Tsuyoshi Nakagawa

Background and Objectives: This study compares the clinical properties of original breast ultrasound images and those synthesized by a generative adversarial network (GAN) to assess the clinical usefulness of GAN-synthesized images. Materials and Methods: We retrospectively collected approximately 200 breast ultrasound images for each of five representative histological tissue types (cyst, fibroadenoma, scirrhous, solid, and tubule-forming invasive ductal carcinomas) as training images. A deep convolutional GAN (DCGAN) image-generation model synthesized images of the five histological types. Two diagnostic radiologists (reader 1 with 13 years of experience and reader 2 with 7 years of experience) were given a reading test consisting of 50 synthesized and 50 original images (≥1-month interval between sets) to assign the perceived histological tissue type. The percentages of correct diagnoses were calculated, and the reader agreement was assessed using the kappa coefficient. Results: The synthetic and original images were indistinguishable. The correct diagnostic rates from the synthetic images for readers 1 and 2 were 86.0% and 78.0% and from the original images were 88.0% and 78.0%, respectively. The kappa values were 0.625 and 0.650 for the synthetic and original images, respectively. The diagnoses made from the DCGAN synthetic images and original images were similar. Conclusion: The DCGAN-synthesized images closely resemble the original ultrasound images in clinical characteristics, suggesting their potential utility in clinical education and training, particularly for enhancing diagnostic skills in breast ultrasound imaging.

Background This study investigated the cause of skin flap necrosis following total mastectomy to prevent skin flap necrosis. Methods For 79 patients who underwent total mastectomy at our institution, the skin incision line was set at operation, and each dissection distance from the skin incision line to the area of mastectomy was measured and photographed. The photographs were analyzed to determine the skin resection area. The approximate area of the total anterior chest on the operative side was also measured by preoperative positron emission tomography-computed tomography (PET-CT) to determine the ratio of the skin resection area to total anterior chest area on the operative side. The results were compared for the necrosis and non-necrosis groups. Results The skin resection area and the perimeter of the skin incision line were significantly greater in the necrosis group (p = 0.009, 0.004); the ratio of the skin resection area to total anterior chest area on the operative side was also significantly greater in the necrosis group (p = 0.005). Intraoperative indocyanine green angiography showed significant differences in the skin resection area and the ratio of the skin resection area to anterior chest area (p = 0.006, 0.025) compared between the cases with areas of relative perfusion ≤ 11% and two other groups. The skin resection area affected blood perfusion of the skin flap, causing a partial reduction in blood flow. Conclusions In total mastectomy, larger skin resection significantly increases the risk of necrosis due to reduced blood perfusion of the skin flap.

Ulceration of a reconstructed nipple occurred in a woman in her 50s who had undergone mastectomy, axillary lymph node dissection, and deep inferior epigastric artery perforator flap reconstruction for right breast cancer. The implanted cartilage was removed on suspicion of infection and the ulcer was biopsied. Local recurrence was identified on histopathological examination. Local recurrence near a reconstructed nipple can cause ulceration because of the fragility of the reconstructed nipple tissue. If erosion or ulceration develops in the reconstructed nipple relatively long after surgery, pathological examination is warranted.

We investigated whether ¹⁸F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography images restored via deep learning (DL) improved image quality and affected axillary lymph node (ALN) metastasis diagnosis in patients with breast cancer. Using a five-point scale, two readers compared the image quality of DL-PET and conventional PET (cPET) in 53 consecutive patients from September 2020 to October 2021. Visually analyzed ipsilateral ALNs were rated on a three-point scale. The standard uptake values SUV_max and SUV_peak were calculated for breast cancer regions of interest. For “depiction of primary lesion”, reader 2 scored DL-PET significantly higher than cPET. For “noise”, “clarity of mammary gland”, and “overall image quality”, both readers scored DL-PET significantly higher than cPET. The SUV_max and SUV_peak for primary lesions and normal breasts were significantly higher in DL-PET than in cPET (p < 0.001). Considering the ALN metastasis scores 1 and 2 as negative and 3 as positive, the McNemar test revealed no significant difference between cPET and DL-PET scores for either reader (p = 0.250, 0.625). DL-PET improved visual image quality for breast cancer compared with cPET. SUV_max and SUV_peak were significantly higher in DL-PET than in cPET. DL-PET and cPET exhibited comparable diagnostic abilities for ALN metastasis.

Tumor-associated macrophages (TAMs) and abnormalities in cancer cells affect cancer progression and response to therapy. TAMs are a major component of the tumor microenvironment (TME) in breast cancer, with their invasion affecting clinical outcomes. Programmed death-ligand 1 (PD-L1), a target of immune checkpoint inhibitors, acts as a suppressive signal for the surrounding immune system; however, its expression and effect on TAMs and the clinical outcome in breast cancer are unknown. In this study, we used high-throughput multiple immunohistochemistry to spatially and quantitatively analyze TAMs. We subjected 81 breast cancer specimens to immunostaining for CD68, CD163, PD-1, PD-L1, CD20, and pan-CK. In both stromal and intratumoral areas, the triple-negative subtype had significantly more CD68/CD163, CD68/PD-L1, and CD163/PD-L1 double-positive cells than the estrogen receptor (ER)/progesterone receptor (PR) subtype. Interestingly, a higher number of CD68+/PD-L1+/CK-/CD163- TAMs in the intratumoral area was correlated with a favorable recurrence rate (p = 0.048). These findings indicated that the specific subpopulation and localization of TAMs in the TME affect clinical outcomes in breast cancer.

The uptake of ¹⁸F-fluorothymidine (¹⁸F-FLT) depends on cells’ proliferative rates. We compared the characteristics of ¹⁸F-FLT positron emission tomography/computed tomography (PET/CT) with those of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET/CT for breast cancer. We prospectively diagnosed patients with breast cancer who underwent ¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT. Subsequently, significant differences and correlation coefficients of the maximum standardized uptake value (SUVmax) in primary breast cancer and axillary lymph nodes were statistically evaluated. We enrolled eight patients with breast cancer. In six treatment-naive patients, the SUVmax for primary lesions showed a significant difference (mean, 2.1 vs. 4.1, p = 0.031) and a strong correlation (r = 0.969) between ¹⁸F-FLT and ¹⁸F-FDG. Further, although the SUVmax for the axillary lymph nodes did not show a significant difference between ¹⁸F-FLT and ¹⁸F-FDG (P = 0.246), there was a strong correlation between the two (r = 0.999). In a patient-by-patient study, there were cases in which only ¹⁸F-FDG uptake was observed in lymph nodes and normal breasts. Bone metastases demonstrated lower accumulation than bone marrow on the ¹⁸F-FLT PET/CT. In conclusion, a strong correlation was observed between the ¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT uptake. Differences in the biochemical characteristics of ¹⁸F-FLT and ¹⁸F-FDG were reflected in the accumulation differences for breast cancer, metastatic lesions, and normal organs.

A woman in her 70s was diagnosed with left breast cancer and left axillary lymph node metastasis by an ultrasound-guided biopsy. ¹⁸F-FDG-PET/CT showed strong FDG accumulation in the tumor in the left breast and a left axillary lymph node. Neoadjuvant chemotherapy (NAC) was administered in combination with a G-CSF injection to prevent febrile neutropenia. The post-treatment ¹⁸F-FDG-PET/CT showed the disappearance of the left breast tumor and left axillary lymph node and revealed a solitary new area of strong FDG accumulation in the sternum. To rule out the possibility of sternal metastasis, a sternal biopsy was performed at the same time as surgery, which revealed no malignant findings. Although very rare, focal uptake on ¹⁸F-FDG-PET/CT performed after anticancer drug therapy with G-CSF may mimic a solitary bone metastasis. A bone biopsy may be a useful technique to avoid an immediate misdiagnosis of bone metastasis.

Bone marrow carcinomatosis (BMC) associated with breast cancer is a rare but often difficult-to-treat condition; we report a case of a female stage IV breast cancer patient in her seventies with BMC that improved with endocrine monotherapy. The patient had hemoglobinopenia and thrombocytopenia at the time of diagnosis. The diagnosis of BMC due to estrogen receptor-positive invasive lobular carcinoma was confirmed. After transfusion of 4 units of concentrated red blood cells, endocrine treatment with letrozole improved the hematopenia. Ten months after the treatment started, bone metastases worsened, so the patient was changed to combination therapy with palbociclib and fulvestrant, after which there was no worsening of the disease.

Introduction: Clinical sequencing has provided molecular and therapeutic insights into the field of clinical oncology. However, despite its significance, its clinical utility in Japanese patients remains unknown. Here, we examined the clinical utility of tissue-based clinical sequencing with FoundationOne^® CDx and FoundationOne^® Heme. Between August 2018 and August 2019, 130 Japanese pretreated patients with advanced solid tumors were tested with FoundationOne^® CDx or FoundationOne^® Heme. Results: The median age of 130 patients was 60.5 years (range: 3 to 84 years), and among them, 64 were males and 66 were females. Major cancer types were gastrointestinal cancer (23 cases) and hepatic, biliary, and pancreatic cancer (21 cases). A molecular tumor board had been completed on all 130 cases by October 31, 2019. The median number of gene alterations detected by Foundation testing, excluding variants of unknown significance (VUS) was 4 (ranged 0 to 21) per case. Of the 130 cases, one or more alterations were found in 123 cases (94.6%), and in 114 cases (87.7%), actionable alterations with candidates for therapeutic agents were found. In 29 (22.3%) of them, treatment corresponding to the gene alteration was performed. Regarding secondary findings, 13 cases (10%) had an alteration suspected of a hereditary tumor. Of the 13 cases, only one case received a definite diagnosis of hereditary tumor. Conclusions: Our study showed that clinical sequencing might be useful for detecting gene alterations in various cancer types and exploring treatment options. However, many issues still need to be improved.