The Number of Metastatic Lymph Nodes is a Significant Risk Factor for Bone Metastasis and Poor Outcome After Surgery for Linitis Plastica-type Gastric Carcinoma

BACKGROUND: Linitis plastica-type gastric carcinoma remains a disease with poor prognosis despite an aggressive surgical approach. Although a prominent pattern of disease failure is peritoneal carcinomatosis, some patients experience rapid disease progression without signs of the peritoneal disease. METHODS: Clinicopathologic data from 178 patients with linitis plastica-type gastric cancer operated on between 1991 and 2000 were analyzed. Survival stratified by curability of surgery, pN stage, and patterns of failure were evaluated by using the Kaplan-Meier method, and chi(2) test was used to evaluate correlation between the number of metastatic lymph nodes in terms of pN categories and the incidence of various patterns of metastasis and recurrence. Cox regression hazard model was used to identify independent prognostic factors. RESULTS: R0 resection was performed only among 82 patients (46% of those who underwent laparotomy). Node metastasis was frequent with only 22 patients classified as pN0. Peritoneal carcinomatosis was observed in 131 patients and was the commonest pattern of recurrence. Bone metastasis, found in 13 patients, was associated with poor outcome, and its incidence was significantly correlated with the number of metastatic nodes. pT4 status and pN3 status were identified as significant independent prognostic determinants. CONCLUSION: Treatment strategy for the linitis plastica should in general combine surgery with aggressive treatment directed toward peritoneal disease. However, patients with >16 metastatic nodes more often are associated with bone metastasis than those with modest nodal involvement and suffer from poor prognosis.     

Expression of the Prothymosin-α Gene as a Prognostic Factor in Lung Cancer

Prothymosin-α (PTα) is known to play a role in cell proliferation, and the PTα mRNA level may reflect the degree of proliferation of tumor cells. It has been reported that PTα mRNA levels are higher in human colon and liver cancer tissues than in the adjacent normal tissues. We examined the mRNA levels of PTα and c-myc in 20 lung cancers, using Bas 2500Mac systems. The PTα and c-myc mRNA levels in lung cancer tissues were higher than those in normal lung tissues; however, the PTα mRNA levels did not correlate with the stage or pathological subtype of the lung cancer and there was no correlation between the expression of PTα and c-myc. PTα mRNA overexpression in lung cancer was correlated with a poor prognosis. Received: October 13, 2000 / Accepted: May 15, 2001     

Left circumflex coronary aneurysm with separated left main trunk

We report a left circumflex coronary aneurysm associated with separated left main coronary trunks (LMT). A 66-year-old man was admitted to our hospital for further examination of dyspnea on effort. He has been performed maintenance hemodialysis since 1999 for chronic renal failure. Coronary angiography and multislice spiral computed tomography (CT) revealed an unusual coronary anatomic variance in which separate origins of the left anterior descending (LAD) and left circumflex (LCx) coronary arteries arose from the left coronary aortic sinus. Furthermore, these images of the LCx revealed an aneurysm 2 cm in diameter and 99% stenosis at the proximal of side of the aneurysm. Under cardioplegic arrest, the aneurysm was ligated and coronary artery bypass grafting (left thoracic artery to posterolateral branch) was performed. The patient was discharged at the 20th postoperative day without any complication.     

Lactate dehydrogenase is a prognostic indicator for prostate cancer patients with bone metastasis

We analyzed clinical data to identify prognostic indicators in prostate cancer patients with bone metastasis. The subjects were 60 patients with bone metastasis out of 165 patients diagnosed with prostate cancer at our clinic over 6 years from January 1998 to December 2003. The age at the initial diagnosis was 61 to 91 (mean: 73.7 +/- 7.5) years old. The following items were considered to be possible prognostic indicators: T (type) classification, N (node) classification, Gleason score, prostate specific antigen (PSA) value before therapy, disease grade, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), serum calcium (Ca), hemoglobin (Hgb), and platelet count (Plt). The 5-year overall survival rate was 45.7% in the 60 patients. Univariate analysis showed statistically significant differences in N (1), Gleason score 7 + 8/Gleason score 9 + 10, and LDH level (p = 0.0053, 0.0261, and 0.0049, respectively). Multivariate Cox proportional hazard analysis of these three items showed a statistically significant difference in LDH level and Gleason score 9 +/- 10 (p = 0.0167 and 0.0371). LDH was suggested to be an excellent prognostic indicator, because of its objectivity and convenience of measurement, in prostate cancer patients with bone metastasis.     

Optic radiation tractography integrated into simulated treatment planning for Gamma Knife surgery

OBJECT: No definitive method of preventing visual field deficits after stereotactic radiosurgery for lesions near the optic radiation (OR) has been available so far. The authors report the results of integrating OR tractography based on diffusion tensor (DT) magnetic resonance imaging into simulated treatment planning for Gamma Knife surgery (GKS). METHODS: Data from imaging studies performed in 10 patients who underwent GKS for treatment of arteriovenous malformations (AVMs) located adjacent to the OR were used for the simulated treatment planning. Diffusion tensor images performed without the patient's head being secured by a stereotactic frame were used for DT tractography, and the OR was visualized by means of software developed by the authors. Data from stereotactic 3D imaging studies performed after frame fixation were coregistered with the data from DT tractography. The combined images were transferred to a GKS treatment-planning workstation. Delivered doses and distances between the treated lesions and the OR were analyzed and correlated with posttreatment neurological changes. RESULTS: In patients presenting with migraine with visual aura or occipital lobe epilepsy, the OR was located within 11 mm from AVMs. In a patient who developed new quadrantanopia after GKS, the OR had received 32 Gy. A maximum dose to the OR of less than 12 Gy did not cause new visual field deficits. A maximum dose to the OR of 8 Gy or more was significantly related to neurological change (p < 0.05), including visual field deficits and development or improvement of migraine. CONCLUSIONS: Integration of OR tractography into GKS represents a promising tool for preventing GKS-induced visual disturbances and headaches. Single-session irradiation at a dose of 8 Gy or more was associated with neurological change.     

Erythropoietin protects the kidneys against ischemia reperfusion injury by activating hypoxia inducible factor-1alpha

BACKGROUND: Ischemia/reperfusion (I/R) injury is closely associated with tissue damage in various organs, as well as in kidney transplants. Erythropoietin (EPO) has been shown to have a cytoprotective effect against hypoxia. We examined the effect of EPO against renal I/R injury and the underlying mechanism. METHODS: Human umbilical vein endothelial cells and human renal proximal tubular epithelial cells were cultured under hypoxic conditions with various EPO concentrations at 37 degrees C and examined the mechanism of cell proliferation by EPO. Moreover, to demonstrate the renoprotective effect in vivo, we treated Sprague-Dawley rats with 100 IU/kg EPO every 2 days for 2 weeks (a total of 6 doses). One day after the last injection, the operations to produce renal I/R injury (bilateral renal occlusion for 60 min) were done, and rats were killed at the end of the reperfusion period (24 hr and 72 hr after reperfusion began). RESULTS: First, we demonstrated in vitro that EPO increased hypoxia inducible factor-1alpha (HIF-1alpha) expression and stimulated proliferation of both cells under hypoxic conditions. Next, we demonstrated in vivo that EPO treatment increased the number of HIF-1alpha-positive cells, and markedly induced the expression of vascular endothelial growth factor messenger RNA. Using pimonidazole, a molecular probe that detects hypoxia, we found that EPO markedly attenuated tubular hypoxia, and reduced the number of terminal transferase dUTP nick end labeling-positive apoptotic cells and alpha-smooth muscle actin-positive interstitial cells. CONCLUSIONS: We suggested a novel HIF-1alpha induction pathway by EPO under hypoxic conditions. Thus, EPO may protect the kidneys against ischemia reperfusion injury by activating HIF-1alpha.     

Triple pelvic osteotomy: Report of our mid-term results and review of literature

A wide variety of pelvic osteotomies have been developed for the treatment of developmental dysplasia of the hip (DDH). In the present paper, we present a detailed review of previous studies of triple osteotomy as an alternative treatment for DDH. We also report our experience treating 6 adult cases of DDH by triple osteotomy in order to highlight the various aspects of this procedure.The mean age of our patients was 31.2 years with a mean follow-up period of 6 years. We assessed range of motion, center-edge angle, acetabular index angle, Sharp angle, acetabulum head index, head lateralization index, Japanese Orthopedic Association score, Harris hip score, patient satisfaction, and the difference between lower limb lengths before and after the procedure. At final follow-up, clinical scores were significantly improved and radiographic parameters also showed good correction of acetabulum.     

Dietary l-Lysine Prevents Arterial Calcification in Adenine-Induced Uremic Rats

Vascular calcification (VC) is a life-threatening complication of CKD. Severe protein restriction causes a shortage of essential amino acids, and exacerbates VC in rats. Therefore, we investigated the effects of dietary l-lysine, the first-limiting amino acid of cereal grains, on VC. Male Sprague-Dawley rats at age 13 weeks were divided randomly into four groups: low-protein (LP) diet (group LP), LP diet+adenine (group Ade), LP diet+adenine+glycine (group Gly) as a control amino acid group, and LP diet+adenine+l-lysine·HCl (group Lys). At age 18 weeks, group LP had no VC, whereas groups Ade and Gly had comparable levels of severe VC. l-Lysine supplementation almost completely ameliorated VC. Physical parameters and serum creatinine, urea nitrogen, and phosphate did not differ among groups Ade, Gly, and Lys. Notably, serum calcium in group Lys was slightly but significantly higher than in groups Ade and Gly. Dietary l-lysine strongly suppressed plasma intact parathyroid hormone in adenine rats and supported a proper bone-vascular axis. The conserved orientation of the femoral apatite in group Lys also evidenced the bone-protective effects of l-lysine. Dietary l-lysine elevated plasma alanine, proline, arginine, and homoarginine but not lysine. Analyses in vitro demonstrated that alanine and proline inhibit apoptosis of cultured vascular smooth muscle cells, and that arginine and homoarginine attenuate mineral precipitations in a supersaturated calcium/phosphate solution. In conclusion, dietary supplementation of l-lysine ameliorated VC by modifying key pathways that exacerbate VC.Medial vascular calcification is common in aging, diabetes, and CKD.^1–4 Because the presence of vascular calcification is strongly associated with increased cardiovascular morbidity and mortality, several studies in both animals and humans have sought ways to reduce the extent of vascular calcification.^5–10 However, satisfactory therapies have not yet been established.¹¹Adenine-induced renal failure is one of the commonly used animal models for studying the development of vascular calcification, but the prevalence of vascular calcification in this model is not very high. Indeed, Price et al. reported that vascular calcification was detected in only 30% of rats with adenine-induced chronic renal failure (adenine rats) fed a normal-protein diet.⁵ These authors speculated that consistent vascular calcification might require a longer period of adenine feeding. On the basis of this idea, they designed a low-protein (LP) diet in an attempt to reduce the nitrogen load and thus enable the rats to thrive on the adenine diet for longer periods. As a result of this attempt, Price et al. unexpectedly found that adenine rats fed a LP diet had extensive vascular calcification without a longer feeding period.⁵ All 13 adenine rats fed the LP diet had uniform alizarin red staining of the aorta, whereas only 3 of the 11 adenine rats fed a normal-protein diet had partial calcification.⁵ These findings indicated that dietary protein deficiency correlates with the extent of vascular calcification.Proteins are usually made from 20 kinds of amino acids. On the basis of nutritional requirements, these amino acids can be divided into two groups: essential amino acids (EAAs) and non-EAAs. Because restriction of dietary protein results in a shortage of EAAs, the level of dietary EAAs may be relevant to the extent of vascular calcification. Among nine EAAs, this study focused on l-lysine (l-Lys) based on the following three reasons. First, l-Lys is the first-limiting amino acid in most cereal grains.¹² Second, the safety of l-Lys supplementation has been verified in the area of animal husbandry. l-Lys has long been added to feed grains in order to improve the utility of feed proteins.¹³ Third, several studies have demonstrated that dietary supplementation with l-Lys protects bones from osteoporosis, a pathologic condition that often coexists with vascular calcification.^14,15 These points prompted us to hypothesize that supplementation with l-Lys would ameliorate vascular calcification. Therefore, in this study, we tested this hypothesis using adenine rats.     

Endoscopic submucosal dissection for colorectal neoplasia during the clinical learning curve

Background

The efficacy of colorectal endoscopic submucosal dissection (ESD) has been reported mainly from Japanese referral centers. However, ESD is technically difficult and associated with a higher risk of adverse events than endoscopic mucosal resection, especially for novices performing colorectal ESD with little experience in gastric ESD. The current study evaluated the results of colorectal ESD during the clinical learning curve by retrospectively examining the results of colorectal ESD performed by four endoscopists who had experience with fewer than five cases of gastric ESD.

Methods

The study retrospectively investigated the first 20 cases managed by each endoscopist, for a total of 80 cases. The main outcome measurements were procedural time, en bloc resection rate with tumor-free margins (R0 resection rate), and adverse events rate. From among clinicopathologic characteristics, factors that affected main outcome measurements were identified.

Results

Of the 80 cases (56 colonic and 24 rectal lesions; 44 granular laterally spreading tumors (LSTs) and 23 nongranular LSTs, 5 depressed, and 8 protruding), 54 cases (67.5 %) had resection using a standard tip-type knife, and 26 cases (32.5 %) had resection using a small scissors-type knife. The mean tumor diameter was 34.9 ± 14.1 mm, and the mean procedural time was 108.8 ± 53.4 min. The resection in 75 cases (93.8 %) was performed en bloc, and the R0 resection rate was 75 % (60/80). Perforation occurred in six cases (7.5 %) and postoperative hemorrhage in three cases (3.8 %). Multivariate analyses showed that colonic lesions and larger lesions (≥40 mm) were significantly associated with prolonged procedural time (≥90 min). Use of the scissors-type knife was significantly associated with a higher R0 resection rate. Perforation occurred only in colonic lesions.

Conclusions

For novices in colorectal ESD, beginning with rectal and smaller lesions may be advisable. Also, using scissors-type knives may increase the R0 resection rate.     

Aortic root replacement with a freestyle stentless valve for aortitis syndrome with ascending aortic aneurysm and aortic regurgitation.

A 47-year-old woman who had been diagnosed as having aortitis syndrome underwent aortic root replacement for an ascending aortic aneurysm and aortic regurgitation. Because the patient has been treated with steroids for more than 20 years, a Freestyle stentless valve was used to avoid the risk of valve detachment. There were no complications observed during the postoperative course. Although long-term follow-up will be necessary to observe the valve durability, the Freestyle stentless valve seems to be useful for aortic root replacement in patients at high risk of valve detachment due to aortitis syndrome.