Two-Year-Span Breast Cancer Screening Uptake in Japan after the COVID-19 Pandemic and Its Association with the COVID-19 Vaccination.

There is limited information on whether the COVID-19 pandemic was associated with decreased breast cancer screening uptake and if COVID-19 vaccination was associated with an increase in screening uptake. Our study explored the uptake of breast cancer screening in Japan after the COVID-19 pandemic and assessed its association with the COVID-19 vaccination. We analyzed data from the Japan COVID-19 and Society Internet Survey (JACSIS), a web-based prospective cohort survey, and we included 6110 women without cancer history who were aged 40 to 74 years that participated in the 2012 and 2022 surveys. We examined the regular breast cancer screening uptake before and after the pandemic and employed a multivariable Poisson regression model to seek any association between COVID-19 vaccination and screening uptake. Of 6110, 38.2% regularly participated in screening before the pandemic and 46.9% did so after the pandemic. Individuals unvaccinated due to health reasons (incidence rate ratio (IRR) = 0.47, 95% CI: 0.29-0.77, p = 0.003) and for other reasons (IRR = 0.73, 95% CI: 0.62-0.86, p < 0.001) were less likely to undergo screening compared to fully vaccinated individuals. There was no long-term decrease in breast cancer screening uptake after the pandemic in Japan. Vaccination was linked to increased uptake, but there was no dose relationship.

Pneumocystis Pneumonia in Locally Advanced Breast Cancer Despite Prophylactic Use of Trimethoprim-Sulfamethoxazole During Prednisolone Treatment for a Pembrolizumab-Induced Immune-Related Adverse Event: A Case Report.

Pneumocystis pneumonia (PCP) primarily affects immunosuppressed patients, with trimethoprim-sulfamethoxazole (TMP-SMX) commonly used for prophylaxis. However, there is insufficient information on PCP occurrence despite TMP-SMX prophylaxis. We encountered a 57-year-old woman with locally advanced breast cancer developing PCP despite prophylactic intake of TMP-SMX, during treatment with prednisolone for Stevens-Johnson syndrome (SJS) induced by pembrolizumab. This case underscores the need to pay attention to the possibility of PCP development even during TMP-SMX prophylaxis. Dosage and duration adjustments according to the patient's condition and weight may be required.

Soluble interleukin-2 receptor as a predictive and prognostic marker for patients with familial breast cancer.

The incidence of breast cancer increases annually, and it has become common within families of breast cancer patients. Interleukin-2 activates cytotoxic T lymphocytes, which are important for cancer immunity. To identify markers of increased familial breast cancer risk, soluble interleukin-2 receptor levels and immunologic factors were investigated in familial breast cancer and non-familial breast cancer patients. Of 106 untreated breast cancer patients in this study, 24 had familial breast cancer and 82 had non-familial breast cancer. The patients' soluble interleukin-2 receptor, interleukin-10, vascular endothelial growth factor, interleukin-17, regulatory T cell, myeloid-derived suppressor cell, white blood cell, and C-reactive protein levels, and their neutrophil-to-lymphocyte ratios were measured, and their prognoses were compared according to the soluble interleukin-2 receptor levels. Additionally, postoperative tissues from the patients with high soluble interleukin-2 receptor levels were stained with programmed cell death ligand 1 and cluster of differentiation 8. The soluble interleukin-2 receptor level in the familial breast cancer patients was significantly higher, and it showed significantly stronger correlations with the neutrophil-to-lymphocyte ratio and the interleukin-10, vascular endothelial growth factor, interleukin-17, regulatory T cell, myeloid-derived suppressor cell, white blood cell, and C-reactive protein levels, than in the non-familial breast cancer patients. The regulatory T cell and myeloid-derived suppressor cell levels were significantly higher in the patients with high soluble interleukin-2 receptor levels, and the overall survival and disease-free-survival rates were significantly worse for the familial breast cancer patients than for the non-familial breast cancer patients. Triple-negative breast cancer tissues from the familial breast cancer patients with high soluble interleukin-2 receptor levels stained well for programmed cell death ligand 1 and cluster of differentiation 8. Soluble interleukin-2 receptor levels can be used to predict the prognosis of familial breast cancer patients. Prospectively identifying patients who are less likely to have non-familial breast cancer is vital for improving their overall survival.

A case of lipoma, calcification, and brain malformations in the midline of the skull.

Few cases of pericallosal lipoma with several other lesions, including specific forms of calcification and brain malformations, have been reported. We present the case of an asymptomatic 83-year-old man with a pericallosallipoma with peculiar symmetrical morphology in the midline of the skull. We posit that the lesions began forming in the very early embryonic period and were closely associated with the cranial neural crest cells. We report the neuroradiological findings of this characteristic lesion and discuss several literature reviews on the process of its formation.

Ingestion of Okinawa Island Vegetables Increases IgA Levels and Prevents the Spread of Influenza RNA Viruses.

BACKGROUND: It has been hypothesized that flavonoid ingestion stimulates immunity, promotes health, and prevents human illness. The aim of this analysis was to evaluate the association of the levels of immunoglobulin A (IgA) with the prevention of influenza infections and with the polyphenols contained in Okinawan vegetables. METHODS: IgA, immunoglobulin G (IgG), immunoglobulin M (IgM), and soluble interleukin-2 receptor (sIL-2R) levels were measured in 44 outpatients who regularly ingested vegetables grown on Okinawa Island (200-300 g/day for ≥ 300 days/year) with no history of influenza infection and in 73 patients who ingested the vegetables irregularly or not at all with a history of influenza infection. RESULTS: The patients who regularly ate Okinawan vegetables had higher IgA, IgG, and IgM levels than those who did not. On the other hand, patients who did not consume Okinawan vegetables and had influenza had lower IgA, IgG, and IgM levels. In addition, the IgA and IgG levels showed significant positive correlations with the sIL-2R levels in both groups. CONCLUSIONS: It may be beneficial to eat vegetables abundant in polyphenols every day. Secretory IgA antibodies are an important part of the immune defense against viral diseases. People who ingest Okinawan vegetables have high IgA levels and might be more likely to develop immunity against influenza RNA viruses.

Ficus pumila L. improves the prognosis of patients infected with HTLV-1, an RNA virus.

Human T-cell leukemia virus type 1 was isolated as the retrovirus to be identified in humans. Here, we focused on Ficus pumila L. as a factor that be effective against human T-cell leukemia virus type 1. The significant and novel findings is that symptoms of patients with drinking Ficus pumila L. extracts did not worsen despite a lack of aggressive pharmacotherapy against adult T-cell leukemia, a human T-cell leukemia virus type 1-associated myelopathy, or T-cell leukemia virus type 1 uveitis. Twenty-eight of the 194 inpatients who underwent showed high levels of human T-cell leukemia virus type 1.Among human T-cell leukemia virus type 1-infected patients, those who were administered Ficus pumila L. extracts had no human T-cell leukemia virus type 1-related symptoms, while those who were not administered Ficus pumila L. extracts had human T-cell leukemia virus type 1-related diseases and a significantly poorer prognosis. This suggests that the Ficus pumila L. extracts may show some utility against virus infection.

Cluster of differentiation 8 and programmed cell death ligand 1 expression in triple-negative breast cancer combined with autosomal dominant polycystic kidney disease and tuberous sclerosis complex: a case report.

BACKGROUND: Autosomal dominant polycystic kidney disease is defined as an inherited disorder characterized by renal cyst formation due to mutations in the PKD1 or PKD2 gene, whereas tuberous sclerosis complex is an autosomal dominant neurocutaneous syndrome caused by mutation or deletion of the TSC2 gene. A TSC2/PKD1 contiguous gene syndrome, which is caused by a chromosomal mutation that disrupts both the TSC2 and PKD1 genes, has been identified in patients with tuberous sclerosis complex and severe early-onset autosomal dominant polycystic kidney disease. The tumor tissue of patients with breast cancer with contiguous gene syndrome has a high mutation burden and produces several neoantigens. A diffuse positive immunohistochemistry staining for cluster of differentiation 8+ in the T cells of breast cancer tissue is consistent with neoantigen production due to high mutation burden. CASE PRESENTATION: A 61-year-old Japanese woman who had been undergoing dialysis for 23 years because of end-stage renal failure secondary to autosomal dominant polycystic kidney disease was diagnosed as having triple-negative breast cancer and underwent mastectomy in 2015. She had a history of epilepsy and skin hamartoma. Her grandmother, mother, two aunts, four cousins, and one brother were also on dialysis for autosomal dominant polycystic kidney disease. Her brother had epilepsy and a brain nodule. Another brother had a syndrome of kidney failure, intellectual disability, and diabetes mellitus, which seemed to be caused by mutation in the CREBBP gene. Immunohistochemistry of our patient's breast tissue showed cluster of differentiation 8 and programmed cell death ligand 1 positivity. CONCLUSIONS: Programmed cell death ligand 1 checkpoint therapy may be effective for recurrence of triple-negative breast cancer in a patient with autosomal dominant polycystic kidney disease and tuberous sclerosis complex.

Association between cognitive impairment patient with solid cancer and insulin resistance.

OBJECTIVES: In an aging population, an increase in the number of elderly cancer patients with cognitive impairment is expected. The possible association between cancer and cognitive impairment is important to elucidate, because it can have a serious impact on quality of life. Here, we focused on glucose metabolism as a factor that links cancer and cognitive impairment. RESULTS: Thirteen subjects with solid cancers and cognitive impairment were recruited. As a control group, 14 subjects with cognitive impairment alone and 8 subjects with cancer alone were recruited. A Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and that of ß-cell function (HOMA-B) were used. In comparison with patients with solid cancer alone, those with cognitive impairment alone and those with both cancer and cognitive impairment had increased HOMA-IR values. Insulin resistance was increased in patients with cognitive impairment alone and those with both cognitive impairment and solid cancer than in patients without cognitive impairment; however, ß-cell function was not affected. The present data indicated that elderly cancer patients with high HOMA-IR score may be at a relatively high risk for developing cognitive impairment. Furthermore, early treatment to reduce insulin sensitivity may prevent cognitive impairment.

Prognostic impact of interleukin-6 and C-reactive protein on patients with breast cancer.

The prognostic impacts of preoperative C-reactive protein (CRP) and interleukin (IL)-6 expression levels in patients with breast cancer remain controversial. A total of 55 female patients with invasive breast cancer were enrolled, and preoperative prognostic parameters including IL-6 and CRP were analyzed. Overall survival (OS) and recurrence-free survival (RFS) were estimated using the Kaplan-Meier method, and candidates' prognostic factors were examined using a Cox proportional hazard model. Using receiver operating characteristic curve analysis, IL-6 at 10.0 pg/ml and CRP at 0.12 mg/dl were determined as threshold values to predict OS and RFS, respectively. Patients with IL-6 ≥10.0 pg/ml had poorer OS compared with those with IL-6 <10.0 pg/ml (P=0.003), and patients with CRP ≥0.12 mg/dl had poorer RFS compared with those with CRP <0.12 mg/dl (P<0.001). Serum IL-6 level (hazard ratio, 13.230; 95% confidence interval, 1.285-136.214; P=0.030) and triple-negative subtype (hazard ratio, 11.739; 95% confidence interval, 1.415-97.362; P=0.023) were independent prognostic factors for OS, and CRP expression level was an independent prognostic factor for RFS in patients with breast cancer (hazard ratio, 18.571; 95% confidence interval, 2.240-153.949; P=0.007). In patients with invasive breast cancer, preoperative serum IL-6 and triple-negative subtype may be independent prognostic factors for OS, while for RFS, preoperative CRP may be a more accurate prognostic factor compared with those currently established.

MLH1 germline mutation associated with Lynch syndrome in a family followed for more than 45 years.

BACKGROUND: Lynch syndrome, is an autosomal dominantly inherited disease that predisposes individuals to a high risk of colorectal cancers, and some mismatch-repair genes have been identified as causative genes. The purpose of this study was to investigate the genomic rearrangement of the gene in a family with Lynch syndrome followed for more than 45 years. CASE PRESENTATION: The family with Lynch syndrome is family N, who received colorectal cancer treatment for 45 years. The proband of family N had multiple colorectal and uterine cancers. Because the proband met the diagnostic Amsterdam criteria and was Microsatellite instability (MSI) - positive, we performed genetic testing several times. However, germline mutations in MLH1 and MSH2 genes were not found by long-distance PCR or RT-PCR/direct sequencing analysis within the 45-year follow-up. MLPA analysis showed that the genomes of the proband and proband's daughter contained a deletion from exon 4 through exon 19 in the MLH1 gene. Her son's son and her daughter's son were found to be carriers of the mutation. CONCLUSIONS: For carriers of mismatch-repair gene mutation among families with Lynch syndrome, the onset risk of associated cancers such as uterine cancer is particularly high, including colorectal cancer. The diagnosis of carriers among non-onset relatives is important for disease surveillance.

[A Case of Rectal Colon Cancer with Paraneoplastic Cerebellar Degeneration].

A case complicated with colorectal and prostate cancers in paraneoplastic(subacute)cerebellar degeneration(PCD)is extremely rare. We report a retrospective case of rectal carcinoma with paraneoplastic cerebellar degeneration. A 79-year-old man with Parkinson's disease was unable to walk because of paralysis. Brain MRI showed cerebellar atrophy. He was admitted to our hospital for anal bleeding and was diagnosed with colon cancer. An associated diagnosis of PCD was made. After resection, his paralysis and dysarthria were resolved to the extent of beingable to walk and speak fluently. Brain MP-RAGE showed no findings suggestive of metastasis or atrophy. He was treated surgically, which resulted in a transient improvement in PCD symptoms. Per blood testing, cytokines IL-6 and IL-10 were lower postoperatively. Immunosuppressive levels of myeloid- derived suppressor cells(MDSCs)were lower compared with the preoperative values. Thus, innate immunocompetence and resolution of paralysis followed the surgical intervention.

[A Case of Recurrent Colon Cancer with Peritoneal Dissemination Treated with Aflibercept Showing Partial Response for One Year].

We report a case of recurrent colon cancer that achieved partial response with chemotherapy of combined 5-fluorouracil (5-FU), irinotecan, Leucovorin(FOLFIRI), and aflibercept. A 65-year-old man was diagnosed with colon cancer with lymph node metastasis. He underwent surgery, but after 1 year, he had a recurrence of peritoneal dissemination, nodal enlargement, and liver metastases. He received chemotherapy(mFOLFOX plus bevacizumab), but suffered progressive disease. Thereafter, FOLFIRI plus aflibercept was administered, and CT revealed a decrease in peritoneal dissemination after 2 cycles of chemotherapy. After 23 cycles, a PET-CT showed no evidence of the disease. We also examined 9 recent cases treated with aflibercept in terms of Grade 3 and 4 adverse effects, leukopenia, neutropenia, thrombocytopenia, hypertension, and sweating. Placentalderived growth factor(PIGF)has been reported to stimulate macrophages and induce production of IL-6, and thus it promotes inflammation and growth of extant cancer. Among the responses to chemotherapy based on the RECIST criteria, a partial response was significantly higher in patients with a low neutrophil-to-lymphocyte ratio(NLR)(p≤0.05)compared to those with high NLR. As regards the relationship between NLR and OS in patients treated with FOLFIRI plus aflibercept, OS was significantly worse in patients with high NLR than those with low NLR(p≤0.05). NLR may be a useful marker in conjunction with aflibercept treatment.

Poland syndrome accompanied by internal iliac artery supply disruption sequence: a case report.

BACKGROUND: Poland syndrome is a congenital malformation characterized by ipsilateral hand and chest wall depression, including an absence or hypoplasia of the breast and pectoral muscles. These hypoplastic defects are reportedly caused by a subclavian artery supply disruption sequence. CASE PRESENTATION: A 45-year-old Japanese woman, an out-patient, underwent an emergency examination for intense left lower abdominal pain. Computed tomography images revealed a hydronephrotic left kidney and dilatation of the left ureter. No ureteral calculus or neoplasm was found. In addition, no abnormalities connected to her left abdominal pain were found. Nephritis was diagnosed based on the results of urine analysis, and a course of antibiotics was administered. Computed tomography images also revealed a history of breast reconstruction with a custom-made silicone implant in her right breast. The present case showed symptoms of Poland syndrome, which were absence of the sternal head of the right pectoralis major and asymmetrical malformation of the chest wall due to hypoplasia of the right rib cage. In addition to typical Poland syndrome symptoms, she had hypoplasia of her right kidney, hypoplasia of the right gluteus minimus muscle, right-sided pelvic hypoplasia, spinal curvature to the right, and a cystic mass in her right ovary. CONCLUSIONS: In the present case of Poland syndrome, computed tomography images revealed malformation of the chest wall, absence of the pectoral muscle, and hypoplasia of a left kidney. Unilateral visceral hypoplasia is reported to be caused by a subclavian artery supply disruption sequence that occurs around 7 to 8 weeks of gestation. The present case can be considered a rare atypical phenotype of Poland syndrome with possible subclavian artery supply disruption sequence with internal iliac artery supply disruption.

Prognostic impact of elevated preoperative C-reactive protein on patients with differentiated thyroid carcinoma.

BACKGROUND: C-reactive protein (CRP) has been reported to be associated with poorer prognosis in various malignancies. However, the relationship between CRP and differentiated thyroid carcinoma (DTC) remains to be elucidated. METHODS: A total of 45 patients, including 32 patients with preoperative DTC and 13 DTC patients with metastatic disease, were included in the study. The relationships between CRP levels and clinicopathological features were retrospectively analyzed. RESULTS: Analysis using a receiver operating characteristic curve revealed a preoperative CRP cutoff value of 0.155 mg/dL. Patients with preoperative CRP ≥ 0.155 mg/dL, those with T3 + T4, those with extrathyroidal invasion, or those with stage II, showed a statistically shorter recurrent-free survival than those with preoperative CRP < 0.155 mg/dL, those with T1 + T2, those without extrathyroidal invasion, or those with stage I (P = 0.001, P = 0.004, P = 0.024, and P = 0.025, respectively). Preoperative CRP ≥ 0.155 mg/dL was an independent prognostic factor for recurrent-free survival in the DTC patients (hazard ratio = 6.334, 95% confidence interval: 1.023-39.234, P = 0.037). The proportion of patients aged ≥55 y, and those with T3 + T4, was statistically higher in those with preoperative CRP ≥ 0.155 mg/dL than in those with preoperative CRP < 0.155 mg/dL (P = 0.037 and P = 0.038, respectively). CONCLUSIONS: Higher preoperative CRP levels have a robust prognostic impact on recurrence-free survival in DTC patients. In addition, higher preoperative CRP levels were associated with age ≥ 55 y and T3 + T4.

Prognostic impact of soluble intercellular adhesion molecule-1 in hepatocellular carcinoma.

The identification of novel biomarkers for hepatocellular carcinoma (HCC) is of great importance in improving the outcome of patients with HCC. The present study aimed to determine the prognostic significance of the soluble intercellular adhesion molecule (sICAM)-1 in patients with HCC. The present study prospectively collected clinicopathological data from 36 patients with HCC who had undergone successful hepatectomy. An analysis using a receiver operating characteristic (ROC) curve was performed to determine the cut-off value for predicting prognosis. Overall survival (OS), recurrence-free survival (RFS) and potential prognostic factors were analyzed. The ROC curve analysis revealed a sICAM-1 cut-off value of 440 ng/ml. HCC patients with sICAM-1 ≥440 ng/ml exhibited a poorer OS and RFS than those with sICAM-1 <440 ng/ml (P=0.002). sICAM-1 ≥440 ng/ml (hazard ratio=3.623; 95% confidence interval: 1.145-11.458; P=0.028) and Child B (hazard ratio=1.514; 95% confidence interval: 1.066-2.150; P=0.021) were independent prognostic factors for OS, and sICAM-1 ≥440 ng/ml was an independent prognostic factor for RFS (hazard ratio=3.625; 95% confidence interval: 1.233-10.659; P=0.019). Serum sICAM-1 may be a promising predictor for the overall and recurrence-free survival of patients with HCC.

Prognostic impact of preoperative lymphocyte-to-monocyte ratio in patients with colorectal cancer with special reference to myeloid-derived suppressor cells.

AIMS: We aimed to investigate the relationship of colorectal cancer prognosis and inflammatory parameters, including neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR), with reference to circulating myeloid-derived suppressor cells (MDSCs) in the current study. PATIENTS AND METHODS: Thirty-five patients who underwent curative-intent surgery were enrolled.　A receiver-operating characteristic curve (ROC) was used to assess the usefulness of candidates for prognostic factors. Recurrence-free survival (RFS) was calculated using the Kaplan-Meier method, and the candidates for prognostic factors were assessed by a Cox proportional hazard model. RESULTS: ROC curve analyses determined cutoff values for NLR and LMR as 2.9 and 2.4, respectively. The percentage of MDSCs in patients with LMR ≤ 2.4 was statistically higher than in those with LMR > 2.4 (p = 0.012). The patients with LMR ≤ 2.4 exhibited a statistically lower RFS than those with LMR > 2.4 (p = 0.008). These results were also observed in patients with stage II + III disease. LMR was an independent prognostic factor of RFS in colorectal cancer patients (hazard ratio: 7.757, 95% confidence interval: 1.462-41.152, p = 0.016). CONCLUSION: Lower LMR was associated with poor prognosis in colorectal cancer patients; whereas, higher circulating MDSCs were observed in patients with lower LMR.

Serum transthyretin level is associated with prognosis of patients with gastric cancer.

BACKGROUND: The goal of the present study was to determine whether serum transthyretin level can be used as a novel prognostic biomarker for patients with gastric cancer. PATIENTS AND METHODS: Serum levels of transthyretin were examined before treatment in 42 patients with gastric cancer, 30 of whom underwent curative operation and had their prognostic factors analyzed. RESULTS: In an analysis using a receiver operating characteristic curve, transthyretin was evaluated as a useful biomarker to predict the overall survival of the patients (P = 0.033), and a level of 22.8 mg/dL was determined as the cut off value. The transthyretin levels exhibited statistically significant correlations with total protein (r = 0.598, P < 0.001), albumin (r = 0.626, P < 0.001), and retinol binding protein (r = 0.753, P < 0.001). On the other hand, the transthyretin levels showed statistically significant inverse correlations with tumor size (r = -0.753, P < 0.001) and the numbers of involved lymph nodes (r = -0.453, P = 0.012). The patients with serum transthyretin levels of <22.8 mg/dL showed poorer prognosis than those with levels of ≥22.8 mg/dL (P = 0.033); therefore, serum transthyretin level was an independent prognostic factor for the gastric cancer patients (hazard ratio: 0.420, 95% confidence interval: 0.180-0.985, P = 0.042). CONCLUSIONS: Anthropometric measurement of serum transthyretin can be useful for predicting the prognosis of patients with gastric cancer.

Eccrine porocarcinoma arising from the knee.

Enlarged eccrine porocarcinoma of the knee was encountered as a hemorrhagic bulky tumor. After controlling bleeding with Mohs' paste, local excision of the lesion was the mainstay of treatment. Pathological examination revealed poroid cells, cuticle cells, and prickle cells cancer components, suggesting that malignancy must be excluded by resection.

[A Case of Esophageal Cancer with Cervical Lymph Node Recurrence Six Years after Complete Response to Definitive Chemoradiotherapy].

Neoadjuvant chemotherapy plus surgery is recommended for clinical StageⅡ and Ⅲ esophageal cancer treatment by the JCOG9906. In contrast, definitive chemoradiotherapy(dCRT)is also a curative treatment. We encountered a case of recurrence in the cervical lymph nodes that was confirmed 6 years later, although thoracic esophageal cancer had completely disappeared following dCRT. Since there was no recurrence or metastasis in the primary lesion or other organs, we performed bilateral cervical lymph node dissection. There were 3 lymph node metastases among the dissected cervical lymph nodes pathologically. After the surgery, no relapses have occurred without the adjuvant chemotherapy.