Effect of proton pump inhibitors on the development of hypomagnesemia induced by panitumumab.

Panitumumab, a therapeutic agent for unresectable advanced/recurrent colorectal cancer, is a human IgG2 monoclonal antibody that binds to and inhibits the activity of the epidermal growth factor receptor (EGFR). The onset of hypomagnesemia is a known side effect of anti-EGFR inhibitors, including panitumumab, and it is thought that inhibition of reabsorption of Mg in renal tubules is one of the causes. In addition, recent reports have shown that long-term administration of proton pump inhibitors (PPIs) reduces serum magnesium levels. Therefore, in this study, 102 patients who received oral PPIs treated with panitumumab were classified into a PPI combination group and a PPI non-combination group, and the effect of PPIs on the development of grade 2 or higher hypomagnesemia was investigated. The incidence of hypomagnesemia in the PPI combination group (46.9%, 15/32) was higher than that in the PPI non-combination group (25.7%, 18/70). A comparison of the backgrounds of the two groups of patients showed a significant difference in serum albumin levels. PPI administration was significantly associated with panitumumab-induced hypomagnesemia development when adjusted for known risk factors, serum albumin level, renal function, and oral magnesium oxide tablets in Cox proportional hazards regression analysis (hazard ratio 2.09; 95% confidence interval 1.03-4.22; P =0.040). These results indicate that detailed monitoring of serum magnesium levels is recommended for patients treated with panitumumab and co-administration of PPIs.

Venous thromboembolisms and rheology in ovarian cancer patients after postoperative adjuvant paclitaxel and carboplatin therapy.

In ovarian cancer patients, chemotherapy can be an independent risk factor for the development of thromboembolic complications, such as venous thromboembolism (VTE). The factors and their values that lead to the development of VTE are remaining unknown in patients undergoing chemotherapy with paclitaxel and carboplatin. This study investigated serial rheological parameters (D-dimer, red blood cell count, hematocrit, and plasma viscosity) for VTE that developed following chemotherapy for ovarian cancer. Forty-eight ovarian cancer patients undergoing chemotherapy were enrolled in this study. A significant difference in the mean values of plasma viscosity and hematocrit was observed between the VTE group (n = 5) and the non-VTE group (n = 43) (P < 0.10). Univariate and multiple regression analyses by stepwise selection identified plasma viscosity as the independent variable associated with VTE development. The VTE incidence was the same as in previous reports. The results support the contention that plasma viscosity could be an index for development of VTE in ovarian cancer after chemotherapy.

A dosimetric comparison of RapidArc and IMRT with hypofractionated simultaneous integrated boost to the prostate for treatment of prostate cancer.

OBJECTIVE: To compare the dosimetric results and treatment delivery efficiency among RapidArc® (Varian Medical Systems, Palo Alto, CA), 7-field intensity-modulated radiotherapy (7-f IMRT) and 9-field IMRT (9-f IMRT) with hypofractionated simultaneous integrated boost to the prostate. METHODS: RapidArc, 7-f IMRT and 9-f IMRT plans were created for 21 consecutive patients treated for high-risk prostate cancer using the Eclipse™ treatment planning system (Varian Medical Systems). All plans were designed to deliver 70.0 Gy in 28 fractions to the prostate planning target volume (PTV) while simultaneously delivering 50.4 Gy in 28 fractions to the pelvic nodal PTV. Target coverage and sparing of organs at risk (OARs) were compared across techniques. The total number of monitor units (MUs) and the treatment time were used to assess treatment delivery efficiency. RESULTS: RapidArc resulted in slightly superior conformity and homogeneity of prostate PTV, whereas all plans were comparable with respect to dose to the nodal PTV. Although OARs sparing for RapidArc and 7-f IMRT plans were almost equivalent, 9-f IMRT achieved better sparing of the rectum and bladder than RapidArc and 7-f IMRT. RapidArc provided the highest treatment delivery efficiency with the lowest MUs and shortest treatment time. CONCLUSION: RapidArc resulted in similar OAR sparing to 7-f IMRT, whereas 9-f IMRT provided the best OAR sparing. Treatment delivery efficiency is significantly higher for RapidArc. ADVANCES IN KNOWLEDGE: This study validated the feasibility and limitations of RapidArc in the treatment of high-risk prostate cancer with complex pelvic target volumes.

[Merits and surgical procedure for conducting transmanubrial osteomuscular sparing approach for lung cancer invading the anterior part of the thoracic inlet].

The surgical technique to achieve complete resection for superior sulcus tumor invading major anatomical sites including the subclavian vessels is challenging. The anterior transcervical-thoracic approach applied by Dartevelle and colleagues provides excellent exposure of the subclavian vessels. Grunenwald and associates have improved on this approach to preserve the clavicle and sternoclavicular joint. This paper describes the merits of this approach and details how to perform this surgical procedure.

A comparison of radiation treatment plans using IMRT with helical tomotherapy and 3D conformal radiotherapy for nasal natural killer/T-cell lymphoma.

The purpose of this study was to compare radiation treatment plans (RTPs) that used intensity-modulated radiation therapy (IMRT) with helical tomotherapy (HT) or three-dimensional conformal radiation therapy (3D-CRT) for nasal natural killer/T-cell lymphoma (NNKTL). We created RTPs that used IMRT with HT or 3D-CRT for eight NNKTL patients previously treated at our institution and conducted a pilot comparison between the two modalities using the parameters of the target coverage and homogeneity for the planning target volume (PTV) and the maximum and mean doses for organs at risk (OARs). The clinical target volume (CTV) included the gross tumour volume with an additional margin of 1.5 cm and the nasopharynx, palates and nasal cavity; the PTV with the CTV plus a 2 mm margin received a total dose of 50 Gy. IMRT achieved significantly better PTV coverage, with more than 99% of the PTV receiving 90% and 95% of the prescribed dose, whereas 3D-CRT could not provide adequate coverage of the PTV, with 89.1+/-2.6% and 84.5+/-2.7% of the PTV receiving 90% and 95% of the prescribed dose, respectively (both p <0.0001). The homogeneity index was 0.29+/-0.06 for IMRT and 0.046+/-0.022 for 3D-CRT, which was statistically significant (p <0.0001). IMRT tended to provide equivalent or slightly better OAR avoidance than 3D-CRT. In conclusion, 3D-CRT could not provide adequate coverage of the PTV because the PTV was close to many OARs. IMRT should be used for NNKTL because a lack of optimal RTPs could cause local failure.

Helical tomotherapy for brain metastases: dosimetric evaluation of treatment plans and early clinical results.

The purpose of this study was to evaluate the feasibility and treatment plans of intensity-modulated radiation therapy using helical tomotherapy (HT) for brain metastases. Twenty-three patients with 1 to 4 brain metastases were treated with HT. In combination with whole-brain radiotherapy (simultaneous plans), metastatic lesions, and the whole brain were treated with 50 Gy and 30 Gy, respectively, in 10 fractions, with a simultaneous integrated boost technique. In patients treated for brain metastases alone (focal plans), metastatic lesions were treated with 35 or 37.5 Gy in 5 fractions. The treatment plans were compared regarding the conformation number (CN) and homogeneity index (HI), and differences in these indexes between simultaneous and focal plans were examined by Student's t-test. Seven and 16 patients were treated with simultaneous plans and focal plans, respectively. The mean +/- SD of CN and HI values were 0.75 +/- 0.13 and 0.063 +/- 0.042, respectively, for simultaneous plans, and 0.73 +/- 0.12 and 0.052 +/- 0.023, respectively, for focal plans. The CN and HI between the two plans were not significantly different. Response rates in 13 patients with follow-up imaging were approximately 90% for both plans and the local control rate at 1 year was 69%. One patient with a huge tumor (34.0 cc) and WHO performance status 3 treated with focal plans experienced severe headache, requiring prolongation of the treatment time, and died at 8 days after completion of treatment. The exact cause of deterioration was uncertain as no radiological investigation was performed in this patient. No late complications were observed during follow-up periods up to 20 months. HT is a viable non-invasive technique for treatment of brain metastases and achieves high accuracy in terms of dose conformity and homogeneity.

Localized mediastinal lymph node amyloidosis showing an unusual unsynchronized pattern of enlargement and calcification on serial CT.

Amyloidosis is an unusual cause of mediastinal lymphadenopathy. A localized form of amyloidosis manifesting solely in the intrathoracic lymphnode is extremely rare. We describe a case of intrathoracic lymphadenopathy caused by a localized form of amyloidosis. Calcification has been reported in amyloidosis; however, it has been considered as non-specific. In our case, serial CT carried out over a period of 3 years and 3 months showed an unusual and unsynchronized pattern of enlargement and calcification.

Intra-arterial chemoradiotherapy for locally advanced oral cavity cancer: analysis of therapeutic results in 134 cases.

The objective of this study was to investigate the therapeutic results of arterial injection therapy via the superficial temporal artery for 134 cases of stages III and IV (M0) oral cavity cancer retrospectively, and to clarify the prognostic factors. We administered intra-arterial chemoradiotherapy by continuous infusion of carboplatin in 65 cases from January 1993 to July 2002. Systemic chemotherapy was performed on 26 cases at the same time. We administered intra-arterial chemoradiotherapy by cisplatin with sodium thiosulphate in 69 cases from October 2002 to December 2006. Systemic chemotherapy was performed on 48 cases at the same time. The 3-year local control rate was 68.6% (T2-3: 77.9%; T4: 51.3%), and the 3-year survival rate was 53.9% (stage III: 62.9%; stage IV: 45.3%). Regarding the results of multivariate analysis of survival rates, age (<65), selective intra-arterial infusion, and the use of cisplatin as an agent for intra-arterial infusion were significant factors. The therapeutic results of intra-arterial chemoradiotherapy via the superficial temporal artery were not inferior to the results of surgery. In particular, the results of arterial injection therapy by cisplatin with sodium thiosulphate were excellent, so we believe that it will be a new therapy for advanced oral cavity cancer.

[An adult congenital bronchoesophageal fistula with massive hemoptysis; report of a case].

A 67-year-old female was referred to our hospital because of bronchoesophageal fistula detected by upper gastro-intestinal series for cancer screening. The patient has had a history of coughing on liquid ingestion since childhood and she has been hospitalized 4 times for treatment of pneumonia during the past 20 years. While waiting the treatment, she was emergently admitted to the hospital because of massive hemoptysis. Transcatheter embolization of feeding arteries including the right inferior phrenic artery successfully controlled her hemoptysis. After reembolization of the feeding arteries for preventing massive hemorrhage during operation, posterolateral thoracotomy was performed. Surgical findings disclosed the bronchoesophageal fistula without inflammatory changes. She underwent fistulectomy combined resection of the middle and lower lobes which were destroyed by the repeated pneumonia. This case was considered type I congenital bronchoesophageal fistula according to Braimbridge and Keith classification because of the presence of diverticular projection which connected to the bronchus. Early diagnosis and rapid treatment are thought to be important for treating this disease.

[Extrapleural pneumonectomy for thoracic malignancies].

Extrapleural pneumonectomy has been used by thoracic surgeons in the treatment of malignant pleural mesothelioma as well as other pleural diseases, such as tuberculous empyema. Recently, this operative procedure has been also sporadically applied for the treatment of carcinomatous pleuritis of lung cancer and/or invasive thymoma in some institutions. We performed this operation in 24 patients with thoracic malignancy: 15 patients with carcinomatous pleuritis of primary lung adenocarcinoma (6 patients with T4N0 disease, 2 with T4N1, and 7 with T4N2), 3 patients with stage IV a thymoma, and 6 patients with malignant pleural mesothelioma (2 patients with stage II disease, 3 with stage III, and 1 with stage IV). All patients survived the operation and were discharged from the hospital. Major complications were intrathoracic hemorrhage and empyema in 2 patients each. The median survival time and 5-year survival rate of lung cancer patients were 34 months and 45.5%, respectively. All patients with thymoma are alive now without disease 9 to 133 months after operation. All patients with malignant pleural mesothelioma except 1, who lately underwent this treatment, died of disease from 15 to 27 months after surgery. Our results indicate that carefully selected patients with carcinomatous pleuritis of lung cancer and thymoma may be candidates for extrapleural pneumonectomy for cure. Nevertheless, the ultimate value of this surgical treatment should be ascertained in a prospective study with a large number of patients.

Atypical adenomatous hyperplasia of the lung: a clinicopathological study of 118 cases including cases with multiple atypical adenomatous hyperplasia.

BACKGROUND: Atypical adenomatous hyperplasia (AAH) of the lung is a putative precursor lesion of adenocarcinoma, according to many immunohistochemical and genetical studies, but few clinicopathological studies on a large number of cases have been reported. The aim of this study was to clarify the clinicopathological characteristics of lung cancer patients with AAH lesions. METHODS: A retrospective study was carried out on 508 consecutive primary lung cancer patients operated on at National Cancer Center Hospital East. The relationship between the number and location of AAH lesions and the clinicopathological features of the lung cancer patients was analysed statistically. RESULTS: A total of 311 AAH lesions were found in 118 (23.2%) of the 508 cases. AAH lesions were detected in 121 of 572 lobes examined, usually in both upper lobes, and occurred most frequently in patients with adenocarcinoma (OR 2.97; 95% CI 1.82 to 4.85). AAH lesions were more frequently detected in patients with multiple primary carcinomas than in those with a single carcinoma (OR 3.06; 95% CI 1.56 to 6.00). The presence of AAH lesions was not significantly correlated with sex, age, smoking status, familial history of malignancy, or preceding malignancy. Patients with multiple AAH lesions were found to have a significantly higher frequency of preceding malignancies. CONCLUSIONS: The present study highlights the clinicopathological characteristics of AAH lesions, showing them to be significantly associated with both adenocarcinoma and multiple primary carcinoma of the lung and suggesting common factors in the histogenesis of multiple AAH lesions and preceding malignancy.

Treatment of solitary small hepatocellular carcinoma: consideration of hepatic functional reserve and mode of recurrence.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) recurs frequently after initial treatment. The subsequent prognosis varies with the mode of recurrence. Some patients die of hepatic failure even though the HCC is controlled. We consider the clinical stage (CS), using the modified Child-Pugh classification, to be an important factor influencing the prognosis of these patients. METHODOLOGY: To determine the most effective treatment for HCC, we examined 105 patients with solitary small HCC who were followed-up for more than 1 year after initial treatment. All of them were judged to be cured according to imaging or histological studies. The initial treatments were hepatic resection (n = 43), percutaneous ethanol injection therapy (PEIT, n = 33), and percutaneous microwave coagulation therapy (PMCT, n = 29). The modes of recurrence were divided into intrahepatic metastasis (IM) and multicentric occurrence (MO). RESULTS: Prognosis of MO was superior to that of IM in CS I patients, but there was no difference in prognosis between these modes in CS II. The hepatic resection group had more MO recurrences in CS I patients and more IM recurrences in CS II patients. IM developed frequently after PEIT and PMCT, regardless of the CS. Prognosis with hepatic resection was superior to that of the other treatments in CS I patients, but there was no difference in prognosis among the 3 treatment modalities in CS II patients. CONCLUSIONS: These data indicate that hepatic resection is the first choice for treating HCC in CS I patients, and that PEIT or PMCT is preferable for CS II patients.

Coping skills in Japanese women with eating disorders.

The aim of this study was to investigate coping skills in the different types of eating disorders in Japan. Groups of patients with eating disorders diagnosed with DSM-IV and 22 controls were studied. Coping skills were assessed with the Stress Coping Inventory. The mean Problem-focused coping score tended to be lower in the bulimia nervosa purging-type group (n = 20) than in the control group. The former group and the bulimia nervosa nonpurging-type group (n = 6) used significantly less planful problem solving and less positive reappraisal coping than the control group, while the anorexia nervosa restricting-type group of 11 tended to use less positive reappraisal, and the anorexia nervosa binge-eating/purging-type (n = 11) tended to use less planful problem solving and less positive reappraisal than the control group. As some uses of coping skills by patients with eating disorders were lower than those of the control group, developing coping skills may be useful in treatment for eating disorders in Japan.

Treatment of a Brodie bite by lower lateral expansion: a case report and fourth year follow-up.

The patient was a 4 year 4 month old boy at the first visit. The chief complaint was chewing dysfunction. The intra-oral and facial films, study casts, cephalometrics, muscle-balance monitor, temporomandibular joint radiographs were analyzed. The patient presented with a Brodie bite or unilateral posterior cross bite. The upper dental arch was wider than other children of his age. The lower dental arch was significantly smaller than the upper dental arch. The lower dental arch was expanded using a Schwarz appliance. The period of treatment was one year and two months. The period of observation was four years and ten months. First the patient underwent chewing training and secondarily then was treated by lateral expansion. After this treatment the patient achieved good occlusion and muscle function, while the morphology and function of the temporomandibular joints were improved, as well.

A new pedicled seromuscular flap technique for high-risk intestinal anastomoses.

A new method for protecting intestinal anastomoses in patients at high risk of anastomotic dehiscence or fistula formation is described herein. This method involves raising a seromuscular flap on a pedicle from the stump of the intestine to be anastomosed. The anastomosis is performed, then covered with the seromuscular flap.

[Small increase of CR1 and CR3 by C5a-receptors on polymorphonuclear leukocytes in systemic lupus erythematosus].

One of the anaphylatoxins, C5a, is known to increase the expression of the complement receptors, CR1 and CR3, on PMNs which play important roles in the phagocytosis. We measured the expression of these receptors before and after the stimulation with C5a and C5a-receptors (C5aR) on PMNs in patients with systemic lupus erythematosus (SLE). PMNs from 16 patients and 11 normal controls were tested. All the patients with SLE were administered with prednisolone orally and were in the inactive stage. The CR1 expression in SLE was significantly weak (p < 0.01) before and after stimulation with 4.55 nM (50 micrograms/ml) of C5a. There was no significant difference of CR3 expression before stimulation. However, after the stimulation with C5a, the increase of CR3 on PMNs from SLE was significantly small (p < 0.01). C5aR on PMNs showed no difference between the two groups. However, the expression of C5aR was significantly suppressed in patients treated with a high dosage of prednisolone (> = 10 mg/day) compared to those with a low dosage of prednisolone (< 10 mg/day). There was no significant difference of CR1 and CR3 expression between these groups. It is concluded that the increase of CR1 and CR3 on PMNs by C5a in small in SLE, of which impaired increase is not due to C5aR on PMNs, and that the expression of C5aR is suppressed by prednisolone.

[Effect of macrophage colony-stimulating factor on complement receptors and complement regulatory proteins on human peripheral white blood cells].

The effect of M-CSF and C5a on the expression of complement-related membrane proteins on the peripheral white blood cells was investigated. M-CSF or C5a was added into the suspension of the peripheral white blood cells. The expression of the complement receptors, CD35 (CR1) and CD11b/18 (CR3), and inhibitory membrane proteins, DAF and MCP, was measured by flow cytometry. M-CSF increased CR3 on polymorphonuclear cells (PMNs) and CR1, CR3, MCP and DAF on monocytes. C5a increased CR1, CR3 and DAF on PMNs, but did not affect the expression of those on monocytes. It is concluded that M-CSF possessed the activity of increase expression of both complement regulatory proteins and complement receptors of monocytes and C5a selectively affected the expression of those on PMNs.