Comparison of Callisphere Drug-Eluting Beads Transarterial Chemoembolization and Conventional Transarterial Chemoembolization for the treatment of Hepatocellular Carcinoma.

Objective: To compare the efficacy of CalliSphere drug-eluting beads (DEBs) and conventional (c) transarterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC). Methods: We retrospectively reviewed the clinical data of 125 patients with HCC who had received treatment in Affiliated Hospital of North Sichuan Medical College from January 2018 to February 2019. Sixty-one patients underwent DEB-TACE (observation group) and 64 patients underwent cTACE (control group). The clinical efficacies, overall survivals, and incidence of postoperative adverse reactions between the two groups were compared. Results: The objective response rate in the observation group (85.25%) was higher than that in the control group (70.31%; P<0.05). The disease control in the observation group (96.72%) was higher than that in the control group (85.94%; P<0.05). The median survival time of the observation group (24.85 months) was significantly higher than that in the control group (18.18 months; P<0.05). The incidence of adverse reactions in the observation group (4.92%) was lower than that in the control group (17.19%, P<0.05). Conclusions: In the treatment of HCC, Callisphere DEB-TACE has better efficacy and longer patient survival with fewer adverse reactions compared to cTACE.

Survival analysis of laparoscopic surgery and open surgery for hilar cholangiocarcinoma: a retrospective cohort study.

BACKGROUND/PURPOSE: This study compared the clinical efficacy and safety of laparoscopic versus open resection for hilar cholangiocarcinoma (HCCA) and analyzed potential prognostic factors. METHODS: The study included patients who underwent HCCA resection at our center from March 2012 to February 2022. Perioperative complications and postoperative prognosis were compared between the laparoscopic surgery (LS) and open surgery (OS) groups. RESULTS: After screening 313 HCCA patients, 68 patients were eligible for the study in the LS group (n = 40) and OS group (n = 28). Kaplan-Meier survival curve analysis revealed that overall survival > 2 years and 3-year disease-free survival (DFS) were more common in the LS than OS group, but the rate of 2-year DFS was lower in the LS group than OS group. Cox multivariate regression analysis revealed age (< 65 years), radical resection, and postoperative adjuvant therapy were associated with reduced risk of death (hazard ratio [HR] = 0.380, 95% confidence interval [CI] = 0.150-0.940, P = 0.036; HR = 0.080, 95% CI = 0.010-0.710, P = 0.024 and HR = 0.380, 95% CI = 0.150-0.960, P = 0.040), whereas preoperative biliary drainage was an independent factor associated with increased risk of death (HR = 2.810, 95% CI = 1.130-6.950, P = 0.026). Perineuronal invasion was identified as an independent risk factor affecting DFS (HR = 5.180, 95% CI = 1.170-22.960, P = 0.030). CONCLUSIONS: Compared with OS, laparoscopic HCCA resection does not significantly differ in terms of clinical efficacy. Age (<65 years), radical resection, and postoperative adjuvant therapy reduce the risk of death, and preoperative biliary drainage increases the risk of death.

Short-Term Outcomes Following Laparoscopic vs Open Pancreaticoduodenectomy in Patients With Pancreatic Ductal Adenocarcinoma: A Randomized Clinical Trial.

Importance: The safety and efficacy of laparoscopic pancreaticoduodenectomy for pancreatic ductal adenocarcinoma remain controversial. Objective: To compare laparoscopic and open pancreaticoduodenectomy performed by experienced surgeons in patients with pancreatic ductal adenocarcinoma. Design, Setting, and Participants: This was a noninferiority, open-label randomized clinical trial between September 20, 2019 and March 20, 2022, at 10 hospitals in China. A total of 412 adult patients were assessed for eligibility; 200 patients with histologically confirmed or clinically diagnosed pancreatic ductal adenocarcinoma who were eligible to undergo pancreaticoduodenectomy were enrolled. Study recruitment is complete, and follow-up is ongoing. This article reports prespecified early safety results from the trial. Interventions: Participants were randomized in a 1:1 ratio to undergo either laparoscopic or open pancreaticoduodenectomy, to be performed by experienced surgeons who had already performed at least 104 laparoscopic pancreaticoduodenectomy operations. Main Outcomes and Measures: The primary end point is 5-year overall survival, but the data for this end point are not yet mature; thus, secondary short-term outcomes, including operative findings, complications, mortality, and oncological results are reported here. The outcomes were analyzed according to a modified intention-to-treat and per-protocol principle. Results: Among 412 patients for eligibility, 200 patients were enrolled and randomly assigned 1:1 to have laparoscopic pancreaticoduodenectomy or open pancreaticoduodenectomy. The mean (SD) age was 61.3 (9.3) years, and 78 participants (39%) were female. Laparoscopic procedures had longer operative times (median [IQR], 330.0 [287.5-405.0] minutes vs 297.0 [245.0-340.0] minutes; P < .001). Patients in the laparoscopic group lost less blood than those in the open group (median [IQR], 145.0 [100.0-200.0] mL vs 200.0 [100.0-425.0] mL; P = .02). Ninety-day mortality occurred in 2 of 100 patients in the laparoscopic group and 0 of 100 patients in the open group. There was no difference in the rates of complications of the Clavien-Dindo grades III-IV (n = 17 [17.0%] vs n = 23 [23.0%]; P = .29), comprehensive complication index (median [IQR], 0.0 [0.0-22.6] vs 8.7 [0.0-26.2]; P = .79) or median (IQR) postoperative length of stay (14.0 [11.0-17.0] days vs 14.0 [12.0-18.5] days; P = .37) between the 2 groups. Conclusions and Relevance: Laparoscopic pancreaticoduodenectomy performed by experienced surgeons in high-volume specialized institutions resulted in similar short-term outcomes compared with open pancreaticoduodenectomy among patients with pancreatic ductal adenocarcinoma. Trial Registration: ClinicalTrials.gov Identifier: NCT03785743.

Advances in nanomedicines for lymphatic imaging and therapy.

Lymph nodes play a pivotal role in tumor progression as key components of the lymphatic system. However, the unique physiological structure of lymph nodes has traditionally constrained the drug delivery efficiency. Excitingly, nanomedicines have shown tremendous advantages in lymph node-specific delivery, enabling distinct recognition and diagnosis of lymph nodes, and hence laying the foundation for efficient tumor therapies. In this review, we comprehensively discuss the key factors affecting the specific enrichment of nanomedicines in lymph nodes, and systematically summarize nanomedicines for precise lymph node drug delivery and therapeutic application, including the lymphatic diagnosis and treatment nanodrugs and lymph node specific imaging and identification system. Notably, we delve into the critical challenges and considerations currently facing lymphatic nanomedicines, and futher propose effective strategies to address these issues. This review encapsulates recent findings, clinical applications, and future prospects for designing effective nanocarriers for lymphatic system targeting, with potential implications for improving cancer treatment strategies.

Expression and prognostic value of PRDX family in colon adenocarcinoma by integrating comprehensive analysis and in vitro and in vivo validation.

Background: The peroxiredoxin family, a crucial regulator of redox reactions, is strongly associated with various tumorigenesis. However, the role of peroxiredoxin4 (PRDX4) in colon adenocarcinoma (COAD) remains poorly understood. Methods: Multicenter databases, including GEPIA, HPA, UALCAN, cBioPortal, cancerSEA, STRING, CCLE, and LinkedOmics, comprehensively analyzed transcriptional expression, prognostic value, genetic alterations, signaling pathways, and associated genes of the PRDXs in COAD patients. Colony formation, transwell, flow cytometry, sphere formation, and xenograft assays were performed to validate further in vitro and in vivo. Results: Members of the PRDX family were differentially expressed in COAD, with each member showing varying degrees of genetic alterations. Intriguingly, only PRDX4 significantly correlated with COAD prognosis and stage. The single-cell sequencing suggested that PRDX4 is positively correlated with proliferation, apoptosis, and invasion, whereas negatively correlated with stemness. Moreover, PRDX4 involved in a series of critical biological processes, such as cell growth. Furthermore, in vivo and in vitro analyses indicated that knocking down PRDX4 inhibits the proliferation and invasion of HCT116 cells while promoting apoptosis and stemness. Conclusions: We identified PRDX4 expression as a novel potential prognostic marker in COAD.

An exploratory human study of superstable homogeneous lipiodol-indocyanine green formulation for precise surgical navigation in liver cancer.

The clinical applications of transcatheter arterial embolization (TAE) conversion therapy combined with hepatectomy have been severely restricted by ill-defined tumoral boundaries and miniscule hidden lesions. Fluorescent surgical navigation is a promising method for overcoming these barriers. However, sufficient delivery of the fluorescent probe into the tumor region after long-term TAE is challenging due to blockade of the tumor-supplying artery. Here, a super-stable homogeneous intermix formulating technology (SHIFT) to physically mix lipiodol and indocyanine green (ICG) formulation (SHIFT and ICG) for fluorescent surgical navigation after long-term TAE conversion therapy is provided. Through the retrospective study of 45 clinical liver cancer patients, it is found that SHIFT and ICG formulation have excellent tumor deposition effect and safety. During surgical resection after long-term TAE conversion therapy, SHIFT and ICG could clearly identify in real time the full tumor regions and boundaries and had a high signal-to-normal tissues ratio-even the indistinguishable satellite lesions could be identified with a strong fluorescence intensity. Meanwhile, SHIFT and ICG could improve operative, anesthetic, and postoperative variables associated with postoperative complications. This simple and effective SHIFT could provide precise fluorescent navigation for surgical resection following long-term embolization therapy in clinical practice and has great potential for a translational pipeline.

Targeting SHP2 reverses BRAF inhibitor tolerance in anaplastic thyroid carcinoma.

PURPOSE: To explore the possibility of a combination of dabrafenib and SHP2 inhibitor in the treatment of anaplastic thyroid carcinoma and to provide a new therapeutic strategy for the treatment of anaplastic thyroid cancer. PATIENTS AND METHODS: Firstly, a drug resistance model was established, and the expression levels of related RTK were detected by qPCR. Western blot was used to detect the protein expression levels of Akt and MAPK signaling pathways in the control group, single-drug group and two-drug combination group. The gene silencing of SHP2 was achieved by transfection of siRNA and verified by Western blot. CCK8 kit and clone formation assay were used to detect cell proliferation activity. In vivo model of mutant thyroid cancer cells was established by subcutaneous injection of mice and then divided into four groups. Tumor diameter was measured every two days. Immunohistochemistry was used to evaluate the expression of p-ERK, p-AKT and Ki67 in mouse tumors. RESULTS: In this study, dabrafenib-resistant ATC cells were first constructed, and the response of RTKs in drug-resistant cells was upregulated to activate Akt and MER/ERK pathways. The activation of Akt and MEK/ERK pathways in the combination group was significantly inhibited, and the proliferation ability of tumor cells was significantly reduced compared with Dabrafenib, SHP099 group and DMSO group. To verify that SHP099 was not off-target, we also silenced SHP2 expression by transfection with siRNA and obtained the same results. Finally, by building a mouse drug resistance model, we confirmed that dabrafenib and SHP099 can also play a powerful anti-cancer effect in vivo. CONCLUSION: The SHP2 inhibitor SHP099 can effectively reverse the drug resistance of dabrafenib through inhibiting the reactivated RAS signaling pathway in anaplastic thyroid cancer.The combination of dabrafenib with SHP2 inhibitor has shown significant tumor suppressive effects for dabrafenib-resistant cells and it may be a new therapeutic strategy with longer lasting therapeutic benefits.

Superstable homogeneous lipiodol-ICG formulation: initial feasibility and first-in-human clinical application for ruptured hepatocellular carcinoma.

The most common treatment of spontaneous tumor rupture hemorrhage (STRH) is transcatheter arterial embolization (TAE) followed by liver resection, and surgical navigation using near-infrared fluorescence is effective method for detecting hidden lesions and ill-defined tumor boundaries. However, due to the blockage of the tumor-supplying artery after effective TAE treatment, it is difficult to deliver sufficient fluorescent probes to the tumor region. In this study, we report on the successful application of superstable homogeneous intermixed formulation technology (SHIFT) in precise conversion hepatectomy for ruptured hepatocellular carcinoma (HCC). A homogeneous lipiodol-ICG formulation obtained by SHIFT (SHIFT-ICG) was developed for clinical practice for STRH. A ruptured HCC patient received the combined protocol for embolization and fluorescence surgical navigation and exhibited excellent hemostatic effect. Lipiodol and ICG were both effectively deposited in the primary lesion, including a small metastatic lesion. In follow-up laparoscopic hepatectomy, SHIFT-ICG could clearly and precisely image the full tumor regions and boundaries in real time, and even indistinguishable satellite lesions still expressed a remarkable fluorescence intensity. In conclusion, the simple and green SHIFT-ICG formulation can be effectively used in emergency embolization hemostasis and later precise fluorescence navigation hepatectomy in patients with ruptured HCC bleeding and has high clinical application value.

Occurrence-regression-recurrence of hepatocellular carcinoma without any intervention: A case report.

Background: Spontaneous regression of primary liver cancer is a rare event, and currently the exact pathogenesis of spontaneous tumor regression remains unclear. Case description: Clinical information was collected from a patient with spontaneous regression of liver cancer at our center. The patient was a 41-year-old male. He was admitted to the hospital on 3 May 2019, due to aversion to fatty or greasy food, anorexia, loss of appetite, and abdominal distension. Laboratory examination results included hepatitis B surface antigen positivity, hepatitis B e antigen positivity, and hepatitis B core antibody positivity and tumor marker levels of alpha-fetoprotein 142,938.20 µg/L, abnormal prothrombin 4,599.91 mAU/ml, and carbohydrate antigen 19-9 82.05 U/ml. Upper abdominal enhanced computed tomography indicated right hepatocellular carcinoma with portal vein tumor thrombus formation. The patient declined any treatment. The tumor in the right lobe of the liver completely regressed after 1 year, and the patient is still undergoing follow-up. Conclusions: We encountered a hepatocellular carcinoma patient who underwent spontaneous regression, but the exact pathogenesis remains unknown. Understanding the pathogenesis of spontaneous regression of hepatocellular carcinoma has the potential to contribute to the development of an effective treatment for hepatocellular carcinoma.

A clinical trial of super-stable homogeneous lipiodol-nanoICG formulation-guided precise fluorescent laparoscopic hepatocellular carcinoma resection.

BACKGROUND: Applying traditional fluorescence navigation technologies in hepatocellular carcinoma is severely restricted by high false-positive rates, variable tumor differentiation, and unstable fluorescence performance. RESULTS: In this study, a green, economical and safe nanomedicine formulation technology was developed to construct carrier-free indocyanine green nanoparticles (nanoICG) with a small uniform size and better fluorescent properties without any molecular structure changes compared to the ICG molecule. Subsequently, nanoICG dispersed into lipiodol via a super-stable homogeneous intermixed formulation technology (SHIFT&nanoICG) for transhepatic arterial embolization combined with fluorescent laparoscopic hepatectomy to eliminate the existing shortcomings. A 52-year-old liver cancer patient was recruited for the clinical trial of SHIFT&nanoICG. We demonstrate that SHIFT&nanoICG could accurately identify and mark the lesion with excellent stability, embolism, optical imaging performance, and higher tumor-to-normal tissue ratio, especially in the detection of the microsatellite lesions (0.4 × 0.3 cm), which could not be detected by preoperative imaging, to realize a complete resection of hepatocellular carcinoma under fluorescence laparoscopy in a shorter period (within 2 h) and with less intraoperative blood loss (50 mL). CONCLUSIONS: This simple and effective strategy integrates the diagnosis and treatment of hepatocellular carcinoma, and thus, it has great potential in various clinical applications.

A Consensus Meeting on Expert Recommendations on Operating Specifications for Laparoscopic Radical Resection of Hilar Cholangiocarcinoma.

Background: With advances in techniques and technologies, laparoscopic radical resection of hilar cholangiocarcinoma (HCCA) has gradually been carried out in major medical centers in China. Its feasibility and safety have been accepted by a group of Chinese surgical experts. Methods: To standardize perioperative management of HCCA by using laparoscopic resectional approach, to ensure safety of the patient with standardized management, improve prognosis of the patient, and enable proper application and refinement of this surgical approach, the expert group on specifications for laparoscopic radical resection of HCCA in China organized a consensus meeting. Results: Laparoscopic radical resection of HCCA is difficult and associated with high risks. Appropriate patients should be carefully selected and this surgical approach should be promoted gradually. The experts met and arrived at 16 recommendations on perioperative management of HCCA by using laparoscopic surgery. There were three recommendations on preoperative diagnosis and evaluation; one recommendation on surgical principles of treatment; one recommendation on indications and contraindications; one recommendation on credentialing, staffing, and equipment; nine recommendations on laparoscopic techniques in different stages of operation; and one recommendation on indications for conversion to open surgery. Conclusion: Laparoscopic surgery for HCCA is still in the early phase of development. This consensus provides a clinical reference with the aim to promote and to facilitate its further development.

Bioinformatic Analysis of Immune Significance of RYR2 Mutation in Breast Cancer.

BACKGROUND: Currently, immunotherapy is widely used for breast cancer (BC) patients, and tumor mutation burden (TMB) is regarded as a valuable independent predictor of response to immunotherapy. However, specific gene mutations and their relationship with TMB and tumor-infiltrating immune cells in BC are not fully understood. METHODS: Comprehensive bioinformatic analyses were performed using data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. Survival curves were analyzed via Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses were used for prognosis analysis. Gene set enrichment analysis (GSEA) was performed to explore regulatory mechanisms and functions. The CIBERSORT algorithm was used to calculate the tumor-infiltrating immune cell fractions. RESULTS: We analyzed somatic mutation data of BC from TCGA and ICGC datasets and found that 19 frequently mutated genes were reported in both cohorts, namely, SPTA1, TTN, MUC17, MAP3K1, CDH1, FAT3, SYNE1, FLG, HMCN1, RYR2 (ryanodine receptor 2), GATA3, MUC4, PIK3CA, KMT2C, TP53, PTEN, ZFHX4, MUC16, and USH2A. Among them, we observed that RYR2 mutation was significantly associated with higher TMB and better clinical prognosis. Moreover, GSEA revealed that RYR2 mutation-enriched signaling pathways were related to immune-associated pathways. Furthermore, based on the CIBERSORT algorithm, we found that RYR2 mutation enhanced the antitumor immune response by enriching CD8+ T cells, activated memory CD4+ T cells, and M1 macrophages. CONCLUSION: RYR2 is frequently mutated in BC, and its mutation is related to increased TMB and promotes antitumor immunity; thus, RYR2 may serve as a valuable biomarker to predict the immune response.

Precision Interventional Brachytherapy: A Promising Strategy Toward Treatment of Malignant Tumors.

Precision interventional brachytherapy is a radiotherapy technique that combines radiation therapy medicine with computer network technology, physics, etc. It can solve the limitations of conventional brachytherapy. Radioactive drugs and their carriers change with each passing day, and major research institutions and enterprises worldwide have conducted extensive research on them. In addition, the capabilities of interventional robotic systems are also rapidly developing to meet clinical needs for the precise delivery of radiopharmaceuticals in interventional radiotherapy. This study reviews the main radiopharmaceuticals, drug carriers, dispensing and fixation technologies, and interventional robotic precision delivery systems used in precision brachytherapy of malignant tumors. We then discuss the current needs in the field and future development prospects in high-precision interventional brachytherapy.

Expression and prognostic significance of CBX2 in colorectal cancer: database mining for CBX family members in malignancies and vitro analyses.

BACKGROUND: The Chromobox (CBX) domain protein family, a core component of polycomb repressive complexes 1, is involved in transcriptional repression, cell differentiation, and program development by binding to methylated histone tails. Each CBX family member plays a distinct role in various biological processes through their own specific chromatin domains, due to differences in conserved sequences of the CBX proteins. It has been demonstrated that colorectal cancer (CRC) is a multiple-step biological evolutionary process, whereas the roles of the CBX family in CRC remain largely unclear. METHODS: In the present study, the expression and prognostic significance of the CBX family in CRC were systematically analyzed through a series of online databases, including Cancer Cell Line Encyclopedia (CCLE), Oncomine, Human Protein Atlas (HPA), and Gene Expression Profiling Interactive Analysis (GEPIA). For in vitro verification, we performed cell cloning, flow cytometry and transwell experiments to verify the proliferation and invasion ability of CRC cells after knocking down CBX2. RESULTS: Most CBX proteins were found to be highly expressed in CRC, but only the elevated expression of CBX2 could be associated with poor prognosis in patients with CRC. Further examination of the role of CBX2 in CRC was performed through several in vitro experiments. CBX2 was overexpressed in CRC cell lines via the CCLE database and the results were verified by RT-qPCR. Moreover, the knockdown of CBX2 significantly suppressed CRC cell proliferation and invasion. Furthermore, the downregulation of CBX2 was found to promote CRC cell apoptosis. CONCLUSIONS: Based on these findings, CBX2 may function as an oncogene and potential prognostic biomarker. Thus, the association between the abnormal expression of CBX2 and the initiation of CRC deserves further exploration.

CDC20 promotes the progression of hepatocellular carcinoma by regulating epithelial­mesenchymal transition.

Hepatocellular carcinoma (HCC) is a type of primary liver cancer, which is associated with high mortality. HCC is one of the most common malignant tumors worldwide. Cell division cycle 20 (CDC20) has been reported to be associated with the development of various malignant tumors and epithelial­mesenchymal transition (EMT) has been reported to be involved in the malignant metastasis of HCC. Therefore, the present study hypothesized that CDC20 may participate in the malignant biological behavior of HCC via EMT. The present study analyzed the expression levels of CDC20 in HCC and the association between CDC20 and poor prognosis. Furthermore, the effects of CDC20 on the proliferation, invasion and migration of HCC cells were examined using proliferation, migration and invasion assays. Finally, alterations in EMT were analyzed. The results revealed that CDC20 was highly expressed in HCC and HCC cell lines (P<0.05), and its high expression level was significantly associated with poor prognosis in patients with HCC (P<0.05). CDC20 silencing inhibited the proliferation, migration and invasion of HCC cells. Furthermore, CDC20 silencing increased the expression levels of E­cadherin, and decreased the expression levels of N­cadherin, vimentin and Ki­67. In conclusion, the present study reported that CDC20 may be a novel therapeutic target in HCC and CDC20 could promote the progression of HCC by regulating EMT.

The critical role of peroxiredoxin-2 in colon cancer stem cells.

Colon cancer stem cells (CCSCs) play an important role in facilitating colon cancer occurrence, metastasis and drug resistance. The results of our previous studies confirmed that the well-studied antioxidant gene peroxiredoxin-2 (PRDX2) promotes colon cancer progression. However, the underlying function and mechanisms associated with PRDX2 remodeling in the context of CCSCs have remained poorly studied. In our present study, we demonstrated that PRDX2 is highly expressed in CD133/CD44-positive colon cancer tissues and spheroid CD133+CD44+ CCSCs. PRDX2 overexpression was shown to be closely correlated with CD133+CD44+ CCSCs in colon cancer. Furthermore, PRDX2 depletion markedly suppressed CD133+CD44+ CCSC stemness maintenance, tumor initiation, migration and invasion and liver metastasis. Furthermore, the expression of various EMT markers and Wnt/ß-catenin signaling proteins was altered after PRDX2 inhibition. In addition, PRDX2 knockdown led to increased ROS production in CD133+CD44+ CCSCs, sensitizing CCSCs to oxidative stress and chemotherapy. These results suggest that PRDX2 could be a possible therapeutic target in CCSCs.

[The difficulties and surgical decision analysis of laparoscopic technique in treating complicated hepatolithiasis].

Objective: To explore the difficulties and surgical decision of laparoscopic technique in patients with complicated hepatolithiasis. Methods: The clinical data of 13 patients with complicated hepatolithiasis who underwent laparoscopic hepatectomy at Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College from December 2019 to December 2020 were collected. There were 3 males and 10 females with average age of 50.8 years (range: 14 to 67 years). All patients had upper abdominal pain and a history of cholecystectomy, 4 of them had fever.Seven cases underwent laparoscopic left hemihepatectomy+bile duct exploration, 2 cases underwent laparoscopic right hemihepatectomy+bile duct exploration, 2 cases underwent laparoscopic quadrate hepatectomy (liver 4B+Part 5)+hilar cholangioplasty+bile duct exploration, 2 cases underwent laparoscopic quadrate lobe resection (liver 4B+Part 5)+cholangioplasty+cholangiojejunostomy. All patients were re-examined with abdominal ultrasound and choledochoscope 3 months after operation. Results: The median operation time was 5.2 hours (range: 3.6-6.5 hours), blood loss was 278 ml (range: 120-580 ml). During the operation, 1 case had duodenal bulb injury, and the defect area was about 1.0 cm × 1.2 cm. After timely detection, the defect area was carefully evaluated and trimmed. Absorbable suture was used to suture duodenal bulb, and gastrojejunostomy was performed after repair. One case had small intestinal serosa injury, which was intermittently sutured and embedded with absorbable suture. All the patients recovered smoothly without death. Three months after the operation, 12 patients completed abdominal ultrasound and T-tube sinus choledochoscopy. Residual stones were found in 3 patients, stones were removed in 2 patients by T-tube sinus choledochoscopy 3 months after the operation, 1 patient was still in the recovery period (within 3 months after surgery). No residual stones were found in the remaining 10 patients. Conclusion: The three key laparoscopic techniques in operation of complex hepatolithiasis: adhesiolysis and porta hepatis exposure, laparoscopic hepatectomy, and laparoscopic choledochojejunostomy are very important.

Mucin 4 mutation is associated with tumor mutation burden and promotes antitumor immunity in colon cancer patients.

At present, immunotherapy is widely used for different mismatch repair (dMMR) or highly microsatellite instability (MSI-H) colorectal cancer patients, and tumor mutation burden (TMB) is a valuable independent predictor of response to immunotherapy. However, specific gene mutations and their relationship with TMB and tumor-infiltrating immune cells in colon cancer remains unclear. In the present study, we analyzed somatic mutation data of colon cancer from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets, and found that 17 frequently mutated genes were occurred in both cohorts, including APC, TP53, TNN, KRAS, MUC16, MUC4 (mucin 4), SYNE1, FLG, FAT4, OBSCN, FAT3, RYR2, PIK3CA, FBXW7, DNAH11, MUC5B and ZFHX4. Interestingly, only MUC4 mutation was associated with higher TMB and patient clinical prognosis among the 17 mutated genes. Moreover, according to gene set enrichment analysis (GSEA) and the CIBERSORT algorithm, we revealed that MUC4 mutation activated signaling pathways involved in the immune system and enhanced the antitumor immune response. In conclusion, MUC4 may have important clinical implications for immune therapy of colon cancer.

Risk of hematologic malignancies after breast ductal carcinoma in situ treatment with ionizing radiation.

The increased incidence of secondary hematologic malignancies (SHM) is a well-known, potentially fatal, complication after cancer treatment. It is unknown if patients with ductal carcinoma in situ (DCIS) of the breast treated with external beam radiotherapy (RT) and who survive long-term have increased risks of secondary hematologic malignancies (SHM), especially for low/intermediate-risk subsets with limited benefits from RT. DCIS patients in Surveillance, Epidemiology, and End Results (SEER) registries (1975-2016) were identified. Relative risks (RR), hazard ratio (HR), and standardized incidence ratios (SIR) were calculated to assess the SHM risk and subsequent survival times. SHM development, defined as a nonsynchronous SHM occurring ≥1 year after DCIS diagnosis, was our primary endpoint. Of 184,363 eligible patients with DCIS, 77,927 (42.3%) in the RT group, and 106,436 (57.7%) in the non-RT group, 1289 developed SHMs a median of 6.4 years (interquartile range, 3.5 to 10.3 years) after their DCIS diagnosis. Compared with DCIS patients in the non-RT group, RT was associated with increased early risk of developing acute lymphoblastic leukemia (ALL; hazard ratio, 3.15; 95% CI, 1.21 to 8.17; P = 0.02), and a delayed risk of non-Hodgkin lymphoma (NHL; hazard ratio, 1.33; 95% CI, 1.09 to 1.62; P < 0.001). This increased risk of ALL and NHL after RT was also observed in subgroup analyses restricted to low/intermediate-risk DCIS. In summary, our data suggest that RT after breast conserving surgery for DCIS patients should be cautiously tailored, especially for low and intermediate-risk patients. Long-term SHM surveillance after DCIS diagnosis is warranted.