[Status and challenges of neoadjuvant immunotherapy for hepatocellular carcinoma].

With the development of modern liver surgical techniques and the progress of perioperative management,the survival rate after resection of hepatocellular carcinoma has been greatly improved,but the high recurrence and metastasis rate still limits the long-term survival after surgery. Preoperative neoadjuvant therapy has been confirmed to significantly reduce the postoperative recurrence rate and prolong survival in other types of cancer,but there has been a lack of effective systemic therapy for hepatocellular carcinoma for a long time,so the efficacy and regimen of neoadjuvant therapy for hepatocellular carcinoma are still controversial. PD-1/PD-L1 monoclonal antibody combined with anti-angiogenic targeted drugs has become a first-line regimen in systemic therapy for advanced hepatocellular carcinoma. This regimen has definite efficacy and high safety,bringing hope for neoadjuvant therapy of hepatocellular carcinoma. Recently,three clinical trials of neoadjuvant immunotherapy for hepatocellular carcinoma have been published internationally,which preliminarily suggest the efficacy and safety of neoadjuvant immunotherapy for hepatocellular carcinoma and lay a solid foundation for carrying out larger sample clinical studies in the future.

[Efficacy and safety of neoadjuvant immunotherapy for hepatocellular carcinoma].

Objective: To study the surgical safety and efficacy of preoperative neoadjuvant therapy with immune checkpoint inhibitors combined with anti-angiogenic drugs in patients with China liver cancer staging(CNLC)-Ⅱb and Ⅲa resectable hepatocellular carcinoma. Methods: The data of 129 patients with Ⅱb and Ⅲa hepatocellular carcinoma who underwent surgery at the First Affiliated Hospital of Nanjing Medical University from January 2018 to December 2020 were analyzed. All patients were divided into two groups: the neoadjuvant therapy group(n=14,13 males and 1 female,aged (55.4±12.6)years(range:34 to 75 years)) received immune combined targeted therapy before surgery,immune checkpoint inhibitor camrelizumab was administered intravenously at a dose of 200 mg each time,every 2 weeks for 3 cycles,anti-angiogenesis drug apatinib was taken orally and continuously with a dose of 250 mg for 3 weeks and the conventional surgery group(n=115,103 males and 12 females,aged (55.8±12.0)years(range:21 to 83 years)) did not receive antitumor systemic therapy before surgery. There were 3 patients with CNLC-Ⅱb,11 with CNLC-Ⅲa in the neoadjuvant group;28 patients with CNLC-Ⅱb,87 with CNLC-Ⅲa in the conventional group. Student's t test or rank-sum test was used to compare the differences between two groups for quantitative data, Fisher's exact probability method was used to compare the differences of proportions between two groups, and Log-rank test was used to compare survival differences between two groups. Results: The 1-year recurrence rate in the neoadjuvant group was 42.9%,and the 1-year recurrence rate in the conventional group was 64.0%,with a statistically significant difference between the two groups(χ²=3.850,P=0.050);The 1-year survival rate in the neoadjuvant group was 100% and that in the conventional group was 74.2%,with a statistically significant difference between the two groups(χ²=5.170,P=0.023). According to the stratified analysis of the number of tumors,for single tumor,the 1-year recurrence rate in the neoadjuvant group was 25.0%,and that in the conventional surgery group was 71.0%,and the difference between the two groups was statistically significant(χ²=5.280, P=0.022). For multiple tumors, the 1-year recurrence rate in the neoadjuvant group was 66.7%,and the 1-year recurrence rate in the conventional surgery group was 58.9%,with no significant difference between the two groups(χ²=0.110,P=0.736). The operative time,intraoperative blood loss,and postoperative hospital stay in the neoadjuvant group were similar to those in the conventional group,and their differences were not statistically significant. Conclusions: Immune checkpoint inhibitors combined with anti-angiogenic targeted drugs as a neoadjuvant therapy for resectable hepatocellular carcinoma can reduce the 1-year recurrence rate and improve the 1-year survival rate,especially for those with solitary tumor. Limited by the sample size of the neoadjuvant group,the safety of immune combined targeted therapy before surgery cannot be observed more comprehensively,and further studies will be explored.

Contour prognostic model for predicting survival after resection of colorectal liver metastases: development and multicentre validation study using largest diameter and number of metastases with RAS mutation status.

BACKGROUND: Most current models for predicting survival after resection of colorectal liver metastasis include largest diameter and number of colorectal liver metastases as dichotomous variables, resulting in underestimation of the extent of risk variation and substantial loss of statistical power. The aim of this study was to develop and validate a new prognostic model for patients undergoing liver resection including largest diameter and number of colorectal liver metastases as continuous variables. METHODS: A prognostic model was developed using data from patients who underwent liver resection for colorectal liver metastases at MD Anderson Cancer Center and had RAS mutational data. A Cox proportional hazards model analysis was used to develop a model based on largest colorectal liver metastasis diameter and number of metastases as continuous variables. The model results were shown using contour plots, and validated externally in an international multi-institutional cohort. RESULTS: A total of 810 patients met the inclusion criteria. Largest colorectal liver metastasis diameter (hazard ratio (HR) 1.11, 95 per cent confidence interval 1.06 to 1.16; P < 0.001), number of colorectal liver metastases (HR 1.06, 1.03 to 1.09; P < 0.001), and RAS mutation status (HR 1.76, 1.42 to 2.18; P < 0.001) were significantly associated with overall survival, together with age, primary lymph node metastasis, and prehepatectomy chemotherapy. The model performed well in the external validation cohort, with predicted overall survival values almost lying within 10 per cent of observed values. Wild-type RAS was associated with better overall survival than RAS mutation even when liver resection was performed for larger and/or multiple colorectal liver metastases. CONCLUSION: The contour prognostic model, based on diameter and number of lesions considered as continuous variables along with RAS mutation, predicts overall survival after resection of colorectal liver metastasis.

[Repair mechanisms of the wounds with exposed bone structures using an artificial dermis].

Objective: To investigate the repair mechanisms of the wounds with bone exposed by artificial dermis transplantation. Methods: Seventy two rabbits were randomly divided into 3 groups of 24 rabbits, the wound model was made on the top of head. In the skin defect group (SD group), skin was removed and skull periosteum was retained. In the periosteal defect group (PD group), the skin and skull periosteum were both removed, and the skull was exposed. In the skull burn group (SB group), after the periosteum was removed, the exposed skull bone was burned out with electric iron to cause skull surface necrosis, then the artificial dermis transplantation were performed in each group. In 1, 2, 3 and 4 weeks after transplantation, 2 specimens including artificial dermis and the underlying tissue in each group were cut for biopsy with HE staining to observe the angiogenesis in artificial dermis. Evans Blue perfusion was performed in four animals from each group to quantify angiogenesis in artificial dermis. Results: One week after transplantation, in SD group, a few microvessels can be observed in artificial dermis, but in the rest of the two groups, only a small amount of inflammatory cells can be seen. Two weeks after transplantation, in SD group, a large number of new blood vessels and fibroblasts can be seen filling in the artificial dermis, but angiogenesis delayed obviously in the PD and SB group. Three weeks after transplantation, the angiogenesis of artificial dermis in the PD and SB group accelerated obviously, and a thin layer of blood rich tissue membrane can be seen over the burned skull. The Evans Blue perfusion showed that the content of dye perfusion in the artificial dermis was closed to the peek value at 2 weeks after transplantation in the SD group, which was significantly higher than that in PD and SB group [(2 741±976) vs (1 039±590) and (403±209) µg/g, P<0.01]. Three weeks after transplantation, the content of Evans Blue in artificial dermis reached the peek value in SD and PD group, no significant difference was found between this two groups, but both significantly higher than that in SB group [(2 943±793) and (2 255±316) vs (1 125±404) µg/g, P<0.01]. Four weeks after transplantation, the content of Evans Blue in artificial dermis reached the peek value in SB group, although the value was still lower than that in SD and PD group, the difference was not significant [(1 609±787) vs (2 298±778) and (2 141±385) µg/g, P>0.05]. Conclusions: Lack or injury of periosteum can cause vascularization delay after artificial dermis transplantation. The vascularization of artificial dermis mainly originates from the normal tissues surrounding the wound when artificial dermis is transplanted on the wound with periosteum defect or bone exposed.

Performance measures of surgeon-performed colonoscopy in a Veterans Affairs medical center.

BACKGROUND: Quality indicators are increasingly emphasized in the performance of colonoscopy. This study aimed to determine the standard of care rendered by surgeon-endoscopists in a Veterans Affairs (VA) medical center by evaluating the indications for colonoscopy and outcome performance measures according to established quality indicators for colonoscopy. METHODS: A prospective standardized computer endoscopic reporting database (ProVation MD) was retrospectively reviewed. All colonoscopies performed by attending surgeons at the San Diego VA medical center between 1 January 2004 and 31 July 2007 were included in the study. Patients with charts that had incomplete reporting were excluded. The quality indicators used included the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) criteria for colorectal cancer screening, the American Cancer Society (ACS) guidelines for postcancer resection surveillance, and the American Society of Gastrointestinal Endoscopists (ASGE) quality indicators for colonoscopy. RESULTS: The data for 558 patients (96% men) were analyzed. The average patient age was 63 years (range, 25-93 years). Almost all the colonoscopies (99%) were performed in accordance with established criteria. The most common indications for colonoscopy were screening (n = 143, 26%), non-acute gastrointestinal bleeding (n = 127, 23%), polyp surveillance (n = 100, 18%), postcancer resection surveillance (n = 91, 17%), abdominal pain (n = 19, 4%), and anemia (n = 14, 3%). Postcancer resection surveillance colonoscopies were performed according to recommended criteria in 98% of the cases. The cecal intubation rate was 97%, and the overall adenoma detection rate was 26%. Two patients (<1%) experienced complications requiring intervention. CONCLUSION: The study data indicate that surgeon-performed colonoscopies meet standard quality criteria for indications and performance measures. The authors therefore conclude that surgeon-endoscopists demonstrate proficiency in the standard of care for colonoscopy examinations.

Rate of Organ Space Infection Is Reduced with the Use of an Air Leak Test During Major Hepatectomies.

BACKGROUND: Organ/space surgical site infections (OSIs) constitute an important postoperative metric. We sought to assess the impact of a previously described air leak test (ALT) on the incidence of OSI following major hepatectomies. METHODS: A single-institution hepatobiliary database was queried for patients who underwent a major hepatectomy without biliary-enteric anastomosis between January 2009 and June 2015. Demographic, clinicopathologic, and intraoperative data-including application of ALT-were analyzed for associations with postoperative outcomes, including OSI, hospital length of stay (LOS), morbidity and mortality rates, and readmission rates. RESULTS: Three hundred eighteen patients were identified who met inclusion criteria, of whom 210 had an ALT. ALT and non-ALT patients did not differ in most disease and treatment characteristics, except for higher rates of trisegmentectomy among ALT patients (53 vs. 34 %, p = 0.002). ALT patients experienced lower rates of OSI and 90-day morbidity than non-ALT patients (5.2 vs. 13.0 %, p = 0.015 and 24.8 vs. 40.7 %, p = 0.003, respectively). In turn, OSI was the strongest independent predictor of longer LOS (OR = 4.89; 95 % CI, 2.80-6.97) and higher rates of 30- (OR = 32.0; 95 % CI, 10.9-93.8) and 45-day readmissions (OR = 29.4; 95 % CI, 10.2-84.6). CONCLUSIONS: The use of an intraoperative ALT significantly reduces the rate of OSI following major hepatectomy and may contribute to lower post-discharge readmission rates.

Cooling a low noise amplifier with a micromachined cryogenic cooler.

The sensitivity of antenna systems increases with increasing active area, but decreases at higher noise figure of the low-noise amplifier (LNA). Cooling the LNA locally results in significant improvement in the gain and in lowering the noise figure of the LNA. Micromachined Joule-Thomson (JT) coolers can provide a cryogenic environment to the LNA. They are attractive because they have no cold moving parts and can be scaled down to match the size and the power consumption of LNAs. The performance of a LNA mounted on a JT microcooler with dimensions of 60.0 × 9.5 × 0.72 mm(3) is reported in this paper. The microcooler is operated with nitrogen gas and the cold-end temperature is controlled at 115 K. The measured net cooling power of the microcooler is about 43 mW when the LNA is not operating. The power dissipation of the LNA is 26 mW, with a supply voltage of 2 V. At room temperature the noise figure of the LNA is 0.83 dB and the gain lies between 17.9 and 13.1 dB, in the frequency range of 0.65 and 1.05 GHz. Upon cooling to 115 K, the noise figure drops to 0.50 dB and the increase in gain varies in the range of 0.6-1.5 dB.

Lower body negative pressure treadmill exercise is more comfortable and produces similar physiological responses as weighted vest exercise.

Lower body negative pressure (LBNP) treadmill exercise can generate a hypergravity load on the lower body that may improve athlete performance by mechanical and cardiovascular adaptations. This study compared the cardiovascular responses, subjective exertion and discomfort levels produced by LBNP exercise with those generated by a weighted vest (WV). We hypothesized that LBNP exercise is more comfortable than WV exercise at comparable levels of exercise. Nine subjects exercised on a treadmill at nine conditions, at 5.5 mph for 15 minutes, in which they ran in random order to avoid confounding effects: 100 %, 110 %, 120 %, 130 %, and 140 % body weight (BW), the latter four conditions were achieved by either LBNP chamber or WV. Heart rate (HR) and oxygen consumption (.VO(2)) were monitored continuously using ECG and open circuit spirometry. At the end of each test, subjects were asked to give discomfort and exertion scores using a ten-point visual analog scale (10 = maximal discomfort and exertion). For both HR and .VO(2), no significant differences were observed between LBNP and WV. Subjects reported significantly higher discomfort levels when exercising with the WV than with the LBNP at 120 % BW (5.1 +/- 0.55 vs. 3.1 +/- 0.64; p < 0.05), 130 % BW (6.2 +/- 0.42 vs. 2.3 +/- 0.44; p < 0.01) and 140 % BW (6.9 +/- 0.27 vs. 4.7 +/- 0.60; p < 0.01), while maintaining similar exertions at all conditions. Based on these results, LBNP exercise is more comfortable than standard WV exercise, while maintaining similar exertion, HR and .VO(2) values.