Single-dose daily treatment with cyclosporin A for relapsing nephrotic syndrome: report of a case showing poor response.
Explore the source record for details and available documents.
Child↗
Biomedical subjects
K Tsugawa
Publications and source records attributed to K Tsugawa.
Implication of the peak serum level of mizoribine for control of the serum anti-dsDNA antibody titer in patients with lupus nephritis.
AIM: Mizoribine (MZR) is a novel selective inhibitor of inosine monophosphatase dehydrogenase that was developed in Japan. We previously reported the efficacy and safety of oral MZR pulse therapy, which is associated with elevated peak serum MZR levels, in selected patients with lupus nephritis. However, only limited information is available as yet on the optimal peak serum level of MZR that would yield an enhanced clinical efficacy without serious toxicity in patients with lupus nephritis. METHODS: A total of 11 patients with clinically stable lupus nephritis treated with oral MZR pulse therapy combined with low-dose prednisolone were enrolled in the cross-sectional study. The peak serum concentrations of MZR (as determined by HPLC) and the serum anti-dsDNA antibody titers (as determined by ELISA) were examined in the patients in order to evaluate the correlation between these two parameters. The correlation between the dose of MZR (mg/kg) administered orally as a single daily dose and the peak serum level of the drug was also examined. In two of the patients, serial measurements of the changes in the peak serum levels of MZR and anti-dsDNA titers could be conducted over 10 months. RESULTS: A significant inverse correlation (r = -0.596, p = 0.0116) was observed between the peak serum levels of MZR and the serum anti-dsDNA antibody titers in the study participants, while the dose of prednisolone remained unchanged. The peak level of MZR in the serum was significantly correlated with the single dose of MZR (r = 0.509, p = 0.0371). In the two patients in whom serial measurements were conducted, the first patient who showed a peak serum MZR level of less than 2.5-3.0 microg/ml eventually developed an increase of the serum anti-dsDNA titer with hypocomplementemia and proteinuria. On the other hand, in the second patient who showed a peak serum MZR level in excess of 4.0 microg/ml, persistently low serum anti-dsDNA titers with normocomplementemia were observed. CONCLUSION: Although this study is only a preliminary study conducted on a small sample, we speculate from the results that a peak serum level of MZR of at least more than 2.5-3.0 mirog/ml is necessary to achieve satisfactory clinical efficacy of the drug for the treatment of lupus nephritis. Further study is needed to confirm these preliminary findings.
Administration, Oral↗
C1-C2 point monitoring of low-dose cyclosporin a given as a single daily dose in children with steroid-dependent relapsing nephrotic syndrome.
AIM: It has been reported that the pharmacokinetics of cyclosporin A (CsA) in children is different from that in adults. It appears that, in general, pediatric patients metabolize CsA more rapidly than adult patients, necessitating the use of higher dose of the drug in pediatric transplant recipients. In this context, we speculated that single-dose daily administration of low-dose CsA may be associated with a higher peak blood level without associated trough blood level elevation, and thereby yield better results and allow safer use of the drug than the conventional twice daily administration dosing used for the treatment of childhood idiopathic nephrotic syndrome (INS). METHODS: A total of 10 children with steroid-dependent relapsing INS (9 with biopsy-proven minimal-change disease) who showed steroid toxicity were enrolled in the study. The initial daily dose of CsA (Neoral) used was around 2.0 mg/kg, given as a single daily dose before breakfast. The dose was subsequently adjusted to achieve a C1-C2 point blood level between 600 - 800 ng/ml. The dose of the concomitantly administered prednisolone was tapered following the commencement of CsA. RESULTS: The mean daily CsA dosage, the mean C1-C2 point blood level and the mean trough blood level in the subjects were 2.2 +/- 0.8 mg/kg, 754.0 +/- 71.9 ng/ml and 42.7 +/- 29.2 ng/ml, respectively. At the latest observation, after a mean duration of 17 months (6 - 24 months) of CsA therapy, the minimum dose of prednisolone required for maintenance of clinical remission and the calculated relapse rate were significantly decreased as compared to the respective pretreatment values (0.52 +/- 0.46 mg/kg on alternate days, vs. 0.97 +/- 0.63 mg/kg on alternate days, and 0.28 +/- 0.32 times per six months, vs. 1.06 +/- 0.41 times per six months, respectively, p = 0.005). No significant change was observed in the mean estimated GFR value as compared to the pretreatment value (183.1 +/- 35.4 ml/min/1.73 m2vs. 185.4 +/- 39.3 ml/min/1.73 m2). No evidence of CsA nephrotoxicity was observed in a repeat renal biopsy performed around 12 months after the commencement of CsA therapy in two patients. CONCLUSIONS: Despite the limitations of the study, our results suggest that administration of low-dose CsA as a single daily dose with C1-C2 point blood level monitoring might be an equally effective and safe and, therefore, more cost-beneficial, protocol for the treatment of steroid-dependent cases of relapsing INS, as conventional twice-daily administration of CsA with trough blood level monitoring. Further studies to confirm the long-term efficacy and safety of this CsA treatment protocol in larger numbers of patients are, however, needed.
Adolescent↗
Mizoribine pulse therapy for patients with flares of lupus nephritis: a 1-year observation.
Explore the source record for details and available documents.
Adolescent↗
Mizoribine for the treatment of lupus nephritis in children and adolescents.
AIM: The optimal treatment for lupus nephritis in the pubertal age group is still unclear. We therefore retrospectively evaluated the efficacy and safety of mizoribine (MZR), a novel selective inhibitor of inosine monophosphatase dehydrogenase, developed in Japan for the treatment of lupus nephritis in pubertal patients, because MZR has been reported to have relatively less clinically toxicity than conventionally used drugs. METHODS: Over the past 12 years, we have treated 20 children with newly diagnosed, biopsy-proven lupus nephritis at our hospital. Of these, 10 patients who received a 2-year course of MZR in combination with prednisolone (PSL) as initial maintenance therapy and who could be observed for at least two years after the commencement of the MZR treatment, were enrolled in this study. MZR was given orally at the dose of 4 - 5 mg/kg per day in two divided doses. Changes in the clinical parameters, such as the urinary protein excretion, serum anti-dsDNA antibody titer, serum hemolytic complement activity (CH50) and serum creatinine, and in the frequency of disease flares defined as persistent worsening of those clinical parameters, were examined pre- and posttreatment for comparison, and the steroid-sparing effect of MZR was analyzed. RESULTS: As induction therapy, all the patients had received high-dose oral PSL or intravenous methylprednisolone pulse therapy. Five female patients who were diagnosed to have proliferative lupus nephritis (WHO class III or IV) were scheduled to receive an 8-week course of oral cyclophosphamide (CPA) combined with high-dose steroids prior to the commencement of MZR, but CPA needed to be discontinued in four of these patients because of clinical drug toxicity. The clinical parameters showed significant improvement after the 2-year treatment with MZR combined with PSL, as compared to the pretreatment values (mean urinary protein excretion: 1.6+/-1.9 g/day vs.0.1 +/-0.1 g/day, serum CH50 value: 12.6+/-5.4 U/ml vs. 34.5+/-7.7 U/ml, serum anti-dsDNA antibody titer: 141.8+/-128.2 IU/ml vs. 18.5+/-17.7 IU/ml, respectively (p <0.01)). The serum creatinine remained normal. Although the daily dose of the concomitantly administered PSL to maintain clinical remission could be decreased significantly in all the study participants (39.5+/-1.6 mg/day vs. 6.8+/-5.1 mg/day, p < 0.01), two patients developed flares while on treatment, which were successfully treated by transiently increasing the dose of PSL. The MZR therapy could be completed in all of the patients without significant clinical toxicity being reported. At their most recent follow-up (mean 4.3 years), none of the 10 patients had renal insufficiency, and complete remission without any need for further medication had been achieved in two patients. CONCLUSION: Although this case series is without controls, maintenance therapy with MZR administered in combination with PSL may be beneficial and clinically less toxic in at least a proportion of pubertal patients with lupus nephritis.
Adolescent↗
Quantitative evaluation of metastases in axillary lymph nodes of breast cancer.
We have established a highly sensitive and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method to detect axillary lymph node metastases of breast cancer. Amplifying cytokeratin 19 (CK19) mRNA transcripts using real-time TaqMan PCR made it possible to quantify axillary metastatic burden. Metastases in 358 axillary lymph nodes obtained from 23 breast cancers of 22 patients were investigated by conventional haematoxylin and eosin (H&E) staining, immunohistochemical staining and quantitative RT-PCR assay. The detection rates of axillary lymph node metastasis using H&E staining, immunohistochemistry and RT-PCR assay were 4.5, 5.9 and 13.1%, respectively. RT-PCR assay was the most sensitive of these three methods for detecting lymph node metastases. Cytokeratin 19 mRNA expression values of both histologically and immunohistochemically positive lymph nodes were significantly higher than the values for lymph nodes judged to be negative by both histological and immunohistochemical methods (P<0.0001), and those of histologically negative, but immunohistochemically positive lymph nodes were significantly higher than the values for lymph nodes judged to be negative by both histological and immunohistochemical methods (P<0.0001). Furthermore, metastatic rates of sentinel nodes were higher than the rates of nonsentinel lymph nodes as measured by all three methods. These results indicate that quantitative RT-PCR assay is a sensitive and reliable method for detecting lymph node metastasis. Furthermore, quantification of metastases in sentinel lymph nodes by quantitative RT-PCR assay may be useful to assess the entire axillary burden of breast cancer patients.
Adult↗
Mizoribine oral pulse therapy for patients with disease flare of lupus nephritis.
AIM: Mizoribine (MZR) is a newly developed immunosuppressive agent in Japan. To relieve disease flare of lupus nephritis, a prospective pilot study of oral MZR pulse therapy (a phase II trial) is conducted as an alternative therapy to dose up of corticosteroids. METHODS: Six Japanese patients with biopsy-proven lupus nephritis who experienced disease flare were prospectively evaluated. MZR at a dose of 5 - 10 mg/kg per day (up to 500 mg) in 1 or 2 divided daily doses was orally administered twice a week for 3 months. At the time of disease flare, 4 patients had refused to take dose up of corticosteroids, and the other 2 had complained of opportunistic infection. RESULTS: At presentation, urine protein excretion, serum hemolytic complement activity (CH50) and serum anti-dsDNA antibody were 1.9 +/- 0.6 g/day, 15.7 +/- 5.8 U/ml (normal 23 - 46 U/ml) and 164.8 +/- 184.0 IU/ml (normal < 12.0 IU/ml), respectively. Urine protein excretion and serum anti-dsDNA antibody decreased significantly following MZR oral pulse therapy (0.2 +/- 0.1 g/day and 29.7 +/- 23.4 IU/ml (p < 0.05), respectively), and serum CH50 recovered to normal (35.1 +/- 10.4 U/ml, p < 0.05). Moreover, a significant histologic improvement was observed in a patient who received repeat renal biopsies at pre- and post-treatment. Reported peak serum MZR levels enough to inhibit human mixed-lymphocyte reaction (3.0 - 6.0 microg/ml) were achieved in all patients. No serious adverse effects were observed. CONCLUSION: Although we had no control subjects in this series, MZR oral pulse therapy may be of benefit to a proportion of patients with disease flare of lupus nephritis as an alternative therapy to dose up of corticosteroids.
Administration, Oral↗
Intraoperative lymphatic mapping and sentinel lymph node biopsy in patients with papillary carcinoma of the thyroid gland.
We examined the feasibility of sentinel lymph node biopsy for thyroid cancer. Thirty-eight patients with papillary thyroid carcinoma underwent intraoperative lymphatic mapping and sentinel lymph node biopsy. At surgery, we exposed the thyroid gland and used a tuberculin syringe to inject 0.2 ml of 1% patent blue dye directly into the thyroid mass. The lymphatics and the lymph node dyed with blue dyes, was excised as a sentinel lymph node. Modified radical neck dissection was performed following sentinel lymph node biopsy and the diagnostic ability of sentinel lymph node biopsy was examined. A sentinel lymph node was identified successfully in 27 (71%) of 38 patients. Sentinel lymph node biopsy removed one to three lymph nodes (median, two nodes). Eighteen patients had paratracheal sentinel lymph nodes, five patients had jugular sentinel lymph nodes, and four patients had both. Histological nodal metastasis was recognized in 16 of 27 cases. The positive rate of cancer metastases in sentinel lymph nodes was 58%, which was significantly higher than 11% in non-sentinel lymph nodes. Diagnostic ability of sentinel lymph node biopsy showed that accuracy was 89%, sensitivity was 84%, and specificity was 100%. Our preliminary study indicated that sentinel lymph node biopsy was available on detection of non-palpable nodal metastasis in the patients with thyroid cancer; however, further experience and refinement are needed.
Adult↗
Immunohistochemical localization of vascular endothelial growth factor in the rat portal hypertensive gastropathy.
BACKGROUND AND AIMS: Portal hypertensive gastropathy (PHG) is now recognized to be a distinct entity. Recently, angiogenesis has been noticed as a key factor in clarifying the pathophysiology of various diseases. Angiogenesis in the PHT of explored gastric mucosa has yet to be explored. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. The aim of the present study was thus to investigate whether the hypoxic state exists in PHG, and whether VEGF appears more strongly in PHG than in normal gastric mucosa and, if so, what exactly is the role of the hypoxic state and VEGF in PHG. METHODS: At 1, 3, 7 and 14 days after either a portal ligation or sham operation, the portal venous pressure, the gastric mucosal blood flow volume and the blood gas were measured and, the expression of VEGF and antiproliferating cell nuclear antigen (PCNA) in gastric mucosal specimens was immunohistochemically assessed. RESULTS: The portal pressure (PP) and the gastric mucosal blood flow (GMBF) in the PHT rats were significantly greater than in the control (CTR). Both the SaO2 and PaO2 of the arterial blood gas were lower in the PHT rats than in the control rats. The percentage of VEGF expression in the PHG was found to be higher than that in the control gastric mucosa. The percentage of PCNA expression in the PHG was higher than that in the control gastric mucosa. CONCLUSION: The levels of SaO2 and PaO2 were lower in the PHT rats. There is a possibility that a kind of portal hypertensive gastric change may trigger an enhanced histochemical expression of VEGF. The increased activity of VEGF may have a possibility of the hypoxic gastric mucosal state caused by the presence of active congestion. This damaged mucosal state 'PHG' may thus facilitate the fragility in PHG and such lesions may be slow and insidious, which may therefore lead to sudden and severe anemia, thus causing massive and sometimes fatal hemorrhaging.
Animals↗
Gene therapy for gastric ulcers with single local injection of naked DNA encoding VEGF and angiopoietin-1.
BACKGROUND & AIMS: Angiogenesis, formation of new capillary blood vessels, is crucial for gastroduodenal ulcer healing because it enables delivery of oxygen and nutrients to the healing site. Because angiogenesis is stimulated by vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1), we studied whether local gene therapy with nonviral DNA encoding VEGF and/or Ang1 into the ulcer base could accelerate ulcer healing through enhanced angiogenesis. METHODS: Gastric ulcers were induced in rats by acetic acid applied to the serosal surface of the stomach, and the site around the ulcer was injected with nonviral plasmid-encoding full-length complementary DNA (cDNA) of human recombinant (rh) VEGF165, rhAng1, or their combination. For some studies, neutralizing anti-VEGF antibody was administered. RESULTS: Single local injection of plasmids encoding VEGF165 and Ang1 significantly increased neovascularization and accelerated ulcer healing. A neutralizing anti-VEGF antibody significantly reduced the acceleration of ulcer healing resulting from the treatment. Coinjection of both plasmids encoding rhVEGF165 and rhAng1 resulted in formation of more mature vessels and to more complete restoration of gastric glandular structures within the ulcer scar. However, this did not result in further reduction of ulcer size. CONCLUSIONS: VEGF and Ang1 gene therapy, with limited duration of target gene expression, significantly accelerates gastric ulcer healing. Coinjection of both plasmids leads to more complete structural restoration. Inhibition of accelerated healing by a neutralizing anti-VEGF antibody indicates an essential role for VEGF and enhanced angiogenesis in ulcer healing.
Angiopoietin-1↗
Defective mitogen-activated protein kinase (ERK2) signaling in gastric mucosa of portal hypertensive rats: potential therapeutic implications.
Portal hypertensive (PHT) gastropathy is a frequent, serious complication of liver cirrhosis. PHT gastric mucosa has numerous abnormalities such as reduced mucosal potential differences, reduced surface oxygenation, and increased susceptibility to injury caused by alcohol, aspirin, and other noxious factors. Because such mucosal injury is initially mediated by oxygen free radicals, and because mitogen-activated protein (MAP) kinase (ERK2) protects against cellular stress and induces cell proliferation, we postulated that oxidative stress-induced ERK2 activation is defective in PHT gastric mucosa. Here we show that in PHT gastric mucosa, ERK2 activation by oxidative stress is impaired. This impairment is mediated by overexpression of MAP kinase phosphatase-1 (MKP-1), which results from the underlying and continual oxidative state associated with portal hypertension, and is ameliorated by inhibiting MKP-1. Furthermore, we found that supplementing vitamin E, a free radical scavenger, reduces the oxidative state in PHT gastric mucosa, normalizes MKP-1 expression, and thereby reverses impairment of oxidative stress-induced ERK2 activation. Finally, we show that orally administered vitamin E completely reverses the increased susceptibility of PHT gastric mucosa to alcohol injury. Our findings point to a new molecular and mechanistic basis for PHT gastropathy and provide a new therapeutic modality for protection of PHT gastric mucosa.
Animals↗
A comparison of an open and laparoscopic appendectomy for patients with liver cirrhosis.
Liver cirrhosis is a critical factor contributing to morbidity and mortality in abdominal surgery, because patients with cirrhosis have a particularly high risk of developing bleeding, infection, and ascites. Laparoscopic appendectomy (LA) recently has gained a lot of attention around the world; however, comparisons between the benefits of LA and those of conventional open appendectomy (OA) for patients with liver cirrhosis have yet to be sufficiently compiled. In the present retrospective study, 40 patients with liver cirrhosis who were diagnosed with acute appendicitis before surgery underwent an appendectomy (OA in 25 patients and LA in 15 patients). This study focused on the operative time, amount of postoperative pain, use of analgesics, the restart of a normal diet, number of complications, length of hospital stay, and cost-effectiveness of the procedure in such patients. The amount of postoperative pain and the length of hospital stay were significantly smaller in the LA group. The mean values of the serum C-reactive protein on postoperative days 1, 3, and 7 were significantly less in the LA group. The number of wound infections and wound bleeding was also less in the LA group. The difference in the total cost of hospitalization was not significant. The cost of the operation was greater in the LA group than in the OA group, whereas the hospitalization cost in the LA group was less than that in the OA group. The results of this study suggest that LA may be superior to OA for the treatment of postoperative pain and postoperative complications for patients with liver cirrhosis. Long-term follow-up studies are still necessary, however, to determine any possible decrease in the number of late complications.
Aged↗
Internal mammary chain sentinel lymph node identification in breast cancer.
BACKGROUND AND OBJECTIVES: Sentinel lymph node (SLN) biopsy is not usually performed with respect to the internal mammary lymph node chain. However, the SLN may be located in the internal mammary chain, particularly with medial lesions. We carried out this study to investigate whether lymphatic mapping and SLN biopsy can detect internal mammary involvement in patients with breast cancer. METHODS: A dye- and gamma probe-guided SLN biopsy was performed in a consecutive series of 41 patients with tumor in situ or clinical stage I or II breast cancer. After the biopsy, these patients underwent either a modified radical mastectomy or breast-conserving surgery including axillary lymph node dissection. Biopsy of internal mammary lymph nodes was performed in 19 of these patients. RESULTS: No involvement of internal mammary lymph nodes was found histologically in 5 patients in whom lymphatic flow or a "hot nodule" in the internal mammary chain was found using lymphoscintigraphy. Nodal involvement was demonstrated histologically in only 1 of 5 cases where lymphatic vessels showed dye staining or faintly stained nodes. Internal mammary lymph node biopsy also was performed in 14 of 36 patients with neither stained lymphatic vessels or nodes, nor with lymphatic flow or a hot nodule by lymphoscintigraphy. Nodal involvement was found histologically in 1 of these patients. CONCLUSION: SLN biopsy guided by lymphatic mapping is unreliable for identifying metastases to internal mammary lymph nodes.
Adult↗
Sentinel lymph node biopsy in breast cancer using blue dye with or without isotope localization.
BACKGROUND: The purpose of this study was to determine the feasibility of sentinel lymph node (SLN) biopsy using blue dye with or without isotope localization to predict the presence of axillary and internal mammary lymph node (IMN) metastases in patients with breast cancer. We also investigated whether multiple sectioning of the SLN could improve the accuracy of frozen section examination. METHOD: One-hundred twenty-six patients underwent dye-guided or dye- and gamma probe-guided SLN biopsy followed by complete axillary lymph node dissection (ALND). No ALND was performed in the 14 patients with small tumors and a negative SLN. In addition, 69 patients underwent IMN biopsy. RESULTS: The axillary SLN was identified in 123 of 140 (88%) patients. An accuracy rate of 90% was obtained by frozen section examination of the SLN, which increased to 100% in patients examined with a greater number of sections. Lymphatic flow to the IMN and/or a radioactive hot spot in the IMN was found in 9 of 102 (9%) patients, while a hot node was detected using a gamma probe in only 2 of these patients. No involvement of the IMNs was found histologically in these 9 patients. IMN involvement was found in 7 of 61 (11%) patients without lymphatic flow to the IMNs or a hot spot by lymphoscintigraphy or who did not undergo lymphoscintigraphy. CONCLUSION: ALND can be avoided in patients with small breast cancers and a negative SLN. SLN biopsy guided by lymphatic mapping is unreliable for identifying metastases to IMNs.
Adult↗
Dye- and gamma probe-guided sentinel lymph node biopsy in breast cancer patients: using patent blue dye and technetium-99m-labeled human serum albumin.
BACKGROUND: Sentinel lymph node (SLN) biopsy is a promising method for the diagnosis of the axillary nodal status. We examined the availability of the SLN biopsy using two mapping procedures: the dye- and gamma probe-guided method, and preoperative lymphoscintigraphy by gamma camera imaging. METHODS: We enrolled 48 patients with breast cancer. Technetium-99m-labeled human serum albumin was injected into the subdermal tissue above the primary tumor or biopsy cavity, and preoperative gamma camera imaging was performed. After induction of general anesthesia, patent blue dye was injected into the peritumoral area prior to the surgical procedure. A handheld gamma-detection probe was used to assist in SLN detection. Careful dissection was performed to identify blue-stained afferent lymphatic vessels and nodes. An SLN was defined as any blue and/or radioactive node, and was excised. After SLN biopsy, axillary lymph node dissection of level I, II, and III was completed, in order to confirm the diagnostic ability of the SLN biopsy. RESULTS: Intraoperative SLN identification of axillary lesions was successful in 43 of 48 patients (90%). The dye- and gamma probe-guided method was successful in 25 patients (52%), the dye-guided method alone succeeded in 11 patients (23%), and the gamma probe-guided method alone succeeded in 7 patients (15%). Preoperative lymphoscintigraphy revealed axillary focal accumulations in 29 of 48 patients (60%). All patients who underwent successful preoperative SLN identification by lymphoscintigraphy had successful intraoperative SLN identification. A diagnostic accuracy of 95%, a sensitivity of 89%, and a specificity of 100% were achieved in the diagnosis of axillary metastasis. Internal mammary SLNs were identified in four patients intraoperatively, but we could not detect cancer metastasis in the internal mammary SLNs. CONCLUSIONS: The dye-guided and gamma probe-guided methods were complementary. Preoperative lymphoscintigraphy was useful to predict intraoperative SLN identification. Further study is necessary to assess the role of SLN biopsy of the internal mammary lymph nodes.
Adult↗
Clinical and pathologic factors predicting axillary lymph node involvement in breast cancer.
The diagnosis of axillary disease remains a challenge in the management of breast cancer and is a subject of controversy. In 1998, the Japanese Breast Cancer Society conducted a study assessing axillary lymph node involvement in breast cancer. The study included (a) clinical assessment by pre-operative imaging modalities, (b) histologic assessment for peritumoral lymphatic invasion, (c) biologic assessment by gelatinolytic activity using film in situ zymography, and (d) sentinel lymph node (SLN) biopsy. Clinical assessments by CT, PET, and US as well as biologic assessment were limited in their ability to detect axillary lymph node disease, although these imaging techniques may be useful to exclude node-positive patients from the need for SLN biopsy. Histologic assessment for peritumoral lymphatic invasion was useful, particularly for detecting false-negative cases by SLN biopsy. Nevertheless, the utility of SLN biopsy in assessing axillary nodal status was confirmed. Axillary lymph node dissection (ALND) can be avoided in patients with a small tumor and a negative SLN. However, further studies will be required to investigate the value of SLN biopsy for predicting regional control and survival before it can replace routine ALND as the optimal staging procedure for operable breast cancer.
Axilla↗
A multicenter validation study of sentinel lymph node biopsy by the Japanese Breast Cancer Society.
Several pilot studies have indicated that SLN biopsy can be used to identify axillary lymph node metastases in patients with breast cancer. To confirm this finding, a multicenter study in a variety of practice settings was performed. A total of 674 patients with breast cancer at five institutions were enrolled. The techniques of SLN identification included the vital dye-guided and the vital dye- and gamma probe-guided methods. The SLN was removed, and complete axillary lymph node dissection (ALND) was performed. SLN and ALND specimens were examined separately. The SLN was successfully identified in 214 (94%) of 227 patients using the combined dye- and gamma probe-guided methods. The SLN was identified in 332 (74%) of 447 patients using vital dye-guided method alone. Patient age of at least 21 years, medially located primary tumor, and clinically positive nodes were correlated with failure to identify the SLN. The accuracy of SLN biopsy for the detection of metastatic disease was 96% (522 of 546), and the sensitivity was 90% (203 of 226). Accuracy of 100% was achieved in the patients with tumors less than 1.6 cm in diameter. All 23 false negative results occurred with larger primary tumors. SLN biopsy can accurately predict the presence or absence of axillary lymph node metastases, particularly in patients with small (< or = 1.5 cm) breast cancers.
Adult↗
Role of endothelin-1 in congestive gastropathy in portal hypertensive rats.
BACKGROUND: The aim of this study was to determine the role of endothelin (ET)-1 in portal hypertensive gastropathy (PHG) under portal hypertension, in order to investigate whether the ET(A/B) receptor inhibitor improves the permeability of gastric mucosal microvessels in PHG. METHODS AND RESULTS: Portal hypertensive rats (PVL) and sham-operated rats (CTR) were prepared and then the concentration of plasma ET-1 was measured and the vasopressor response to ET-1 was compared between the two groups. The plasma ET-1 levels in PVL increased significantly compared with CTR; however, the vasopressor response to ET-1 in PVL decreased more than in CTR. Next, the portal venous pressure was measured in both CTR and PVL pretreated with or without a nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), before the injection of ET-1. The portal venous pressure of PVL after receiving ET-1 and being pretreated with L-NAME significantly increased in comparison to the pressure of PVL treated with ET-1 alone (without L-NAME). Moreover, Evans-Blue was injected into each rat and the absorbancy of the gastric contents was measured. The absorbancy of Evans-Blue in PVL increased significantly compared with CTR; however, the absorbancy in PVL+ ET(A/B) receptor inhibitor (Ro47-0203) decreased significantly more than in PVL. CONCLUSIONS: This study showed that ET-1 is a potent vasoconstrictive substance that also has a transitory vasodilative response through NO induced by ET-1 in portal hypertension. In addition, it was found that the vascular permeability of the gastric mucosa increased in portal hypertension and that Ro47-0203 inhibited the hyper-permeability. Accordingly, ET-1 may, thus, play an important role in the development of PHG through NO induced by ET-1. Ro47-0203 may, therefore, be a useful substance for improving PHG in portal hypertension.
Animals↗