Double cancer (lung and colon cancer) that showed complete remission with irinotecan and cisplatin combined chemotherapy

We report a rare case of double (colon and lung) cancer which showed complete remission with chemotherapy with irinotecan (CPT-11) and cisplatin (CDDP). The patient was a 67-year-old man who was diagnosed as having double cancer (stage IIIb pulmonary adenocarcinoma and stage 0 [or 1] well-differentiated adenocarcinoma of the ascending colon). Two courses of chemotherapy (CPT-11, 60 mg/m², days 1 and 8; CDDP, 30 mg/m², days 1 and 8) were performed. The combination therapy of CPT-11 and CDDP was very effective. In Japan, there have been few published reports describing the use of CPT-11 for the treatment of gastrointestinal cancer. We think that the use of CPT-11 in gastrointestinal cancer is promising. Received: August 18, 1999 / Accepted: March 24, 2000     

Prevalence of total knee arthroplasty and its predictive factors in Japanese patients with rheumatoid arthritis: Analysis using the NinJa cohort

Objectives. The aim of this study was to clarify the prevalence and the predictive factors for undergoing total knee arthroplasty (TKA) among patients with rheumatoid arthritis (RA).

Methods. The data of 1,134 patients with RA who were enrolled in the Japanese nationwide cohort database NinJa in 2003 and consecutively followed up until 2009 were analyzed.

Results. Seventy-six patients underwent TKA during the observation period. The yearly progression of the modified Health Assessment Questionnaire or mHAQ score from 2003 to 2004, but not the yearly progression of the Disease Activity Score in 28 Joints or DAS28 or patient visual analog scale (VAS) score, was significantly higher in the patients who underwent TKA than those who did not.

Multivariate analysis showed that knee involvement in the disease, high Steinbrocker stage (III or IV), and high patient VAS score at the time of enrollment were powerful predictive factors, with hazard ratios of 4.01, 3.71, and 1.20, respectively.

According to survival analysis with TKA as an endpoint, patients with knee involvement in the disease at the time of enrollment had a significantly worse 5-year survival rate than did those without knee involvement (83.5% vs. 97.0%, respectively).

Conclusion. Several factors were elucidated as predictive factors for undergoing TKA among patients with RA.     

Coronary angiographic characteristics in Japanese patients with heterozygous familial hypercholesterolemia

Coronary angiographic findings were analyzed in 51 consecutive patients (36 males and 15 females) with heterozygous familial hypercholesterolemia (FH) and 279 consecutive patients (216 males and 63 females) without FH (non-FH). The coronary stenosis index and over 75% stenosis vessel subset were almost three times as high in the FH group. The incidence of myocardial infarction was almost twice as high in the FH group. Levels of total cholesterol and its lipoprotein fractions, except HDL-cholesterol, were almost twice as high in the FH group. In the FH group aged under 50 years, the two parameters of coronary angiogram and the incidence of myocardial infarction were significantly higher in males than in females. However, in the group aged over 50 years, all three parameters were not significantly different between those in males and females. The level of HDL-cholesterol was significantly lower in males than in females. A significantly higher incidence (18%) of coronary ectasia was observed in the FH group compared with the incidence (2%) in non-FH. All patients with coronary ectasia were males, except one female with FH. On comparison of the males among the FH patients with those among the non-FH patients matched for total cholesterol, age and other risk factors, the FH patients were associated with a significantly higher degree of coronary atherosclerosis and lower level of HDL-cholesterol. Seven FH patients with a normal coronary angiogram were observed. However, any factors as regards age, total cholesterol, HDL-cholesterol and Achilles tendon thickness failed to distinguish between the FH patients with a normal coronary angiogram and those without.(ABSTRACT TRUNCATED AT 250 WORDS)     

A case of pulmonary squamous cell carcinoma coexisting with pulmonary actinomycosis]

A 71-year-old man was referred to our hospital complaining of cough. Chest radiography revealed a mass opacity in the right upper lung field. A transbronchial biopsy specimen revealed non-specific inflammatory changes. Percutaneous lung aspiration biopsy under ultrasound guidance demonstrated gram-positive rods, suggesting actinomyces. On the diagnosis of pulmonary actinomycosis, the patient was treated with penicillin-G and his symptoms were relieved. In a three-month follow-up, the mass shadow in the right upper lung field was found to have increased in size. Squamous cell lung cancer was diagnosed on the basis of repeated transbronchial tumor biopsies, and right upper lobectomy was performed. Most cases of pulmonary actinomycosis have been diagnosed from post-surgical tumor specimens taken on suspicion of the presence of lung cancer. However, the lung cancer in this case was difficult to diagnose because the lung cancer was co-existent with pulmonary actinomycosis.     

Response of Human Insulinoma Cells to Extracellular Calcium Is Different from Normal B Cells

The preoperative determination of thelocalization of a small insulinoma is sometimesdifficult using routine imaging techniques. We have usedthe selective arterial calcium injection (SACI) test todetermine the location of the tumor preoperatively. Thepathophysiologic basis of the SACI test is based on theresponsiveness of insulinomas to calcium injected intothe feeding artery. In this study, we demonstrated the in vitro response of the insulinoma cellsto the extracellular calcium challenge by usingprimary-cultured insulinoma cells. Human insulinomacells were obtained from three patients. MIN6 cells(normal pancreatic B cells) were used as a control;their insulin response to various stimuli resembles thatof normal B cells. The insulin secretory dynamics inresponse to extracellular calcium were observed using a perfusion system. Second, the change ofthe concentration of cytosolic free calcium([Ca²⁺]_i) was monitored byfluorometry using fura-2/AM. When the concentration ofextracellular calcium ([Ca²⁺]_o) was changed from 2.54 mM to 10 mM, insulinsecretion from the insulinoma cells was markedlyincreased within 6 min (10- to 18-fold at maximum), andrapidly returned to the basal level; at the same time, [Ca²⁺]_i was immediatelyelevated and reached a peak within 1 min. In contrast,in the MIN6 cells, the insulin secretion and [Ca2+]iwere not significantly changed when[Ca²⁺]_o was switched to 10 mM. The results of these in vitro experiments agreedwith the clinical results of the SACI test. The positiveresponse of the insulinoma to the SACI test is probablydue to the different response of insulinoma cells to the extracellular calcium challengecompared with normal B cells. The role of[Ca²⁺]_i may be important in themechanism underlying the SACI test.     

Blockade of Death Ligand TRAIL Inhibits Renal Ischemia Reperfusion Injury

Renal ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI). Many investigators have reported that cell death via apoptosis significantly contributed to the pathophysiology of renal IRI. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor superfamily, and induces apoptosis and inflammation. However, the role of TRAIL in renal IRI is unclear. Here, we investigated whether TRAIL contributes to renal IRI and whether TRAIL blockade could attenuate renal IRI. AKI was induced by unilateral clamping of the renal pedicle for 60 min in male FVB/N mice. We found that the expression of TRAIL and its receptors were highly upregulated in renal tubular cells in renal IRI. Neutralizing anti-TRAIL antibody or its control IgG was given 24 hr before ischemia and a half-dose booster injection was administered into the peritoneal cavity immediately after reperfusion. We found that TRAIL blockade inhibited tubular apoptosis and reduced the accumulation of neutrophils and macrophages. Furthermore, TRAIL blockade attenuated renal fibrosis and atrophy after IRI. In conclusion, our study suggests that TRAIL is a critical pathogenic factor in renal IRI, and that TRAIL could be a new therapeutic target for the prevention of renal IRI.     

Lipoteichoic acid may affect the pathogenesis of PBC-like bile duct damage and might be involved in systemic multifocal epithelial inflammations in chronic colitis-harboring TCRα−/−×AIM−/− mice

Background: Chronic colitis-harboring TCRα^{? / ?} × AIM^{? / ?} mice showed PBC-like bile duct damage in the liver. Bacterial infection is one of the candidates for the pathogenesis of PBC. We demonstrated that the bacterial cell wall component lipotheicoic acid (LTA) was detected at sites of inflammation around damaged bile ducts in PBC patients. The aim of this study was to investigate the pathophysiology of the liver and other organs in TCRα^{? / ?} × AIM^{? / ?} mice.

Methods: Thirteen female TCRα^{? / ?} × AIM^{? / ?} mice were sacrificed at 24 weeks of age. The liver, stomach, small intestine, colon, pancreas, kidney and spleen were studied for pathological examination. Using anti-LTA antibody as the primary antibody, an immunohistochemical study was carried out.

Results: In the liver, LTA was mainly detected in the portal area with inflammation, and some of the cytoplasm of hepatocytes. Inflammations were also observed in the stomach, intestine, pancreas and kidney. Throughout the gastrointestinal tract, from the stomach to the colon, LTA was detected in the epithelium at sites of inflammation. Furthermore, LTA was detected around both pancreatic ducts with inflammation and distal renal tubules with inflammation.

Conclusions: The development of inflammations in the liver as well as extensive organs, strongly suggests a close relationship between bile duct damage and systemic multifocal epithelial inflammations, perhaps involving bacterial LTA, in TCRα^{? / ?} × AIM^{? / ?} mice.     

A significant imbalance in mitosis versus apoptosis accelerates the growth rate of sessile serrated adenoma/polyps

Sessile serrated adenoma/polyps (SSA/Ps) of the colon are thought to be precursors of sporadic carcinomas. Although it is suggested that SSA/P may grow rapidly from the early stage, its cell kinetics remains obscure. To solve this problem, we analyzed the mitotic and apoptotic activity of normal crypts, microvesicular hyperplastic polyps (MVHPs), and tubular adenomas (TAs), using phospho-histone H3 and cleaved caspase 3 immunohistochemistry. The mitotic index for SSA/Ps (mean, 5.63) and TAs (6.98) was significantly higher than those for normal crypts (2.72) and MVHPs (2.86). Of all tested lesions, the apoptotic index was lowest for SSA/Ps (0.96; normal, 2.71; MVHPs, 2.62; TAs, 6.01) with statistically significant differences. The net growth ratio was close to 1.0 in normal crypts (1.07) while remaining low in MVHPs (1.06) and TAs (1.38), but was markedly elevated in SSA/Ps (7.32, P?<?0.01) due to the large imbalance between mitosis and apoptosis. As to apoptosis regulatory proteins, expression of anti-apoptotic Bcl-2 was significantly reduced or undetectable in MVHPs and SSA/Ps, while TAs showed stronger staining than normal crypts. Expression of pro-apoptotic Bax and its activators, Bim and Bad, was significantly reduced in MVHPs and SSA/Ps. We suggest that other complex mechanisms may act synergistically with Bax, Bim, or Bad deficiency to regulate apoptosis suppression in SSA/Ps.