Surgical technique for complete resection of the extrahepatic portion of the common bile duct and the ampulla of Vater for tumors of the ampulla of Vater

Background

Ampullary tumors have to be completely resected, but substantial morbidity and mortality rates are associated with pancreaticoduodenectomy (PD). Local resection can be the procedure of choice in selected ampullary lesions for high-risk patients.

Methods

Preoperative examination indicated that the ampullary tumor extended into the common bile duct without evidence of pancreatic duct involvement and no definite invasion into either the duodenum or the pancreas. We performed a complete resection of the extrahepatic bile duct and the ampulla of Vater, including the tumor, without performing PD by dissecting the intrapancreatic bile duct from the pancreas both downward towards the ampulla of Vater and upward using a transduodenal approach.

Results

The operation was successfully completed, and the postoperative course was uneventful, with the exception of a minor pancreatic fistula from retropancreatic dissection. The final pathological examination demonstrated well-differentiated tubular adenocarcinoma limited to the mucosa with negative surgical margins.

Conclusion

Complete resection of the extrahepatic bile duct and the ampulla of Vater through a transduodenal approach can be a feasible and safe surgical procedure for selected ampullary tumors in high-risk patients.     

Dual Function MITO-Porter,a Nano Carrier Integrating Both Efficient Cytoplasmic Delivery and Mitochondrial Macromolecule Delivery

Mitochondrial dysfunction is associated with a variety of human diseases including inherited mitochondrial diseases, neurodegenerative disorders, diabetes mellitus, and cancer. Effective medical therapies for mitochondrial diseases will ultimately require an optimal drug delivery system, which will likely be achieved through innovations in the nanotechnology of intracellular trafficking. To achieve efficient mitochondrial drug delivery, two independent processes, i.e., “cytoplasmic delivery through the cell membrane” and “mitochondrial delivery through the mitochondrial membrane” are required. In previous studies, we developed an octaarginine (R8) modified nano carrier for efficient cytoplasmic delivery, showing that R8-modified liposomes were internalized into cells efficiently. On the other hand, we also constructed MITO-Porter for the mitochondrial delivery of macromolecules, a liposome-based carrier that delivers cargos to mitochondria via membrane fusion. Here, we report the development of a dual function MITO-Porter (DF-MITO-Porter), based on the concept of integrating both R8-modified liposomes and MITO-Porter. We show that the DF-MITO-Porter effectively delivers exogenous macro-biomolecules into the mitochondrial matrix, and provide a demonstration of its potential use in therapies aimed at mitochondrial DNA.     

Protective role of melatonin in progesterone production by human luteal cells

This study investigated whether melatonin protects luteinized granulosa cells from reactive oxygen species (ROS) as an antioxidant to enhance progesterone production in the follicle during ovulation. Follicular fluid was sampled at the time of oocyte retrieval in women undergoing in vitro fertilization and embryo transfer (IVF-ET). Melatonin concentrations in the follicular fluid were positively correlated with progesterone concentrations (r = 0.342, P < 0.05) and negatively correlated with the concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative stress marker (r = -0.342, P < 0.05). The progesterone and 8-OHdG concentrations were negatively correlated (r = -0.246, P < 0.05). Luteinized granulosa cells were obtained at the time of oocyte retrieval in women undergoing IVF-ET. Cells were incubated with H(2)O(2) (30, 50, 100 μm) in the presence or absence of melatonin (1, 10, 100 μg/mL). Progesterone production by luteinized granulosa cells was significantly inhibited by H(2)O(2). Melatonin treatment overcame the inhibitory effect of H(2) O(2) . Twenty-five patients who had luteal phase defect (serum progesterone concentrations <10 ng/mL during the mid-luteal phase) were divided into two groups during the next treatment cycle: 14 women were given melatonin (3 mg/day at 22:00 hr) throughout the luteal phase and 11 women were given no medication as a control. Melatonin treatment improved serum progesterone concentrations (>10 ng/mL during the mid-luteal phase) in nine of 14 women (64.3%), whereas only two of 11 women (18.1%) showed normal serum progesterone levels in the control group. In conclusion, melatonin protects granulosa cells undergoing luteinization from ROS in the follicle and contributes to luteinization for progesterone production during ovulation.     

Comparison of the effects of nitroprusside versus nicorandil on the slow/no-reflow phenomenon during coronary interventions for acute myocardial infarction

Although slow/no-reflow is a serious problem complicating primary percutaneous coronary interventions (PCI) for acute myocardial infarction (AMI) and is associated with a poor prognosis, its efficacious treatment remains problematic. We compared the acute, in-hospital and long-term (1 year) effects of nitroprusside (NTP) with those of nicorandil (NC) on the slow/no-reflow phenomenon. Forty-nine of 442 consecutive patients with AMI who underwent primary PCI complicated by slow/no-reflow and who received intracoronary NTP (n = 25) or NC (n = 24) administration were studied. Both NTP and NC induced significant improvements in coronary flow, with increases in TIMI flow grade from 1.64 ± 0.62 to 2.74 ± 0.36 (p < 0.001) and 1.60 ± 0.86 to 2.23 ± 0.91 (p < 0.001), and in corrected TIMI frame count from 37.8 ± 15.1 to 13.7 ± 7.1 (p < 0.001) and 30.8 ± 20.7 to 19.3 ± 17.9 (p < 0.001), respectively. The degree of improvement in TIMI flow grade (post–pre/pre) and TIMI frame count (pre–post/pre) showed that NTP was more effective than NC (NTP vs. NC: 0.88 ± 0.79, 0.37 ± 0.37, p = 0.008; 0.59 ± 0.23, 0.36 ± 0.27, p = 0.003, respectively). Congestive heart failure did not tend to last beyond 3 days after onset in the NTP group, which was more than in the NC group, during hospitalization (1/25, 4/24, p = 0.143, respectively). At the 1-year follow-up, the NTP group tended to show more improvement than the NC group in MACE (5/25, 9/24, p = 0.175, respectively). NTP is a more effective treatment for slow/no-reflow associated with PCI in patients with AMI and may improve long-term clinical outcomes compared with NC.     

Hypocomplementemic urticarial vasculitis syndrome is associated with high levels of serum IgG4: a clinical manifestation that mimics IgG4-related disease

A 58-year-old Japanese woman presented with recurrent abdominal pain, chronic urticaria, and petechiae on her extremities, and hypocomplementemia, findings that were consistent with hypocomplementemic urticarial vasculitis syndrome (HUVS). A laboratory examination revealed that she had markedly elevated IgG levels (4,448 mg/dL; normal range, 870-1,700 mg/dL) with particularly high IgG4 levels (1,050 mg/dL; normal range, 48-105 mg/dL) and a high IgG4/total IgG ratio (0.22; normal range, 0.02-0.05). A skin biopsy demonstrated leukocytoclastic vasculitis with IgG4 deposition in the vascular lumen and vascular walls. A lymph node biopsy revealed reactive lymphoid hyperplasia with numerous IgG4-positive cells in the perifollicular area, but no sclerotic findings. A chromosomal analysis of an enlarged lymph node, without phytohemagglutinin (PHA) stimulation, demonstrated that one in every three analyzed cells had abnormalities, such as 44, XX, -13, add(15)(p11), -17, -17, and mar.     

Red blood cell production from immortalized progenitor cell line

The supply of transfusable red blood cells (RBCs) is not sufficient in many countries. If immortalized erythroid progenitor cell lines able to produce transfusable RBCs in vitro were established, they would be valuable resources. However, such cell lines have not been established. We have developed a robust method to establish immortalized erythroid progenitor cell lines following the induction of hematopoietic differentiation of mouse embryonic stem (ES) cells and have established many immortalized erythroid progenitor cell lines so far. Although their precise characteristics varied among cell lines, each of these lines could differentiate in vitro into more mature erythroid cells, including enucleated RBCs. Following transplantation of these erythroid cells into mice suffering from acute anemia, the cells proliferated transiently, subsequently differentiated into functional RBCs, and significantly ameliorated the acute anemia. Considering the number of human ES cell lines that have been established so far and the number of induced pluripotent stem cell lines that will be established in future, the intensive testing of a number of these lines for establishing immortalized erythroid progenitor cell lines may allow the establishment of such cell lines similar to the mouse erythroid progenitor cell lines.