A case of non-palpating breast cancer with huge lymph node metastasis

We report a case of non-palpating breast cancer with huge lymph node metastasis. The patient was a 58-year-old woman who had a huge tumor at her right armpit. The tumor was 4 cm in diameter. Aspiration biopsy cytology for the tumor was performed. The diagnosis is Class V. Mammography showed an ill-defined mass at her right breast. Ultrasonography revealed a low echoic mass at the C area of her right breast. A core needle biopsy for the breast tumor led to a diagnosis of an invasive ductal carcinoma positive for estrogen receptor and progesterone receptor, and negative for HER2/neu protein expression. She received 4 cycles of CEF (E: 60 mg/tri-weekly) plus 12 cycles of paclitaxe (l80 mg/weekly). After chemotherapy, she received muscle preserving mastectomy plus axillary lymph nodes dissection. In histopathology, there were no carcinoma cells in resected breast tissue and resected lymph nodes. Therefore, the effect of chemotherapy was diagnosed as a pathological complete response. After operation, she was administered aromatase inhibitor. The patient has been well and remained disease-free during a follow-up period of 6 years.     

The combined effect of Paclitaxel and toremifene therapy for estrogen receptor positive and aromatase inhibitor resistant metastatic breast cancer

Multidrug resistance proteins such as P-glycoprotein (P-gp) are potential targets for improving the efficacy of paclitaxel (PTX), a mitotic inhibitor used in cancer chemotherapy. The selective estrogen receptor modulator toremifene (TOR) moderate P-gp was related to a drug resistance in vitro. A comparison of PTX alone with PTX+TOR in hormone-receptor-positive metastatic breast cancer patients (MBC) was conducted to determine the therapeutic value of adding TOR to a PTX regiment. Thirteen MBC patients received 80 mg/m2 PTX weekly (PTX group) and 14 MBC patients received the same weekly dose of PTX plus 120 mg/day TOR daily (PTX+TOR group). All 27 patients were repeatedly treated with a combination of PTX and TOR as long as disease progression or unmanageable severe adverse events were defined. The PTX group was compared with PTX+TOR group with respect to best overall response, response rate, clinical benefit rate, time to progression, adverse events and toxic profile of PTX and TOR. No significant difference in response rate was observed between the PTX group and the PTX+TOR group. However, clinical benefit rate and time to progression improved significantly in the PTX+TOR group in comparison with the PTX group. TOR did not significantly enhance the adverse events of PTX. These results suggested that combined treatment of PTX and TOR for MBC patients improves a patient response over PTX alone.     

Safety and feasibility of laparoscopy-assisted distal gastrectomy with suprapancreatic nodal dissection for clinical stage I gastric cancer: a multicenter phase II trial (JCOG 0703)

Background  

Although the number of patients undergoing laparoscopy-assisted distal gastrectomy (LADG) has been increasing, a prospective study with a sample size sufficient to investigate the benefit of LADG has never been reported. We conducted a multi-institutional phase II trial to evaluate the safety of LADG with nodal dissection for clinical stage I gastric cancer patients.     

Synergistic effects of topoisomerase I inhibitor, 7-ethyl-10-hydroxycamptothecin, and irradiation in a cisplatin-resistant human small cell lung cancer cell line.

7-ethyl-10-[4-(1-piperidyl)-1-piperidyl] carbonyloxy-camptothecin, a topoisomerase I (topo I) inhibitor, is one of the most active agent against lung cancer, and its radiosensitizing effect has been reported recently. We evaluated a combination in vitro effect of irradiation and 7-ethyl-10-hydroxy-CPT (SN-38), an active metabolite of 7-ethyl-10-[4- (1-piperidyl)-1-piperidyl] carbonyloxy-camptothecin, on a human small cell lung cancer cell line (SBC-3) and its cisplatin-resistant subline (SBC-3/CDDP). Growth-inhibitory effects of irradiation with or without SN-38 were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. A modified isobologram method was used to evaluate the treatment interaction. The combination of irradiation and SN-38 showed a synergistic inhibitory effect on the growth of SBC-3/CDDP despite its cross-resistance to irradiation and SN-38. In contrast, the same combination showed only an additive effect on the growth of parental SBC-3 cells. There was no significant difference in topo I protein expression between these two cell lines. In SBC-3 cells, topo I catalytic activity was suppressed by 4 Gy of irradiation, without a decrease of nuclear topo I protein, whereas the exposure of SBC-3 cells to 1 microM SN-38 subsequent to irradiation showed no remarkable additional effects on both topo I activity and protein content. On the other hand, in SBC-3/CDDP cells, topo I activity was unchanged by irradiation, but the subsequent exposure to SN-38 gave rise to a decrease in topo I activity, which was accompanied by a significant decrease in the topo I protein content (P = 0.02). These observations may indicate that SN-38 induces sequestration of topo I onto DNA in radiation-treated SBC-3/CDDP cells and suggest that the synergistic effect of irradiation and SN-38 in SBC-3/CDDP cells was considered attributable to DNA repair-related enhanced recruitment of topo I onto the damaged DNA.     

Depletion of CD4+CD25+ regulatory T cells enhances interleukin-2-induced antitumor immunity in a mouse model of colon adenocarcinoma

Interleukin 2 (IL)-2 induces antitumor immunity and clinical responses in melanoma and renal cell carcinoma. However, IL-2 also increases the number of CD4(+)CD25(+) regulatory T (Treg) cells that suppress antitumor immune responses. The aim of the present study was to elucidate the effect of depletion of Treg cells on IL-2-induced antitumor immunity. IL-2-transfected mouse colon adenocarcinoma (MC38/IL-2) cells were implanted subcutaneously or intrahepatically into male C57BL/6 mice, and tumor growth and the proportion of tumor-infiltrating lymphocytes with Treg-cell depletion in response to treatment with anti-CD25 monoclonal antibody (PC61) were determined. In mice treated with phosphate-buffered saline, 40-60% of MC38/IL-2 tumors were rejected. In contrast, all MC38/IL-2 tumors were rejected in mice treated with PC61. The number of tumor-infiltrating CD8(+) T cells in mice treated with PC61 was approximately twice that in mice treated with PBS. The numbers of tumor-infiltrating CD4(+) and natural killer cells were also increased significantly. To test the antimetastatic effects of IL-2 treatment in combination with Treg-cell depletion, human recombinant IL-2 (rIL-2) and PC61 were administered to mice implanted with MC38/mock cells in the spleen, and hepatic metastasis was investigated. The average liver weight in mice treated with rIL-2 plus PC61 was 1.04 +/- 0.03 g, less than that in mice treated with rIL-2 (2.04 +/- 0.51 g) or PC61 alone (1.81 +/- 0.38 g). We conclude that IL-2-induced antitumor immunity is enhanced by Treg-cell depletion and is due to expansion of the tumor-infiltrating cytotoxic CD8(+) T-cell population.     

Study on the Fatigue Crack Initiation and Growth Behavior in Bismuth- and Lead-Based Free-Cutting Brasses

Several studies have been conducted on the fatigue behavior of copper and 7-3, and 6-4 brasses. However, there have been fewer studies on the fatigue behavior and fatigue crack growth (FCG) properties of free-cutting brass, primarily because emphasis has been placed on the development of lead-free free-cutting brass. In this study, fatigue experiments were performed in the atmosphere at room temperature using three types of free-cutting, two types of bismuth (Bi)-based (with different grain sizes), and lead (Pb)-based brasses. It was found that lead-free Bi-based free-cutting brass had approximately the same fatigue performance as that of Pb-based free-cutting brass. It was also clarified that the addition of Bi or Pb initiated fatigue cracks, and that the crack growth period occupied most of the fatigue life. Differences in the FCG behavior of the three free-cutting brasses were observed in the low ΔK range. The modified linear fracture mechanics parameter M was used to quantitatively analyze the fatigue life and FCG behavior (short surface cracks). A comparison between the calculated and experimental results showed that M was useful.     

Heterotopic Gastric Mucosa in Middle Esophagus Complicated with Esophageal Ulcers

Heterotopic gastric mucosa (HGM) of esophagus, primarily occurring in cervical esophagus, is usually asymptomatic. A healthy woman (mid-40s) with postprandial heartburn was diagnosed with middle esophageal HGM and esophageal ulcers by esophagogastroduodenoscopy. Using 8-channel pH monitoring, a sensor near the HGM area detected postprandial acid phase (pH 3-4), while areas adjacent to the proximal and distal sensors were neutral, suggesting acid secretion from the HGM. A biopsy showed fundic gland tissue expressing H⁺/K⁺-ATPase and pepsinogen-I. Oral vonoprazan improved the clinical symptoms and endoscopic findings. This is the first report using 8-channel pH monitoring to diagnose extremely rare middle esophageal HGM.     

Ivabradine as an Adjuvant Agent for Severe Heart Failure Occurring in the Early Phase after Allogeneic Hematopoietic Cell Transplantation

Cardiotoxicity is a critical complication of allogeneic hematopoietic cell transplantation (allo-HCT). In particular, management of severe cardiotoxicity occurring in the early phases of allo-HCT is challenging. We encountered a case of severe cardiotoxicity resulting from AHF six days after allo-HCT, which resisted catecholamines and diuretics. The patient was treated with anthracycline-containing regimens and underwent myeloablative conditioning, including high-dose cyclophosphamide. As invasive circulatory assisting devices were contraindicated because of his immunocompromised status and bleeding tendency, we successfully treated the patient with ivabradine-containing medications. Ivabradine may therefore be considered an alternative drug for the treatment of severe cardiotoxicity induced by cytotoxic agents.     

Denoising using deep-learning-based reconstruction for whole-heart coronary MRA with sub-millimeter isotropic resolution at 3 T: a volunteer study

PURPOSEThe aim of this study was to assess the usefulness of denoising deep-learning-based reconstruction (dDLR) to improve image quality and vessel delineation in noncontrast 3-T whole-heart coronary magnetic resonance angiography (WHCMRA) with sub-millimeter isotropic resolution (Sub-mm) compared with a standard resolution without dDLR (Standard).METHODSFor 10 healthy volunteers, we acquired the WHCMRA with Sub-mm with and without dDLR and Standard to quantify signal- (SNR) and contrast-to-noise ratio (CNR) and vessel edge signal response (VESR) in all the 3 image types. Two independent readers subjectively graded vessel sharpness and signal homogeneity of 8 coronary segments in each patient. We used Kruskal–Wallis test with Bonferroni correction to compare SNR, CNR, VESR, and the subjective evaluation scores among the 3 image types and weighted kappa test to evaluate inter-reader agreement on the scores.RESULTSSNR was significantly higher with Sub-mm with dDLR (P < .001) and Standard (P = .005) than with Sub-mm without dDLR and was comparable between Sub-mm with dDLR and Standard (P = .511). CNR was significantly higher with Sub-mm with dDLR (P < .001) and Standard (P = .005) than with Sub-mm without dDLR and was comparable between Sub-mm with dDLR and Standard (P = .560). VESR was significantly greater with Sub-mm with (P = .001) and without dDLR (P = .017) than with Standard and was comparable between Sub-mm with and without dDLR (P = 1.000). In the proximal, middle, distal, and all the coronary segments, the subjective vessel sharpness was significantly better with Sub-mm with dDLR than Sub-mm without dDLR and Standard (P < .001, for all) and was comparable between Sub-mm without dDLR and Standard (P > .05); the subjective signal homogeneity was significantly improved from Sub-mm without dDLR to Standard to Sub-mm with dDLR (P < .001). The inter-reader agreement was excellent (kappa = 0.84).CONCLUSIONApplication of dDLR is useful for improving image quality and vessel delineation in the WHCMRA with Sub-mm compared with Standard.

Main points

• A denoising method with deep-learning-based reconstruction (dDLR) uses a deep convolution neural network to reduce image noise in magnetic resonance images without additional scan time.
• dDLR can be applied to improve signal- (SNR) and contrast-noise ratio in noncontrast 3-T whole-heart coronary magnetic resonance angiography (WHCMRA) using a spoiled gradient-echo sequence, which offers lower SNR than a steady-state free precession sequence commonly applied at 1.5 T.
• Combined application of dDLR and sub-millimeter isotropic resolution is useful for improving vessel sharpness, signal homogeneity, and delineation of the coronary arteries in the WHCMRA.

Three-dimensional (3D) whole-heart coronary magnetic resonance angiography (WHCMRA) is a noninvasive imaging method for assessing coronary artery stenosis and is advantageous over coronary computed tomography angiography (CCTA) because it does not require radiation exposure or contrast media administration and is only slightly susceptible to calcium-related artifacts.^1-3 Because WHCMRA is commonly limited in delineation of distal coronary segments and quantification of vessel lumen stenosis due to its insufficient spatial resolution and anisotropy, some investigators have used various techniques to acquire WHCMRA with sub-millimeter isotropic resolution (Sub-mm) whose image quality is not necessarily satisfactory at 1.5 T, within an acceptable acquisition time.^4-6 While a steady-state free precession (SSFP) sequence has been commonly applied in noncontrast WHCMRA at 1.5 T, increased B1 field inhomogeneity, frequency offset from tissue susceptibility variation, and specific absorption rate limit consistency of SSFP at 3 T. As such, the spoiled gradient-echo sequence, which decreases the signal-to-noise ratio (SNR) of the coronary arteries, has often been used at 3 T.^7-10A 3-T clinical MR scanner with a maximum gradient magnetic field of 100 mT/m (the slew rate: 200 mT/m/ms) has been recently introduced and can offer thinner slice images at the same bandwidth (i.e., the same sampling interval/time). With this scanner, a denoising method with deep-learning-based reconstruction (dDLR) has been newly developed using a convolution neural network (CNN) to improve SNR in high-resolution MR images without additional scan time.¹¹ Currently, this dDLR algorithm (Advanced intelligent Clear-IQ Engine [AiCE], Canon Medical Systems Corporation) is clinically available only from the single vendor. While some smoothing filters frequently applied in clinical settings are designed to reduce high-frequency noise at the cost of image blurring, we hypothesized that dDLR should only reduce image noise without any negative influence on the delineation of the coronary vessels in WHCMRA. Thus, we performed volunteer studies to assess usefulness of dDLR to improve image quality and coronary vessel delineation in noncontrast WHCMRA with Sub-mm compared with a standard resolution without dDLR (Standard) using this 3-T scanner.