Effects of extramedullary disease on patients with newly diagnosed multiple myeloma / 中华血液学杂志

Objective: To summarize the characteristics of patients with newly diagnosed multiple myeloma (NDMM) admitted at Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine. We compared the clinical characteristics and prognoses among patients with non-extramedullary disease (EMD), bone-related extramedullary (EM-B) disease, and extraosseous extramedullary (EM-E) disease and further explored the effects of autologous hematopoietic stem cell transplantation (ASCT) for EMD. Methods: From January 2015 to January 2022, data of 114 patients (22%) with EMD out of 515 patients with NDMM were retrospectively analyzed; 91 (18%) and 23 (4%) patients comprised the EM-B and EM-E groups, respectively. The clinical characteristics of patients in all groups were compared with the Chi-square test. Progression-free survival (PFS) and overall survival (OS) of patients were analyzed by the Kaplan-Meier method. Independent prognostic factors were determined using multivariate Cox proportional hazard model. Results: There were no significant differences in age, gender, ISS stage, light chain, creatinine clearance, cytogenetic risk, 17p deletion, ASCT, and induction regimens among the three groups. Overall, 13% of EM-E patients had IgD-type M protein, which was significantly higher than that in EM-B patients (P=0.021). The median PFS of patients in the non-EMD, EM-B, and EM-E groups was 27.4, 23.1, and 14.0 months; the median OS was not reached, 76.8 months, and 25.6 months, respectively. The PFS (vs non-EMD, P=0.004; vs EM-B, P=0.036) and OS (vs non-EMD, P<0.001; vs EM-B, P=0.002) were significantly worse in patients with EM-E, while those were not significantly different between patients with EM-B and those with non-EMD. In the multivariate analysis, EM-E was an independent prognostic factor for OS in patients with NDMM (HR=8.779, P<0.001) and negatively impacted PFS (HR=1.874, P=0.050). In those who did not undergo ASCT, patients with EM-B had significantly worse OS than those with non-EMD (median 76.8 months vs. not reached, P=0.029). However, no significant difference was observed in the PFS and OS of patients with EM-B and those with non-EMD who underwent ASCT. Conclusions: Compared to patients with either non-EMD or EM-B, those with EM-E had the worst prognosis. EM-E was an independent risk factor for OS in patients with NDMM. ASCT can overcome the poor prognosis of EM-B.

A meta-analysis of single-stage versus two-stage management for concomitant gallstones and common bile duct stones.

OBJECTIVE: To conduct a randomized controlled trial (RCT) meta-analysis to evaluate the safety and effectiveness of single-stage [laparoscopic cholecystectomy (LC)+laparoscopic common bile duct exploration (LCBDE)] vs. two-stage management [preoperative endoscopic retrograde cholangiopancreatography (ERCP)+LC] for concomitant gallstones and common bile duct stones. METHODS: RCTs that met the inclusion criteria for data extraction were identified from electronic databases (PubMed, Embase, Science Citation Index, and the Cochrane Library) up to August 2014. The relevant congressional proceedings were also searched. The primary outcomes were stone clearance from the common bile duct, postoperative morbidity and mortality. The secondary outcomes were conversion to other procedures, length of hospital stay, total operative time, and hospitalization charges. The outcomes were calculated as odds ratios (ORs) with 95% confidence intervals (CIs) using RevMan 5.2. RESULTS: Eight RCTs, which included 1130 patients, were identified for analysis in our study. The meta-analysis revealed that the common bile duct stone clearance rate in the single-stage group was higher (OR=1.56, 95% CI: 1.05 to 2.33, P=0.03). The lengths of hospital stay (MD=-1.02, 95% CI: -1.99 to -0.04, P=0.04) and total operative times (MD=-16.78, 95% CI: -27.55 to -6.01, P=0.002) were also shorter in the single-stage group. There was no statistically significant difference between the two groups regarding postoperative morbidity (OR=1.12, 95% CI: 0.79 to 1.59, P=0.52), mortality (OR=0.29, 95% CI: 0.06 to 1.41, P=0.13) and conversion to other procedures (OR=0.82, 95% CI: 0.37 to 1.82, P=0.62). CONCLUSION: Single- and two-stage management for cholecysto-choledocholithiasis had similar mortality and complication rates; however, the single-stage strategy was better in terms of stone clearance, hospital stay and total operative time.

Laparoscopic versus open surgery in children with choledochal cysts: a meta-analysis.

OBJECTIVE: To compare the safety and efficacy between laparoscopic and open cyst excision with hepaticojejunostomy for children with choledochal cysts using meta-analysis. METHODS: Studies comparing the laparoscopic and the open choledochal cyst excision that met the inclusion criteria for data extraction were identified from electronic databases (PubMed, Embase, Science Citation Index, and the Cochrane Library) up to November 2014. The proceedings of relevant congress were also searched. The outcomes were operative time, intraoperative blood loss, time to food intake, postoperative morbidity and mortality, length of hospital stay. Outcomes were calculated as odds ratios (ORs) with 95% confidence intervals (CIs) using RevMan 5.2. RESULTS: Seven retrospective studies were finally included, involving a total of 1016 patients, of whom, 408 cases underwent laparoscopic cyst excision and Roux-en-Y hepaticojejunostomy (LH) and 608 cases underwent open cyst excision and Roux-en-Y hepaticojejunostomy (OH). In LH group compared with OH group, the operative time was longer (MD = 59.11, 95% CI 27.61-90.61, P = 0.0002), while the length of postoperative hospital stay was less (MD = -2.01, 95% CI -2.49 to -1.54, P < 0.00001), the intraoperative blood loss was lower (MD = -37.14, 95% CI -66.69 to -7.60, P = 0.01) and time to food intake was less (MD = -1.14, 95% CI -1.61 to -0.67, P = 0.01). The rate of postoperative morbidity was more in the OH group, but there is no statistically significant difference between the two groups in postoperative morbidity (OR = 0.52, 95% CI 0.13-2.06, P = 0.35). CONCLUSION: Laparoscopic surgery is a feasible, safe treatment of choledochal cyst with less postoperative morbidity, a shorter length of stay and a lower blood loss when compared with open approach. With the improvement of laparoscopic techniques and deftness of surgeons practice, laparoscopic surgery may become the first choice procedure for choledochal cyst.

Potential biomarkers for sensitivity of gallbladder cancer cells to gemcitabine.

Gemcitabine (Gem)-based chemotherapies are the main therapeutic regimens for patients with unresectable advanced or metastatic gallbladder cancer (GBC). However, the modest ORR and mild benefit on survival demonstrates the need for finding biomarkers for sensitivity to Gem and hence improving the therapy. In present work, two GBC cell lines with vast difference in sensitivity to Gem were subjected to DNA microarray analysis. Dramatic expression difference was found in protein kinase A signaling, P2Y purigenic receptor signaling, ErbB signaling and p70S6K signaling. Predicted low expression of KRAS and inactivation of AKT/ERK signaling in Gem-resistant GBC cells was validated by quantitative PCR and immunoblotting, respectively. However, p70S6K, p38MAPK and NF-κB signaling was probably activated in Gem-resistant GBC cells, which deserves further investigation in more GBC cell lines and tissues. Our work provides potential pathway signatures for Gem sensitivity of GBC patients.

Immunomodulation of inducible co-stimulator (ICOS) in human cytokine-induced killer cells against cholangiocarcinoma through ICOS/ICOS ligand interaction.

OBJECTIVE: To evaluate the immunomodulation of inducible co-stimulator (ICOS) in cytokine-induced killer (CIK) cells against cholangiocarcinoma. METHODS: CIK cells were generated from normal peripheral blood mononuclear cells. Methyl thiazolyl tetrazolium assay was performed to assess proliferation of CIK-ICOS and controlled CIK cells; ELISA was used to analyze the expression of cytokines. Reverse transcription-polymerase chain reaction and immunohistochemistry were performed to evaluate the expression of ICOS ligand (ICOSL) in CIK cells and human cholangiocarcinoma cell line QBC939 cells. The cytotoxicity of CIK cells was determined either by lactate dehydrogenase-releasing assay in vivo or alteration of tumor size prior to and after the treatment of CIK cells in vivo. RESULTS: CIK-ICOS cells proliferated more and expressed higher secretion a level of interferon-γ than the controlled CIK. These cells exhibited higher cytotoxicity against cholangiocarcinoma cell lines at all efficacy: toxicity (E:T) ratios tested than the controlled CIK cells. More importantly, the anti-ICOSL antibody was able to attenuate the elevated cytotoxicity mediated by ICOS overexpression. When injected into cholangiocarcinoma xenografts in severe combined immunodeficiency mice, CIK-ICOS cells survived better than the controlled CIK cells around xenografts and significantly reduced the growth rate of cholangiocarcinoma, with least volume increase and more severe necrosis of the xenografts than controlled mice treated with saline, CIK or CIK-enhanced green fluorescent protein. CONCLUSION: ICOS can enhance the cytotoxic effect of CIK cells against cholangiocarcinoma both in vitro and in vivo. This effect is mediated by ICOS-augmented cytokine secretion and cell proliferation, and in part through ICOS-ICOSL interaction.

A prospective study of the efficacy of endoscopic biliary stenting on common bile duct stones.

OBJECTIVE: To investigate the efficacy of endoscopic biliary stenting on common bile duct stones. METHODS: Fifty patients with choledocholithiasis were treated with endoscopic biliary stenting and followed. The early and late outcome was assessed. RESULTS: The procedure was successful in all patients and there was only one patient with mild pancreatitis. The patency rates of stent at 6 months, 12 months and 24 months after biliary stenting were 94%, 79% and 58%, respectively. The rate of reduction in size of stone was 60%. CONCLUSION: Endoscopic biliary stenting was not a definitive treatment of choledocholithiasis. It may be an option for patients clinically unfit for definitive treatment.

Laparoscopic treatment of choledocholithiasis with novel self-releasing biliary stent.

OBJECTIVES: The aim of this study was to evaluate the effect of a self-releasing biliary stent antegradely placed during laparoscopic common bile duct exploration (LCBDE) for choledocholithiasis. MATERIALS AND METHODS: The soft biliary stent, made of polyurethane, was designed as a J-umbrella form with a pigtailed duodenal part and an umbrella-like biliary anchoring part shaped with the rapidly absorbable suture. After the clearance of stones during LCBDE, a guide wire was inserted into the duodenum through the choledochoscope. The stent was advanced over the guide wire until the pigtail of the stent entered the duodenum. The choledochotomy was primarily closed. RESULTS: This technique has been performed on 33 patients with choledocholithiasis. The median length of postoperative hospital stay was 4.3 (3-8) days. All the stents were eliminated from the bile ducts and discharged out of the body. The median time of the stent stay in the body was 13.6 (+/- 2.55) days. Transient hyperamylasemia occurred in 4 of the 33 (12.1%) patients, and stent occlusion occurred in 1 patient who recovered soon after treatment. No bile leak, biliary infection, or stent dislocation was observed. During the follow-up of 12 months, no biliary infection, residual calculi, or stricture occurred. CONCLUSION: This novel self-releasing stent is safe and effective in the laparoscopic treatment of choledocholithiasis, and the subsequent removal of the stent can be avoided.

Outcome of gallbladder preservation in surgical management of primary bile duct stones.

AIM: To evaluate the methods and outcome of gallbladder preservation in surgical treatment of primary bile duct stones. METHODS: Thirty-five patients with primary bile duct stones and intact gallbladders received stone extraction by two operative approaches, 23 done through the intrahepatic duct stump (RBD-IDS, the RBD-IDS group) after partial hepatectomy and 12 through the hepatic parenchyma by retrograde puncture (RBD-RP, the RBD-RP group). The gallbladders were preserved and the common bile duct (CBD) incisions were primarily closed. The patients were examined postoperatively by direct cholangiography and followed up by ultrasonography once every six months. RESULTS: In the RBD-IDS group, residual bile duct stones were found in three patients, which were cleared by a combination of fibrocholedochoscopic extraction and lithotripsy through the drainage tracts. The tubes were removed on postoperative day 22 (range: 16-42 days). In the RBD-RP group, one patient developed hemobilia and was cured by conservative therapy. The tubes were removed on postoperative day 8 (range: 7-11 days). Postoperative cholangiography showed that all the gallbladders were well opacified, contractile and smooth. During 54 (range: 6-120 months) months of follow-up, six patients had mildly thickened cholecystic walls without related symptoms and further changes, two underwent laparotomies because of adhesive intestinal obstruction and gastric cancer respectively, three died of cardiopulmonary diseases. No stones were found in all the preserved gallbladders. CONCLUSION: The intact gallbladders preserved after surgical extraction of primary bile duct stones will not develop gallstones. Retrograde biliary drainage is an optimal approach for gallbladder preservation.