Oncological prognosis and morbidity of hepatectomy in elderly patients with hepatocellular carcinoma: a propensity score matching and multicentre study.

PURPOSE: With increasing life expectancy, the number of elderly patients (≥ 65 years) with hepatocellular carcinoma (HCC) has steadily increased. Hepatectomy remains the first-line treatment for HCC patients. However, the prognosis of hepatectomy for elderly patients with HCC remains unclear. METHODS: Clinical and follow-up data from 1331 HCC patients who underwent surgery between 2008 and 2020 were retrospectively retrieved from a multicentre database. Patients were divided into elderly (≥ 65 years) and non-elderly (< 65 years) groups, and PSM was used to balance differences in the baseline characteristics. The postoperative major morbidity and cancer-specific survival (CSS) of the two groups were compared and the independent factors that were associated with the two study endpoints were identified by multivariable regression analysis. RESULTS: Of the 1331 HCC patients enrolled in this study, 363 (27.27%) were elderly, while 968 (72.73%) were not. After PSM, 334 matched samples were obtained. In the propensity score matching (PSM) cohort, a higher rate of major morbidity was found in elderly patients (P = 0.040) but the CSS was similar in the two groups (P = 0.087). Multivariate analysis revealed that elderly age was not an independent risk factor associated with high rates of major morbidity (P = 0.117) or poor CSS (P = 0.873). The 1-, 3- and 5-year CSS rates in the elderly and non-elderly groups were 91.0% versus 86.2%, 71.3% versus 68.8% and 55.9% versus 58.0%, respectively. Preoperative alpha fetoprotein (AFP) level, Child‒Pugh grade, intraoperative blood transfusion, extended hemi hepatectomy, and tumour diameter could affect the postoperative major morbidity and preoperative AFP level, cirrhosis, Child‒Pugh grade, macrovascular invasion, microvascular invasion (MVI), satellite nodules, and tumor diameter were independently and significantly associated with CSS. CONCLUSION: Age itself had no significant effect on the prognosis of elderly patients with HCC after hepatectomy. Hepatectomy can be safely performed in elderly patients after cautious perioperative management.

Online calculator for predicting the risk of malignancy in patients with pancreatic cystic neoplasms: A multicenter, retrospective study.

BACKGROUND: Efficient and practical methods for predicting the risk of malignancy in patients with pancreatic cystic neoplasms (PCNs) are lacking. AIM: To establish a nomogram-based online calculator for predicting the risk of malignancy in patients with PCNs. METHODS: In this study, the clinicopathological data of target patients in three medical centers were analyzed. The independent sample t-test, Mann-Whitney U test or chi-squared test were used as appropriate for statistical analysis. After univariable and multivariable logistic regression analysis, five independent factors were screened and incorporated to develop a calculator for predicting the risk of malignancy. Finally, the concordance index (C-index), calibration, area under the curve, decision curve analysis and clinical impact curves were used to evaluate the performance of the calculator. RESULTS: Enhanced mural nodules [odds ratio (OR): 4.314; 95% confidence interval (CI): 1.618-11.503, P = 0.003], tumor diameter ≥ 40 mm (OR: 3.514; 95%CI: 1.138-10.849, P = 0.029), main pancreatic duct dilatation (OR: 3.267; 95%CI: 1.230-8.678, P = 0.018), preoperative neutrophil-to-lymphocyte ratio ≥ 2.288 (OR: 2.702; 95%CI: 1.008-7.244, P = 0.048], and preoperative serum CA19-9 concentration ≥ 34 U/mL (OR: 3.267; 95%CI: 1.274-13.007, P = 0.018) were independent risk factors for a high risk of malignancy in patients with PCNs. In the training cohort, the nomogram achieved a C-index of 0.824 for predicting the risk of malignancy. The predictive ability of the model was then validated in an external cohort (C-index: 0.893). Compared with the risk factors identified in the relevant guidelines, the current model showed better predictive performance and clinical utility. CONCLUSION: The calculator demonstrates optimal predictive performance for identifying the risk of malignancy, potentially yielding a personalized method for patient selection and decision-making in clinical practice.

Clinical online nomogram for predicting prognosis in recurrent hepatolithiasis after biliary surgery: A multicenter, retrospective study.

BACKGROUND: Methods for predicting the prognosis of patients undergoing surgery for recurrent hepatolithiasis after biliary surgery are currently lacking. AIM: To establish a nomogram to predict the prognosis of patients with recurrent hepatolithiasis after biliary surgery. METHODS: In this multicenter, retrospective study, data of consecutive patients in four large medical centers who underwent surgery for recurrent hepatolithiasis after biliary surgery were retrospectively analyzed. We constructed a nomogram to predict the prognosis of recurrent hepatolithiasis in a training cohort of 299 patients, following which we independently tested the nomogram in an external validation cohort of 142 patients. Finally, we used the concordance index (C-index), calibra-tion, area under curve, decision curve analysis, clinical impact curves, and visual fit indices to evaluate the accuracy of the nomogram. RESULTS: Multiple previous surgeries [2 surgeries: Odds ratio (95% confidence interval), 1.451 (0.719-2.932); 3 surgeries: 4.573 (2.015-10.378); ≥ 4 surgeries: 5.741 (1.347-24.470)], bilateral hepatolithiasis [1.965 (1.039-3.717)], absence of immediate clearance [2.398 (1.304-4.409)], neutrophil-to-lymphocyte ratio ≥ 2.462 [1.915 (1.099-3.337)], and albumin-to-globulin ratio ≤ 1.5 [1.949 (1.056-3.595)] were found to be independent factors influencing the prognosis. The nomogram constructed on the basis of these variables showed good reliability in the training (C-index: 0.748) and validation (C-index: 0.743) cohorts. Compared with predictions using traditional classification models, those using our nomogram showed better agreement with actual observations in the calibration curve for the probability of endpoints and the receiver operating characteristic curve. Dichloroacetate and clinical impact curves showed a larger net benefit of the nomogram. CONCLUSION: The nomogram developed in this study demonstrated superior performance and discriminative power compared to the three traditional classifications. It is easy to use, highly accurate, and shows excellent calibration.

Safety and efficacy of thalidomide in patients with transfusion-dependent ß-thalassemia: a randomized clinical trial.

Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent ß-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non ß0/ß0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.

Nomogram based on inflammation-related markers for predicting survival of patients undergoing hepatectomy for hepatocellular carcinoma.

BACKGROUND: Previous nomograms for hepatocellular carcinoma (HCC) did not include the neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR). This study aimed to establish an effective nomogram capable of estimating the association between preoperative inflammatory factors and overall survival (OS) of HCC patients after hepatectomy. AIM: To analyse the factors affecting the prognosis of HCC and establish a nomogram. METHODS: A total of 626 HCC patients (410 training set patients from the First Affiliated Hospital of Anhui Medical University and 216 validation set patients from the First Affiliated Hospital of University of Science and Technology of China) underwent hepatectomy from January 2014 to December 2017 and were followed up every 3-6 mo. The nomogram was based on OS-related independent risk factors identified by Cox regression analysis. The C-index, calibration curve, and area under the curve (AUC) were used to evaluate the nomogram's accuracy. RESULTS: The 1-, 2- and 3-year OS rates were 79.0%, 68.0% and 45.4% in the training cohort (median OS = 34 mo) and 92.1%, 73.9% and 51.2% in the validation cohort (median OS = 38 mo). Higher α-fetoprotein [hazard ratio (HR) = 1.812, 95% confidence interval (CI): 1.343-2.444], NLR (HR = 2.480, 95%CI: 1.856-3.312) and PLR (HR = 1.974, 95%CI: 1.490-2.616), tumour size ≥ 5 cm (HR = 1.323, 95%CI: 1.002-1.747), and poor differentiation (HR = 3.207, 95%CI: 1.944-5.290) were significantly associated with shortened OS. The developed nomogram integrating these variables showed good reliability in both the training (C-index = 0.71) and validation cohorts (C-index = 0.75). For predicting 1-, 2- and 3-year OS, the nomogram had AUCs of 0.781, 0.743 and 0.706 in the training cohort and 0.789, 0.815 and 0.813 in the validation cohort. The nomogram was more accurate in predicting prognosis than the AJCC TNM staging system. CONCLUSION: The prognostic nomogram combining pathological characteristics and inflammation indicators could provide a more accurate individualized risk estimate for the OS of HCC patients with hepatectomy.

T-tube drainage versus choledochojejunostomy in hepatolithiasis patients with sphincter of Oddi laxity: study protocol for a randomized controlled trial.

BACKGROUND: Residual and recurrent stones remain one of the most important challenges of hepatolithiasis and are reported in 20 to 50% of patients treated for this condition. To date, the two most common surgical procedures performed for hepatolithiasis are choledochojejunostomy and T-tube drainage for biliary drainage. The goal of the present study was to evaluate the therapeutic safety and perioperative and long-term outcomes of choledochojejunostomy versus T-tube drainage for hepatolithiasis patients with sphincter of Oddi laxity (SOL). METHODS/DESIGN: In total, 210 patients who met the following eligibility criteria were included and were randomized to the choledochojejunostomy arm or T-tube drainage arm in a 1:1 ratio: (1) diagnosed with hepatolithiasis with SOL during surgery; (2) underwent foci removal, stone extraction and stricture correction during the operation; (3) provided written informed consent; (4) was willing to complete a 3-year follow-up; and (5) aged between 18 and 70 years. The primary efficacy endpoint of the trial will be the incidence of biliary complications (stone recurrence, biliary stricture, cholangitis) during the 3 years after surgery. The secondary outcomes will be the surgical, perioperative and long-term follow-up outcomes. DISCUSSION: This is a prospective, single-centre and randomized controlled two-group parallel trial designed to demonstrate which drainage method (Roux-en-Y hepaticojejunostomy or T-tube drainage) can better reduce biliary complications (stone recurrence, biliary stricture, cholangitis) in hepatolithiasis patients with SOL. TRIAL REGISTRATION: Clinical Trials.gov: NCT04218669 . Registered on 6 January 2020.

Long-term outcomes after hepatectomy of huge hepatocellular carcinoma: A single-center experience in China.

BACKGROUND: Currently, hepatectomy remains the first-line therapy for hepatocellular carcinoma (HCC). However, surgery for patients with huge (>10 cm) HCCs is controversial. This retrospective study aimed to explore long-term survival after hepatectomy for patients with huge HCC. METHODS: The records of 188 patients with pathologically confirmed HCC who underwent curative hepatectomy between 2007 and 2017 were reviewed; patients were divided into three groups according to tumor size: huge (>10 cm; n = 84), large (5-10 cm; n = 51) and small (<5 cm; n = 53) HCC. Kaplan-Meier analysis was used to assess overall survival (OS) and disease-free survival (DFS), and log-rank analysis was performed for pairwise comparisons among the three groups. Risk factors for survival and recurrence were analyzed using the Cox proportional hazard model. RESULTS: The median follow-up period was 20 months. Although the prognosis of small HCC was better than that of huge and large HCC, OS and DFS were not significantly different between huge and large HCC (P = 0.099 and P = 0.831, respectively). A family history of HCC, poor Child-Pugh class, vascular invasion, diolame, pathologically positive margins, and operative time ≥240 min were identified as independent risk factors for OS and DFS in a multivariate model. Tumor size (>10 cm) had significant effect on OS, and postoperative antiviral therapy and postoperative complications also had significant effects on DFS. CONCLUSIONS: Huge HCC is not a contraindication of hepatectomy. Although most of these patients experienced recurrence after surgery, OS and DFS were not significantly different from those of patients with large HCC after resection.

Randomized clinical trial of BiClamp forceps versus clamp-crushing technique in open liver resection.

BACKGROUND: The aim of this trial was to compare the efficacy and safety of BiClamp forceps with the "gold-standard" clamp-crushing technique for open liver resection. METHODS: From October 2014 to May 2016, 86 consecutive patients scheduled to undergo hepatic resection were randomized to a BiClamp forceps group (n = 43) or to a clamp-crushing technique group (n = 43). RESULTS: Background characteristics of the two groups were closely matched. There were no significant differences between the BiClamp forceps group and clamp-crushing group in total intraoperative blood loss (339.81 ± 257.20 ml vs. 376.73 ± 303.67 ml, respectively; P = 0.545) or blood loss per transection area (5.35 ± 3.27 ml/cm2 vs. 5.44 ± 3.02 ml/cm2 , respectively; P = 0.609). Liver transection speed, the need of blood transfusion, morbidity, length of postoperative hospital stay, total hospitalization cost and liver function recovery were similar in the two groups. Multivariate logistic regression analysis identified major hepatectomy, multiple resections and liver transection time ≥30 min as significantly unfavorable factors for decreased intraoperative blood loss. CONCLUSIONS: Liver parenchymal transection with BiClamp forceps is as safe and feasible as the gold-standard clamp-crushing technique.

One-layer versus two-layer duct-to-mucosa pancreaticojejunostomy after pancreaticoduodenectomy: study protocol for a randomized controlled trial.

BACKGROUND: Although various pancreaticojejunal duct-to-mucosa anastomosis methods have been developed to reduce the postoperative risks of pancreaticoduodenectomy, pancreatic fistula remains the most serious complication with a high incident rate. The aim of this study is to compare the safety and effectiveness of one-layer and two-layer duct-to-mucosa pancreaticojejunostomy in patients undergoing pancreaticoduodenectomy. METHODS/DESIGN: In this study, adult patients who sign consent forms will be recruited and scheduled for elective pancreaticoduodenectomy. One hundred and fourteen patients will be included and randomized before pancreaticojejunal reconstruction and after resection of the lesion from the pancreatic or periampullary region. The primary efficacy endpoint is the incident rate of postoperative pancreatic fistula. Statistical analysis will be based on the intention-to-treat population. Patients will be followed up for 3 months by monitoring for complications and other adverse events. DISCUSSION: This prospective, single-center, randomized, single-blinded, two-group parallel trial is designed to compare one-layer with two-layer duct-to-mucosa anastomosis for pancreaticojejunal anastomosis during elective pancreaticoduodenectomy. TRIAL REGISTRATION: Clinical Trials.gov: NCT02511951 . Registered on 29 July 2015.

BiClamp® forcep liver transection versus clamp crushing technique for liver resection: study protocol for a randomized controlled trial.

BACKGROUND: Blood loss and the requirement of blood transfusions during liver transection have been shown to correlate well with higher morbidity and mortality rates and a worse prognosis. Various devices for liver parenchymal transection have been developed to reduce intraoperative blood loss. The goal of this study is to evaluate the safety and effectiveness of BiClamp® forcep transection compared to a clamp crushing technique in patients undergoing liver resection. METHODS/DESIGN: This study will include patients 18 years and older scheduled for hepatectomy with hepatic vascular exclusion who give informed consent. A sample size of 48 patients in each randomization arm will be calculated to detect a difference in the reduction of blood loss of approximately 200 ml (90% power and α = 0.05 (two-tailed)). The primary efficacy endpoint of the trial will be the total intraoperative blood loss based on the randomized dissection technique. The statistical analysis is based on the intention-to-treat population. Patients will be followed up on for three months for complications and adverse events. DISCUSSION: This prospective, single-center, randomized controlled, single-blinded, two-group parallel trial is designed to assess the efficacy and safety of BiClamp forcep hepatectomy versus clamp crushing for parenchymal transection during elective hepatic resection. TRIAL REGISTRATION: This trial was registered with Clinicaltrials.gov (identifier: NCT02197481 ) on 15 July 2014.

Examining the response pressure along a fluid-filled elastic tube to comprehend Frank's arterial resonance model.

Frank first proposed the arterial resonance in 1899. Arteries are blood-filled elastic vessels, but resonance phenomena for a fluid-filled elastic tube has not drawn much attention yet. In this study, we measured the pressure along long elastic tubes in response to either a single impulsive water ejection or a periodic water input. The experimental results showed the low damped pressure oscillation initiated by a single impulsive water input; and the natural frequencies of the tube, identified by the peaks of the response in the frequency domain, were inversely proportional to the length of the tube. We found that the response to the periodic input reached a steady distributed oscillation with the same period of the input after a short transient time; and the optimal pressure response, or resonance, occurred when the pumping frequency was near the fundamental natural frequency of the system. We pointed out that the distributed forced oscillation could also be a suitable approach to analyze the arterial pressure wave. Unlike Frank's resonance model in which the whole arterial system was lumped together to a simple 0-D oscillator and got only one natural frequency, a tube has more than one natural frequency because the pressure P(z,t) is a 1-D oscillatory function of the axial position z and the time t. The benefit of having more than one natural frequency was then discussed.

Single-incision versus conventional three-port laparoscopic appendectomy: A meta-analysis of randomized controlled trials.

PURPOSE: The aim of this article was to compare the advantages and disadvantages of single-incision laparoscopic appendectomy (SILA) and conventional three-port laparoscopic appendectomy (CTLA). MATERIAL AND METHODS: A meta-analysis was performed by analyzing all randomized controlled trials (RCTs) published in English that compared SILA and CTLA for appendicitis in adults and children. These studies compared these two methods from different angles including outcomes of interest, patient characteristics, operative time, pain visual analogue scales scores (VAS scores), length of hospital stay, time to return to full activity, resumption of diet, postoperative complications and cosmetic results The risk ratios (RR) and mean difference (MD) with 95% confidence intervals (CIs) were employed to assess the outcome. RESULTS: Seven recent RCTs encompassing 1170 patients (586 SILA and 584 CTLA cases) were included in this meta-analysis. The pooled results demonstrated that conversion rate, drain inserted, reoperation, length of hospital stay, resumption of normal diet and postoperative complications were statistically comparable between the two groups. The postoperative abdominal pain within 24 h was -0.57 in favor of the SILA technique (p = 0.05). Compared with CTLA, SILA showed a better cosmetic satisfaction score (SMD, 0.58; 95% CI, 0.32-0.83; p < 0.0001) and shorter time to recover normal activity (WMD, -0.69; 95% CI, -1.11-0.26; p = 0.001). However, SILA has a longer operative time (WMD, 5.38; 95% CI, 2.94-7.83; p < 0.0001). CONCLUSIONS: In selected patients, SILA was confirmed to be as safe and effective as CTLA. Despite the longer operative time, SILA has higher cosmetic satisfaction and shorter recovery time to normal activity. Due to the limitations of the available data, further research is needed.

Development of a Standard Protocol for the Harmonic Analysis of Radial Pulse Wave and Assessing Its Reliability in Healthy Humans.

This study was aimed to establish a standard protocol and to quantitatively assess the reliability of harmonic analysis of the radial pulse wave measured by a harmonic wave analyzer (TD01C system). Both intraobserver and interobserver assessments were conducted to investigate whether the values of harmonics are stable in successive measurements. An intraclass correlation coefficient (ICC) and a Bland-Altman plot were used for this purpose. For the reliability assessments of the intraobserver and the interobserver, 22 subjects (mean age 45 ± 14 years; 14 males and 8 females) were enrolled. The first eleven harmonics of the radial pulse wave presented excellent repeatability ([Formula: see text] and [Formula: see text]) for the intraobserver assessment and high reproducibility (ICCs range from 0.83 to 0.96 and [Formula: see text]) for the interobserver assessment. The Bland-Altman plot indicated that more than 90% of harmonic values fell within two standard deviations of the mean difference. Thus, we concluded that the harmonic analysis of the radial pulse wave using the TD01C system is a feasible and reliable method to assess a hemodynamic characteristic in clinical trial.

Pancreaticogastrostomy is associated with significantly less pancreatic fistula than pancreaticojejunostomy reconstruction after pancreaticoduodenectomy: a meta-analysis of seven randomized controlled trials.

OBJECTIVES: This study aimed to compare pancreaticojejunostomy (PJ) with pancreaticogastrostomy (PG) after pancreaticoduodenectomy (PD). METHODS: A literature search of PubMed and the Cochrane Central Register of Controlled Trials for studies comparing PJ with PG after PD was conducted. The primary outcome for meta-analysis was pancreatic fistula. Secondary outcomes were morbidity, mortality, biliary fistula, intra-abdominal fluid collection, hospital length of stay (LoS), postoperative haemorrhage and reoperation. Outcome measures were odds ratios (ORs) and mean differences with 95% confidence intervals (CIs). RESULTS: Seven recent RCTs encompassing 1121 patients (559 PJ and 562 PG cases) were involved in this meta-analysis. Incidences of pancreatic fistula (10.6% versus 18.5%; OR 0.52, 95% CI 0.37-0.74; P = 0.0002), biliary fistula (2.3% versus 5.7%; OR 0.42, 95% CI 0.03-3.15; P = 0.03) and intra-abdominal fluid collection (8.0% versus 14.7%; OR 0.50, 95% CI 0.34-0.74; P = 0.0005) were significantly lower in the PG than the PJ group, as was hospital LoS (weighted mean difference: -1.85, 95% CI -3.23 to -0.47; P = 0.008). Subgroup analysis indicated that severe pancreatic fistula (grades B or C) occurred less frequently in the PG than the PJ group (8.3% versus 20.5%; OR 0.37, 95% CI 0.23-0.59; P < 0.00001). However, there was no significant difference in morbidity (48.9% versus 51.0%; OR 0.90, 95% CI 0.70-1.16; P = 0.41), mortality (3.2% versus 3.5%; OR 0.82, 95% CI 0.43-1.58; P = 0.56), delayed gastric emptying (16.6% versus 14.7%; relative risk: 1.02, 95% CI 0.62-1.68; P = 0.94), postoperative haemorrhage (9.6% versus 11.1%; OR 0.82, 95% CI 0.54-1.24; P = 0.35) or reoperation (9.9% versus 9.8%; OR 0.93, 95% CI 0.60-1.43; P = 0.73). CONCLUSIONS: Pancreaticogastrostomy provides benefits over PJ after PD, including in the incidences of pancreatic fistula, biliary fistula and intra-abdominal fluid collection and in hospital LoS. Therefore, PG is recommended as a safer and more reasonable alternative to PJ reconstruction after PD.

[Family survey and clinical analysis of von Hippel-Lindau syndrome].

OBJECTIVE: To study the clinical characteristics and summary diagnostic and therapeutical experience of von Hippel-Lindau syndrome. METHODS: von Hippel-Lindau syndrome genealogy and clinical characteristics was investigated. Then a dendrogram was drawn and a genetic analysis was performed. Last the diagnostic and therapeutical experience of von Hippel-Lindau syndrome was investigated according to literatures. RESULTS: There are 6 members attacked by the von Hippel-Lindau syndrome of 5 generations which includes 42 members. Three patients underwent operation. Two of the three patients who suffered operation had been removed of right lobe of liver tumor and one cerebellar hemangioblastomas independently. The third patient sustained three operations for removal of three cerebellar hemangioblastomas and left renal clear cell carcinoma. Three patients died of this syndrome. CONCLUSIONS: The characteristic of this kindred is according with that of autosomal dominant inheritance disease. Until now, von Hippel-Lindau syndrome involves in multisystem, the prognosis of this syndrome is not very well. However, patients and their family members may get much benefit from genetic testing, periodic surveillance, early diagnosis and prompt treatment.