, Fisher exact probability method was used for comparison between groups. Results:(1) Surgical conditions and postoperative histopathological examination: all patients underwent open operation, including 21 cases of pancreaticoduodenec-tomy, 6 cases of distal pancreatectomy, 2 cases of total pancreatectomy, 1 case of mid-segment preserving pancreatectomy. There were 16 cases combined with portal vein-superior mesenteric vein resection and 3 cases combined with left adrenal resection. For the dissection area of superior mesenteric artery-celiac axis, one cycle was conducted in 5 of 30 patients, one and a quarter cycle in 8 patients, one and a half cycle in 8 patients, one and three quarters?two cycles in 9 patients. There were 16 cases with left gastric vein dissection and 14 cases with left gastric vein preservation. The operative time of 30 patients was 287 minutes (range, 165?495 minutes) and the volume of intraoperative blood loss was 275 mL(range, 50?800 mL). Nine patients received intraoperative transfusion of red blood cells or frozen plasma. Postoperative histopathological examination showed that the tumor diameter was 3.4 cm (range, 1.2?7.3 cm), the number of harvested lymph nodes was 20 (range, 9?35), the number of positive lymph nodes was 2 (0?19). Of the 30 patients,20 cases had moderately differentiated tumor and 10 cases had poorly differentiated tumor. R 0 resection was achieved in 9 patients, 1 mm R 1 resection in 17 patients, and R 1 resection in 4 patients. Postoperative pathological T stages: 3 of 30 patents were in stage T1, 18 cases were in stage T2, 5 cases were in stage T3, and 4 cases were in stage T4. Postoperative pathological N stages: 9 of 30 patents were in stage N0, 13 cases were in stage N1, and 8 cases were in stage N2. Postoperative pathological TNM stages: 2 of 30 patents were in stage Ⅰa, 2 cases were in stage Ⅰb, 3 case were in stage Ⅱa, 11 cases were in stage Ⅱb, 12 cases were in stage Ⅲ. (2) Postoperative recovery situations: 20 of 30 patients had postoperative complications, including 6 cases of Clavien-Dindo grade I complications, 9 cases of grade Ⅱ complications, 3 cases of grade Ⅲa complications, 2 cases of grade V complications. The incidence of postoperative diarrhea was 0 in cases with one cycle dissection of tissues around superior mesenteric artery-celiac axis, 1/8 in cases with one and a quarter cycle dissection, 4/8 in cases with one and a half cycle dissection, 9/9 in cases in with one and three quarters-two cycles dissection, showing a significant difference between the four groups ( P<0.05). The incidence of delayed gastric emptying was 5/16 in patients with left gastric vein dissection, versus 1/14 in patients with left gastric vein preservation, showing no significant difference between the two groups ( P>0.05). Nineteen of 30 patients received adjuvant chemotherapy.Twenty-eight of 30 patients were successfully discharged from hospital, with the duration of postoperative hospital stay of 15 days(range, 8?68 days) and the rest of 2 patients died. Three patients had unplanned readmission within postoperative 90 days. (3) Follow-up: all the 28 patients discharged from hospital were followed up for 1.0?9.0 months, with the median follow-up time of 6.5 months. During the follow-up, one patient with locally advanced pancreatic cancer had local recurrence, 9 patients had liver metastasis (including 4 cases with resectable pancreatic cancer, 4 cases with borderline resectable pancreatic cancer, 1 case with borderline resectable pancreatic cancer), and 1 patient with borderline resectable pancreatic cancer had peritoneal metastasis. The rest of 17 patients survived without tumor recurrence. Conclusions:TRIANGLE operation in the radical resection of pancreatic cancer has high radicality and low postoperative local recurrence, but a slightly high morbidity and mortality rate. Its long-term efficacy needs to be further evaluated. It is recommend that this procedure should be performed for selected patients after neoadjuvant chemotherapy in high-volume pancreatic surgery centers.

Dexmedetomidine attenuates inflammation and pancreatic injury in a rat model of experimental severe acute pancreatitis via cholinergic anti-inflammatory pathway / 中华医学杂志(英文版)

BACKGROUND@#Excessive inflammatory responses play a critical role in the development of severe acute pancreatitis (SAP), and controlling such inflammation is vital for managing this often fatal disease. Dexmedetomidine has been reported to possess protective properties in inflammatory diseases. Therefore, this study aimed to investigate whether dexmedetomidine pre-treatment exerts an anti-inflammatory effect in rats with SAP induced by sodium taurocholate, and if so, to determine the potential mechanism.@*METHODS@#SAP was induced with sodium taurocholate. Rats received an intraperitoneal injection of dexmedetomidine 30 min before sodium taurocholate administration. α-bungarotoxin, a selective alpha-7 nicotinic acetylcholine receptor (α7nAchR) antagonist, was injected intra-peritoneally 30 min before dexmedetomidine administration. The role of the vagus nerve was evaluated by performing unilateral cervical vagotomy before the administration of dexmedetomidine. Efferent discharge of the vagal nerve was recorded by the BL-420F Data Acquisition & Analysis System. Six hours after onset, serum pro-inflammatory cytokine (tumor necrosis factor α [TNF-α] and interleukin 6 [IL-6]) levels and amylase levels were determined using an enzyme-linked immunosorbent assay and an automated biochemical analyzer, respectively. Histopathological changes in the pancreas were observed after hematoxylin and eosin staining and scored according to Schmidt criteria.@*RESULTS@#Pre-treatment with dexmedetomidine significantly decreased serum levels of TNF-α, IL-6, and amylase, strongly alleviating pathological pancreatic injury in the rat model of SAP (TNF-α: 174.2 ± 30.2 vs. 256.1±42.4 pg/ml; IL-6: 293.3 ± 46.8 vs. 421.7 ± 48.3 pg/ml; amylase: 2102.3 ± 165.3 vs. 3186.4 ± 245.2 U/L). However, the anti-inflammatory and pancreatic protective effects were abolished after vagotomy or pre-administration of α-bungarotoxin. Dexmedetomidine also significantly increased the discharge frequency and amplitude of the cervical vagus nerve in the SAP rat model (discharge frequency: 456.8 ± 50.3 vs. 332.4 ± 25.1 Hz; discharge amplitude: 33.4 ± 5.3 vs. 20.5 ± 2.9 μV).@*CONCLUSIONS@#Dexmedetomidine administration attenuated the systemic inflammatory response and local pancreatic injury caused by SAP in rats through the cholinergic anti-inflammatory pathway involving vagus- and α7nAChR-dependent mechanisms.

Effect of lycopene on glycolipid metabolism and pancreatic tissue through regulation of TLR4/MyD88/NF-κB signaling pathway in high-fat diet induced obese mice / 中草药

Objective: To investigate the effects of lycopene on glycolipid metabolism and pancreatic tissue inflammation in obese mice and its underlying mechanism. Methods: The obese mouse model was induced by a high-fat diet (HFD). The effects of lycopene on body weight, blood glucose, blood lipid and body fat were observed after 8 weeks of administration. Pathological changes of pancreas were observed by HE staining. Protein expressions involved in TLR4/MyD88/NF-κB signaling pathway were detected by Western blotting, and the degree of macrophage infiltration in the pancreatic tissues of obese mice were detected by IHC. Results: Lycopene significantly inhibited body weight gain and reduced fasting blood glucose, as well as improved glucose tolerance and blood lipid level in obese mice. In addition, lycopene also reduced vacuolization, edema degeneration, islet hypertrophy and other inflammatory lesions in pancreatic tissues. Moreover, the protein expression levels of TLR4, MyD88 and NF-κB in pancreatic tissue were decreased and the inflammatory infiltration was reduced. Conclusion: Lycopene can improve blood glucose, lipid metabolism and pancreatic inflammation in obese mice, and its mechanism may be related to the regulation of TLR4/MyD88/NF-κB signaling pathway.

Pain control for chronic pancreatitis: conservative or surgical treatment / 中华胰腺病杂志

Pain control is one of the primary objectives in the treatment for chronic pancreatitis (CP). More and more evidence clearly shows that early surgery is superior to endoscope-surgery step-up strategy in pain control, and how to accelerate the translation of high-level evidence into clinical practice will be the next initiative. Meanwhile, how to establish the diagnosis for early CP and prediction model(s) for the effectiveness of endoscopic treatment in CP are two related key directions for future research. Multidiscipline cooperation is an important component in CP treatment, and will be an important way to promote an individualized, reasonable and precise management for CP.

Historical inspiration and practical thinking of enhanced recovery after surgery / 中华消化外科杂志

In recent years,enhance recovery after surgery (ERAS) has attracted many attentions in the surgical field.ERAS is a new model of perioperative management,in which more attention is paid to patients' perception to the medical treatment.This new medical model is different from the past one which is completely led by medical practitioners,thus full of humanistic concerns and rationality.With the premise of medical safety guaranteed,a series of measures,especially evidence-based medical interventions,are implemented to optimize the perioperative management and promote the recovery of patients in ERAS.A certain level of economic and social benefit will be gained with this process.The development history of ERAS was systemically reviewed in current editorial to help the readers to get a better understanding of the origin and evolving process of ERAS.It tracked back to the 1960s when "two reductions and one guarantee" and "removal of two tubes and one prohibition " were proposed as a revolutional perioperative management mode by the surgical community in our country.The goals pursued and measures implemented by our surgical predecessors back in those days were astonishingly similar to those in today's ERAS practice.They actually enlightened the initiation of ERAS in China.While ERAS is widely implemented nowadays,this new medical model should be objectively evaluated.A patient-centered medical system should be built,and ERAS should be promoted from an academic perspective,through which the ultimate goal of "surgery without danger and pain" could be finally achieved.

Historical inspiration and practical thinking of enhanced recovery after surgery / 中华消化外科杂志

In recent years, enhance recovery after surgery (ERAS) has attracted many attentions in the surgical field. ERAS is a new model of perioperative management, in which more attention is paid to patients′ perception to the medical treatment. This new medical model is different from the past one which is completely led by medical practitioners, thus full of humanistic concerns and rationality. With the premise of medical safety guaranteed, a series of measures, especially evidence-based medical interventions, are implemented to optimize the perioperative management and promote the recovery of patients in ERAS. A certain level of economic and social benefit will be gained with this process. The development history of ERAS was systemically reviewed in current editorial to help the readers to get a better understanding of the origin and evolving process of ERAS. It tracked back to the 1960s when "two reductions and one guarantee" and "removal of two tubes and one prohibition" were proposed as a revolutional perioperative management mode by the surgical community in our country. The goals pursued and measures implemented by our surgical predecessors back in those days were astonishingly similar to those in today′s ERAS practice. They actually enlightened the initiation of ERAS in China. While ERAS is widely implemented nowadays, this new medical model should be objectively evaluated. A patient-centered medical system should be built, and ERAS should be promoted from an academic perspective, through which the ultimate goal of "surgery without danger and pain" could be finally achieved.

Presence of serum antinuclear antibodies correlating unfavorable overall survival in patients with chronic lymphocytic leukemia / 中华医学杂志(英文版)

BACKGROUND@#Serum antinuclear antibodies (ANAs) are positive in some patients with chronic lymphocytic leukemia (CLL), but the prognostic value of ANAs remains unknown. The aim of this study was to evaluate the role of ANAs as a prognostic factor in CLL.@*METHODS@#This study retrospectively analyzed clinical data from 216 newly diagnosed CLL subjects with ANAs test from 2007 to 2017. Multivariate Cox regression analyses were used to screen the independent prognostic factors related to time to first treatment (TTFT), progression free survival (PFS) and overall survival (OS). Receiver operator characteristic curves and area under the curve (AUC) were utilized to assess the predictive accuracy of ANAs together with other independent factors for OS.@*RESULTS@#The incidence of ANAs abnormality at diagnosis was 13.9%. ANAs positivity and TP53 disruption were independent prognostic indicators for OS. The AUC of positive ANAs together with TP53 disruption was 0.766 (95% confidence interval [CI]: 0.697-0.826), which was significantly larger than that of either TP53 disruption (AUC: 0.706, 95% CI: 0.634-0.772, P = 0.034) or positive ANAs (AUC: 0.595, 95% CI: 0.520-0.668, P < 0.001) in OS prediction. Besides, serum positive ANAs as one additional parameter to CLL-international prognostic index (IPI) obtained superior AUCs in predicting CLL OS than CLL-IPI alone.@*CONCLUSION@#This study identified ANAs as an independent prognostic factor for CLL, and further investigations are needed to validate this finding.

Influence of smoking on insulin resistance in male patients with obstructive sleep apnea-hypopnea synddrome / 医学研究生学报

Objective Smoking can induce and aggravate obstructive sleep apnea-hypopnea synddrome (OSAHS), but there are few reports on its influence on insulin resistance of OSAHS patients. The article aimed to discuss the influence of smoking on insulin resistance in male patients with OSAHS.Methods A total of 141 OSAHS patients were divided into smoking group (n=104) and non-smoking group (n=37) according to smoking history. The smoking group were subdivided into two subgroups: ≥600 cigarettes/year and < 600 cigarettes/year according to smoking index. General clinical data of all patients were collected,while night sleeping data were gained by PSG overnight sleep monitoring. Fasting insulin(FINS), fasting blood glucose (FBG), concentration of serum C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interletkin-6 (IL-6), lipidperoxide (LPO) and activity of superoxide dismutase (SOD), glutathione peroxides (GSH-PX) were detected on all patients. Insulin resistance was evaluated by measuring HOMA-IR and FINS.Results Compared with non-smoking group, the patients in smoking group had a longer lack of oxygen time, lower oxygen saturation, higher CRP, TNF-alpha, IL-6 , LPO levels and lower SOD, GSH-PX activity. Significant differences were found in FBG, FINS, HOMA-IR and IR incidence between 2 subgroups(P<0.05), and the indexes of these 2 subgroups were both higher than those of non-smoking gorup, representing statistical significance(P<0.05).Conclusion Smoking is likely to be one of the important factors that lead to insulin resistance in male OSAHS patients. Oxidative stress, inflammation, hypoxia may be its influencing factors.

Analysis of risk factors and outcomes for delayed gastric emptying following pancreaticoduodenectomy: a single center experience of 492 cases / 中华外科杂志

Objective@#To evaluate risk factors for delayed gastric emptying(DGE)following pancreaticoduodenectomy(PD).@*Methods@#There were 492 consecutive patients who underwent PD in Pancreas Center, the First Affiliated Hospital with Nanjing Medical University between January 2012 and December 2014 were identified from a prospective database.There were 315 male and 177 female patients with a median age of 60.5 years.Univariate and multivariate analyses were performed to investigate the independent risk factors for clinically relevant DGE(CR-DGE).@*Results@#The overall incidence of DGE was 29.5%, with Grade B and C occurring at 4.3% and 5.9%, respectively.In multivariate analysis, pancreatic duct diameter less than 3 mm(OR=1.888, P=0.042), pylorus-preserving pancreaticoduodenectomy(OR=2.627, P=0.005) and clinically relevant postoperative pancreatic fistula(OR=2.740, P=0.007) were independently associated with CR-DGE.Other main complications such as postoperative pancreatic fistula, pyoperitoneum, intraabdominal infection were also associated with the severity of DGE(χ2=21.360, 14.422, 14.378; P=0.011, 0.002, 0.002). DGE patients had a significantly prolonged postoperative length of stay(31(24-41)d vs. 13(11-17)d) and increased medical cost((122 367.5±66 068.3)yuan vs. (78 200.7±27 043.9)yuan)(both P<0.01).@*Conclusions@#Small pancreatic duct, underwent pylorus-preserving pancreaticoduodenectomy and suffered postoperative pancreatic fistula might indicate a high risk of CR-DGE.