Hydration with magnesium and mannitol without furosemide prevents the nephrotoxicity induced by cisplatin and pemetrexed in patients with advanced non-small cell lung cancer

Background

The aim of this study was to examine the effect of hydration with magnesium and mannitol without furosemide on the nephrotoxocity accompanying combination chemotherapy using cisplatin and pemetrexed in patients with advanced non-small cell lung cancer (NSCLC).

Methods

Fifty patients with NSCLC who received cisplatin plus pemetrexed, using either old hydration protocol including normal saline with mannitol and furosemide, or a new one including normal saline with magnesium and mannitol without furosemide were retrospectively analyzed. Nephrotoxicity was compared between patients treated using the old protocol and those treated with the new protocol. Univariate and multivariate analyses were performed to identify the independent factors associated with protection against nephrotoxicity in patients with NSCLC who received cisplatin plus pemetrexed.

Results

Thirty patients received the old hydration protocol, while 20 patients were treated using the new hydration protocol. The patients treated using the new hydration protocol showed a significantly greater increase in creatinine clearance (P=0.0004) and a decrease in the serum creatinine level (P=0.0148) after one course of chemotherapy compared with those treated using the old hydration protocol. There were no differences in the chemotherapeutic response or overall survival between the groups (P=0.572). The new hydration protocol with supplemented magnesium with mannitol without furosemide was an independent factor for the protection against nephrotoxicity induced by cisplatin and pemetrexed in patients with advanced NSCLC [HR 0.232 (95% CI: 0.055-0.986), P=0.039].

Conclusions

These results demonstrate that the new hydration protocol comprising supplementation with magnesium without furosemide could prevent the nephrotoxicity induced by cisplatin and pemetrexed without affecting the treatment outcome.KEY WORDS : Lung cancer, cisplatin, magnesium, nephrotoxicity, pemetrexed     

Omentin as a novel biomarker of metabolic risk factors

Background

Omentin is an adipocytokine that is abundantly expressed in visceral fat tissue. We investigated the association of omentin with the number of metabolic risk factors.

Finding

The study population comprised 201 Japanese men who underwent annual health checkups. Plasma omentin levels were determined by enzyme-linked immunosorbent assay. We divided the subjects into 4 groups according to omentin levels. A reduction of plasma omentin levels significantly correlated with an increase in the mean number of metabolic risk factors such as increased waist circumference, dyslipidemia, high blood pressure and glucose intolerance.

Conclusions

Circulating omentin levels negatively correlated with the multiplicity of metabolic risk factors, suggesting that omentin acts as a biomarker of metabolic disorders.     

Spontaneous regression of hepatocellular carcinoma repeated 3 times with invasion of portal vein and inferior vena cava: report on a rare case

A 65-year-old man suffered from advanced hepatocellular carcinoma in the right lobe of the liver, for which he received no treatment. His serum was positive for hepatitis C antibody. In spite of his poor prognosis, he remained in good clinical condition and at 6-month follow-up the tumor had regressed without specific treatment, as assessed both radiologically and from a decrease of a previously elevated serum tumor marker level (1st regression). The tumor regrew in size, but at 23-month follow-up could no longer be visualized radiologically (2nd regression). A follow-up computed tomography (CT) scan did not show any relapse of hepatocellular carcinoma until March 2005. At that time, a new lesion had developed in the caudate lobe and tumor size had increased to ≥10 cm in diameter, and in June 2006 had invaded the portal vein and inferior vena cava. Afterwards, the tumor lesion gradually decreased again. In June 2007, a CT scan showed a further reduction of tumor size (3rd regression). Here, we report a rare case of spontaneous regression of hepatocellular carcinoma in which spontaneous regression and recurrence were repeated 3 times.     

Surgical margin status and recurrence pattern in invasive vulvar Paget’s disease: A Japanese Gynecologic Oncology Group study

ObjectiveTo examine the association between surgical margin status and recurrence pattern in invasive vulvar Paget’s disease.MethodsThis is a preplanned secondary analysis of a previously organized nationwide retrospective study in Japan (JGOG-1075S). Women with stage I-IV invasive vulvar Paget’s disease who received surgical treatment from 2001-2010 were examined (n=139). Multivariable analysis was performed to assess local-recurrence, distant-recurrence, and all-cause mortality based on surgical margin status.ResultsThe median age was 70 years. The majority had stage I disease (61.2%), and the median tumor size was 5.0cm. Nodal metastasis was observed in 15.1%. Simple vulvectomy (46.0%) was the most common surgery type followed by radical vulvectomy (28.1%). More than half received vulvar reconstructive surgery (59.0%). Positive surgical margin was observed in 35.3%, and close margin <1cm was observed in 29.5%. Vulvectomy type was not associated with surgical margin status (P=0.424). The median follow-up was 5.8 years. Positive surgical margin was associated with increased local-recurrence (5-year cumulative rates for positive versus negative margin: 35.8% versus 15.0%, P=0.010) but not distant-recurrence (18.3% versus 16.0%, P=0.567). Positive surgical margin was also associated with increased all-cause mortality (5-year overall survival rates for positive versus negative margin: 72.6% versus 88.2%, P=0.032). In multivariable analysis, positive surgical margin remained an independent factor associated with increased risk of local-recurrence (hazard ratio 2.80, 95% confidence interval 1.18-6.63) and all-cause mortality (hazard ratio 2.87, 95% confidence interval 1.20-6.83).ConclusionPositive surgical margin appears to be common in invasive vulvar Paget’s disease that is associated with increased local-recurrence and all-cause mortality risks. Role of alternative surgical technique or adjuvant therapy merits further investigation to improve local disease control.     

Efficient palliative involved-field radiotherapy on highly progressive diffuse large B-cell primary gastric lymphoma with liver cirrhosis

We report the case of a 73-year-old woman having diffuse large B-cell primary gastric lymphoma with a cirrhotic liver caused by hepatitis C virus infection. She visited our hospital with symptoms of nausea and vomiting, which appeared to be caused by stenosis due to the tumor. Metastatic tumors were seen in the gastric and jugular lymph nodes. The clinical stage was IVB with a high risk of poor prognosis according to the international index. Because of poor hepatic reserve function, standard chemotherapy could not be administered. To maintain her quality of life, palliative involved-field radiotherapy was performed. The symptoms and tumor markers significantly improved, and computed tomography and endoscopy indicated the disappearance of the primary gastric tumor. Two months after radiotherapy and her return home, she died of pneumonia. Autopsy showed neither lymphoma cells nor stenosis of gastric lesion. The significant anti-tumor effect on primary tumor in our case suggests that the involved-field radiotherapy, although palliative, can be a therapeutic option for primary gastric lymphoma patients with various complications.     

Comparison of clinical, tumour-related and dosimetric factors in grade 0-1, grade 2 and grade 3 radiation pneumonitis after stereotactic body radiotherapy for lung tumours

Objective

The aim of this study was to investigate significant clinical, tumour-related and dosimetric factors among patients with grade 0–1, grade 2 and grade 3 radiation pneumonitis (RP) after stereotactic body radiotherapy (SBRT) for lung tumours.

Methods

Patients (n=128) with a total of 133 lung tumours treated with SBRT of 50 Gy in 5 fractions were analysed. RP was graded according to the Common Terminology Criteria for Adverse Events v.3.0. Significant factors were identified by univariate and multivariate analyses. Threshold dose–volume histograms (DVHs) were constructed to identify the incidence of RP.

Results

The median follow-up period was 12 months (range, 6–45 months). In univariate analyses, gender, operability, forced expiratory volume in 1 s (FEV1), internal target volume, lung volumes treated with doses >5–30 Gy (V5–30) and mean lung dose were significant factors differentiating between grade 0–1 and grade 2 RP, and V15–30 were significant factors differentiating between grade 2 and grade 3. However, no factors were significant between grade 0–1 and grade 3 RP. Multivariate analysis showed that female gender, high FEV1 and high V15 were significant factors differentiating between grade 0–1 and grade 2 RP. Threshold DVH curves were created based on ≤5% and ≤15% risk of grade 2 RP among patients with grade 0–2 RP.

Conclusions

Grade 0–2 RP was dose–volume dependent, and female gender and high FEV1 were significant predictive clinical factors for grade 2 RP among patients with grade 0–2 RP. However, incidences of V15–30 in grade 3 RP were significantly lower than those in grade 2 RP, and no significant clinical or tumour-related factors were found. Further studies are needed to identify the mechanism underlying the development of grade 3 RP after SBRT for lung tumours.Previously, we investigated the clinical and dosimetric factors that correlate with severe radiation pneumonitis (RP) in patients with lung tumours treated with stereotactic body radiotherapy (SBRT) [1]. We found that, among a variety of factors, only a short latent period was a significant correlate of severe RP.Other reports [2-6] have also analysed the clinical and dosimetric factors correlated with RP after SBRT. Various dosimetric factors were reported to significantly correlate with RP after SBRT, which included the mean dose in the ipsilateral lung, V7 and V10 by Kyas et al [2], normal tissue complication probability (NTCP) by Ricardi et al [3], lung volumes treated with doses higher than 2.5–50 Gy (V2.5–50) by Guckenberger et al [4], mean lung dose by Barriger et al [5] and contralateral V5 by Ong et al [6].We found a discrepancy in the significant clinical and dosimetric factors between the results of these five studies on low-grade RP [2-6] and our study on severe RP [1]. We speculated that the mechanism underlying the development of grade ≥3 RP might be different from that of grade 2 RP. Additionally, the treatment of grade ≥3 RP was much more critical than that of grade 2 RP. Most patients with grade ≥3 RP needed to be admitted to hospital and steroids or oxygen therapy were administered. By contrast, patients with grade 2 RP were simply followed up carefully without administration of medication as outpatients.In the present study, to ascertain this discrepancy, we analysed the clinical and dosimetric factors that correlated with RP after SBRT among patients with grade 0–1, grade 2 and grade 3 RP in the same sample of patients as that included in our previous study [1].     

Transmission of Bordetella holmesii during pertussis outbreak, Japan

We describe the epidemiology of a pertussis outbreak in Japan in 2010-2011 and Bordetella holmesii transmission. Six patients were infected; 4 patients were students and a teacher at the same junior high school. Epidemiologic links were found between 5 patients. B. holmesii may have been transmitted from person to person.     

Bi-linear dose–response relationship in general populations with low-level cadmium exposures in non-polluted areas in Japan

Background and objectives  

Previous findings suggest that the dose (e.g., cadmium in urine)–response (e.g., tubular dysfunction markers in urine) relationship after environmental exposure to cadmium (Cd) may be in a shape of a hockey stick with a steep slope when Cd exposure exceeds a certain level, i.e., the point of flexion. However, less attention has been paid to the relation below the flexion point whether it is linear or not. The present study was initiated to examine through epidemiological analyses whether the assumption of linearity holds true when Cd exposure is low.