[A Case of Aortitis Caused by Pegfilgrastim Use during Neoadjuvant Chemotherapy for Treating Breast Cancer].

Granulocyte colony-stimulating factor(G-CSF)is useful for preventing febrile neutropenia induced by chemotherapy. Recently, some cases of aortitis have been reported following administration of G-CSF. Here, we present a case of aortitis induced by pegfilgrastim(peg-G)use during neoadjuvant chemotherapy for treating breast cancer. A 61-year-old woman with breast cancer(cT2N1M0, stage ⅡB, triple negative)started neoadjuvant chemotherapy FEC(100). Eleven days after the third course of peg-G administration, the patient developed a fever and general malaise. Blood test results showed an increase in inflammatory markers and severe anemia. The symptoms were not controlled with antibiotics. Blood and urine culture test results were negative. Computed tomography revealed remarkable wall thickening of the aorta. Therefore, we suspected aortitis induced by peg-G. The symptoms rapidly improved with prednisolone therapy. The possibility of aortitis should be considered for those with fever or raised inflammatory markers following the use of G-CSF. Steroids can be used for the treatment of G-CSF-induced aortitis.

Effectiveness of eribulin as first-line or second-line chemotherapy for HER2-negative hormone-resistant advanced or metastatic breast cancer: findings from the multi-institutional, prospective, observational KBCRN A001: E-SPEC study.

BACKGROUND: The optimal positioning of eribulin treatment remains unclear. This study aimed to investigate the effectiveness of eribulin administration as first- and second-line chemotherapy in patients with endocrine-resistant advanced or metastatic breast cancer (AMBC) in the real-world clinical setting. METHODS: This multi-institutional prospective cohort study enrolled patients with triple-negative AMBC or estrogen receptor-positive AMBC refractory to at least one previous endocrine therapy. The overall survival (OS) from the start of first-line (OS1) and second-line chemotherapy (OS2) was assessed. Data analysis included real-world chemotherapy sequences of first- to third-line chemotherapy regimens. The adjusted hazard ratio (HR) with 95% confidence interval (CI) for treatment regimen comparison was calculated using a stratified proportional hazards model. RESULTS: Among 201 patients enrolled, 180 were included in the final analysis. Eribulin was administered as first- and second-line chemotherapy to 46 (26.6%) and 70 (47.9%) patients, respectively. Median OS1 and OS2 were 2.25 (95% CI 1.07-2.68) and 1.75 (95% CI, 1.28-2.45) years for first- and second-line eribulin, respectively. Oral 5-FU followed by eribulin had a numerically longer OS1 (2.84 years) than the other sequences. Among patients who proceeded to second-line or later chemotherapy, the median OS1 for those treated with anthracycline or taxane as first- or second-line (n = 98) was 2.56 years (95% CI 2.27-2.74), while it was 2.87 years (95% CI 2.20-4.32) for those who avoided anthracycline and taxane as first- and second-line (n = 48) (adjusted HR, 1.20; 95% CI 0.70-2.06). In the exploratory analysis, OS1 was 2.55 (95% CI 2.14-2.75) and 2.91 years (95% CI 2.61-4.32) for those aged < 65 and ≥ 65 years, respectively (adjusted HR of ≥ 65, 0.91; 95% CI 0.56-1.46). CONCLUSIONS: Eribulin or oral 5-FU administration in first- and second-line chemotherapy without anthracycline/taxane was acceptable in the real-world setting. TRIAL REGISTRATION: This study is registered with Clinical Trials.gov (NCT 02,551,263).

[A Case of Esophageal Gastrointestinal Stromal Tumor Resected by Mediastinoscope-Assisted Transhiatal Esophagectomy].

A 58-year-old man was followed up for esophageal submucosal tumor at our hospital. Esophagogastroduodenoscopy showed the tumor was located on the left side of the thoracic esophagus and had gradually increased in size. Endoscopic ultrasonography revealed an 18×11.5mm hypoechoic tumor connected to the fourth layer of the esophagus and fine needle biopsy revealed c-kit(+), desmin(-)and a-SMA(-). Double-contrast barium study detected a tumor of diameter 20 mm in the middle-lower thoracic esophagus. We diagnosed an esophageal gastrointestinal stromal tumor(GIST)and performed mediastinoscope-assisted transhiatal esophagectomy with gastric tube reconstruction. The maximum tumor diameter was 25mm and pathological evaluation showed c-kit(+), Ki-67 index of less than 5%, and low-risk GIST by the Fletcher classification. Mediastinoscope-assisted transhiatal esophagectomy might be a useful approach for esophageal GIST, because dissection along the esophagus can be performed without thoracotomy.

Incidental detection of clinically unexpected breast lesions by computed tomography.

BACKGROUND: Increased use of computed tomography (CT) has resulted in greater detection of incidental breast lesions unrelated to the primary diagnostic inquiry. PURPOSE: To investigate the morphology and clinical significance of breast abnormalities detected incidentally by conventional CT. MATERIAL AND METHODS: A total of 2945 female patients underwent CT examinations of the body, including the chest, from May 2006 to April 2010. Two radiologists interpreted these CT scans independently and pointed out a mass or non-mass-like lesion as abnormalities in the breast. Patients who incidentally showed breast lesions on CT scans were identified by a computer-based search of the diagnostic reports and were enrolled in this study. The morphology and enhancement patterns of CT-detected breast lesions were evaluated according to BI-RADS-MRI. RESULTS: In total, 32 clinically unexpected abnormal breast lesions were found in 31 (1.1%) patients. Twenty-nine of the 32 lesions were detected by contrast-enhanced CT and three by unenhanced CT. Ten breast cancers were found in 10 patients (0.34%), which yielded the prevalence for malignancy of 31% (10/32). Invasive ductal carcinomas accounted for eight lesions, while two were ductal carcinomas in situ (DCIS). Nine lesions were depicted as a mass and one DCIS was a non-mass-like lesion. Good morphological predictors of breast cancers for a mass were an irregular shape, a lobulated shape, and an irregular margin. Benign lesions accounted for 22 lesions from 21 patients (0.71%). Of these, 13 lesions in 13 patients were depicted as a mass and nine lesions in nine patients as a non-mass-like lesion. CONCLUSION: Unexpected breast lesions can be identified as a mass or non-mass-like lesion on conventional chest CT scans. Among these, breast cancers that are not clinically apparent occur with considerable prevalence. We suggest that careful interpretation of the breast should be a routine part of CT examinations.

[A case of scirrhous carcinoma of the stomach with malignant pleural and peritoneal carcinomatosis responding to the local administration of docetaxel (TXT)].

We report the case of a 34-year-old woman who underwent total gastrectomy for scirrhous carcinoma in the stomach (T4, N0, H0, CY1, P1, Stage IV). Despite adjuvant chemotherapy with TS-1 and/or CDDP, ascites caused by peritoneal carcinomatosis increased four months after gastrectomy. Therefore, intraperitoneal administration of docetaxel (TXT) at a dosage of 45 mg/m2 was applied. This therapy successfully maintained her good quality of life by inhibiting the increase of ascites without any severe adverse side effects for more than six months. When the left effusion from pleural carcinomatosis appeared nine months after the surgery, the intrathoracic administration of TXT succeeded in inhibiting the increase of pleural effusion over five months or more. In this case, intraperitoneal and intrapleural administrations of TXT were effective and temporarily improved the patient's quality of life without any side effects. We thought that the local administration of TXT was a useful treatment without severe toxicities for malignant pleural effusion and ascites in scirrhous carcinoma of the stomach.

Chromosome arm 20q gains and other genomic alterations in esophageal squamous cell carcinoma, as analyzed by comparative genomic hybridization and fluorescence in situ hybridization.

BACKGROUND/AIMS: Our recent analysis of gastric cancers and colorectal cancers using comparative genomic hybridization revealed a novel, high frequent copy number increases the long arm of chromosome 20 in association with possible involvement of liver metastases and poor prognosis. This led to further comparative genomic hybridization analysis of chromosomal aberrations in primary tumors of esophageal squamous cell carcinoma. The aim of the study presented here was to analyze the chromosomal aberrations and to determine the numbers of copies of AIB1, BTAK, DcR3 and E2F1 as putative target genes on chromosome 20q as well as their expression and relation to clinicopathological features in 41 primary tumors of esophageal squamous cell carcinoma. METHODOLOGY: We used comparative genomic hybridization to screen 41 primary tumors of esophageal squamous cell carcinoma for changes in the number of copies of DNA sequences. To further characterize the gain of DNA sequences at 20q, we also performed fluorescence in situ hybridization analysis. We examined the relationship between these changes and clinicopathological factors. RESULTS: Gains in chromosome arm 20q were detected (34.1%) as well as a high level of gain in 20q12-13 (4.8%). AIB1 amplification was observed in 4.9% (2/41), BTAK amplification in 9.8% (4/41), DcR3 amplification was in 4.9% (2/41), and E2F1 amplification in 7.3% (3/41). The survival of patients with BTAK or E2F1 amplification was significantly lower than that of patients without these abnormalities. CONCLUSIONS: These findings provide evidence for a number of previously unknown genomic aberrations in esophageal squamous cell carcinoma, suggesting the existence of target regions relevant to its progression. Esophageal squamous cell carcinoma with 20q gain showed extensive lung metastases, pleural effusion and liver metastases and poorer prognosis compared to cases without 20q gain. Our results suggest that amplification of BTAK or E2F1 are likely to lead to an increase in the number of malignant phenotypes of esophageal squamous cell carcinoma and that these aberrations can be expected to be useful as markers of poor prognosis.

Mutations in exon 11 of the c-kit gene in a myogenic tumor and a neurogenic tumor as well as in gastrointestinal stromal tumors. Utility of c-kit mutation as a prognostic biomarker for gastrointestinal mesenchymal tumor.

BACKGROUND/AIMS: Gain-of-function mutations in exons 9, 11 and 13 of the c-kit gene in gastrointestinal stromal tumors (GISTs) have been identified, and it has been reported that the prognosis is worse for patients with mutation-positive GISTs than for those with mutation-negative GISTs. We studied c-kit mutations in gastrointestinal mesenchymal tumors. By chance, the c-kit mutation in exon 11 was found in myogenic and neurogenic tumors as well as in GISTs. Furthermore, we studied the clinical prognostic utility of these mutations. METHODS: Ten gastrointestinal mesenchymal tumors were stained with HE and immunohistochemically analyzed with alpha-smooth muscle actin, S-100 protein, CD34 and c-kit. In these tumors, as well as in 11 cases of leiomyomas, PCR-amplified DNA from the juxtamembrane (JM) domain of exon 11, the extracellular domain of exon 9 and the tyrosine kinase domain 1 of exon 13 showed a high frequency of c-kit mutation and was sequenced. RESULTS: Although c-kit mutations have previously been reported only in GISTs, we found c-kit mutations in the JM domain of exon 11 in one myogenic and one neurogenic tumor as well as in two GISTs. No c-kit mutation was seen in the 11 cases of leiomyomas. In addition, all four cases with c-kit mutation in exon 11 suffered a relapse sooner than the other cases without c-kit mutations. CONCLUSION: Clinically, the prognosis was worse for the patients with mutation-positive gastrointestinal mesenchymal tumors than for those with mutation-negative tumors. We therefore conclude that the gain-of-function mutation in exon 11 of the c-kit gene is an important prognostic factor for gastrointestinal mesenchymal tumors, including myogenic and neurogenic tumors as well as GISTs.