Efficacy and long-term prognosis of gastrojejunostomy for malignant gastric outlet obstruction: A systematic review and Bayesian network meta-analysis.

BACKGROUND: Gastrojejunostomy (GJ) is becoming a standard surgical treatment for ameliorating malignant gastric outlet obstruction (MGOO). However, data on the long-term outcomes of MGOO treatment are lacking. This network meta-analysis aimed to compare overall survival (OS) rates and subsequent anticancer treatment outcomes of GJwith other therapies in MGOO. METHODS: We searched four electronic databases, including PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials, from inception to August 1, 2022. Studies reporting OS associated with GJ versus other treatments for MGOO were selected. The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary outcome assessed was OS, whereas the secondary outcome was subsequent anticancer treatment. We performed a Bayesian network meta-analysis to produce hazard ratios (HR) and odds ratios (OR) with 95% credible intervals (CrIs). RESULTS: We identified 24 retrospective studies that included 2473 patients. The studies assessed the outcomes of six treatments to alleviate MGOO. Results showed that GJ (hazard ratio: 0.83, 95% CrI: 0.78-0.88) was the most effective treatment for patients with MGOO, with the greatest surface under the cumulative ranking curve (SUCRA) values (79.9%) versus non-resection, palliative chemotherapy (13.9%) in terms of OS. Similarly, GJ (SUCRA: 46.5%) improved subsequent anticancer treatment requirements, ranking second only to jejunostomy/gastrostomy (JT/GT) (SUCRA: 95.9%). CONCLUSIONS: Our study demonstrates that GJ improves OS and follow-up treatments versus other non-resection treatments in patients with MGOO. These findings may serve for selecting appropriate therapy for MGOO.

Comprehensive analysis of m6A related gene mutation characteristics and prognosis in colorectal cancer.

BACKGROUND: Colorectal cancer is considered as the second most common cancer worldwide. Studies have shown that m6A RNA methylation abnormalities play an important role in the pathogenesis of many human diseases, including cancer. The current study was designed to characterize the mutation of m6A related genes and explore their prognostic role in colorectal cancer. METHODS: RNA-seq data and somatic mutation data of TCGA-COAD and TCGA-READ were downloaded from UCSC xena for comprehensive analysis. M6A related genes were selected from previous literatures, including "Writer" protein (METTL3, METTL5, METTL14, METTL16, ZC3H13, RBM15, WTAP, KIAA1429), "Reader" protein YTHDF1, YTHDF2, YTHDF3, YTHDC1, YTHDC2, HNRNPC, IGF2BP1, IGF2BP2, IGF2BP3), and "Eraser" protein (FTO, ALKBH5). Kaplan-Meier diagrams were used to explore the correlation between m6A-related genes and colorectal cancer prognosis. The correlations between m6A-related genes and clinical parameters and immune-related indicators were explored by Spearman correlation analysis. And finally, the expression patterns of five key genes (RBMX, FMR1, IGF2BP1, LRPPRC and YTHDC2) were detected by qPCR in CRC specimens. RESULTS: In CRC, the expressions of m6A-related genes were significantly different between CRC and normal control except METTL14, YTHDF2, YTHDF3. Some of CRC patients (178 in 536) have a m6A-related genes mutation. ZC3H13 has highest mutation frequency of all m6A-related genes. M6A-related genes mainly enrich in regulation of mRNA metabolic process pathway. Patients with high expressions of FMR1, LRPPRC, METTL14, RBMX, YTHDC2, YTHDF2, YTHDF3 have poor prognosis in CRC. There was a significant correlation between the FMR1, LRPPRC, RBMX, YTHDC2, IGF2BP1 expression and the clinical characteristics of CRC. In addition, these genes are significantly associated with immune-related indicators. According to the expression patterns of FMR1, LRPPRC, RBMX, YTHDC2, and IGF2BP1, patients with CRC were clustered into two groups, and their survival was significantly different. By evaluating the tumor microenvironment in two clusters using ssGSEA, expressions of immune checkpoints and GSVA enrichment analysis, we observed that the immune and stem cell index of two cluster were much different. The qPCR results showed that RBMX expression was markedly elevated in cancerous tissues than in the normal colonic tissues. CONCLUSION: Our study identified novel prognostic markers associated with immune of CRC cancer patients. Moreover, the potential mechanisms of prognostic markers in regulating the etiology of CRC cancer were investigated. These findings enrich our understanding of the relationships between m6a related genes and CRC, and may provide novel ideas in the therapy of CRC patients.

Intraoperative and postoperative short-term outcomes of intracorporeal anastomosis versus extracorporeal anastomosis in laparoscopic right hemicolectomy.

Background: Intracorporeal anastomosis (IA) is a difficult but popular anastomotic approach for reconstruction of digestive tract after laparoscopic right hemicolectomy, which may reduce some limitations faced during extracorporeal anastomosis (EA). Methods: A retrospective review of 78 patients who underwent laparoscopic right hemicolectomy by a veteran surgeon in a high-volume public tertiary hospital, including 50 patients with IA and 28 patients with EA. The intraoperative-related factors and short-term results of the two anastomotic approaches were compared. Results: There was no significant difference in demographics and clinical characteristics between the two groups (P>0.05). The intraoperative blood loss was less (P=0.010) and the incision length was shorter (P<0.001) in the intracorporeal group. Postoperative farting time was faster (P=0.005) and postoperative pain score (VAS) was lower (P<0.001) in IA group. Although the anastomotic time of IA was shorter (P<0.001), the operative time of the two groups were similar. And number of lymph nodes harvested, NLR from POD1 to POD3, postoperative hospital stay and overall hospital stay between the two groups were comparable. Except for significant difference in abdominal infection rate, the Clavien-Dindo classification and the incidence of other postoperative complications were not statistically different. Moreover, the morbidity of abdominal infection decreased with time in the IA group (P=0.040). Conclusion: IA is a reliable and feasible procedure, which has faster anastomotic time, earlier return of bowel function and superior postoperative comfort of patient, compared to EA. The postoperative complication rate of IA is similar to that of EA, and may be improved with the IA technical maturity of surgeons, which potentially contributes to the development of ERAS.

New strategy in hemorrhagic gastric cancer: A case report of complete pathological remission after neoadjuvant chemotherapy.

RATIONALE: Strategy for hemorrhagic gastric cancer should both handle the potential life-threatening situation caused by bleeding and increase probability of long-term survival. For hemorrhagic patients with locally advanced gastric cancer, surgical resection is always the preferred option for the reason that it eliminates both the tumor and risk of rebleeding. However, the long-term survival after resection is still unsatisfactory. PATIENT CONCERNS: Here, we report a patient with hemorrhagic locally advanced gastric cancer achieved pathological complete response after neoadjuvant chemotherapy. DIAGNOSES: In this case, a 58-year-old man presenting with gastrointestinal hemorrhage and hemodynamic instability was admitted to the emergency department. Gastroscopy and biopsy revealed a large hemorrhagic ulcerated carcinoma located in the antrum, gastric angle, and lower part of gastric body. Abdominal CT indicated an infiltrative ulcerated carcinoma with perigastric lymph nodes metastasis. INTERVENTIONS: After fluid resuscitation, blood transfusion, application of proton pump inhibitors, and Octreotide, the patient recovered gradually. Then, nasojejunal feeding tube was placed for enteral nutrition and tumor exclusion. Subsequently, the patient received 5 cycles of neoadjuvant S-1 plus oxaliplatin regimen, without signs of rebleeding, followed by radical distal gastrectomy. OUTCOMES: Pathological examination confirmed that the patient received pathological complete response. LESSONS: This case suggests that neoadjuvant chemotherapy is feasible in selected hemorrhagic gastric cancer patients and tumor exclusion is helpful in reducing rebleeding risk.

The analysis and validation of the prediction value of conventional and contrast-enhanced ultrasonography for BRAF mutant papillary thyroid microcarcinoma.

Background: BRAF has certain potential in distinguishing aggressive papillary thyroid microcarcinoma (PTMC). However, it is not recommended to conduct BRAF analysis for all suspicious thyroid nodules <1 cm. In order to investigate the ultrasound value indicating BRAF mutation among PTMC, which showed discrepancy in previous studies, we aimed to establish a predictive model based on conventional and contrast-enhanced ultrasonography. Methods: We consecutively and retrospectively enrolled patients with PTMC who underwent fine-needle aspiration biopsy (FNAB) at our hospital between January 2020 and January 2021. All PTMC patients received conventional and contrast-enhanced ultrasound prior to FNAB, samples gained went through cytological analysis and BRAF testing subsequently. The following conventional ultrasonography data were analyzed: maximum diameter, echogenicity, echo homogeneity, echogenic foci, location, shape, boundary, aspect ratio, and blood flow volume. Moreover, the following contrast-enhanced ultrasonography data were also analyzed: degree, homogeneity, completeness, and enhancement method. Time-intensity curves from contrast-enhanced ultrasonography were analyzed using VueBox software for different regions of interest, including the entire tumor, the area of strongest enhancement, and healthy thyroid glands. The independent risk factors for BRAF mutation in PTMC were identified using univariate and multivariate logistic regression. Their predictive value was tested through internal validation. Results: Of the 103 PTMC lesions analyzed, 72 involved BRAF mutations. Five independent ultrasonographic risk factors for BRAF mutation were identified: relative time to peak value in the area of strongest enhancement, unclear boundary, location adjacent to thyroid capsules, maximum diameter >0.5 cm, and punctate echogenic foci. A predictive model based on these factors was able to diagnose BRAF mutations in PTMC, with an area under the curve (AUC) of 0.824. During internal validation, this model showed an AUC of 0.723. Conclusions: Conventional and contrast-enhanced ultrasound characteristics, including relative time to peak value in the area of strongest enhancement, unclear boundary, location adjacent to thyroid capsules, maximum diameter >0.5 cm, and punctate echogenic foci, may be useful for predicting BRAF mutations in patients with PTMC.

Efficacy and Safety of Neoadjuvant Chemotherapy Combined with Adjuvant Chemotherapy for Locally Advanced Colon Cancer: A Propensity Score-Matching Analysis.

Background and Objectives: Increasing evidence supports the use of neoadjuvant chemotherapy (NAC) for locally advanced colon cancer (LACC). However, its effectiveness remains controversial. This study explored the safety and efficacy of NAC combined with laparoscopic radical colorectal cancer surgery and adjuvant chemotherapy (AC) for LACC. Materials and Methods: We retrospectively analyzed 444 patients diagnosed with LACC (cT4 or cT3, with ≥5 mm invasion beyond the muscularis propria) in our hospital between 2012 and 2015. Propensity score matching (PSM; 1:2) was performed to compare patients treated with NAC and those treated with adjuvant chemotherapy (AC). Results: Overall, 42 patients treated with NAC were compared with 402 patients who received only AC. After PSM, 42 patients in the NAC group were compared with 84 patients in the control group, with no significant differences in the baseline characteristics between groups. The pathological tumor sizes in the NAC group were significantly smaller than those in the AC group (3.1 ± 2.1 cm vs. 5.8 ± 2.5 cm). Patients in the NAC group had a significantly lower T stage than those in the AC group (p < 0.001). After neoadjuvant chemotherapy, a significant response was observed in four (9.6%) patients, with two (4.8%) showing a complete response. The 5-year overall survival rates (88.1% vs. 77.8%, p = 0.206) and 5-year disease-free survival rates (75.1% vs. 64.2%, p = 0.111) did not differ between the groups. However, the 5-year cumulative rate of distant recurrence was significantly lower in the NAC than in the AC group (9.6% vs. 29.9%, p = 0.022). Conclusions: NAC, combined with AC, could downstage primary tumors of LACC and seems safe and acceptable for patients with LACC, with a similar long-term survival between the two treatments.

The role of intraoperative electron radiotherapy in centrally located hepatocellular carcinomas treated with narrow-margin (<1 cm) hepatectomy: a prospective, phase 2 study.

Background: Postoperative radiotherapy (RT) is known to play an important role in the treatment of hepatocellular carcinomas (HCCs), but the specific role of intraoperative electron radiotherapy (IOERT) in HCCs remains unclear. The aim of this study was to investigate the safety and efficacy of IOERT in centrally located HCCs treated with narrow-margin (<1 cm) hepatectomy. Methods: This was a single-center, phase 2, prospective non-randomized controlled study, including 268 patients with centrally located HCCs who underwent narrow-margin hepatectomy. The patients were subsequently allocated to the IOERT group (n=59) or to the control group (n=65). The primary outcome of the study was to compare recurrence-free survival (RFS) between the IOERT group and the control group, and the secondary outcome was to compare overall survival (OS) rate between the two groups. Results: Of 268 patients enrolled, a total of 124 were included in the study: 59 in IOERT group, 65 in control group. The 1-, 2-, 3-year RFS rates were 79.3%, 62.1% and 45.8% for patients in the IOERT group, and 47.6%, 28.6%, and 22.9% for patients in the control group, respectively (P=0.025). The 1-, 2-, and 3-year OS rates were 100.0%, 94.9%, and 83.7% for patients in the IOERT group, and 92.3%, 87.5%, and 79.4% for patients in the control group, respectively (P=0.314). Subgroup analysis of MVI (+) patients revealed that RFS and OS are significantly prolonged in the IOERT subgroup as compared to the control, whereas there was no significant difference of RFS and OS between the two groups in MVI (-) patients. Conclusions: IOERT for centrally located HCCs with concurrent narrow-margin hepatectomy was feasible and safe. Statistically better RFS rate was observed in the IOERT group compared to the control group. Subgroup analysis revealed that IOERT was more beneficial for postoperative survival of HCC patients with MVI. Trial Registration: ChiCTR-TRC-12002802; www.who.int/ictrp.

The safety and efficacy of laparoscopic gastrectomy for patients with locally advanced gastric cancer following neoadjuvant chemotherapy.

Limited researches focused on the application of laparoscopic gastrectomy (LG) in locally advanced gastric cancer (LAGC) patients following neoadjuvant chemotherapy (NACT). In this study, we aimed at illustrating the surgical and survival outcome of LG in LAGC patients following NACT. We performed a retrospective study of patients with LAGC who received either LG following NACT or upfront LG at Fujian Provincial Hospital between March 2013 and October 2018. Perioperative parameters, short-term and long-term outcomes were compared. The Kaplan-Meier estimator was used to describe the survival curves, and the differences were examined by the log-rank test. In total, 76 consecutive patients were enrolled into the NACT-LG (41 patients) and LG (35 patients) group. The postoperative hospital stay was significantly longer for LG than for NACT-LG (11.0 vs. 12.0 day, P = 0.031). Significant difference was found in Grade ≥ III severe postoperative complications in two groups (0 vs. 17.1%, P = 0.001). No patient died of postoperative complications in the NACT-LG group, and one patient (1/35, 2.9%) died of postoperative complications in the LG group. A forest plot revealed that most subgroups of LG group were at great risks of postoperative complications. Compared with the LG group, the NACT-LG group had a significantly better DFS (14.4% vs. 5.7%, P = 0.0299) and better OS (34.1% vs. 8.6%, P = 0.0061) at 3 years. NACT increased the safety of LG for patients with LAGC and offer better disease-free and overall survival. For patients with LAGC, LG following NACT should be the priority treatment.

Effect of KRAS mutations and p53 expression on the postoperative prognosis of patients with colorectal cancer.

BACKGROUND: In the occurrence and development of colorectal cancer, p53 is an important regulator downstream of the MAPK signaling pathway and plays an important role in inhibiting abnormal proliferation signals generated by KRAS mutations. The purpose of this study is to explore the correlation between KRAS mutations and p53 expression and evaluate their prognosis values in colorectal cancer. METHODS: PCR technology and immunohistochemical (IHC) staining were used to detect KRAS mutation status and p53 expression level in 266 specimens of colorectal adenocarcinoma. Based on p53 expression level, these were divided into high expression and normal groups. Patients with KRAS mutations were divided into mutant and wild-type groups. The two were combined with each other to analyze the relationship between patients' clinical data and their impact on the prognosis. RESULTS: KRAS mutations were found in 38.6% of the patients and 40.8% had a high p53 expression. There was no significant difference in the overall survival rate of patients, with or without KRAS gene mutations, and p53 expression level. In the group of patients with KRAS mutations, the survival time of patients with a high p53 expression was significantly lower than that of patients with a normal p53 expression (p = 0.020, log-rank test). Multivariate analysis showed that p53 high expression is an independent risk factor for the overall survival time of patients with KRAS mutations (HR = 2.330, 95% CI = 1.041-5.216, p < 0.05). CONCLUSION: Colorectal cancer patients with KRAS mutations with a high p53 expression have a poor prognosis.

Superiority of Laparoscopic Gastrojejunostomy Combined With Multimodality Therapy for Gastric Outlet Obstruction Caused by Advanced Gastric Cancer.

BACKGROUND: Data are limited concerning the survival outcomes of patients with gastric outlet obstruction (GOO) caused by advanced gastric cancers according to laparoscopic gastrojejunostomy (LGJ) combined with multimodality therapy (MMT). Therefore, the purpose of this study was to examine the feasibility and efficacy of these therapies. METHODS: This single-centered, retrospective analysis included data of 184 patients with GOO due to advanced gastric cancer (AGC). Treatment models were: laparoscopic gastrojejunostomy combined with multimodality therapy (LGJ+MMT), endoscopic metal stent placement combined with multimodality therapy (EMSP+MMT), and multimodality therapy (MMT). RESULTS: Improved oral intake, better nutritional indices, and better response to chemotherapy were observed in the LGJ+MMT group. Subsequent gastrectomy was performed in 43 (61.4%) patients in the LGJ+MMT group, 23 (37.7%) in the EMSP+MMT group, and 11 (20.8%) in the MMT group (P<0.001). LGJ+MMT was associated with better long-term prognosis. As confirmed by propensity scores and multivariate analyses, the 3-year survival rates in the three treatment models were 31.4% with LGJ+MMT, 0% with EMSP+MMT, and 0% with MMT in conversion therapy, and 50.0% with LGJ+MMT, 33.3% with EMSP+MMT, and 23.5% with MMT in NAC. A forest plot revealed that LGJ+MMT was related to a decreased risk of death. CONCLUSIONS: LGJ combined with MMT was associated with better nutritional status, higher rates of subsequent gastrectomy, and good prognosis. LGJ combined with MMT may improve the long-term survival of patients with GOO caused by AGC.

Laparoscopic Gastrojejunostomy with Conversion Therapy in Gastric Outlet Obstruction Caused by Incurable Advanced Gastric Cancer.

PURPOSE: The benefits of laparoscopic gastrojejunostomy (LGJ) combined with conversion therapy for malignant gastric outlet obstruction (GOO) caused by incurable advanced gastric cancer (AGC) are unclear. This study aimed to examine the feasibility and efficacy of LGJ followed by enteral nutrition and conversion therapy in malignant GOO. PATIENTS AND METHODS: The clinical outcomes for 66 patients with GOO due to incurable AGC were retrospectively evaluated. The patients were classified into multimodal therapy (LGJ, enteral nutrition, and chemotherapy, n = 35) and chemotherapy alone (n = 31) groups. Conversion surgery was defined as surgery aimed at R0 resection in initially incurable tumours. RESULTS: Compared to the chemotherapy group, multimodal therapy patients had improved oral intake, more chemotherapy cycles, better nutritional indices, less sarcopenia, and improved quality of life (QOL) post-treatment. Conversion surgery was performed in 17 multimodal therapy patients, with no perioperative mortality, and R0 resection achieved in 15 patients (88.2%). The median survival time of multimodal therapy patients was 16.7 months, compared to 4.5 months for chemotherapy patients. Multimodal therapy patients with conversion surgery had significantly longer overall survival than those without surgery (44.2 vs 8.5 months, respectively, P< 0.001). Multivariate analysis identified multimodal therapy and improved or stable QOL as independent prognostic factors. CONCLUSION: Multimodal therapy was associated with better nutritional and metabolic status, a safely induced high conversion surgery rate with a high R0 resection rate, and a good prognosis. LGJ with enteral nutrition and conversion therapy may improve long-term survival in obstructive incurable AGC.

Laparoscopic gastrojejunostomy versus endoscopic stenting combined with conversion therapy for gastric outlet obstruction.

OBJECTIVE: There have been no studies comparing laparoscopic gastrojejunostomy (LGJ) and endoscopic metal stent placement (EMSP) combined with conversion therapy for gastric outlet obstruction (GOO) due to incurable advanced gastric cancer (GC). Therefore, the present study examined the short- and long-term outcomes and compared their therapeutic effects. METHODS: We retrospectively evaluated the clinical outcomes of 94 patients with GOO due to incurable advanced GC. Patients were assigned to the LGJ (n = 48) or EMSP (n = 46) groups. Multivariate analyses were conducted to identify the factors associated with overall survival. A propensity score-matched analysis was performed to avoid confounding bias. RESULTS: Compared to the EMSP group, patients in the LGJ group had fewer postoperative complications, better nutritional and inflammatory status, and a lower positive rate of tumor markers (p < .05). Conversion surgery was performed in 23 and 11 patients in the LGJ and EMSP groups, respectively. The median survival time (MST) in the LGJ group was 13.2 months, compared to 6.8 months for the EMSP group (p < .0001). Propensity score analyses confirmed this result. The MST of patients receiving conversion surgery was significantly better than that of patients without surgery in both the LGJ and EMSP groups (LGJ group: 38.3 months versus 7.6 months; EMSP group: 19.2 months versus 5.3 months, respectively, p < .0001). Multivariate analysis identified treatment selection and conversion surgery as independent prognostic factors for overall survival. CONCLUSION: LGJ is an effective and feasible alternative to conversion therapy in terms of short- and long-term outcomes.

Suppressing the KIF20A/NUAK1/Nrf2/GPX4 signaling pathway induces ferroptosis and enhances the sensitivity of colorectal cancer to oxaliplatin.

Oxaliplatin resistance can develop in colorectal cancer (CRC), which may involve inhibition of ferroptosis, although further research is needed to understand this potential mechanism. We evaluated CRC cells with acquired oxaliplatin resistance (HCT116-Or) or congenital resistance (H716) to determine whether a ferroptosis inducer (RSL3) or inhibitor (liproxstatin-1) could modulate the effects of oxaliplatin. The results suggested that induction of ferroptosis could significantly reverse the oxaliplatin resistance of the CRC cells. Bioinformatic and cytobiological searches also revealed that KIF20A was highly expressed in the oxaliplatin-resistant cell lines and was strongly correlated with survival among CRC patients. Silencing KIF20A enhanced cellular sensitivity to oxaliplatin both in vivo and in vitro, and silencing KIF20A also suppressed NUAK1 activation, while a NUAK1 agonist (ETC-1002) could reverse the oxaliplatin sensitivity of KIF20A-silenced cells. Moreover, silencing NUAK1 up-regulated the expression of PP1ß, down-regulated the phosphorylation of downstream GSK3ßSer9, suppressed the nuclear import of Nrf2, inhibited the expression of a ferroptosis key negative regulatory protein (GPX4), and blocked cellular resistance. Applying a Nrf2 agonist (oltipraz) also reversed the oxaliplatin sensitivity of NUAK1-silenced cells. Therefore, cellular ferroptosis may be inhibited via the KIF20A/NUAK1/PP1ß/GPX4 pathway in CRC cells, which may underly the resistance of CRC to oxaliplatin.

Surgical outcomes of hand-assisted laparoscopic liver resection vs. open liver resection: A retrospective propensity score-matched cohort study.

OBJECTIVE: Hand-assisted laparoscopic liver resection has the advantages of open and laparoscopic surgeries. There is still lack of comparison of surgical outcomes between hand-assistied laparoscopic liver resection (HALLR) and open liver resection (OLR). This study compared the surgical outcomes of the two approaches between well-matched patient cohorts. METHODS: Patients who received liver resection during January 2014 and October 2017 in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College were included in this retrospective study. Propensity score matching (PSM) was performed to reduce selection bias between the two groups. Operation and short-term surgical outcomes were compared between the well matched groups. RESULTS: During this period, 232 patients with a median age of 55.1 years old received OLR, while 49 patients with a median age of 54.7 years old received HALLR. Compared with HALLR group, OLR group has a higher proportion in male patients (190/232, 81.9% vs. 34/49, 69.4%, P=0.048) and lower albumin (43.2±4.5 vs. 44.8±3.7, P=0.020). After PSM, 49 patients from each group were included in the following analysis. Two groups were well balanced in their baseline characteristics, liver functions, preoperative treatments, abdominal surgery history, and surgical difficulty. None perioperative mortality was observed in both groups. Operation time and postoperative complications were similar in two groups (P=0.935, P=0.056). The HALLR group showed less bleeding amount (177.8±217.1 mL vs. 283.1±225.0 mL, P=0.003) and shorter postoperative stay period (6.9±2.2 d vs. 9.0±3.5 d, P=0.001). CONCLUSIONS: We demonstrated that hand-assisted laparoscopic surgery is feasible and safe for liver resection, including some difficult cases. HALLR can provide better bleeding control and faster recovery after surgery.

High Frame Rate Contrast-Enhanced Ultrasound Imaging for Slow Lymphatic Flow: Influence of Ultrasound Pressure and Flow Rate on Bubble Disruption and Image Persistence.

Contrast-enhanced ultrasound (CEUS) utilising microbubbles shows great potential for visualising lymphatic vessels and identifying sentinel lymph nodes (SLNs) which are valuable for axillary staging in breast cancer patients. However, current CEUS imaging techniques have limitations that affect the accurate visualisation and tracking of lymphatic vessels and SLN. (i) Tissue artefacts and bubble disruption can reduce the image contrast. (ii) Limited spatial and temporal resolution diminishes the amount of information that can be captured by CEUS. (iii) The slow lymph flow makes Doppler-based approaches less effective. This work evaluates on a lymphatic vessel phantom the use of high frame rate (HFR) CEUS for the detection of lymphatic vessels where flow is slow. Specifically, the work particularly investigates the impact of key factors in lymphatic imaging, including ultrasound pressure and flow velocity as well as probe motion during vessel tracking, on bubble disruption and image contrast. Experiments were also conducted to apply HFR CEUS imaging on vasculature in a rabbit popliteal lymph node (LN). Our results show that (i) HFR imaging and singular value decomposition (SVD) filtering can significantly reduce tissue artefacts in the phantom at high clinical frequencies; (ii) the slow flow rate within the phantom makes image contrast and signal persistence more susceptible to changes in ultrasound amplitude or mechanical index (MI), and an MI value can be chosen to reach a compromise between images contrast and bubble disruption under slow flow condition; (iii) probe motion significantly decreases image contrast of the vessel, which can be improved by applying motion correction before SVD filtering; (iv) the optical observation of the impact of ultrasound pressure on HFR CEUS further confirms the importance of optimising ultrasound amplitude and (v) vessels inside rabbit LN with blood flow less than 3 mm/s are clearly visualised.

Quantification of Vaporised Targeted Nanodroplets Using High-Frame-Rate Ultrasound and Optics.

Molecular targeted nanodroplets that can extravasate beyond the vascular space have great potential to improve tumor detection and characterisation. High-frame-rate ultrasound, on the other hand, is an emerging tool for imaging at a frame rate one to two orders of magnitude higher than those of existing ultrasound systems. In this study, we used high-frame-rate ultrasound combined with optics to study the acoustic response and size distribution of folate receptor (FR)-targeted versus non-targeted (NT)-nanodroplets in vitro with MDA-MB-231 breast cancer cells immediately after ultrasound activation. A flow velocity mapping technique, Stokes' theory and optical microscopy were used to estimate the size of both floating and attached vaporised nanodroplets immediately after activation. The floating vaporised nanodroplets were on average more than seven times larger than vaporised nanodroplets attached to the cells. The results also indicated that the acoustic signal of vaporised FR-targeted-nanodroplets persisted after activation, with 70% of the acoustic signals still present 1 s after activation, compared with the vaporised NT-nanodroplets, for which only 40% of the acoustic signal remained. The optical microscopic images revealed on average six times more vaporised FR-targeted-nanodroplets generated with a wider range of diameters (from 4 to 68 µm) that were still attached to the cells, compared with vaporised NT-nanodroplets (from 1 to 7 µm) with non-specific binding after activation. The mean size of attached vaporised FR-targeted-nanodroplets was on average about threefold larger than that of attached vaporised NT-nanodroplets. Taking advantage of high-frame-rate contrast-enhanced ultrasound and optical microscopy, this study offers an improved understanding of the vaporisation of the targeted nanodroplets in terms of their size and acoustic response in comparison with NT-nanodroplets. Such understanding would help in the design of optimised methodology for imaging and therapeutic applications.

High Beclin-1 and ARID1A expression corelates with poor survival and high recurrence in intrahepatic cholangiocarcinoma: a histopathological retrospective study.

BACKGROUND: Although surgical resection provides a cure for patients with intrahepatic cholangiocarcinoma (ICC), the risk of mortality and recurrence remains high. Several biomarkers are reported to be associated with the prognosis of ICC, including Beclin-1, ARID1A, carbonic anhydrase IX (CA9) and isocitrate dehydrogenase 1 (IDH1), but results are inconsistent. Therefore, a histopathological retrospective study was performed to simultaneously investigate the relationship of these four potential biomarkers with clinicopathological parameters and their prognostic values in patients with ICC. METHODS: A total of 113 patients with ICC were enrolled from Cancer Hospital of Chinese Academy of Medical Sciences between January 1999 and June 2015. The expression of Beclin-1, ARID1A, IDH1 and CA9 were determined by immunohistochemical staining. The prognostic values of the four biomarkers were analyzed by Cox regression and the Kaplan-Meier method. RESULTS: Beclin-1, ARID1A, CA9 and IDH1 were highly expressed in ICC tumor tissues. Higher mortality was positively associated with Beclin-1 expression (HR = 2.39, 95% CI = 1.09-5.24) and higher recurrence was positively associated with ARID1A expression (HR = 1.71, 95% CI = 1.06-2.78). Neither CA9 nor IDH1 expression was significantly associated with mortality or disease recurrence. Kaplan-Meier survival curves showed that ICC patients with higher Beclin-1 and ARID1A expression had a lower survival rate and a worse recurrence rate than patients with low Beclin-1 and ARID1A expression (p < 0.05). CONCLUSIONS: High Beclin-1 and ARIDIA expression are strongly associated with poor prognosis in ICC patients, and thus Beclin-1 and ARID1A should be simultaneously considered as potential prognostic biomarkers for ICC patients.

Optimal postoperative adjuvant treatment strategy for HBV-related hepatocellular carcinoma with microvascular invasion: a propensity score analysis.

BACKGROUND: Microvascular invasion (MVI) is the most important risk factor associated with early postoperative recurrence in patients with hepatocellular carcinoma (HCC). However, the efficacy of postoperative adjuvant treatment for preventing recurrence in HCC patients with MVI has not been assessed. This study investigated the efficacy of postoperative adjuvant radiotherapy (RT) and transcatheter arterial chemoembolization (TACE) in HCC patients with MVI. MATERIALS AND METHODS: From July 2008 to December 2016, 117 hepatitis B virus (HBV)-related HCC patients with MVI were retrospectively divided into two groups based on postoperative adjuvant treatments. Propensity score matching (PSM) was performed to adjust for significant differences in baseline characteristics. Relapse-free survival (RFS) and overall survival (OS) of the two groups were analyzed before and after PSM. RESULTS: Of all patients, the RT group had significantly smaller tumor size and milder MVI classification. PSM analysis created 46 pairs of patients. After matching, the two groups of patients were similar in baseline characteristics. Multivariate analysis indicated that tumor size, MVI classification, and postoperative treatment strategies were independently associated with RFS; tumor size and MVI classification were independently associated with OS. Similar multivariate analysis results were demonstrated after matching propensity score. Survival analysis revealed that the estimated median RFS and OS of patients with RT and TACE were 25.74±8.12 vs 9.18±1.67 months (P=0.003) and 60.69±7.36 vs 36.53±5.34 months (P=0.262), respectively. The RT group had significantly longer RFS than the TACE group. CONCLUSION: Postoperative adjuvant RT offers better RFS for HCC patients with MVI than TACE.

Nomogram to Assist in Surgical Plan for Hepatocellular Carcinoma: a Prediction Model for Microvascular Invasion.

BACKGROUND: Microvascular invasion (MVI) relates to poor survival in hepatocellular carcinoma (HCC) patients. In this study, we aim at developing a nomogram for MVI prediction and potential assistance in surgical planning. METHODS: A total of 357 patients were assigned to training (n = 257) and validation (n = 100) cohort. Univariate and multivariate analyses were used to reveal preoperative predictors for MVI. A nomogram incorporating independent predictors was constructed and validated. Disease-free survival was compared between patients, and the potential of the predicted MVI in making surgical procedure was also explored. RESULTS: Pathological examination confirmed MVI in 140 (39.2%) patients. Imaging features including larger tumor, intra-tumoral artery, tumor type, and higher serum AFP independently correlated with MVI. The nomogram showed desirable performance with an AUROC of 0.803 (95% CI, 0.746-0.860) and 0.814 (95% CI, 0.720-0.908) in the training and validation cohorts, respectively. Good calibration were also revealed by calibration curve in both cohorts. The decision curve analysis indicated that the prediction nomogram was of promising usefulness in clinical work. In addition, survival analysis revealed that patients with positive-predicted MVI suffered a higher risk of early recurrence (P < 0.01). There was no difference in disease-free survival between anatomic or non-anatomic resection in large HCC or small HCC without nomogram-predicted MVI. However, anatomic resection improved disease-free survival in small HCC with nomogram-predicted MVI. CONCLUSIONS: The nomogram obtained desirable results in predicting MVI. Patients with predicted MVI were associated with early recurrence and anatomic resection was recommended for small HCC patients with predicted MVI.