Sensitivity to previous irinotecan treatment does not predict the efficacy of combination chemotherapy with cetuximab plus irinotecan for wild-type KRAS metastatic colorectal cancer

The aim of this study was to evaluate the association of sensitivity to previous irinotecan-based chemotherapy with efficacy of cetuximab plus irinotecan therapy in metastatic colorectal cancer (MCRC) patients with wild-type KRAS. We analysed a pooled data set consisting of data from 87 MCRC patients from two previous phase II studies (n = 60) and a group given off-protocol treatment (n = 27) following irinotecan-, oxaliplatin-, and fluoropyrimidine-based chemotherapy. Overall objective response rate to cetuximab plus irinotecan was 28.7%, median progression-free survival (PFS) was 5.3 months, and median overall survival was 12.2 months. Objective response rate did not significantly differ between patients with a favourable response to previous irinotecan (n = 23), stable disease (n = 38), or progressive disease (n = 26), with observed rates of 29.2%, 31.6%, and 23.1%, respectively. Additionally, the non-parametric Spearman rank correlation coefficients (ρ) between the PFS of previous irinotecan-based chemotherapy and that of cetuximab plus irinotecan were quite low (ρ = 0.067 and 0.057 in patients with previous irinotecan as first- and second-line therapies, respectively). Although exploratory nature and small sample size may be limitations of this study, these findings indicate that the efficacy of irinotecan plus cetuximab in MCRC patients with wild-type KRAS did not differ by previous sensitivity to irinotecan.     

Idiopathic retroperitoneal fibrosis diagnosed by CT-guided needle biopsy: a case report

A 72-year-old man was admitted to another hospital because of general fatigue and dyspnea secondary to renal insufficiency. Abdominal computed tomography (CT) and magnetic resonance imaging showed left atrophic kidney, right hydronephrosis, and an intra-pelvic mass of soft-tissue density located anterior to the sacrum, involving the right ureter at the level between the 5th lumber vertebra and the sacrum. He was referred to our hospital after percutaneous nephrostomy was constructed into right kidney. CT-guided needle biopsy revealed the idiopathic retroperitoneal fibrosis, leading us to give him steroid therapy. Three weeks later, radiographic findings showed a remarkable reduction of the mass and the improvement of the right ureteral stricture.     

A case of adenomatoid tumor of the testis treated by testis-sparing surgery: a case report

A 44-year-old man was referred to our hospital with a chief complaint of a painless left intrascrotal mass, palpable at the lower portion of the left testis. Serum levels of tumor markers, human choriogenic gonadotropin (hCG), hCG-beta, and alpha fetoprotein were within the normal limits. Ultrasonography revealed a hyperechoic mass 13 mm in diameter, which was demonstrated as a hypovascular tumor by Gadrinium-enhanced magnetic resonance imaging. Since the tumor was diagnosed as a benign tumor by frozen section examination intraoperatively, testis-sparing surgery was performed. Histological examination revealed adenomatoid tumor originating from the tunica alubuginea of testis. Adenomatoid tumor of the testis is a rare benign tumor, and the present case is the 36th one in the Japanese literature.     

Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RAS mutations

Of 11 children with juvenile myelomonocytic leukemia (JMML) carrying RAS mutations (8 with NRAS mutations, 3 with KRAS2 mutations), 5 had a profound elevation in either or both the white blood cells and spleen size at diagnosis. Three patients had no or modest hepatosplenomegaly and mild leukocytosis at presentation but subsequently showed a marked increase in spleen size with or without hematologic exacerbation, for which nonintensive chemotherapy was initiated. The other three patients with NRAS or KRAS2 glycine to serine substitution received no chemotherapy, but hematologic improvement has been observed during a 2- to 4-year follow up. In the third group, all hematopoietic cell lineages analyzed had the RAS mutations at the time of hematologic improvement, whereas DNA obtained from the nails had the wild type. Additionally, numbers of circulating granulocyte-macrophage progenitors were significantly reduced during the clinical course. Thus, some patients with JMML with specific RAS mutations may have spontaneously improving disease.     

In vitro evaluation of dose-response curve for paclitaxel in breast cancer

Background  The dose-response curve for anticancer agents cannot be evaluated by studying patients directly. To investigate individual differences in the dose-response curve for paclitaxel in breast cancer, we utilized the histoculture drug response assay (HDRA) technique. as]Materials and Methods: Twenty specimens obtained from breast cancer patients who underwent surgical resection were used in this study. The inhibition rates of paclitaxel at several concentrations were measured and fitted to a sigmoid dose-response curve, using non-linear least squares analysis with the fitting equation y=A(l-l/(l+exp(B(x-log(C))))), where A denotes maximal response; B, slope factor; and C, ED50. Results  A dose-response curve was obtained in all tumors. The mean value (±SD) of maximum response, slope factor, and ED50 were 90.2±5.5 %, 9.4 ± 4.3, and 36.8 ± 17.2 μg/g/ml, respectively. The slope factor was higher in nuclear grade 3 tumors compared with nuclear grade 1 and 2 tumors. Conclusion  An individual dose-response curve for paclitaxel in breast cancer can be obtained using the HDRA technique. Nuclear grade 3 tumors appeared to have more uniform chemosensitivity to paclitaxel compared with nuclear grade 1 and 2 tumors.     

Skin barrier structure and function and their relationship to pruritus in end-stage renal disease.

BACKGROUND: The relationship between dry skin and uraemic pruritus remains controversial. In addition, there is a lack of published data describing the structure and function of the stratum corneum (SC) in end-stage renal disease (ESRD). The purpose of the present study was to assess the function and structure of the skin barrier in patients with ESRD and to correlate any abnormalities with uraemic pruritus. METHODS: Thirty-eight subjects participated in the study; 20 with ESRD and 18 healthy controls. Subjects underwent evaluation of SC integrity and permeability barrier recovery, SC surface pH, pruritus and dry skin. The content of glycerol, an important endogenous humectant, was assessed in D-squame tape strips from seven patients with ESRD. Skin biopsies from six of these patients were examined by electron microscopy using ruthenium tetroxide (Ru04)-post-fixation. RESULTS: Although SC integrity was impaired in ESRD patients (P = 0.001), there were no significant differences in permeability barrier recovery rates between ESRD subjects and controls. However, there was a high significant negative correlation between SC glycerol content and dry skin in the arms of ESRD subjects (r = -0.866, P = 0.01). Yet, there was no consistent correlation between pruritus and either dry skin, SC integrity, glycerol content or surface pH. Electron microscopy revealed no significant ultra-structural abnormalities, with particular reference to the lipid bi-layer. CONCLUSIONS: SC integrity, but not permeability barrier recovery, is impaired in dialysis patients. Although dry skin in ESRD is associated with reduced SC glycerol levels, the ultra-structure appears to be unaffected.     

A case of large cell carcinoma of the lung which is suspected of producing granulocyte colony-stimulating factor]

A 41-year-old male complaining of fever and left shoulder pain was admitted to our hospital for further examination of an abnormal shadow on chest X-ray film. His laboratory data on admission showed marked leukocytosis and elevation of serum alkaline phosphatase. The diagnosis of large cell carcinoma of the lung was made by percutaneous biopsy and he was staged clinically as T3N0M0. Chemotherapy including CDDP and VDS resulted in resolution of symptoms and normal laboratory data. After three courses of chemotherapy, he underwent left upper lobectomy with chest wall resection. Pathological diagnosis of the resected tumor was large cell carcinoma with giant cells, and he was staged postoperatively as T3N0M0. Since colony stimulating activity was demonstrated in both homogenate of tumor cells and tumor conditioned medium, and preoperative serum granulocyte colony-stimulating factor (G-CSF) was 105 pg/ml, we concluded that leukocytosis in this patient was caused by G-CSF produced by tumor cells. The patient was in good health two years after surgery with no signs of recurrence.     

Real‐Time Observations of Oriented Crystallization of Poly(ε‐caprolactone) Thin Film,Induced by an AFM Tip

Atomic force microscopy (AFM) was used for modifying the surface structures of poly(ε‐caprolactone) (PCL) thin film. Oriented growth of PCL crystals at a desired area of the film surface was induced by scanning with a strong, normal load. PCL crystals were first grown edge‐on from the induction line and then their orientation changed to flat‐on at a lamellar length. The effects of molecular weight, crystallization temperature, scanning rate, and normal load on the AFM‐tip‐induced crystallization were examined. The growth kinetics of lamellar crystals in the AFM‐tip‐induced crystallization was the same as that in spherulitic crystallization. It was found that the formation of precursors strongly depends on the applied tip load and is facilitated when the applied load is higher than a threshold.

     

Enteritis necroticans 'pigbel' in a Japanese diabetic adult

Enteritis necroticans 'pigbel' is caused by Clostridium perfringens type C but has rarely been reported in developed countries. A 50-year-old Japanese man with untreated diabetes mellitus (DM) presented with diarrhea and abdominal pain. Intraoperative endoscopic and macroscopic examination disclosed segmental annular mucosal lesions characteristic of clostridial enteritis. Clostridial infection type C was verified on pathological, and immunohistochemical analysis. Although rare, the disease is likely to be underdiagnosed. Hence, the pathology and immunohistochemistry of segmental enteritis with annular mucosal lesions should be examined to establish a diagnosis of enteritis necroticans even in mildly affected patients, and especially those with DM.