Border between N1 and N2 stations in lung carcinoma: lessons from lymph node metastatic patterns of lower lobe tumors

OBJECTIVE: Distinction of lymph node stations is one of the most crucial topics still not entirely resolved by many lung cancer surgeons. The nodes around the junction of the hilum and mediastinum are key points at issue. We examined the spread pattern of lymph node metastases, investigated the prognosis according to the level of the involved nodes, and conclusively analyzed the border between N1 and N2 stations. METHODS: We reviewed the records of 604 consecutive patients who underwent complete resection for non-small cell lung carcinoma of the lower lobe. RESULTS: There were 390 patients (64.6%) with N0 disease, 127 (21.0%) with N1, and 87 (14.4%) with N2. Whereas 11.3% of patients with right N2 disease had skip metastases limited to the subcarinal nodes, 32.6% of patients with left N2 disease had skip metastases, of which 64.2% had involvement of N2 station nodes, except the subcarinal ones. The overall 5-year survivals of patients with N0, N1, and N2 disease were 71.0%, 50.8%, and 16.7%, respectively (N0 vs N1 P = .0001, N1 vs N2, P < .0001). Although there were no significant differences in survival according to the side of the tumor among patients with N0 or N1 disease, patients with a left N2 tumor had a worse prognosis than those with a right N2 tumor (P = .0387). The overall 5-year survivals of patients with N0, intralobar N1, hilar N1, lower mediastinal N2, and upper mediastinal N2 disease were 71.0%, 60.1%, 38.8%, 24.8%, and 0%, respectively. Significant differences were observed between intralobar N1 and hilar N1 disease ( P = .0489), hilar N1 and lower mediastinal N2 disease (P = .0158), and lower and upper mediastinal N2 disease (P = .0446). Also, the 5-year survivals of patients with involvement up to station 11, up to station 10, and up to station 7 were 41.4%, 37.9% and 37.7%, respectively (difference not significant). CONCLUSIONS: N1 and N2 diseases appeared as a combination of subgroups: intralobar N1 disease, hilar N1 disease, lower mediastinal N2 disease, and upper mediastinal N2 disease. Interestingly, the survivals of patients with involvement up to interlobar nodes (station 11), main bronchus nodes (station 10), and subcarinal nodes (station 7) were identical. These data constitute the basis for a larger investigation to develop a lymph node map in lung cancer.     

Case of autosomal dominant polycystic kidney disease associated with congenital hepatic fibrosis

A 31-year-old man was admitted to the hospital because of a low-grade fever, general malaise, nausea, vomiting, and a poor appetite. On admission his renal function was severely deteriorated (serum creatinine 16.12 mg/dl, BUN 163 mg/dl), and he had severe anemia (Hb 7.5 g/dl) and thrombocytopenia (67,000/microl). A radiological examination revealed the presence of multiple cysts in his kidneys bilaterally. The patient was diagnosed as having end-stage renal disease due to polycystic kidney disease, and hemodialysis was started on the day of admission. After the initiation of hemodialysis, his symptoms and laboratory tests improved, except for anemia and thrombocytopenia. He was noted to have marked splenomegaly and dilation of the portal vein, raising the suspicion of portal hypertension as the cause of the splenomegaly and pancytopenia. To treat his pancytopenia (anemia and thrombocytopenia) and to determine the reason for his portal hypertension, a splenectomy and open-wedge biopsy of the liver were performed. Histological findings in the liver included extensive fibrosis of the portal areas with an excess of moderately dilated bile ducts, compatible with a diagnosis of congenital hepatic fibrosis. After splenectomy, his red blood cell and platelet counts returned to normal, and he was discharged on maintenance dialysis. Congenital hepatic fibrosis is often associated with autosomal recessive polycystic kidney disease (ARPKD), but not with autosomal dominant polycystic kidney disease (ADPKD). However, both his mother and older brother had multiple renal cysts, indicating that this was an unusual case of ADPKD complicated by congenital hepatic fibrosis.     

Unsuspected gallbladder carcinoma after laparoscopic cholecystectomy

Background/Purpose Many cases have been reported of disastrous port-site recurrence after laparoscopic cholecystectomy (LC) revealed unsuspected gallbladder carcinoma (GBC). Some investigators have reported that the prognosis of patients after LC showed unsuspected GBC is not worsened by laparoscopic procedures. We retrospectively reviewed our cases and the literature to reconfirm the intrinsic risks of LC for unsuspected GBC. Methods Of 1663 patients who underwent LC from January 1991 to December 2003 in a single institution, 9 (0.54%) with unsuspected GBC were reviewed. Results These 9 patients consisted of 5 men and 4 women, whose ages ranged from 58 to 87 years, with a median age of 73 years. Two patients with a pT1a tumor (limited to mucosa) and 2 patients with a pT1b tumor (muscle layer) underwent no further operation. The remaining 5 patients with a pT2 tumor (subserosa) underwent further operations with lymph node dissection. Five patients (2 patients with pT1b and 3 patients with pT2) developed recurrence and all of them died within a median period of 19 months (range 14–37 months) after LC. The causes of death were bone metastases in 1 patient (pT2), local recurrence in 2 patients (pT1b and pT2), and peritoneal metastasis in 2 patients (one elderly patient with pT1b who underwent laparoscopic common bile duct exploration, and one patient with pT2 in whom the cystic duct was damaged during surgery). Four patients (2 with pT1 and 2 with pT2) have been doing well with a median follow-up of 39.5 months (range 12–99 months) after LC. Conclusions Surgeons should always prevent bile spillage during LC and when removing the resected gallbladder. When laparoscopic common bile duct exploration is planned, especially for elderly women, surgeons should also bear in mind the increasing possibility of unsuspected GBC.     

Negative Impact of Blood Transfusion on Recurrence and Prognosis of Hepatocellular Carcinoma After Hepatic Resection

Background  In perioperative management of hepatic resection for hepatocellular carcinoma, excessive blood loss and blood transfusion greatly influence postoperative complications and prognosis of the patients. We evaluated the influence of blood products use on postoperative recurrence and prognosis of patients with hepatocellular carcinoma. Methods  The subjects were 66 patients who underwent elective hepatic resection for hepatocellular carcinoma without concomitant microwave or radiofrequency ablation therapy nor other malignancies between January 2001 and June 2006. We retrospectively investigated the influence of the use of blood products including red cell concentration and fresh frozen plasma on recurrence of hepatocellular carcinoma and overall survival. Results  In multivariate analysis, the dose of blood products transfusion was a significant predictor of disease-free and overall survival. Both disease-free and overall survival rates of those who were given blood products were significantly worse than those who did not receive. On the other hand, in univariate analysis of disease-free and overall survival after hepatic resection and clinical variables, the amount of blood loss was not a significant predictor of recurrence or death. Conclusion  Transfusion of blood products is associated with increased recurrence rate and worse survival after elective hepatic resection for patients with hepatocellular carcinoma.     

Direct imaging of hyperpolarized 129Xe alveolar gas uptake in a mouse model of emphysema

MRI of hyperpolarized ¹²⁹Xe dissolved in pulmonary tissues, and blood has the potential to offer a new tool for regional evaluation of pulmonary gas exchange and perfusion; however, the extremely short T and low magnetization density make it difficult to acquire the image. In this study, an ultrashort echo‐time sequence was introduced, and its feasibility to quantitatively assess emphysema‐like pulmonary tissue destruction by a combination of dissolved‐ and gas‐phase ¹²⁹Xe lung MRI was investigated. The ultrashort echo‐time has made it possible to acquire dissolved ¹²⁹Xe images with reasonably high spatial resolution of 0.625 × 0.625 mm² and to obtain T of 0.67 ± 0.30 ms in a spontaneously breathing mouse at 9.4 T. The regional dynamic alveolar gas uptake as well as subsequent transport by pulmonary blood flow was also visualized. The ratio of ¹²⁹Xe magnetization that diffused into the septa relative to the gas‐phase magnetization F was regionally evaluated. The mean F value of elastase‐treated mice was 2.28 ± 0.46%, which was significantly reduced from that of control mice 3.41 ± 0.48% (P = 0.0052). This reflects the reduced uptake efficiency due to alveolar tissue destruction and is correlated with the histologically derived alveolar surface‐to‐volume ratio. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Three-dimensional brain phantom containing bone and grey matter structures with a realistic head contour

Introduction

A physical 3-dimensional phantom that simulates PET/SPECT images of static regional cerebral blood flow in grey matter with a realistic head contour has been developed. This study examined the feasibility of using this phantom for evaluating PET/SPECT images.

Methods

The phantom was constructed using a transparent, hydrophobic photo-curable polymer with a laser-modelling technique. The phantom was designed to contain the grey matter, the skull, and the trachea spaces filled with a radioactive solution, a bone-equivalent solution of K₂HPO₄, and air, respectively. The grey matter and bone compartments were designed to establish the connectivity. A series of experiments was performed to confirm the accuracy and reproducibility of the phantom using X-ray CT, SPECT, and PET.

Results

The total weight was 1997 ± 2 g excluding the inner liquid, and volumes were 563 ± 1 and 306 ± 2 mL, corresponding to the grey matter and bone compartments, respectively. The apparent attenuation coefficient averaged over the whole brain was 0.168 ± 0.006 cm^?1 for Tc-99 m, which was consistent with the previously reported value for humans (0.168 ± 0.010 cm^?1). Air bubbles were well removed from both grey-matter and bone compartments, as confirmed by X-ray CT. The phantom was well adapted to experiments using PET and SPECT devices.

Conclusion

The 3-dimensional brain phantom constructed in this study may be of use for evaluating the adequacy of SPECT/PET reconstruction software programs.     

Renal involvement in children with influenza A virus infection

Renal involvement in influenza A virus infection has been rarely reported. To define the clinical characteristics and the factors contributing to the development of renal involvement in influenza A virus infection, we reviewed the clinical characteristics, laboratory data, pediatric risk of mortality (PRISM) score, and the number of systemic inflammatory response syndrome (SIRS) criteria and dysfunctional organs in 45 hospitalized children with influenza A virus infection. Eleven (24.4%) patients had renal involvement. All patients with renal involvement suffered from sepsis and multiple organ dysfunction syndrome (MODS) and 5 developed acute renal failure (ARF). The incidences of dehydration, hypotension, disseminated intravascular coagulation (DIC), and rhabdomyolysis were significantly higher in patients with renal involvement. PRISM scores, the numbers of SIRS criteria and dysfunctional organs, and mortality rate were also higher in patients with renal involvement. Influenza A RNA was absent in the renal tissues of 3 patients with ARF. These results suggested that renal involvement in influenza A virus infection occurred in patients with sepsis and MODS; dehydration, hypotension, DIC, and rhabdomyolysis were factors contributing to its development; direct viral injury to the kidney did not seem to occur in influenza A virus infection.     

Predominant role of FcgammaRIII in the induction of accelerated nephrotoxic glomerulonephritis

BACKGROUND: Nephrotoxic glomerulonephritis is induced by the administration of antibody against the glomerular basement membrane (GBM). We demonstrated previously that Fc receptors for immunoglobulin G (IgG) (FcgammaR) play crucial roles in the induction of accelerated nephrotoxic glomerulonephritis by using FcRgamma-deficient (-/-) mice. Since FcRgamma-/- mice lack the cell surface expression of two activating FcgammaRs, FcgammaRI and FcgammaRIII. The present study aims to identify the FcgammaR responsible for the induction of nephrotoxic glomerulonephritis. METHODS: Accelerated anti-GBM glomerulonephritis was induced in FcgammaRI-/-, FcgammaRIII-/-, and FcRgamma-/- mice by preimmunization with rabbit IgG followed by inoculation of rabbit anti-GBM antibody. Histologic analysis and immunostaining of renal sections were performed. RESULTS: FcgammaRI-/- mice as well as wild-type mice showed severe glomerulonephritis with hypernitremia by the administration of anti-GBM antibody. In contrast, FcgammaRIII-/- mice showed much milder renal involvement, similar to FcRgamma-/- mice. Histologically, FcgammaRI-/- mice showed intracapillary proliferation, glomerular thrombosis, and crescent formation, whereas FcgammaRIII-/- mice showed only glomerular hypercellular changes. The depositions of anti-GBM antibodies, autologous antibodies and complement C3 along the GBM were equally observed among all three FcR-/- mouse types by immunostaining. CONCLUSIONS: Accelerated nephrotoxic glomerulonephritis is induced predominantly through FcgammaRIII but not FcgammaRI.     

Climbing exercise enhances osteoblast differentiation and inhibits adipogenic differentiation with high expression of PTH/PTHrP receptor in bone marrow cells

We developed previously a mouse voluntary climbing exercise model as a physiological mechanical loading model and reported that climbing exercise increased bone formation, but its effect on adipogenesis is unknown. We assessed the effects of loading and PTH/PTHrP receptor (PTHR1) on bone marrow adipocyte differentiation in relation with osteoblast differentiation. 8-week-old C57BL/6J male mice were divided into ground control (GC) and climbing exercise (EX) group. Mice were housed in 100-cm towers and climbed up toward a bottle placed at the top of the cage to drink water. The values of bone volume and osteoblast number were significantly higher while those of marrow adipocyte volume and number were significantly lower in the 28dayEX group than 28dayGC group. The mRNA expression levels of adipocyte differentiation genes CCAAT/enhancer-binding proteins (C/EBP) beta and delta were lower in 4dayEX mice, while the adipocyte specific genes fatty acid binding protein (aP2) and phosphoenolpyruvate carboxykinase (PEPCK) expressions were lower in 7dayEX mice. In primary bone marrow cell cultures, the number of alkaline phosphatase-positive colony forming units-fibroblastic (ALP+ CFU-f) and Oil-red-O-positive cells were both increased in the 4dayEX group. Climbing exercise transiently increases both osteogenic and adipogenic potential in bone marrow stromal cells, and inhibits terminal adipocyte differentiation and promotes osteoblast differentiation. Immunoreactivity for the PTHR1 was intense on osteoblastic cell lineage in the endosteal tibial metaphysis. PTHR1 mRNA expression was increased in 4dayEX mice and PTHR1-positive cells were increased after 7 days in the experimental group. Ex vivo addition of PTHR1 antibody decreased and that of PTHrP(1-34) increased the number of ALP+ CFU-f in bone marrow cell cultures obtained at 4 days after the exercise, while the addition of PTHR1 antibody increased and PTHrP(1-34) decreased the number of Oil-red-O-positive cells. Our results indicate that climbing exercise enhanced osteoblast differentiation and inhibited terminal differentiation of adipocyte progenitors with high expression of PTHR1 in bone marrow cells.