Objective To compare the long-term survival of elderly patients with esophageal squamous cell carcinoma (ESCC) treated with surgical versus non-surgical treatment. Methods A retrospective analysis was conducted on the clinical data of elderly patients aged ≥70 years with ESCC who underwent esophagectomy or radiotherapy/chemotherapy at Sichuan Cancer Hospital from January 2009 to September 2017. Patients were divided into a surgical group (S group) and a non-surgical group (NS group) according to the treatment method. The propensity score matching method was used to match the two groups of patients at a ratio of 1∶1, and the survival of the two groups before and after matching was analyzed. Results A total of 726 elderly patients with ESCC were included, including 552 males and 174 females, with 651 patients aged ≥70-80 years and 75 patients aged ≥80-90 years. There were 515 patients in the S group and 211 patients in the NS group. The median follow-up time was 60.8 months, and the median overall survival of the S group was 41.9 months [95%CI (35.2, 48.5)], while that of the NS group was only 24.0 months [95%CI (19.8, 28.3)]. The 1-, 3-, and 5-year overall survival rates of the S group were 84%, 54%, and 40%, respectively, while those of the NS group were 72%, 40%, and 30%, respectively [HR=0.689, 95%CI (0.559, 0.849), P<0.001]. After matching, 138 patients were included in each group, and there was no statistical difference in the overall survival between the two groups [HR=0.871, 95%CI (0.649, 1.167), P=0.352]. Conclusion Compared with conservative treatment, there is no significant difference in the long-term survival of elderly patients aged ≥70 years who undergo esophagectomy for ESCC. Neoadjuvant therapy combined with surgery is still an important choice to potentially improve the survival of elderly patients with ESCC.

Radiopharmaceuticals operate by combining radionuclides with carriers. The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues. In comparison to external beam radiation therapy, radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity. This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment. Several key radionuclides are examined, including ²²³Ra, ⁹⁰Y, Lutetium-177 (¹⁷⁷Lu), ²¹²Pb, and Actinium-225 (²²⁵Ac). It also explores the current development trends of radiopharmaceuticals, encompassing the introduction of novel radionuclides, advancements in imaging technologies, integrated diagnosis and treatment approaches, and equipment-medication combinations. We review the progress in the development of new treatments, such as neutron capture therapy, proton therapy, and heavy ion therapy. Furthermore, we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.
Humans ; Radiopharmaceuticals/therapeutic use* ; Neoplasms/radiotherapy* ; Radioisotopes/therapeutic use* ; Animals

Objective:This multicenter retrospective study aimed to analyze the clinicopathological features of duodenal adenocarcinoma (DA) and identify prognostic factors for postoperative survival.Methods:Demographic characteristics, clinicopathological features, treatment outcomes and survival of DA patients undergoing surgical treatment at 18 Chinese medical centers from January 2012 to December 2023 were retrospectively analyzed.Results:Among the 2 056 DA patients included, 46.8% (963) had extra-ampullary DA (EA-DA), and 53.2% (1 093) had peri-ampullary DA (PA-DA). The 1-, 3-, and 5-year overall survival (OS) rates for patients who underwent radical surgery were 93.2%, 71.0%, and 57.2%, respectively. The median overall survival was 76 months, and the median progression-free survival (PFS) was 65 months. No differences in survival were observed between the laparotomy group and minimally invasive surgery (MIS) group either before or after propensity score matching (OS: 76 vs. 75 months before PSM, P=0.986; OS: 75 vs. 75 months after PSM, P=0.602). Furthermore, there were no significant differences between-group in operation time and postoperative complications ( P＞0.05). The MIS group experienced less intraoperative blood loss and shorter hospital stays. The multivariate Cox regression analysis revealed that advanced age ( HR=1.43,95% CI:1.18-1.73), elevated carbohydrate antigen 19-9 levels ( HR=1.24,95% CI:1.02-1.51), perineural invasion ( HR=1.44,95% CI:1.14-1.81), vascular invasion ( HR=1.35,95% CI:1.07-1.71), advanced T stage (T3-4 vs. T1-2: HR=1.86,95% CI:1.49-2.31), regional lymph node metastasis ( HR=1.93,95% CI:1.58-2.36), preoperative biliary drainage ( HR=1.26,95% CI:1.04-1.53), intraoperative blood loss ( HR=1.34,95% CI:1.11-1.62), clinically significant postoperative pancreatic fistulas ( HR=1.53,95% CI:1.12-2.09), and postoperative hemorrhage ( HR=1.62,95% CI:1.14-2.29) were independent risk factors for poor prognosis after surgery (all P＜0.05). Conclusions:Radical surgery is associated with favorable overall survival among DA patients, and no difference in survival is observed between EA-DA and PA-DA patients. MIS is a reliable alternative for DA treatment.

Objective:This multicenter retrospective study aimed to analyze the clinicopathological features of duodenal adenocarcinoma (DA) and identify prognostic factors for postoperative survival.Methods:Demographic characteristics, clinicopathological features, treatment outcomes and survival of DA patients undergoing surgical treatment at 18 Chinese medical centers from January 2012 to December 2023 were retrospectively analyzed.Results:Among the 2 056 DA patients included, 46.8% (963) had extra-ampullary DA (EA-DA), and 53.2% (1 093) had peri-ampullary DA (PA-DA). The 1-, 3-, and 5-year overall survival (OS) rates for patients who underwent radical surgery were 93.2%, 71.0%, and 57.2%, respectively. The median overall survival was 76 months, and the median progression-free survival (PFS) was 65 months. No differences in survival were observed between the laparotomy group and minimally invasive surgery (MIS) group either before or after propensity score matching (OS: 76 vs. 75 months before PSM, P=0.986; OS: 75 vs. 75 months after PSM, P=0.602). Furthermore, there were no significant differences between-group in operation time and postoperative complications ( P＞0.05). The MIS group experienced less intraoperative blood loss and shorter hospital stays. The multivariate Cox regression analysis revealed that advanced age ( HR=1.43,95% CI:1.18-1.73), elevated carbohydrate antigen 19-9 levels ( HR=1.24,95% CI:1.02-1.51), perineural invasion ( HR=1.44,95% CI:1.14-1.81), vascular invasion ( HR=1.35,95% CI:1.07-1.71), advanced T stage (T3-4 vs. T1-2: HR=1.86,95% CI:1.49-2.31), regional lymph node metastasis ( HR=1.93,95% CI:1.58-2.36), preoperative biliary drainage ( HR=1.26,95% CI:1.04-1.53), intraoperative blood loss ( HR=1.34,95% CI:1.11-1.62), clinically significant postoperative pancreatic fistulas ( HR=1.53,95% CI:1.12-2.09), and postoperative hemorrhage ( HR=1.62,95% CI:1.14-2.29) were independent risk factors for poor prognosis after surgery (all P＜0.05). Conclusions:Radical surgery is associated with favorable overall survival among DA patients, and no difference in survival is observed between EA-DA and PA-DA patients. MIS is a reliable alternative for DA treatment.

Objective:To investigate the surgical treatment and prognosis of thoracic esophageal squamous cell carcinoma (ESCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 2 766 patients with thoracic ESCC who were admitted to Sichuan Cancer Hospital & Institute from January 2010 to December 2017 were collected. There were 2 256 males and 510 females, aged (62±8)years. All patients underwent surgical treatment. Observation indicators: (1) treatment; (2) postoperative complications; (3) postoperative survival. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absolute numbers or percentages. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and the Log-Rank test was used for survival analysis. Result:(1) Treatment. Fifty-two of the 2 766 patients underwent neoadjuvant therapy. There were 1 444 patients undergoing open surgery, including 44 cases conversion to thoracotomy, and there were 1 322 patients undergoing minimally invasive esophagectomy. There were 1 991, 729 and 46 cases with McKeown, Ivor-Lewis and Sweet esophagectomy, respectively. One thousand two hundred and seventy-one of the 2 766 patients underwent postoperative adjuvant therapy. The number of lymph node metastases, the number of lymph node dissected, rate of R 0 resection, operation time of 2 766 patients were 2.1(0,3.0), 22±12, 94.722%(2 620/2 766), (237±66)minutes. (2) Postoperative complications. The overall incidence of postoperative complications was 25.850%(715/2 766). The top two postoperative complications were pneumonia and anastomotic fistula, with incidence rates of 8.604%(238/2766) and 7.484%(207/2766), respectively. One patient may have more than two kinds of postoperative complications. (3) Postoperative survival. The 1-, 3-and 5-year overall survival rates of 2 766 patients were 86.2%, 57.5% and 46.8%, respectively. Further analysis indicated that the 5-year overall survival rates of 510 female patients and 2 256 male patients were 62.0% and 43.3%, respectively, showing a significant difference between them ( χ2=48.94, P<0.05). The 5-year overall survival rates of 693 cases with upper thoracic ESCC, 1 479 cases with middle thoracic ESCC and 594 cases with lower thoracic ESCC were 49.5%, 46.7% and 44.1%, respectively, showing no significant difference among them ( χ2=3.21, P>0.05). The 5-year overall survival rates of 68 cases with stage 0 thoracic ESCC, 259 cases with stage Ⅰ esophageal ESCC, 885 cases with stage Ⅱ thoracic ESCC, 1 222 cases with stage Ⅲ thoracic ESCC, and 332 cases with stage Ⅳ thoracic ESCC were 95.6%, 76.4%, 61.4%, 35.6%, and 14.5%, respectively, showing a significant difference among them ( χ2=500.40, P<0.05). The 5-year overall survival rates of 1 444 patients undergoing open esophagectomy and 1 322 patients undergoing minimally invasive esophagectomy were 42.5% and 51.8%, respectively, showing a significant difference between them ( χ2=31.29, P<0.05). The 5-year overall survival rates of 1 991 cases undergoing McKeown esophagectomy, 729 cases undergoing Ivor-Lewis esophagectomy, and 46 cases undergoing Sweet esophagectomy were 49.5%, 41.2%, and 32.3%, respectively, showing a significant difference among them ( χ2=19.19, P<0.05). Conclusions:Compared with open esophagectomy, minimally invasive esophagectomy brings survival benefits to patients with thoracic esophageal ESCC. Among different esophagectomy methods, the McKeown esophagectomy has also brought survival benefits to patients with esophageal ESCC compared to the Ivor-Lewis esophagectomy and the Sweet esophagectomy.

Brucella is an intracellular pathogen that invades a host and settles in its immune cells; however, the mechanism of its intracellular survival is unclear. Modification of small ubiquitin-related modifier (SUMO) occurs in many cellular activities. E2 conjugating enzyme 9 (Ubc9) is the only reported ubiquitin-conjugating enzyme that links the SUMO molecule with a target protein. Brucella's intracellular survival mechanism has not been studied with respect to SUMO-related proteins and Ubc9. Therefore, to investigate the relationship between Brucella melitensis 16M and SUMO, we constructed plasmids and cells lines suitable for overexpression and knockdown of SUMO1 and Ubc9 genes. Brucella 16M activated SUMO1/Ubc9 expression in a time-dependent manner, and Brucella 16M intracellular survival was inhibited by SUMO1/Ubc9 overexpression and promoted by SUMO1/Ubc9 depletion. In macrophages, Brucella 16M-dependent apoptosis and immune factors were induced by SUMO1/Ubc9 overexpression and restricted by SUMO1/Ubc9 depletion. We noted no effect on the expressions of SUMO1 and Ubc9 in B. melitensis 16M lipopolysaccharide-prestimulated mouse RAW264.7 macrophages. Additionally, intracellular survival of the 16M△VirB2 mutant was lower than that of Brucella 16M (p < 0.05). VirB2 can affect expression levels of Ubc9, thereby increasing intracellular survival of Brucella in macrophages at the late stage of infection. Collectively, our results demonstrate that B. melitensis 16M may use the VirB IV secretion system of Brucella to interact with SUMO-related proteins during infection of host cells, which interferes with SUMO function and promotes pathogen survival in host cells.
Animals ; Apoptosis ; Brucella melitensis ; Brucella ; Immunologic Factors ; Macrophages ; Mice ; Plasmids

Objective To investigate the characteristics of population and the changes of disease spectrum in patients treated by endoscopic retrograde cholangiopancreatography ( ERCP ) . Methods Data of 20170 patients, who underwent ERCP in the First People' s Hospital of Hangzhou from May 2004 to February 2018, were enrolled in the retrospective analysis. According to the year of diagnosis and treatment,patients were divided into 2004-2008, 2009-2013, and 2014-2018 group; according to the postoperative diagnosis of ERCP, they were divided into biliary tract diseases ( including calculus, benign stenosis, malignant stenosis, and other causes ) and pancreatic diseases ( including acute pancreatitis, chronic pancreatitis, pancreatic malignant tumor, and other causes ) group; and according to the age, they were divided into the younger age (0-18 years old), young and middle age (19-65 years old), old age (66-85 years old), and advanced age (>85 years old) group. Statistical analysis was performed in the different groups. Results Among the 20170 patients, there were 10260 males and 9910 females, with age of 62. 65± 17. 11 years. The proportion of the younger age group and the advanced age group was 1. 04％( 24/2308 ) , 1. 69％ ( 127/7520 ) , 2. 39％ ( 247/10342 ) , and 2. 95％ ( 68/2308 ) , 4. 19％( 315/7520 ) , 6. 15％ ( 636/10342 ) , respectively, in the 2004-2008, 2009-2013 and 2014-2018 subgroups, with a rising trend (P<0. 017). A total 20032 patients had a clear postoperative diagnosis, including 15618 ( 77. 97％) of biliary diseases and 4414 ( 22. 03％) of pancreatic diseases. Biliary stones accounted for the majority of biliary diseases (63. 2％, 9863/15618), and its proportion increased from 59. 9％ ( 1191/1987 ) in 2004-2008 to 64. 5％ ( 5118/7939 ) in 2014-2018 ( P= 0. 000 ) . Acute pancreatitis accounted for the majority of pancreatic diseases (67. 4％, 1973/4414), and its proportion increased from 52. 4％ ( 162/309) in 2004-2008 to 69. 9％ ( 1636/2340) in 2014-2018 ( P=0. 000) . The top 3 diseases in the younger group and the advanced age group were acute pancreatitis ( 32. 58％, 129/396) , biliary stones ( 25. 25％, 100/396 ) , chronic pancreatitis ( 22. 22％, 88/396 ) , and biliary stones (56. 46％, 568/1006), malignant biliary stenosis (12. 52％, 126/1006), benign biliary stricture ( 10. 34％, 104/1006) , respectively. Conclusion The main disease of patients receiving ERCP is biliary stone, and the proportion of acute pancreatitis is increased. The overall age of the patients is old, and the proportion of the elderly and underaged patients is gradually increasing. Biliary diseases and pancreatic diseases are the main diseases in elderly patients and younger patients, respectively.

To investigate the feasibility and clinical efficacy of free graft of vascularized iliac bone flap based on deep iliac circumflex vessels for the treatment of osteonecrosis of femoral head (ONFH). Methods Twelve cases of ONFH(13 hips) received free graft of vascularized iliac bone flap based on deep iliac circumflex ves-sels from April, 2016 to July, 2017.The average Harris score was (74.7±6.9) in the second stage and (68.6±9.2) in the third stage. After debriding the necrosis bone of the femoral head, the contralateral vascularized iliac bone flap had been harvested, and then implanted into the femoral head. The deep iliac circumflex artery and its accompanying vein were anastomosed with the transverse branch (or ascending branch) of the lateral circumflex femoral artery and con-comitant vein respectively. The herringbone brace was used for hip fixation for 3 weeks after operation. X-ray exami-nation (1, 3, 6, 9 and 12 months after operation, respectively) and Harris hip score (6 and 12 months after operation, respectively) were performed to evaluate the recovery results of the femoral head. Scores were recorded and analyzed by paired t-test.The difference was considered to statistically significant if P＜0.05. Results The patients were fol-lowed-up for 15(12-20)months. The iliac bone flap of 12 patients (13 hips) healed well. There was no necrosis and collapse in 12 hips, except 1 femoral head collapsed slightly because of weight loading too early. The average Harris score was (91.6±4.5) of the second stage and (84.8±6.1) of the third stage. Compared with scores before the operation, the difference was statistically significant (P＜0.05). Conclusion Free vascularized iliac bone grafting based on deep iliac circumflex vessels is an ideal treatment for ONFH head in middle and advanced stage.

Objective To study the efficacy and safety of endobiliary radiofrequency ablation (RFA) with stent placement in treatment of unresectable extrahepatic cholangiocarcinoma (EHCC).Methods The patients with unresectable EHCC in Hangzhou First People's Hospital between October 2013 and January 2015 were enrolled in a prospective, randomized, single-blind cohort study, and were assigned randomly into two groups: RFA+stent group and stent-only group.The jaundice fade time, stent patency period, overall survival rate, and postoperative adverse events were analyzed between two groups.Results Among 59 patients with non-resectable EHCC, 28 were divided into RFA+stent group, and 31 were in stent-only group.There was no statistical difference in preoperative serum total bilirubin between the two groups.Mean serum bilirubin decrease time was significantly lower in the RFA+stent group than that in the stent-only group[17.9 d(7-22 d) VS 29.9 d(10-55 d),P=0.03].The biliary patency period in RFA+stent group was significantly longer than that of stent-only group (8.9 months VS 4.5 months, P=0.02).The mean survival time in RFA+stent group was significantly longer than that of stent-only group[13.3 months(6.2-16.5 months) VS 8.6 months(4.5-11.7 months), P=0.000).Incidence of postoperative adverse events showed no statistical difference between the two groups(P=0.727).Conclusion RFA with stent placement is effective and safe as a palliative measure in the treatment of non-resectable EHCC, and it can significantly shorten the jaundice fade time, prolong the biliary patency period and overall survival, while without increase of the incidence of adverse events.

[ Abstract] Objective To investigate the clinical efficacy of preoperative three-dimensional radiotherapy (3DRT) with or without concurrent chemotherapy for esophageal carcinoma.Methods We retrospectively analyzed 103 esophageal carcinoma patients who received preoperative 3DRT with or without concurrent chemotherapy from 2004 to 2014 in Cancer Hospital CAMS.The median radiation dose was 40 Gy, and the TP or PF regimen was adopted for concurrent chemotherapy if needed.The overall survival (OS) and disease-free survival ( DFS) were calculated by the Kaplan-Meier method, and the survival difference and univariate prognostic analyses were performed by the log-rank test.The Cox proportional hazards model was used for multivariate prognostic analysis.Results The number of patients followed at 3-years was 54.The 3-year OS and DFS rates were 61.1% and 54.9%, respectively, for all patients.There were no significant differences between the 3DRT and concurrent chemoradiotherapy (CCRT) groups as to OS (P=0.876) and DFS (P=0.521).The rates of complete, partial, and minimal pathologic responses of the primary tumor were 48.0%, 40.2%, and 11.8%, respectively.There were significant differences in OS and DFS between the complete, partial, and minimal pathologic response groups (P=0.037 and 0.003). No significant difference in pathologic response rate was found between the 3DRT and CCRT groups (P=0.953).The lymph node metastasis rate was 26.5%, and this rate for the complete, partial, and minimal pathologic response groups was 14%, 30%, and 67%, respectively, with a significant difference between the three groups (P=0.001).The OS and DFS were significantly higher in patients without lymph node metastasis than in those with lymph node metastasis (P=0.034 and 0.020).The surgery-related mortality was 7.8% in all patients.Compared with the 3DRT group, the CCRT group had significantly higher incidence rates of leukopenia (P=0.002), neutropenia (P=0.023), radiation esophagitis (P=0.008), and radiation esophagitis ( P=0.023).Pathologic response of the primary tumor and weight loss before treatment were independent prognostic factors for OS and DFS (P=0.030,0.024 and P=0.003,0.042). Conclusions Preoperative 3DRT alone or with concurrent chemotherapy can result in a relatively high complete pathologic response rate, hence increasing the survival rate.Further randomized clinical trials are needed to confirm whether preoperative CCRT is better than 3DRT in improving survival without increasing the incidence of adverse reactions.