Use of machine learning with two-dimensional synthetic mammography for axillary lymph node metastasis prediction in breast cancer: a preliminary study.

Background: As of 2020, breast cancer is the most common type of cancer and the fifth most common cause of cancer-related deaths worldwide. The non-invasive prediction of axillary lymph node (ALN) metastasis using two-dimensional synthetic mammography (SM) generated from digital breast tomosynthesis (DBT) could help mitigate complications related to sentinel lymph node biopsy or dissection. Thus, this study aimed to investigate the possibility of predicting ALN metastasis using radiomic analysis of SM images. Methods: Seventy-seven patients diagnosed with breast cancer using full-field digital mammography (FFDM) and DBT were included in the study. Radiomic features were calculated using segmented mass lesions. The ALN prediction models were constructed based on a logistic regression model. Parameters such as the area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Results: The FFDM model yielded an AUC value of 0.738 [95% confidence interval (CI): 0.608-0.867], with sensitivity, specificity, PPV, and NPV of 0.826, 0.630, 0.488, and 0.894, respectively. The SM model yielded an AUC value of 0.742 (95% CI: 0.613-0.871), with sensitivity, specificity, PPV, and NPV of 0.783, 0.630, 0.474, and 0.871, respectively. No significant differences were observed between the two models. Conclusions: The ALN prediction model using radiomic features extracted from SM images demonstrated the possibility of enhancing the accuracy of diagnostic imaging when utilised together with traditional imaging techniques.

Surgery assistance system for continuous resection of brain tumors-proposal of continuous tumor resection forceps, tumor cell separation, dehydration, and isolation mechanism.

The tumor resection ratio must be improved due the increased possibility of recurrence or malignancy. The purpose of this study was to develop a system that includes forceps with a continuous suction function and flow cytometry to diagnose the malignancy of the tumor for safe, accurate, and effective surgery. A newly developed continuous tumor resection forceps consists of a triple pipe structure, which enables continuous suction of the tumor by integrating the reflux water and suction system. The forceps includes tip opening/closure detection switch to control the adsorption and suction strength when tip is opened and closed. To perform accurate tumor diagnosis using flow cytometry, a filtering mechanism was developed for dehydrating reflux water from continuous suction forceps. In addition, a cell isolation mechanism comprising a roller pump and shear force loading mechanism was also newly developed. By using a triple pipe structure, a significantly larger tumor collection ratio was observed compared to the previous double-pipe structure. By performing suction pressure control with the opening/closure detection switch, inaccurate suction can be prevented. By widening the filter area of dehydration mechanism, it was possible to improve the reflux water dehydration ratio. The most appropriate filter area was 85 mm2. By using a newly developed cell isolation mechanism, the processing time can be reduced to less than 1/10 of the original time, keeping the same cell isolation ratio, when compared to the existing pipetting method. Neurosurgery assistance system with continuous tumor resection forceps and a cell separation, dehydration and isolation mechanism was developed. An effective and safe tumor resection, accurate and fast diagnosis of malignancy can be achieved by using the current system.

Efficacy and safety of amrubicin therapy after chemoimmunotherapy in small cell lung cancer patients.

Background: Although the addition of immune checkpoint inhibitors (ICIs) to platinum-doublet chemotherapy has improved the efficacy of first-line therapy in extensive-disease small cell lung cancer (SCLC) patients, the best treatment option for patients with recurrent SCLC has not yet been determined. We conducted a retrospective study to evaluate the efficacy and safety of amrubicin (AMR) therapy after treatment with ICIs. Methods: We retrospectively assessed patients with recurrent SCLC who received AMR after chemoimmunotherapy at the Niigata Lung Cancer Treatment Group from August 2019 to February 2021. Results: This analysis included 30 patients. The median progression-free survival (PFS) and overall survival (OS) were 3.8 (95% CI: 2.7-4.2) and 10 (95% CI: 7.4-14.8) months, respectively. The median PFS and OS did not significantly differ between the sensitive and refractory groups [PFS; 3.1 (95% CI: 1.1-4.0) vs. 4.2 (95% CI: 2.3-4.8) months, P=0.1142, OS; 10.0 (95% CI: 5.2-14.8) vs. 10.4 (95% CI: 3.8-NE) months, P=0.5525]. The most common adverse event was grade ≥3 neutropenia, which occurred in 22 of 30 patients (73%), and 2 patients (7%) discontinued AMR due to adverse events. Conclusions: AMR after chemoimmunotherapy shows good clinical efficacy and safety in patients with recurrent SCLC.

Phase II Trial of the Combination of Alectinib with Bevacizumab in Alectinib Refractory ALK-Positive Nonsquamous Non-Small-Cell Lung Cancer (NLCTG1501).

Anaplastic lymphoma kinase (ALK)-positive lung cancer is a rare cancer that occurs in approximately 5% of non-small-cell lung cancer (NSCLCs) patients. Despite the excellent efficacy of ALK-tyrosine kinase inhibitor in ALK-positive NSCLCs, most patients experience resistance. We conducted a phase II study to investigate the combination of alectinib with bevacizumab in ALK-positive NSCLC patients after failure of alectinib. In this study, ALK-positive nonsquamous NSCLC patients previously treated with alectinib received bevacizumab 15 mg/kg on day 1 every 3 weeks and alectinib 600 mg/day until disease progression. The primary endpoints were progression-free survival (PFS) and the safety of alectinib and bevacizumab. The secondary endpoints included overall survival (OS) and correlation of circulating tumor DNA and plasma proteins with PFS. Of the 12 patients treated, the median PFS was 3.1 months (95% CI 1.2-16.1), and the median OS was 24.1 months (95% CI 8.3-not estimable). The EML4-ALK fusion gene in circulating tumor DNA was significantly correlated with shorter PFS (1.2 months vs. 11.4 months, HR 5.2, p = 0.0153). Two patients experienced grade 3 adverse events; however, none of the patients required dose reduction. Although the primary endpoint was not met, alectinib combined with bevacizumab showed clinical efficacy in ALK-positive patients.

Masked Diabetes Insipidus Hidden by Severe Hyponatremia: A Case of Pituitary Metastasis of Lung Adenocarcinoma.

BACKGROUND Hyponatremia is an electrolyte disorder frequently encountered by clinicians. Secondary adrenal insufficiency due to pituitary metastatic tumors should be considered as an alternative diagnosis when clinicians encounter patients with lung cancer who demonstrate hyponatremia. However, masked central diabetes insipidus should also be considered to prevent critical dehydration when glucocorticoid replacement therapy will be initiated. CASE REPORT A 70-year-old man with advanced lung adenocarcinoma demonstrated high-grade hyponatremia of 122 mmol/L. Magnetic resonance imaging disclosed a metastatic pituitary tumor and endocrinological examinations confirmed panhypopituitarism, including secondary adrenal insufficiency. Hydrocortisone replacement revealed masked diabetes insipidus with elevation of serum sodium levels that reached 151 mmol/L. Desmopressin administration was required to prevent water depletion and to immediately ameliorate the hypernatremia. CONCLUSIONS This is the first case report of masked diabetes insipidus that demonstrated high-grade hyponatremia. Secondary adrenal insufficiency can mask the hypernatremia that is a typical manifestation of diabetes insipidus. Physicians should consider adrenal insufficiency and diabetes insipidus due to pituitary metastasis of advanced malignancies, even when they encounter patients with hyponatremia.

Pharmacist's Intervention Considering the Prognosis for a Terminal Cancer Patient: A Case Report.

Prognostic prediction has been reported to affect the decision of doctors and non-physician health care providers such as nurses, social workers, pastors, and hospice volunteers on the selection of appropriate medical interventions. This was a case of a 65-year-old woman who presented with a poor oral intake. The patient had a history of sigmoid colon cancer with abdominal wall metastasis and peritoneal dissemination. On the day of admission, nausea, anorexia, and malaise were noted, requiring immediate intervention. The patient's prognosis was predicted using the Palliative Prognostic Index. The pharmacist suggested the use of dexamethasone tablets in order to alleviate the patient's symptoms. Indeed, the administration of dexamethasone alleviated the symptoms of nausea, loss of appetite, and malaise. To the best of our knowledge, this is the first case report to demonstrate that prognosis prediction is important not only for other medical staff but also for pharmacists when deciding the need to initiate a treatment and continue such treatment, and when providing pharmacist interventions.

[Investigation of Clinical Utility of Radiological Technologist's Reading Report as a Second Opinion for Medical Doctor Reading of Digital Mammogram].

PURPOSE: We investigated the clinical utility of a radiological technologist's (RT)'s reports (RRs) as a second opinion by the free-response receiver operating characteristic (FROC) observer study that compared the performance of medical doctors' (MDs') reading of digital mammogram with and without consulting the RR. METHOD: One hundred women (39 malignant, 61 benign or normal) who underwent diagnostic mammography were selected from among 1674 routine clinical images classified by the degree of difficulty and categories for inclusion in the FROC study. The first FROC study performed by three RTs (RT 1-3) was conducted to collect the data for RR utilized in the second FROC study. The second FROC study was performed by five MDs, and the statistical significance of MDs' performances with and without reference to the RR was investigated by figure of merit (FOM). RESULT: The FOM values of three RTs obtained in the first FROC study were 0.529, 0.576, and 0.539, respectively. In the second FROC study, RT 2 had the highest FOM, RT 1 the lowest false positives/case, and RT 3 the highest sensitivity. The average FOM values in the second FROC study for the five MDs with/without reference to the RR were as follows: RT 2's RR was 0.534/0.588 (p=0.003), RT 1's RR was 0.500/0.545 (p=0.099), and RT 3's RR was 0.569/0.592 (p=0.324). CONCLUSION: We concluded that the MDs' performance of reading mammogram was statistically improved by consulting the RR when the RT's reading skill was high.

Behavior of Japanese women after being informed about the benefits and disadvantages of breast cancer screening: a questionnaire survey.

BACKGROUND: The US Preventative Services Task Force assessed the efficacy of breast cancer screening according to the sum of its benefits and disadvantages. We estimate that the balance of the benefits and disadvantages varies among women depending on their demographic background. METHODS: Between March 2016 and March 2017, we conducted a questionnaire survey among Japanese women who underwent population-based or opportunistic breast cancer screening at our multicenter institutions. We investigated the behavior modification among women after being informed about the benefits and disadvantages of breast cancer screening depending on their demographic background. RESULTS: Out of 3032 questionnaires that were returned, 2936 (96.8%) were evaluated. The percentage of women with prior knowledge about the benefits and disadvantages of breast cancer screening before reading the leaflets that we created was 24%. However, 95% of the women were willing to undergo screening next time, despite knowing the disadvantages. Regarding overdiagnosis, the young women tended to choose usual treatment, and the elderly women tended to choose active surveillance. In response to the question on the significance of screening, the young women wished to avoid death by breast cancer; whereas, the elderly women wished to live a safe life. CONCLUSION: Our results indicate that the information of disadvantages does not lead to a reduction in screening rates. Additionally, we found that the balance between the benefits and disadvantages of breast cancer screening varies among women depending on their demographic background, especially age.

Metreleptin Supplementation for Improving Lipid and Glycemic Profiles in Acquired Diabetes Lipodystrophy: A Case Report.

Most childhood cancer survivors who undergo hematopoietic stem cell transplantation subsequently develop impaired glucose tolerance and hypertriglyceridemia. These conditions are presumably associated with total-body irradiation-related acquired lipodystrophy and may lead to cardiovascular disease. Metreleptin (recombinant leptin) may help improve the lipoprotein profile, insulin sensitivity, and quality of life of patients with total-body irradiation-related lipodystrophy. This report describes the safe and effective use of metreleptin supplementation for insulin resistance and dyslipidemia in acquired incomplete lipodystrophy. A 24-year-old Japanese woman with diabetes mellitus and hypertriglyceridemia was admitted to our hospital. She was diagnosed with acute lymphocytic leukemia at 3 years of age and had undergone systemic chemotherapy and total-body irradiation before allogeneic stem cell transplantation. She was also diagnosed with hypertriglyceridemia and diabetes mellitus at 11 years of age. She had a low adiponectin level, low-normal leptin level, and diabetes mellitus with marked insulin resistance. Thus, acquired incomplete lipodystrophy was diagnosed. Her serum triglyceride and lipoprotein profiles improved within 1 month of treatment initiation. Glycemic metabolism and insulin sensitivity in the skeletal muscles improved after 6 months. As previously reported, metreleptin therapy is effective in improving lipid and glycemic profiles in generalized lipodystrophy. In the present case, we considered that metreleptin supplementation could reduce the remnant VLDL cholesterol fraction and improve diabetes mellitus. We conclude that it may be an effective alternative therapy for improving the expected prognosis of patients with acquired incomplete lipodystrophy, including childhood cancer survivors.

Intracellular activation of trypsinogen in rat pancreatic acini after supramaximal secretagogue stimulation: cysteine protease and serine protease activity.

OBJECTIVE: The aim of the study was to explore the mechanism by which trypsinogen becomes activated during acute pancreatitis. METHODS: Given the ability of cholecystokinin (CCK) to induce pancreatitis in vivo, the effects of high-dose CCK on preparations of isolated pancreatic acini were examined using immunofluorescence techniques for the detection of trypsinogen activation. Acini were pretreated with weak base or serine or cysteine protease inhibitors before CCK hyperstimulation. RESULTS: CCK was found to stimulate the generation of trypsinogen activation peptide (TAP), a marker for trypsinogen processing. The generation of TAP was inhibited by pretreatment with a weak base, chloroquine (40 micromol/L). TAP generation was also inhibited by pretreatment with serine protease inhibitor FUT-175 (1 micromol/L) but not cysteine protease inhibitor E64 (0.1 mmol/L) or E64-d (0.1 mmol/L). Although treatment with a high dose of E64-d (1 mmol/L) reduced activation, it also caused cell injury. CONCLUSIONS: High-dose CCK stimulated the intracellular activation of trypsinogen within isolated pancreatic acini. This event appears to require an acidic subcellular compartment and serine protease activity. The role for thiol proteases in this model remains unclear.