Successful Pre-Operative Local Control of Skin Invasion of Breast Cancer Using a Combination of Systemic Chemotherapy and Mohs Paste

Locally advanced breast cancer (tumor > 5 cm, widespread infiltration of the skin and muscle, or metastases to lymph nodes) is difficult to resect by surgery, and even when it is resectable, there is a high probability of local recurrence and distant metastasis. Therefore, systemic therapy should be administered first. However, as cutaneous infiltration progresses, the patient''s quality of life is impaired by pain, bleeding, presence of exudates, and a foul-smelling odor. Treatment with Mohs paste with systemic therapy can control symptoms associated with skin infiltration and can also be expected to decrease tumor volume. Herein, we report a case in which a tumor was resected following Mohs paste and systemic chemotherapy administration, and the skin defect was reconstructed with a latissimus dorsi myocutaneous flap. We also review the literature for previously reported cases of breast cancer involving Mohs paste.     

Cystathionine β‐synthase mutations in homocystinuria

The major cause of homocystinuria is mutation of the gene encoding the enzyme cystathionine β‐synthase (CBS). Deficiency of CBS activity results in elevated levels of homocysteine as well as methionine in plasma and urine and decreased levels of cystathionine and cysteine. Ninety‐two different disease‐associated mutations have been identified in the CBS gene in 310 examined homocystinuric alleles in more than a dozen laboratories around the world. Most of these mutations are missense, and the vast majority of these are private mutations. The two most frequently encountered of these mutations are the pyridoxine‐responsive I278T and the pyridoxine‐nonresponsive G307S. Mutations due to deaminations of methylcytosines represent 53% of all point substitutions in the coding region of the CBS gene. Hum Mutat 13:362–375, 1999. © 1999 Wiley‐Liss, Inc.     

Expression of the SART‐1 tumor rejection antigen in breast cancer

We investigated in breast cancers the expression of the SART‐1 gene encoding tumor rejection antigens. SART‐1 mRNA was expressed in all of the samples tested. The SART‐1₈₀₀ antigen was detectable in 20 of 50 (40%) breast cancer tissues and all breast cancer cell lines tested, but not in normal breast tissues. The SART‐1₈₀₀⁺ breast cancer cells transfected with HLA‐A2601 or HLA‐A2402 cDNA were recognized by the HLA‐A26‐restricted and SART‐1‐specific cytotoxic T lymphocytes (CTLs) or the HLA‐A24‐restricted and SART‐1‐specific CTLs, respectively. Among the 20 SART‐1₈₀₀⁺ tumors, 9 or 8 tumors expressed estrogen receptor or progesterone receptor, respectively. Therefore, the patients with HLA‐A26 or ‐A24 haplotype might be appropriate candidates for specific immunotherapy with the SART‐1 peptides independently or in combination with hormone therapy. Int. J. Cancer 80:64–67, 1999. © 1999 Wiley‐Liss, Inc.     

The outcome and characteristics of patients with relapsed adult T cell leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation

Treatment options for patients with adult T cell leukemia/lymphoma (ATLL) who have relapsed disease after allogeneic hematopoietic stem cell transplantation (allo‐HSCT) are limited. To clarify which patients with ATLL are likely to benefit from these treatment options and to define patient populations for novel treatments, we performed a nationwide retrospective analysis of 252 Japanese patients who had relapsed ATLL after allo‐HSCT. Some long‐term survivors remained after tapering and withdrawal of immunosuppressive agents. Thirty‐six patients who received donor lymphocyte infusion had a better overall survival (OS) in comparison to those who did not [hazard ratio (HR), 0.63; 95% confidence interval (CI), 0.43‐0.93; P = .02], suggesting the efficacy of a graft‐versus‐ATLL (GvATLL) effect even after relapse. Multivariate analysis demonstrated that skin lesions at initial relapse of ATLL were independently associated with higher OS (HR, 0.41; 95% CI, 0.22‐0.74; P = .003), indicating that the skin is a susceptible target organ of GvATLL. This study suggested that enhancement of a GvATLL effect is a potential therapeutic option for relapsed disease after allo‐HSCT. Further investigations of incorporation of immune‐based approaches with new molecular target drugs into the therapeutic options of patients with ATLL before and after transplantation are warranted.     

Safety,pharmacokinetics, and efficacy of E6011, an antifractalkine monoclonal antibody,in a first-in-patient phase 1/2 study on rheumatoid arthritis

Objective: Fractalkine (CX3CL1/FKN) is a chemokine that regulates chemotaxis and adhesion of CX3C chemokine receptor 1 (CX3CR1)-expressing inflammatory cells. We conducted the first phase 1/2, open-label, multiple ascending dose study of E6011, a humanized anti-FKN monoclonal antibody, in Japanese rheumatoid arthritis (RA) patients (clinicaltrial.gov identifier: NCT02196558).

Methods: Active RA patients with an inadequate response or intolerance to methotrexate or tumor necrosis factor (TNF) inhibitor received E6011 at week 0, 1, 2, and thereafter every 2 weeks for 12 weeks.

Results: Twelve, 15, and 10 subjects were enrolled in the 100, 200, and 400?mg cohorts, respectively. No severe adverse events (AEs) or deaths occurred, and no major differences were observed in the incidence or severity of AEs across the cohorts. Serum E6011 concentrations increased dose dependently. American College of Rheumatology (ACR) 20, 50, and 70 responses at week 12 were 75.0%, 33.3%, and 8.3% in the 100?mg cohort; 66.7%, 20.0%, and 13.3% in the 200?mg cohort; and 60.0%, 30.0%, and 20.0% in the 400?mg cohort, respectively.

Conclusions: E6011 appeared to be safe and well tolerated in RA patients during this 12-week treatment period, suggesting that E6011 has an effective clinical response in active RA patients.     

Risk of malignancies in autoimmune hepatitis type 1 patients with a long‐term follow‐up in Japan

Aim

The risk of malignancies in autoimmune diseases is high and is regarded to be due to immunological abnormalities, the use of immunosuppressive agents, and/or chronic inflammation. The aim of this study was to investigate the incidence and risk of malignancies in patients with autoimmune hepatitis (AIH) type 1 in Japan.

Methods

Two hundred and fifty‐six patients diagnosed with AIH were enrolled. A person‐year calculation was carried out for AIH patients, and the numbers of expected events were clarified using data from “The Monitoring of Cancer Incidence in Japan Project” in order to examine the standard incident rate (SIR) of each type of malignancy. Biochemical data regarding carcinogenesis and its background factors were also examined.

Results

Twenty‐seven patients (10.5%) developed malignancies; 11 (4.3%) with hepatobiliary cancer and 16 (6.3%) with extrahepatic malignancies. The overall SIR for malignancies in AIH was significantly high at 2.04 (95% confidence interval [CI], 1.34–2.96), and was high among female patients at 2.49 (95% CI, 1.60–3.71). The SIR for hepatobiliary cancer was 14.14 (95% CI, 7.05–25.30), and was markedly high for female patients at 21.83 (95% CI, 10.45–40.16). The SIR for oral/pharyngeal cancer was significantly high for female patients at 14.61 (95% CI, 1.64–52.77). The risk factors for hepatobiliary cancer at the diagnosis of AIH were low levels of alanine aminotransferase (P = 0.0226), low platelet counts (P < 0.0001), and cirrhosis (P = 0.0004). The risk factor for extrahepatic malignancy was relapse of AIH (P = 0.0485).

Conclusion

The risk of malignancies was generally high among AIH patients. Those with the risk factors of malignancies should be carefully followed up.     

Infantile-onset spinocerebellar ataxia type 5 associated with a novel SPTBN2 mutation: A case report

BackgroundSpinocerebellar ataxia type 5 (SCA5), a dominant spinocerebellar ataxia is caused by spectrin beta nonerythrocytic 2 gene (SPTBN2) mutation. It typically consists of a slow progressive cerebellar ataxia with an onset principally in adulthood. Here, we report on the first Japanese patient with infantile-onset SCA5 associated with a novel heterozygous SPTBN2 mutation.Case reportThe patient, a 6-year-old girl, developed delayed motor development and unsteady arm movement during infancy. She also showed gaze-evoked nystagmus, saccadic eye pursuit, dysarthria, dysmetria, intention tremor and mild intellectual disability. Brain MRI revealed moderate cerebellar atrophy and mild pontine atrophy. Comprehensive target capture sequencing to identify the causative gene identified a novel missense mutation in SPTBN2 (c.1309C<G, p.R437G), which was thought to be pathogenic.DiscussionTwo patients with infantile-onset SCA5 associated with another novel heterozygous SPTBN2 mutation have recently been reported; these SPTBN2 mutations, which may have a significant impact on protein function, were located in the second spectrin. Our findings indicate that SPTBN2 mutations may be associated with infantile-onset cerebellar ataxia accompanied with global developmental delay.