Prognosis of hepatocellular carcinoma associated with Child class B and C cirrhosis in relation to treatment: a multivariate analysis of 411 patients at a single center

Background/Purpose: Given that the prognosis of patients with hepatocellular carcinoma (HCC) complicating severe cirrhosis remains uncertain, particularly with regard to various therapeutic strategies, we have evaluated the prognosis in a series of patients with homogeneous diagnostic and therapeutic histories. Methods: From 1990 to 1998, 411 consecutive HCC patients associated with Child class B and class C cirrhosis who did not have lymph node or distant metastasis were treated by partial hepatectomy (PH; n = 48), percutaneous ethanol injection (PEI; n = 105), transcatheter arterial chemoembolization (TACE; n = 189), chemotherapy, or supportive care (chemo/supportive; n = 69). Univariate survival curves were estimated. The Cox model, stratified by the treatment groups, was used for multivariate analysis. Results: As of January 1999, 305 patients (74.2%) had died. Overall median survival was 23.4 months. There were statistically significant differences between the survival times of patients receiving PH or PEI and TACE, as compared with those receiving chemo/supportive care. According to multivariate analysis, the independent predictive survival factors were: albumin level (≥3.0 g/dl), esophageal varices (i.e., absence), tumor size (≤3.0 cm), tumor number (solitary), and α-fetoprotein (AFP) level (<400 ng/ml). According to the total number of risk factors and the median survival, all patients were divided into four subgroups. For the score 0 group (no risk factor group), 3- and 5-year survival rates were 83.1% and 68.0% for PH, and 87.5% and 62.3% for PEI, respectively. In the score 1–2 group (one or two risk factors), survival rates at 3 and 5 years were 53.1% and 40.3% for PH, 54.8% and 33.2% for PEI, and 35.4% and 22.8% for TACE, respectively. For patients with a score of 3 or more, there were no differences among the treatment groups, excluding those with chemo/supportive care. Conclusions: These findings indicate that, in HCC patients with complicating Child B and C cirrhosis, PEI and PH should be considered first for subgroups of patients with scores (risk factors) of 0–2, as an acceptable survival rate was obtained in such patients. Therefore, the advantages and disadvantages of these therapies regarding tumor size and location should be counterbalanced. In patients with a score of 3 or more, TACE, when possible, could be a first choice because of its applicability and its adjuvant nature with respect to other therapies such as liver transplantation. Received: February 6, 2002 / Accepted: May 22, 2002 Offprint requests to: S. Ueno     

Long-term outcomes after hepaticojejunostomy for choledochal cyst: a 10- to 27-year follow-up

Introduction

Choledochal cyst (CC) is closely associated with anomalous arrangement of the pancreaticobiliary duct, which is considered a high-risk factor for biliary tract malignancy. Early diagnosis and early treatment for CC could lead to a good prognosis. This study investigated late complications and long-term outcomes after surgery for CC.

Patients and Methods

Fifty-six patients with CC and over 10 years of postoperative follow-up were analyzed retrospectively. All patients had undergone total resection of the extrahepatic bile duct and hepaticojejunostomy.

Results

Six patients showed liver dysfunction manifested in the first 10 years after surgery, but all returned to normal thereafter. Dilatation of intrahepatic bile ducts persisted in 6 postoperatively, and in 3, this was still apparent more than 10 years after. Recurrent abdominal pain was encountered in 3, 1 had pancreas divisum with a pancreatic stone, and 1 had adhesive small bowel obstruction. Two patients developed biliary tract malignancy. A 14-year-old girl died of recurrent common bile duct cancer 2 years after the initial resection of CC with adenocarcinoma. A 26-year-old man with repeated cholangitis owing to multiple intrahepatic bile stones developed cholangiocarcinoma 26 years after the initial resection of CC. Event-free survival rate and overall survival rate were 89% (50/56) and 96% (54/56), respectively.

Conclusions

Choledochal cyst generally has an excellent prognosis with early total resection and reconstruction. Long-term surveillance for the development of malignancy is still essential, especially if there is ongoing dilatation of the intrahepatic bile duct or biliary stones.     

Regulation of ER molecular chaperone prevents bone loss in a murine model for osteoporosis

Endoplasmic reticulum (ER) stress response is important for protein maturation in the ER. Some murine models for bone diseases have provided significant insight into the possibility that pathogenesis of osteoporosis is related to ER stress response of osteoblasts. We examined a possible correlation between osteoporosis and ER stress response. Bone specimens from 8 osteoporosis patients and 8 disease-controls were used for immunohistochemical analysis. We found that ER molecular chaperones, such as BiP (immunoglobulin heavy-chain binding protein) and PDI (protein-disulfide isomerase) are down-regulated in osteoblasts from osteoporosis patients. Based on this result, we hypothesized that up-regulation of ER molecular chaperones in osteoblasts could restore decreased bone formation in osteoporosis. Therefore, we investigated whether treatment of murine model for osteoporosis with BIX (BiP inducer X), selective inducer BiP, could prevent bone loss. We found that oral administration of BIX effectively improves decline in bone formation through the activation of folding and secretion of bone matrix proteins. Considering these results together, BIX may be a potential therapeutic agent for the prevention of bone loss in osteoporosis patients.     

Sporadic gastric carcinoid tumor successfully treated by two-stage laparoscopic surgery: A case report

We report a case of sporadic gastric carcinoid tumor successfully treated by two-stage laparoscopic surgery. A 38-year old asymptomatic woman was referred to our hospital for evaluation of a submucosal tumor of the stomach. Endoscopic examination showed a solitary submucosal tumor without ulceration or central depression on the posterior wall of the antrum and biopsy specimens were not sufficient to determine the diagnosis. Endoscopic ultrasound revealed a tumor nearly 2 cm in diameter arising from the muscle layer and a computed tomography scan showed the tumor enhanced in the arterial phase. Laparoscopic wedge resection was performed for definitive diagnosis. Pathologically, the tumor was shown to be gastric carcinoid infiltrating the muscle layer which indicated the probability of lymph node metastasis. Serum gastrin levels were normal. As a radical treatment, laparoscopy-assisted distal gastrectomy with regional lymphadenectomy was performed 3 wk after the initial surgery. Finally, pathological examination revealed no lymph node metastasis.     

Pretreatment with small-dose ketamine reduces predicted effect-site concentration of propofol required for loss of consciousness and Laryngeal Mask Airway insertion in women

Study Objective

To investigate the effect of small-dose ketamine on the predicted effect-site concentration of propofol required for loss of consciousness (LOC) and Laryngeal Mask Airway (LMA) insertion.

Design

Randomized, double-blinded study.

Settings

Operating room.

Patients

50 ASA physical status 1 and 2 women scheduled for elective breast or gynecological surgery.

Interventions

Patients were randomly allocated to a ketamine group or a control group. Thirty seconds before propofol injection, ketamine group patients received ketamine 0.2 mg/kg, while control group patients received saline. Propofol was given in a target-controlled infusion and target blood concentration was gradually increased until LOC. The effect-site concentrations for attempting LMA insertion was predetermined by modifying Dixon's up and down method. LMA insertion was attempted without muscular blocking agents.

Measurements

Pain scores on propofol injection, effect-site concentrations at LOC, hemodynamic variables, and patient movement or side effects on LMA insertion were recorded.

Main Results

The effect-site concentration of propofol required for LOC was 2.14 μg/mL for the control group and 1.66 for the ketamine group (P = 0.0082). The predicted effect-site concentration of propofol alone at which 50% of patients did not move with LMA insertion (EC₅₀LMI) was 3.59 μg/mL (95% CI: 3.18∼4.19 μg/mL). Pretreatment with ketamine 0.2 mg/kg decreased EC₅₀LMI from 3.59 (3.18∼4.19) to 2.39 (1.22∼2.99).

Conclusions

Pretreatment with ketamine 0.2 mg/kg reduced the propofol concentration required for both LOC (22%) and LMA insertion (33%) in women.     

Anoikis disruption of focal adhesion-Akt signaling impairs renal cell carcinoma

Background

Quinazoline-based α1-adrenoceptor antagonists suppress tumor growth by inducing apoptosis via an α1-adrenoceptor-independent action. Anoikis is a unique mode of apoptosis consequential to insufficient cell-matrix interactions.

Objective

This study investigated the apoptotic effect of novel quinazoline-based compounds on human renal cancer cells.

Design, setting, and participants

Two cell lines were used: renal cell carcinoma (RCC) 786-0, harboring a von Hippel-Lindau (VHL) tumor-suppressor gene mutation with a highly angiogenic phenotype, and Caki cells (no VHL mutation).

Measurements

The lead compound DZ-50 (10 μM) led to significant inhibition of tumor-cell adhesion, migration, and invasion at a lower dose than doxazosin (25 μM) in both RCC lines.

Results and limitations

Doxazosin induced death-receptor-mediated apoptosis, while DZ-50 led to anoikis via targeting of the focal adhesion complex and AKT signaling that subsequently increased RCC susceptibility to caspase-8-mediated apoptosis. Both quinazoline compounds, doxazosin and DZ-50, significantly reduced RCC metastatic potential in vivo.

Conclusions

Quinazoline-based drugs trigger anoikis in RCC by targeting the focal adhesion survival signaling. This potent antitumor action against human RCC suggests a novel quinazoline-based therapy targeting renal cancer.     

Interventional radiologic treatment for idiopathic portal hypertension

Purpose: To evaluate the usefulness of interventional radiological treatment for idiopathic portal hypertension. Methods: Between 1995 and 1998, we performed an interventional radiological treatment in five patients with idiopathic portal hypertension, four of whom had refused surgery and one of whom had undergone surgery. Three patients with gastroesophageal varices (GEV) were treated by partial splenic embolization (PSE), one patient with esophageal varices (EV) and massive ascites by transjugular intrahepatic portosytemic shunt (TIPS) and PSE, and one patient with GEV by percutaneous transhepatic obliteration (PTO). Midterm results were analyzed in terms of the effect on esophageal and/or gastric varices. Results: In one woman with severe GEV who underwent three sessions of PSE, there was endoscopic confirmation that the GEV had disappeared. In one man his EV shrunk markedly after two sessions of PSE. In two patients slight reduction of the EV was obtained with one application of PSE combined with endoscopic variceal ligation therapy. PTO for GV in one patient resulted in good control of the varices. All patients have survived for 16–42 months since the first interventional treatment, and varices are well controlled. Conclusion: Interventional radiological treatment is effective for patients with idiopathic portal hypertension, whether or not they have undergone surgery.     

Repair of full-thickness articular cartilage defects using injectable type II collagen gel embedded with cultured chondrocytes in a rabbit model

BACKGROUND: Recently, tissue-engineered chondrocyte transplantation has been tried to treat full-thickness cartilage defects. We developed an injectable type II collagen gel scaffold by chemically reacting type II collagen with polyethylene glycol crosslinker. This type II collagen was prepared from the nasal septa of cattle. In the present study, chondrocytes embedded in type II collagen gel were injected into rabbit full-thickness cartilage defects without a periosteal graft, and the feasibility for clinical application of the gel was evaluated. METHODS: Chondrocytes were isolated from 1-kg New Zealand white rabbits. A full-thickness articular cartilage defect (5 mm diameter, 4 mm depth) was created on the patellar groove of the femur of 16 male 3-kg New Zealand white rabbits. A type II collagen solution of mixed chondrocytes at a density of 1 x 10(7) cells/ml was injected and transplanted into the defect in the right knee. The controls were the defect only in the left knee. At 4, 8, 12, and 24 weeks after operation, four cases from each group were evaluated macroscopically and histologically. RESULTS: After injection into the cartilage defect, the gel bonded to the adjacent cartilage and bone within several minutes. Macroscopic examination revealed that the surface of the transplanted area was smooth and exhibited similar coloration and good integration with the surrounding cartilage at 12 and 24 weeks after transplantation. Histological examination at 8 weeks revealed favorable hyaline cartilage regeneration with good chondrocyte morphology. At 12 and 24 weeks, reparative cartilage remained rich in type II collagen. According to O'Driscoll histological scores, significant differences between the transplanted and control groups were apparent at 12 and 24 weeks. Immunohistochemical staining indicated sufficient type II collagen synthesis in regenerated cartilage 8 weeks after transplantation, and it was maintained until 24 weeks. CONCLUSIONS: These results indicate that type II collagen gel is suitable for injection into cartilage defects without any covering of a graft and offers a useful scaffold during chondrocyte transplantation.     

Induction chemoradiotherapy prior to surgery for non-small cell lung cancer invading the left atrium.

We present a case of a 58-year-old man with diagnosis of lung adenocarcinoma invading the left atrium. He was treated with induction chemoradiotherapy for T4N1M0 disease, showing objective response. Then, a left upper lobectomy with a partial resection of the left atrium was performed without cardiopulmonary bypass. No residual tumor cells existed in the resected specimens, showing pathological complete response. Our case suggests that induction chemoradiotherapy prior to surgery can be an appropriate strategy among carefully selected patients with non-small cell lung cancer invading the left atrium.     

Renal L-type fatty acid--binding protein in acute ischemic injury

Fatty acid-binding proteins (FABPs) bind unsaturated fatty acids and lipid peroxidation products during tissue injury from hypoxia. We evaluated the potential role of L-type FABP (L-FABP) as a biomarker of renal ischemia in both human kidney transplant patients and animal models. Urinary L-FABP levels were measured in the first urine produced from 12 living-related kidney transplant patients immediately after reperfusion of their transplanted organs, and intravital video analysis of peritubular capillary blood flow was performed simultaneously. A significant direct correlation was found between urinary L-FABP level and both peritubular capillary blood flow and the ischemic time of the transplanted kidney (both P < 0.0001), as well as hospital stay (P < 0.05). In human-L-FABP transgenic mice subjected to ischemia-reperfusion injury, immunohistological analyses demonstrated the transition of L-FABP from the cytoplasm of proximal tubular cells to the tubular lumen. In addition, after injury, these transgenic mice demonstrated lower blood urea nitrogen levels and less histological injury than injured wild-type mice, likely due to a reduction of tissue hypoxia. In vitro experiments using a stable cell line of mouse proximal tubule cells transfected with h-L-FABP cDNA showed reduction of oxidative stress during hypoxia compared to untransfected cells. Taken together, these data show that increased urinary L-FABP after ischemic-reperfusion injury may find future use as a biomarker of acute ischemic injury.