Surgical Treatment for Biliary Carcinoma Arising After Pancreatoduodenectomy

The clinicopathological features and surgical treatment of biliary carcinoma around the major hepatic duct confluence arising after pancreatoduodenectomy (PD) due to initial bile duct carcinoma are described in three patients. Occurrence of biliary carcinoma more than 12 years after initial surgery and a histological finding of cholangiocellular carcinoma mixed with hepatocellular carcinoma suggested metachronous incidence of biliary carcinoma after PD. Extended right hemihepatectomy with complete removal of the residual extrahepatic bile duct and segmental, resection of the jejunal loop were carried out safely without operative death or severe postoperative complications. Two patients died of tumor recurrence 6 months after surgery, and the remaining patient is currently living a normal life without evidence of recurrence 17 months after surgery. These surgical procedures are a therapeutic option in patients with biliary carcinoma around the major hepatic duct confluence arising after PD.     

Rho-Associated Kinase Inhibitor Reduces Tumor Recurrence After Liver Transplantation in a Rat Hepatoma Model

Tumor recurrence after liver transplantation still remains a significant problem in patients with hepatocellular carcinoma. The small GTPase Rho/Rho-associated kinase (ROCK) pathway is involved in the motility and invasiveness of cancer cells. We investigated whether tacrolimus activated the Rho/ROCK signal pathway to promote the invasiveness of rat hepatocellular carcinoma cells. We also investigated whether the ROCK inhibitor Y-27632 suppressed tumor recurrence after experimental liver transplantation in a rat hepatocellular carcinoma model. Orthotopic liver transplantation was performed in hepatocellular carcinoma cell line McA-RH7777-bearing rats. Tacrolimus was administered to liver transplant rats and these rats were divided into two groups: the Y-27632-treated (10 mg/kg, for 28 days) group and the Y-27632-untreated group. Tacrolimus enhanced the cancer cell migration and stimulated phosphorylation of the myosin light chain (MLC), a downstream effector of Rho/ROCK signaling. Y-27632 suppressed the cancer cell migration and tacrolimus-induced MLC phosphorylation. Suppression of tumor recurrence after liver transplantation and significant prolongation of survival were observed in the Y-27632-treated rats in comparison with theY-27632-untreated rats. Tacrolimus stimulates the Rho/ROCK signal pathway to enhance the invasiveness of hepatocellular carcinoma, and the ROCK inhibitor Y-27632 can be used as a new antimetastatic agent for the prevention of tumor recurrence after liver transplantation.     

Islet purification method using large bottles effectively achieves high islet yield from pig pancreas

Porcine islets are a promising resource for xenotransplantation. However, low efficacy of islet isolation because of their marked fragility remains a problem. Recently we found that the standard purification method using COBE 2991 cell processor (COBE) with Ficoll density gradient solution damaged islets mechanically by high shearing force. In this study, we evaluated our new purification method using large plastic bottles for the efficacy of islet purification. Ten porcine pancreata were used. The average warm ischemic time was over 40 min; therefore, these pancreata were considered to be in a marginal condition. After digestion, the digested tissue was divided into three groups. Each group was purified using either top loading method with bottle (top group) or bottom loading method with bottle (bottom group) or standard COBE method (COBE group). Islet yield per pancreas weight (IEQ/g) and the rate of postpurification recovery in the top group were significantly higher than the COBE group (top: 8060 ± 1652 IEQ/g, bottom: 4572 ± 614 IE/g, COBE: 3900 ± 734 IE/g. p < 0.02 in top vs. COBE; top percentage of recovery: 99.3 ± 12.3%, bottom: 62.6 ± 8.8%, COBE: 49.5 ± 6.7%, p < 0.02 in top vs. bottom and COBE). The average sizes of purified islets in the top and bottom groups were significantly larger than COBE group (Average diameter top: 156 ± 8 μm, bottom: 147 ± 6 μm, COBE: 119 ± 6 μm, p < 0.01 in top vs. COBE and in bottom vs. COBE), which indicated that bottle method can reduce shear force during purification. Our new purification using top loading bottle method enabled us to obtain a high yield of porcine islets from marginal pancreata.     

Mass spectrometry proves under-O-glycosylation of glomerular IgA1 in IgA nephropathy

BACKGROUND: The IgA1 molecule, which is predominantly deposited in glomeruli in IgA nephropathy (IgAN), is a unique serum glycoprotein because it has O-glycan side chains in its hinge region. Our study was conducted to investigate the O-glycan structure in the glomerular IgA1 in IgAN. METHODS: The IgA1 was separated from 290 renal biopsy specimens of 278 IgAN patients and from four serum IgA1 samples (IgAN, 2; control, 2). The variety of O-glycan glycoform was determined by estimating the precise molecular weights of the IgA1 hinge glycopeptides using matrix-assisted laser desorption ionization time of flight mass spectrometry. RESULTS: The peak distribution of IgA1 hinge glycopeptides clearly shifted to lesser molecular weights in both glomerular and serum IgA1 in IgAN compared with the serum IgA1 of controls. In the five major peaks of IgA1 hinge glycopeptides in each sample, the numbers of carbohydrates composing O-glycans (GalNAc, Gal, and NANA) in the deposited and serum IgA1 in IgAN patients were significantly fewer than those in the serum IgA1 in the control groups. CONCLUSION: The O-glycan side chains in the hinge of the glomerular IgA1 were highly underglycosylated in IgAN. These results indicate that the decreased sialylation and galactosylation of the IgA1 hinge glycopeptides play a crucial role in its glomerular deposition in IgAN.     

Characteristics and prognostic factors in patients with differentiated thyroid cancer who underwent a total or subtotal thyroidectomy: Surgical approach for high-risk patients

Differentiated thyroid cancer grows slowly in general. But some patients repeat recurrence and progress finally to death. To clarify the difference of their prognosis and establish the appropriate thyroid surgery, we studied 105 patients with differentiated thyroid cancer who were treated with total or subtotal thyroidectomy, excluding those with small tumors, under uniform conditions regarding thyroidectomy. There were 77 women and 28 men aged 19 to 76 years (mean 54.7 years). More than 60% (alive) were followed up for longer than 10 years. Thirty-eight (36%) patients had recurrences. There were 19 deaths. Twelve of 31 patients with locoregional recurrence died and 7 of these 12 died of locoregional control failure (neck and mediastinum). Age at first operation, tumor size, and local tumor extension increased the rate of recurrence significantly. Multivariate analysis confirmed that age, locoregional recurrence, and distant metastasis significantly affected survival. Although lymph node metastases were not a prognostic factor, for patients at high risk for recurrence who are older, and have large tumors with invasion, complete resection of cervical lymph nodes is advised to prevent local recurrence and prolong the disease-free interval. Prolongation of the disease-free interval may lead to prolonged survival time.     

Correlation between mechanical stress by finite element analysis and 18F‐fluoride PET uptake in hip osteoarthritis patients

¹⁸F‐fluoride positron emission tomography (¹⁸F‐fluoride PET) is a functional imaging modality used primarily to detect increased bone metabolism. Increased ¹⁸F‐fluoride PET uptake suggests an association between increased bone metabolism and load stress at the subchondral level. This study therefore examined the relationship between equivalent stress distribution calculated by finite element analysis and ¹⁸F‐fluoride PET uptake in patients with hip osteoarthritis. The study examined 34 hips of 17 patients who presented to our clinic with hip pain, and were diagnosed with osteoarthritis or pre‐osteoarthritis. The hips with trauma, infection, or bone metastasis of cancer were excluded. Three‐dimensional models of each hip were created from computed tomography data to calculate the maximum equivalent stress by finite element analysis, which was compared with the maximum standardized uptake value (SUV_max) examined by ¹⁸F‐fluoride PET. The SUV_max and equivalent stress were correlated (Spearman's rank correlation coefficient ρ = 0.752), and higher equivalent stress values were noted in higher SUV_max patients. The correlation between SUV_max and maximum equivalent stress in osteoarthritic hips suggests the possibility that ¹⁸F‐fluoride PET detect increased bone metabolism at sites of stress concentration. This study demonstrates the correlation between mechanical stress and bone remodeling acceleration in hip osteoarthritis. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:78–83, 2015.     

Increased circulating endothelial progenitor cells in patients with bacterial pneumonia: evidence that bone marrow derived cells contribute to lung repair

Background: Tissue repair often occurs in organs damaged by various inflammatory diseases including pneumonia. Inflammatory stimuli induce a rapid and massive release of inflammatory cells from the bone marrow. Recent studies have suggested that bone marrow cells have the potential to differentiate into a variety of cell types. It has been shown that administration of lipopolysaccharide (LPS) to murine lungs induces a rapid release of endothelial progenitor cells (EPCs) into the circulation, and that bone marrow derived progenitor cells including EPCs contribute to lung repair after lung injury in mice. This study was undertaken to investigate the mobilisation of EPCs in humans following acute pneumonia.

Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood taken from 23 patients with pneumonia during both the acute and convalescent phase. 1x10⁶ PBMCs were plated on fibronectin coated culture slides and cultured in culture medium for endothelium. The numbers of EPCs were counted 8 days after plating.

Results: The number of circulating EPCs significantly increased in patients with pneumonia (p<0.0001). Patients with low EPC counts tended to have persistent fibrotic changes in their lungs even after their recovery from pneumonia.

Conclusions: Inflammatory stimuli induce a rapid release of EPCs into the circulation in humans. A sufficient number of EPCs is necessary for proper lung repair following bacterial pneumonia.

     

The current diagnosis and treatment of benign biliary stricture

Purpose

As laparoscopic cholecystectomy and liver transplantation (LT) have become more common, so has biliary stricture. Fortunately, endoscopic treatment has almost simultaneously been developed. This article reviews the recent reports concerning the management of benign biliary strictures (BBS).

Methods

The literature regarding the diagnosis and treatment of BBS is reviewed after an electronic search of PubMed from 1982 to 2009 was performed.

Results

Despite the existence of diagnostic tools including tumor markers, brush cytology, intraductal ultrasonography and other imaging modalities, differentiating BBS from malignant stricture remains challenging, as does differentiating IgG4-related sclerosing cholangitis from other benign strictures. Endoscopic treatment with balloon dilation of the stricture and serial insertions of stents is the preferred initial treatment for BBS. However, the outcomes of endoscopic treatments for primary sclerosing cholangitis or chronic pancreatitis are poorer than those for post-surgical biliary stricture. When endoscopic treatments fail to repair complicated biliary strictures such as Bismuth types III, IV, and V, surgical repair is recommended. Among the non-anastomotic BBS, intrahepatic bilateral type strictures after LT may require repeat transplantation.

Conclusion

Early referral to tertiary centers with an alliance among hepatobiliary surgeons, interventional radiologists, and endoscopists is necessary to assure optimal results.     

Prognosis of Patients with Benign Thyroid Diseases Accompanied by Incidental Papillary Carcinoma Undetectable on Preoperative Imaging Tests

Background Despite the recent wide availability of ultrasonography and fine-needle aspiration biopsy, endocrine surgeons often encounter incidental papillary carcinoma (IPC), that is a papillary carcinoma that had gone undetected by preoperative imaging studies but was identified by pathological examination of surgical specimens resected for benign thyroid diseases. Methods The present study was developed to investigate the prognoses of 317 patients who underwent surgery for benign diseases involving IPC in comparison with the prognoses of 1,674 patients with clinically apparent papillary carcinoma detected preoperatively and diagnosed. Results None of the patients underwent further surgery such as completion total thyroidectomy and node dissection immediately after the diagnosis of IPC. To date, 7 patients (2.2%) have had recurrences; 6 of those were locoregional recurrences and one was a bone metastasis. None of the patients have died of thyroid carcinoma. The disease-free survival of IPC patients was significantly better than that of clinically apparent papillary carcinoma patients and was similar to that of the subset of patients with papillary microcarcinoma without clinically apparent metastasis. Conclusions Because IPC is associated with good prognosis, further surgery, such as completion total thyroidectomy or lymph node dissection immediately after the diagnosis of IPC is not necessary.