Rh(III)-Catalyzed meta-C-H Alkenylation with Alkynes.

Rh(III)-catalyzed meta-C-H functionalization reactions are still rare. Herein, we report the first example of Rh(III)-catalyzed meta-C-H alkenylation with disubstituted alkynes directed by a U-shaped nitrile template. Exclusive regio-selectivity has been achieved using unsymmetrical aryl and alkyl-disubstituted alkynes to afford synthetically valuable trisubstituted olefins. Propargyl alcohols are also compatible, affording complex allylic alcohols. Notably, transition metal-catalyzed meta-alkenylation with alkynes has not been successful with Pd catalysts.

Selective occlusion of the hepatic artery and portal vein improves liver hypertrophy for staged hepatectomy.

BACKGROUND: To evaluate the safety and feasibility of selective occlusion of the hepatic artery and portal vein (SOAP) for staged hepatectomy (SOAPS) in patients with hepatocellular carcinoma (HCC) METHODS: From December 2014 to August 2018, 9 patients with unresectable HCC were chosen to undergo SOAPS. SOAP without liver partition was performed in the first stage. The second stage was performed when future liver remnant (FLR) was equal to or bigger than 40% of the standard liver volume (SLV). The growth rate of FLR, perioperative outcomes, and survival data was recorded. RESULTS: In the first stage, all the 9 patients completed SOAP. Two cases received radiological interventional method and 7 cases received open operation. None of them developed liver failure and died following SOAP. After SOAP, FLR increased 145.0 ml (115.0 to 210 ml) and 37.1% (25.6 to 51.7%) on average. The average time interval between the two stages was 14.1 days (8 to 18 days). In the second stage, no in-hospital deaths occurred after SOAPS. One patient suffered from liver failure after SOAPS, and artificial liver support was adopted and his total bilirubin level returned to normal after postoperative day 35. The alpha-fetoprotein level of 8 patients reduced to normal within 2 months after SOAPS. Among 9 patients, 5 patients survived, 4 patients died of intrahepatic recurrence, lung metastasis, or bone metastasis. In the 5 survived cases, bone metastasis and intrahepatic recurrence were found in 1 patient, intrahepatic recurrence was found in another patient, and the remaining 3 patients were free of recurrence. The median disease-free survival time and overall survival time were 10.4 and 13.9 months, respectively. CONCLUSION: SOAP can facilitate rapid and sustained FLR hypertrophy, and SOAPS is safe and effective in patients with unresectable HCC.

Ligand-Promoted RhIII -Catalyzed Thiolation of Benzamides with a Broad Disulfide Scope.

A ligand-promoted RhIII -catalyzed C(sp2 )-H activation/thiolation of benzamides has been developed. Using bidentate mono-N-protected amino acid ligands led to the first example of RhIII -catalyzed aryl thiolation reactions directed by weakly coordinating directing amide groups. The reaction tolerates a broad range of amides and disulfide reagents.

Right hepatic artery thrombosis in an essential polycythemia vera patient following pancreato-biliary surgery for severe pancreatitis.

Hepatic artery thrombosis (HAT) remains one of the major causes of graft failure and mortality in liver transplant recipients. But it is a very rare in non-transplantation patient with the complication of HAT. We reported herein a case of successful urokinase intra-arterial thrombolytic treatment for HAT in an essential polycythemia vera patient following pancreato-biliary surgery. This patient underwent debridement and T-tube drainage in common bile duct for severe pancreatitis and acute suppurative obstructive cholangitis. Significant elevation of liver transaminases and white blood cell counts was noted 30 days after operation and HAT was confirmed by CT-angiography and digital subtracted angiography. Apart from malena and malaise, this patient had scarcity of evident symptoms. The only obvious risk factor relating to HAT is thrombocytosis. This patient was continuously characterized by an excess of platelets from its admission to the onset of HAT. This patient was treated successfully with continuous transcatheter arterial thrombolysis using urokinase. The symptom including malena and malaise disappeared 3 days after thrombolysis. And the patient was treated with hydroxyurea for polycythemia vera thereafter. In conclusion, physicians should be alerted that HAT can be happened in non-transplantation patients especially in those of having hypercoagulability.

Sorafenib prevents the proliferation and induces the apoptosis of liver cancer cells by regulating autophagy and hypoxia-inducible factor-1.

Sorafenib has been approved as a systemic drug for advanced liver cancer; however, the underlying mechanisms remain unclear. The present study aimed to investigate the effects of sorafenib on the proliferation, autophagy and apoptosis of HepG2 cells under hypoxia. Briefly, reverse transcription-quantitative PCR and western blotting was performed to quantify HIF-1, LC3II/I, mTOR and p70s6K expression levels. Cell proliferation was determined using the Cell Counting Kit-8 assay and the cell apoptosis rate was evaluated using flow cytometry. The results demonstrated that autophagy and apoptosis were induced by hypoxia, and that sorafenib further enhanced hypoxia-induced autophagy and apoptosis in HepG2 cells in a dose-dependent manner. Furthermore, the mechanism of sorafenib-mediated autophagy in liver cancer cell were investigated by using chloroquine (CQ). The results showed that CQ significantly inhibited autophagy by decreasing LC3II/LC3I ratio in HepG2 cells treated with sorafenib and/or hypoxia. By contrast, sorafenib could increase the expression of hypoxia-inducible factor-1 (HIF-1) and of the autophagy marker (LC3II/I) and decrease the expression of mammalian target of rapamycin and p70 ribosomal S6 kinase in HepG2 cells under normoxia and hypoxia conditions, suggesting that sorafenib could induce hypoxia and autophagy in liver cancer cells. In addition, sorafenib was demonstrated to prevent proliferation and induce apoptosis of HepG2 cells under normoxia and hypoxia. Sorafenib could also prevent the malignant behavior of HepG2 by inducing hypoxia and autophagy. In summary, the findings from the present study suggested that sorafenib may inhibit liver cancer progression by activating autophagy and HIF-1 signaling pathway.

Rh(III)-Catalyzed C(sp3)-H Acetoxylation of 8-Methylquinolines.

A mild and efficient Rh(III)-catalyzed aliphatic C-H acetoxylation directed by quinolines has been developed with widespread functional groups, including various halogens, which usually can provide precursors for further organic synthesis but easily results in selectivity issues in the Pd- and Ni-catalyzed reaction. Interestingly, Ac2O plays an essential role in promoting the transformation.

Anatomic trisegmentectomy: An alternative treatment for huge or multiple hepatocellular carcinoma of right liver.

BACKGROUND: The patients with huge (≥10cm) or multiple hepatocellular carcinoma (HCC) in the right liver and insufficient size of the remnant left liver can not be performed an operation of right hemihepatectomy because of that liver failure will occur post operation. We designed anatomic trisegmentectomy in right liver to increase the ratio of future liver remnant volume (%FLRV), thus increasing resectability of huge or multiple HCC. METHODS: Thirteen patients were analyzed by preoperative CT scan for liver and tumor volumetries. If the right hemihepatectomy was done, %FLRV would be at the range of 29.6%-37.5%. However, if trisegmentectomy was done, %FLRV would increase by an average of 14.0%. So patients will not undergo postoperative liver failure due to sufficient %FLRV. Therefore, we designed anatomic trisegmentectomy, with retention of segment 5 or segment 8, to increase %FLRV and increase the resectability for huge or multiple HCC. RESULTS: After trisegmentectomy, the inflow and outflow of remnant liver were maintained well. Severe complications and mortality were not happened post operation. Of the 13 patients, 10 survived up to now. Of the 10 living cases, postoperative lung metastasis was found in 2 and intrahepatic recurrence was found in 1. These 3 patients survive with tumor after comprehensive therapies including oral administration of Sorafenib. CONCLUSION: Compared to right hemihepatectomy, anatomic trisegmentectomy in right liver guarantees the maximum preservation of %FLRV to increase the resectability of huge or multiple HCC, thus improving the overall resection rate.

Hepatectomy with primary closure of common bile duct for hepatolithiasis combined with choledocholithiasis.

AIM: To evaluate the feasibility of hepatectomy and primary closure of common bile duct for intrahepatic and extrahepatic calculi. METHODS: From January 2008 to May 2013, anatomic hepatectomy followed by biliary tract exploration without biliary drainage (non-drainage group) was performed in 43 patients with intrahepatic and extrahepatic calculi. After hepatectomy, flexible choledochoscopy was used to extract residual stones and observe the intrahepatic bile duct and common bile duct (CBD) for determination of biliary stricture and dilatation. Function of the sphincter of Oddi was determined by manometry of the CBD. Primary closure of the CBD without T-tube drainage or bilioenteric anastomosis was performed when there was no biliary stricture or sphincter of Oddi dysfunction. Dexamethasone and anisodamine were intravenously injected 2-3 d after surgery to prevent postoperative retrograde infection due to intraoperative bile duct irrigation, and to maintain relaxation of the sphincter of Oddi, respectively. During the same period, anatomic hepatectomy followed by biliary tract exploration with biliary drainage (drainage group) was performed in 48 patients as the control group. Postoperative complications and hospital stay were compared between the two groups. RESULTS: There was no operative mortality in either group of patients. Compared to intrahepatic and extrabiliary drainage, hepatectomy with primary closure of the CBD (non-drainage) did not increase the incidence of complications, including residual stones, bile leakage, pancreatitis and cholangitis (P > 0.05). Postoperative hospital stay and costs were nevertheless significantly less in the non-drainage group than in the drainage group. The median postoperative hospital stay was shorter in the non-drainage group than in the drainage group (11.2 ± 2.8 d vs 15.4 ± 2.1 d, P = 0.000). The average postoperative cost of treatment was lower in the non-drainage group than in the drainage group (29325.6 ± 5668.2 yuan vs 32933.3 ± 6235.1 yuan, P = 0.005). CONCLUSION: Hepatectomy followed by choledochoendoscopic stone extraction without biliary drainage is a safe and effective treatment of hepatolithiasis combined with choledocholithiasis.

Anatomic liver resection of segments 6, 7, and 8 by the method of selective occlusion of hepatic inflow.

Anatomic liver resection not only enables enough tumor-free resection margin but also guarantees maximum preservation of remaining normal liver tissue. We report herein a hepatocellular carcinoma patient who underwent successful anatomic liver resection of segments 6, 7, and 8 by the method of selective occlusion of hepatic inflow. Multiple tumors were found in segments 6, 7, and 8 by computed tomographic (CT) scanning. CT volumetry analyzed that his left hemi-liver volume was less than the minimal limit of safe survival. Therefore, we planned to perform segment 5 remaining, anatomic liver resection of segments 6, 7, and 8 to guarantee the maximum preservation of remaining normal liver tissue. Selective occlusion of hepatic inflow was creatively used twice in this case to divide right hemi-liver Glissonean pedicle and segments 6 and 7 Glissonean pedicle, respectively. Thus, the resection line was determined, and anatomic liver resection of segments 6, 7, and 8 was completed. Selective right hemi-liver Glissonean pedicle occlusion was used, while parenchymal transection was between segments 6 and 5 and between segments 8 and 5. Therefore, liver ischemia reperfusion injury and homodynamic instability were maximally reduced during operation.

Anatomic resection of liver segments 6-8 for hepatocellular carcinoma.

AIM: To report the devised anatomic liver resection of segments 6, 7 and 8 to improve the resection rate for patients with right liver tumors. METHODS: We performed anatomic liver resection of segments 6, 7 and 8 to guarantee the maximum preservation of the remaining normal liver tissue. Segment 5 was determined by two steps of Glissonean pedicle occlusion. And a "┏┛" shaped broken resection line was marked upon the diaphragmatic surface of the liver. Selective right hemihepatic inflow occlusion was used to reduce blood loss during parenchymal transection between segments 6 and 5 and between segments 8 and 5. If needed, total hepatic Glissonean pedicle occlusion was used during parenchymal transection between segment 8 and the left liver. RESULTS: Compared to right hemihepatectomy, the percentage of future liver remnant volume was increased by an average of 13.9% if resection of segments 6, 7 and 8 was performed. Resection of segments 6, 7 and 8 was completed uneventfully. After hepatectomy, the inflow and outflow of segment 5 were maintained. There was no perioperative mortality, postoperative abdominal bleeding or bile leakage in this group. Alpha-fetoprotein (AFP) returned to the normal range within 2 mo after the operation in all the patients. One patient died 383 d postoperatively due to obstructive suppurative cholangitis. One patient suffered from severe liver dysfunction shortly after surgery and had intrahepatic recurrence 4 mo postoperatively. Postoperative lung metastasis was found in one patient. No tumor recurrence was found in the other patients and the parameters including liver function and AFP level were in the normal range. CONCLUSION: Anatomic liver resection of segments 6, 7 and 8 can be a conventional operation to improve the overall resection rate for hepatocellular carcinoma.

Pancreaticojejunostomy, hepaticojejunostomy and double Roux-en-Y digestive tract reconstruction for benign pancreatic diseases.

Surgery such as digestive tract reconstruction is usually required for pancreatic trauma and severe pancreatitis as well as malignant pancreatic lesions. The most common digestive tract reconstruction techniques (e.g., Child's type reconstruction) for neoplastic diseases of the pancreatic head often encompass pancreaticojejunostomy, choledochojejunostomy and then gastrojejunostomy with pancreaticoduodenectomy, whereas these techniques may not be applicable in benign pancreatic diseases due to an integrated stomach and duodenum in these patients. In benign pancreatic diseases, the aforementioned reconstruction will not only increase the distance between the pancreaticojejunostomy and choledochojejunostomy, but also the risks of traction, twisting and angularity of the jejunal loop. In addition, postoperative complications such as mixed fistula are refractory and life-threatening after common reconstruction procedures. We here introduce a novel pancreaticojejunostomy, hepaticojejunostomy and double Roux-en-Y digestive tract reconstruction in two cases of benign pancreatic disease, thus decreasing not only the distance between the pancreaticojejunostomy and choledochojejunostomy, but also the possibility of postoperative complications compared to common reconstruction methods. Postoperatively, the recovery of these patients was uneventful and complications such as bile leakage, pancreatic leakage and digestive tract obstruction were not observed during the follow-up period.