ATP protects anti-PD-1/radiation-induced cardiac dysfunction by inhibiting anti-PD-1 exacerbated cardiomyocyte apoptosis, and improving autophagic flux.

The synergy between radiotherapy and immunotherapy in treating thoracic cancers presents a potent therapeutic advantage, yet it also carries potential risks. The extent and nature of cumulative cardiac toxicity remain uncertain, prompting the need to discern its mechanisms and devise effective mitigation strategies. Radiation alone or in combination with an anti- Programmed cell death protein1 (PD-1) antibody significantly reduced cardiac function in C57BL/6J mice, and this pathologic effect was aggravated by anti-PD-1 (anti-PD-1 + radiation). To examine the cellular mechanism that causes the detrimental effect of anti-PD-1 upon cardiac function after radiation, AC16 human cardiomyocytes were used to study cardiac apoptosis and cardiac autophagy. Radiation-induced cardiomyocyte apoptosis was significantly promoted by anti-PD-1 treatment, while anti-PD-1 combined radiation administration blocked the cardiac autophagic flux. Adenosine 5'-triphosphate (ATP) (a molecule that promotes lysosomal acidification) not only improved autophagic flux in AC16 human cardiomyocytes, but also attenuated apoptosis induced by radiation and anti-PD-1 treatment. Finally, ATP administration in vivo significantly reduced radiation-induced and anti-PD-1-exacerbated cardiac dysfunction. We demonstrated for the first time that anti-PD-1 can aggravate radiation-induced cardiac dysfunction via promoting cardiomyocyte apoptosis without affecting radiation-arrested autophagic flux. ATP enhanced cardiomyocyte autophagic flux and inhibited apoptosis, improving cardiac function in anti-PD-1/radiation combination-treated animals.

Primary hepatic mucosa-associated lymphoid tissue lymphoma and hemangioma with chronic hepatitis B virus infection as an underlying condition.

Primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma has a low incidence and is a rare subtype of hepatic malignant lymphoma. Described here is a rare case of primary hepatic MALT lymphoma and hepatic hemangioma with chronic HBV infection as an underlying condition. Possible treatment modalities, which should be selected in accordance with tumor size, tumor location, tumor number, and underlying liver disease, are discussed in conjunction with a review of the literature. In addition, the potential use of hepatic resection, radio frequency ablation (RFA), or radiotherapy followed by chemotherapy via the R-CHOP regimen is also discussed.

Effect of transplantation route on stem cell migration to fibrotic liver of rats via cellular magnetic resonance imaging.

BACKGROUND AIMS: Assessing mesenchymal stromal cells (MSCs) after grafting is essential for understanding their migration and differentiation processes. The present study sought to evaluate via cellular magnetic resonance imaging (MRI) if transplantation route may have an effect on MSCs engrafting to fibrotic liver of rats. METHODS: Rat MSCs were prepared, labeled with superparamagnetic iron oxide and scanned with MRI. Labeled MSCs were transplanted via the portal vein or vena caudalis to rats with hepatic fibrosis. MRI was performed in vitro before and after transplantation. Histologic examination was performed. MRI scan and imaging parameter optimization in vitro and migration under in vivo conditions were demonstrated. RESULTS: Strong MRI susceptibility effects could be found on gradient echo-weighted, or T2∗-weighted, imaging sequences from 24 h after labeling to passage 4 of labeled MSCs in vitro. In vivo, MRI findings of the portal vein group indicated lower signal in liver on single shot fast spin echo-weighted, or T2-weighted, imaging and T2∗-weighted imaging sequences. The low liver MRI signal increased gradually from 0-3 h and decreased gradually from 3 h to 14 days post-transplantation. The distribution pattern of labeled MSCs in liver histologic sections was identical to that of MRI signal. It was difficult to find MSCs in tissues near the portal area on day 14 after transplantation; labeled MSCs appeared in fibrous tuberculum at the edge of the liver. No MRI signal change and a positive histologic examination were observed in the vena caudalis group. CONCLUSIONS: The portal vein route seemed to be more beneficial than the vena caudalis on MSC migration to fibrotic liver of rats via MRI.

Surgical treatment of complicated hepatolithiasis using the ultrasound-guided fiberoptic choledochoscope.

BACKGROUND: The residual stones of postsurgical intrahepatic calculi have been among the most difficult problems in hepatobiliary surgery. Intraoperative ultrasound can clearly display the morphology of intrahepatic bile ducts and the distribution of calculi as well as the position of the choledochoscope and the calculus extraction instruments. Therefore, intraoperative ultrasound can guide the choledochoscope and its auxiliary equipment for calculus extraction. It is necessary to evaluate the effectiveness and safety of surgeries using an ultrasound-guided fiberoptic choledochoscope for the treatment of complicated hepatolithiasis. METHODS: The 56 cases in group A were selected from patients who had complicated hepatolithiasis treated with calculus extraction therapy using an ultrasound-guided fiberoptic choledochoscope in the authors' hospital between January 2006 and June 2009. The 63 cases of complicated hepatolithiasis in group B were chosen from patients treated with calculus extraction surgeries using a fiberoptic choledochoscope without the guidance of ultrasound from September 2001 through December 2005. Transabdominal ultrasound, T-tube cholangiography, and computed tomography (CT) examination were performed on day 15 after the surgery to compare the complete stone clearance rate, the residual stone rate, and the incidence rate of postoperative complications between groups A and B. RESULTS: The intrahepatic calculi were completely removed in 53 group A cases. The complete stone clearance rate was 94.6%, and the residual stone clearance rate was 5.4%. In group B, 51 cases had complete stone removal, for a stone clearance rate of 81% and a residual stone rate of 19%. The difference in the residual stone rates between the two groups is statistically significant (p=0.025). No hemobilia, biliary perforation, or other complications were observed in either group. CONCLUSION: Use of the intraoperative ultrasound-guided fiberoptic choledochoscope in the treatment of complicated hepatolithiasis can significantly reduce the residual stone rate of intrahepatic biliary calculi and significantly improve the treatment effect of hepatolithiasis.

Ultrasound-guided percutaneous microwave coagulation therapy with a "cooled-tip needle" for the treatment of hepatocellular carcinoma adjacent to the gallbladder.

BACKGROUND: Curative percutaneous microwave coagulation therapy is difficult or contraindicated in patients with tumors adjacent to the gallbladder because of the associated risk of injury. To date, no clinical data have been published regarding the effects and safety of percutaneous microwave coagulation therapy on tumors that are adjacent to the gallbladder. AIMS: We investigated the efficacy and safety of a combined treatment involving laparoscopic cholecystectomy and subsequent percutaneous microwave coagulation therapy in patients with hepatocellular carcinoma adjacent to the gallbladder. METHODS: Twenty-three patients with hepatocellular carcinoma nodules (of less than 5 cm diameter) and adjacent to the gallbladder were treated by percutaneous microwave coagulation therapy with a "cooled-tip needle" after laparoscopic cholecystectomy. The therapeutic efficacy was evaluated with enhanced helical computed tomography and sonography, and the rates of complete necrosis as well as postoperative complications were also analyzed. RESULTS: All of the patients exhibited complete necrosis of their tumor lesions after treatment with percutaneous microwave coagulation therapy. During the follow-up period (which lasted more than 21 months), 22 of 23 patients were alive. Recurrent nodules appeared in other subsegments, but not at the original site treated with percutaneous microwave coagulation therapy. Of note, no fatal complications were observed in any of the patients treated with percutaneous microwave coagulation therapy. CONCLUSION: Our results suggest that combined treatment comprising both laparoscopic cholecystectomy and subsequent percutaneous microwave coagulation therapy is an effective and safe approach for patients with small (<5 cm) hepatocellular carcinomas that are adjacent to the gallbladder.

A novel canine model of esophageal varices with a balloon dilatation constrictor.

BACKGROUND AND OBJECTIVE: The canine model of esophageal varices with an agar constrictor has been used for studies of the endoscopic treatment of esophageal variceal bleeding, but it has limitations in both stability and successful rate. This study was designed to enhance the model's efficiency and success rate by using a novel approach with a balloon dilatation constrictor. METHODS: We used 22 adult mongrel dogs to establish the model by progressively compressing and constricting the portal vein through a rechargeable balloon dilatation constrictor in combination with side-to-side portocaval shunt and inferior vena cava (IVC) ligation to increase portal vein pressure (PVP). The rechargeable balloon dilatation constrictor was composed of a hyaline polypropylene (PP) ring, a silica gel tube with a balloon, and an injection pedestal (silica gel) in an implantable vascular access port. The effects were evaluated with pre- and post-shunt PVP measurement, weekly gastroscopy, and portocaval venography. RESULTS: The mean PVP increased significantly from a preoperative (before side-to-side portocaval shunt and IVC ligation) 12.86 +/- 0.18 cmH(2)O to 26.75 +/- 0.39 cmH(2)O after the model had been established (P < 0.05). After the model was established, gastroscopy performed to assess esophageal varix size demonstrated four varicose veins of grade I, six of grade II, eight of grade III and four of grade IV. The portocaval angiography showed that the IVC and portal vein were completely blocked, that the anastomosis stoma was unobstructed and that the blood flow through esophageal varices via splenetic and gastric veins was blocked. CONCLUSION: The novel canine model developed with a rechargeable balloon dilatation constrictor is feasible and reliable for modeling esophageal varices.

Predictive value of D-dimer for portal vein thrombosis after portal hypertension surgery in hepatitis B virus-related cirrhosis.

AIM: To evaluate the predictive value of D-dimer as a predictive indicator of portal vein thrombosis (PVT) after portal hypertension surgery in hepatitis B virus-related cirrhosis. METHODS: A prospective study was carried out in 52 patients who had undergone surgery for portal hypertension in hepatitis B virus-related cirrhosis. Changes in perioperative dynamic D-dimer were observed. The sensitivity, specificity, positive predictive values and negative predictive values of D-dimer were calculated, and ROC curves were analyzed. RESULTS: The D-dimer levels in the group developing postoperative PVT was significantly higher than those in the group not developing PVT (P = 0.001), and the ROC semiquantitative and qualitative analysis of D-dimer showed a moderate predictive value in PVT (semi-quantitative value Az = 0.794, P = 0.000; qualitative analysis: Az = 0.739, P = 0.001). CONCLUSION: Dynamic monitoring of D-dimer levels in patients with portal hypertension after surgery can help early diagnosis of PVT, as in cases where the D-dimer levels steadily increase and exceed 16 microg/mL, the possibility of PVT is very high.