Analysis of Watson for oncology and clinicians' treatment recommendations for patients with breast cancer in Korea: A single center experience.

Background: Various clinical applications have been attempted using artificial intelligence (AI) clinical decision support system (CDSS), and it has become a starting point for personalized cancer treatment. We aimed to identify the degree of agreement between the AI-CDSS, Watson for Oncology (WFO), and the clinician in treatment recommendations for Korean breast cancer patients and to provide guidelines for future improvement. Methods: One hundred and eighty-three breast cancer patients who underwent treatment at the Pusan National University Hospital between January 1, 2016 and May 31, 2017 were enrolled in this study. The concordance between WFO's and clinicians' treatment recommendations were examined according to various factors. Results: WFO gave the same treatment option recommendations as clinicians in 74 (40.4%) of the cases. According to the logistic regression, the difference in recommendation concordance between stage I and stage III was statistically significant (P = 0.004), and there was no difference among other factors. Conclusion: The concordance of treatment recommendations was low overall. However, this is largely attributable to the differences of medical insurance system and healthcare environment between the United States and Korea. In the future, region-specific features should be considered or reflected during the development of AI-CDSS.

Psychometric Properties of Assessment Tools for Depression, Anxiety, Distress, and Psychological Problems in Breast Cancer Patients: A Systematic Review.

OBJECTIVE: Various and accurate psychiatric assessments in patients with breast cancer who frequently suffer from psychological problems due to long-term survivors are warranted. This systematic review aimed to investigate the current evidence on psychometric properties of psychiatric assessment for evaluating psychological problems in breast cancer patients. METHODS: This systematic review progressed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Four electronic databases such as Web of Science, PubMed, Embase, and Cumulative Index to Nursing and Allied Health Literature were searched. This study protocol was registered on Open Science Framework. RESULTS: Of the 2,040 articles, 21 papers were finally included. Among them, only five studies showed the performance of psychiatric assessment tools. Among 13 assessment tools used in the selected articles, the Hospital Anxiety and Depression Scale (HADS), Distress Thermometer (DT), or Mini-Mental Adjustment to Cancer Scale was frequently used for the evaluation of psychological problems. The DT and Psychosocial Distress Questionnaire-Breast Cancer showed acceptable performances for the prediction of depression and anxiety assessed by the HADS. CONCLUSION: This systematic review found psychiatric assessment tools with acceptable reliability and validity for breast cancer patients. However, comparative studies on reliability and validity of various scales are required to provide useful information for the selection of appropriate assessment tools based on the clinical settings and treatment stages of breast cancer. Joint research among the fields of psychiatry and breast surgery is needed for research to establish the convergent, concurrent, and predictive validity of psychiatric assessment tools in breast cancer patients.

Temporary blindness caused by corneal edema after a local anesthetic injection in the eyebrow region: a case report.

Plastic surgery around the eyes is usually performed under local anesthesia, using a mixture of lidocaine and epinephrine. Blindness is a rare but devastating complication after the injection of local anesthesia in this region. Most cases reported to date have been caused by occlusion of the ophthalmic artery or central retinal artery. In this case report, however, we present a highly unusual case of blindness caused by corneal edema after a local anesthetic injection. A patient visited the emergency room with a laceration on the eyebrow, and local anesthesia was injected before suturing. Immediately after the injection, severe corneal edema developed, making it impossible to observe the structures in the anterior chamber in detail or check the light reflex and visual acuity of the naked eye. An antibiotic (moxifloxacin hydrochloride) and high-concentration steroid eyedrops were promptly applied. High-concentration steroids were also administered orally. On day 13 post-injury, the visual acuity of the naked eye improved to 1.0, and no recurrence of corneal lesions was observed. Although the cause of corneal edema after the local injection could not be conclusively identified, we hope that this report will help raise clinicians' awareness of this complication and appropriate treatment methods.

A nomogram for predicting three or more axillary lymph node involvement before breast cancer surgery.

Based on the American College of Surgeons Oncology Group (ACOSOG)-Z0011, a useful nomogram has been constructed to identify patients who do not require intraoperative frozen sections to evaluate sentinel lymph nodes in the previous study. This study investigated the developed nomogram by ultrasonography (US) and positron emission tomography (PET)/computed tomography (CT) as a modality. In the training set, 89/1030 (8.6%) patients had three or more positive nodes. Larger tumor size, higher grade ultrasonographic ALN classification, and findings suspicious of positive ALN on PET/CT were associated in multivariate analysis. The areas under the receiver operating characteristic curve (AUC) of the nomogram were 0.856 [95% CI 0.815-0.897] in the training set. The AUC in the validation set was 0.866 [95% CI 0.799-0.934]. Application of the nomogram to 1067 patients who met the inclusion criteria of ACOSOG-Z0011 showed that 90 (8.4%) patients had scores above the cut-off and a false-negative result was 37 (3.8%) patients. And the specificity was 93.8%, and the negative predictive value was 96.4%. The upgraded nomogram improved the predictive accuracy, using only US and PET/CT. This nomogram is useful for identifying patients who do not require intraoperative analysis of sentinel lymph nodes and considering candidates for identifying neoadjuvant chemotherapy. The patients consisted of clinical T1-2 and node-negative invasive breast cancer. The training and validation set consisted of 1030 and 781 patients, respectively. A nomogram was constructed by analyzing factors related to three or more axillary lymph node metastases. The patients who matched the ACOSOG-Z0011 criteria were selected and applied to the new nomogram.

The Emotional Status, Attitudes in Decision-Making Process, and Their Impact on Surgical Choices in Korean Breast Cancer Patients.

PURPOSE: We examined the incidence of emotional distress in women with newly diagnosed breast cancer to determine whether the degree of emotional distress affected their choice of breast-conserving surgery (BCS) or mastectomy and evaluated how the patient's preferred role in decision-making influenced her choice of surgical method. METHODS: This prospective study included 85 patients newly diagnosed with in situ or invasive breast cancer eligible for BCS. Their degree of depression/anxiety and attitude toward the decision-making process were measured using the Hospital Anxiety and Depression Scale (HADS) and Control Preference Scale (CPS), respectively. After receiving information on both surgical methods, the patients indicated their preferred surgical method and completed the CPS at their initial and second visits before surgery. RESULTS: After the diagnosis of breast cancer, 75.3% of patients showed abnormal or borderline HADS scores for depression and 41.2% for anxiety. Patients with borderline or abnormal degrees of depression were more likely to have coexisting abnormal degrees of anxiety (p < 0.001). However, the presence of depression or anxiety was not associated with patients' surgical choices (p=0.394 and 0.530, respectively). Patients who preferred a more active role in the decision-making process were more likely to choose mastectomy over BCS, while those who were passive or collaborative chose BCS more frequently (p=0.001). CONCLUSION: Although many patients with newly diagnosed breast cancer experience depression and anxiety before surgery, these do not affect the choice of surgical method; however, their attitudes toward the decision-making process do.

Association between Number of Retrieved Sentinel Lymph Nodes and Breast Cancer-related Lymphedema.

PURPOSE: Sentinel lymph node biopsy (SLNB) has become a standard axillary staging surgery for early breast cancer, and the proportion of patients requiring axillary lymph node dissection (ALND) is decreasing. We aimed to evaluate the association between the number of sentinel lymph nodes (SLNs) retrieved and the risk of lymphedema of the ipsilateral arm. METHODS: Prospectively collected medical records of 910 patients were reviewed. Lymphedema was defined as a difference in circumference > 2 cm compared to the contralateral arm and/or having clinical records of lymphedema treatment in the rehabilitation clinic. RESULTS: Together with an objective and subjective assessment of lymphedema, 36 patients (6.1%) had lymphedema in the SLNB group and 85 patients (27.0%) had lymphedema in the ALND group (p < 0.001). In a multivariate analysis of the whole cohort, risk factors significantly associated risk with the development of lymphedema were body mass index, mastectomy (vs. breast-conserving surgery), ALND, and radiation therapy. In logistic regression models in the SLNB group only, there was no correlation between the number of retrieved SLNs and the incidence of lymphedema. In addition, in the Pearson correlation analysis, no correlation was observed between the number of retrieved SLNs and the difference in circumference between the ipsilateral and contralateral upper extremities (correlation coefficients = 0.067, p =0.111). CONCLUSION: The risk of lymphedema in breast cancer surgery and adjuvant treatments is multifactorial. The number of retrieved lymph nodes during sentinel biopsy was not associated with the incidence of lymphedema.

Humeral shaft fracture and radial nerve palsy in Korean soldiers: focus on arm wrestling related injury.

INTRODUCTION: Humeral shaft fractures can lead to radial nerve injury and may require surgery and rehabilitation. We determined the causative events of humeral fracture, including arm wrestling, in young Korean soldiers and examined whether humeral fracture is related to demographic characteristics and the presence of radial nerve palsy. METHODS: We reviewed 7.5 years (July 2012 to June 2019) of medical records covering patients who had experienced a humeral shaft fracture after entering military service and had received surgery for open reduction and internal fixation. Data were obtained on basic demographics, initial event provoking the fracture, presence of radial nerve palsy, initial and follow-up severity of the weakness, and any discharge from military service because of prolonged radial nerve palsy. RESULTS: Of 123 cases, arm wrestling was the leading cause (52.8%). A high energy injury, such as falling from a height (11.4%), and sports related slips (10.6%) were other causes. All humeral shaft fractures caused by forceful contraction were spiral, while 40% of the fractures caused by external force related events were of a transverse type. The percentage of left-sided fractures was significantly higher for fractures arising from an external force than in those caused by forceful contraction related events. Radial nerve palsy was found in 34 patients (27.6%), and 16 were discharged from the military because of prolonged radial nerve palsy 6 months after the fracture. The causative events and other factors did not affect the presence of radial nerve palsy. CONCLUSION: Arm wrestling was the leading cause of humeral fracture in young Korean soldiers but the chance of developing comorbid radial nerve palsy did not differ from that of other causes. These epidemiologic findings in this young active group may help in understanding the causes of humeral shaft fracture in soldiers and in the wider young population.

Usefulness of using additional ultrasonic dissection device in breast cancer surgery: a retrospective cohort study.

BACKGROUND: In breast cancer surgery, electrocautery (EC) is commonly used with the basic method of knot tying, and there are few reports of using other devices such as ultrasonic dissection device (UDD). This study was designed to compare the case of using EC with the basic method of knot tying and the case of using UDD in breast cancer surgery. METHODS: From April 2019 to March 2020, 376 patients who underwent breast cancer surgery at Pusan National University Hospital were enrolled. We compared operation time, complications, and blood loss volume between surgery with and without UDD. RESULTS: We included 306 patients for the final analysis, 142 in the control group and 164 in the trial group. The operation time [minutes (min)] was significantly reduced in the trial group compared to the control group (111.2 vs. 95.5 min, P<0.001). In subgroup analysis, the operation time in the trial group was significantly reduced. There was no significant difference in intraoperative blood loss (P=0.999) and complications [seroma (P=0.965), hematoma (P=0.999), cellulitis (P=0.999)]. CONCLUSIONS: Our study showed that the use of a UDD for surgeons to select instruments for breast cancer surgery may be a good option for both patients and surgeons.

Breast cancer cell debris diminishes therapeutic efficacy through heme oxygenase-1-mediated inactivation of M1-like tumor-associated macrophages.

Chemotherapy is commonly used as a major therapeutic option for breast cancer treatment, but its efficacy is often diminished by disruption of patient's anti-tumor immunity. Chemotherapy-generated tumor cell debris could hijack accumulated tumor-associated macrophages (TAMs), provoking tumor recurrence. Therefore, reprogramming TAMs to acquire an immunocompetent phenotype is a promising strategy to potentiate therapeutic efficacy. In this study, we analyzed the proportion of immune cells in the breast cancer patients who received chemotherapy. To validate our findings in vivo, we used a syngeneic murine breast cancer (4T1) model. Chemotherapy generates an immunosuppressive tumor microenvironment in breast cancer. Here, we show that phagocytic engulfment of tumor cell debris by TAMs reduces chemotherapeutic efficacy in a 4T1 breast cancer model. Specifically, the engulfment of tumor cell debris by macrophages reduced M1-like polarization through heme oxygenase-1 (HO-1) upregulation. Conversely, genetic or pharmacologic inhibition of HO-1 in TAMs restored the M1-like polarization. Our results demonstrate that tumor cell debris-induced HO-1 expression in macrophages regulates their polarization. Inhibition of HO-1 overexpression in TAMs may provoke a robust anti-tumor immune response, thereby potentiating the efficacy of chemotherapy.

Effects of tamoxifen and aromatase inhibitors on the risk of acute coronary syndrome in elderly breast cancer patients: An analysis of nationwide data.

BACKGROUND: Aromatase inhibitors (AIs) are the preferred endocrine treatment for postmenopausal hormonal receptor-positive breast cancer. However, there is controversy on the long-term cardiovascular and cerebrovascular safety of AIs over that of tamoxifen. METHODS: We analyzed the National Health Information Database (NHID) of 281,255 women over a 20-year-old diagnosed with breast cancer between 2009 and 2016. Cardiovascular events (CVEs) were defined as the development of the following, acute coronary syndrome (ACS), ischemic and hemorrhagic stroke, defined by using insurance claim records. The model was constructed by Cox proportional hazard regression and this model was used to analyze the effects of AI and tamoxifen on CVE. RESULTS: We included 47,569 women for the final analysis. Patients were classified into 'No hormonal treatment (n = 18,807), 'Switch (n = 2097)', 'Tamoxifen (n = 7081)' and 'AI (n = 19,584)'. There were 2147 CVEs in 2032 patients (4.1%). Univariate analysis showed that women with tamoxifen had significantly lower risk for CVEs compared to no-treatment (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.74-0.97) while AI showed no such effect (HR 0.93, 95% CI 0.84-1.02). After adjusting for other risk factors (hypertension, dyslipidemia, family history), the use of tamoxifen was associated with significant protective effect against ACS (HR 0.63, 95% CI 0.47-0.84). CONCLUSIONS: Our results, based on the NHID, supports the protective effect of tamoxifen against CVE in Korean breast cancer patients aged 55 and older that is not seen with AIs. Our results can guide the selection of adjuvant hormonal treatment agents for Korean breast cancer patients based on their risk of developing CVE.

Prediction of pathologic complete response using image-guided biopsy after neoadjuvant chemotherapy in breast cancer patients selected based on MRI findings: a prospective feasibility trial.

PURPOSE: Accurate prediction of pathologic complete response (pCR) in breast cancer using magnetic resonance imaging (MRI) and ultrasound (US)-guided biopsy may aid in selecting patients who forego surgery for breast cancer. We evaluated the accuracy of US-guided biopsy aided by MRI in predicting pCR in the breast after neoadjuvant chemotherapy (NAC). METHODS: After completion of NAC, 40 patients with near pCR (either tumor size ≤ 0.5 cm or lesion-to-background signal enhancement ratio (L-to-B SER) ≤ 1.6 on MRI) and no diffused residual microcalcifications were prospectively enrolled at a single institution. US-guided multiple core needle biopsy (CNB) or vacuum-assisted biopsy (VAB) of the tumor bed, followed by standard surgical excision, was performed. Matched biopsy and surgical specimens were compared to assess pCR. The negative predictive value (NPV), accuracy, and false-negative rate (FNR) were analyzed. RESULTS: pCR was confirmed in 27 (67.5%) surgical specimens. Preoperative biopsy had an NPV, accuracy, and FNR of 87.1%, 90.0%, and 30.8%, respectively. NPV for hormone receptor-negative and hormone receptor-positive tumors were 83.3% and 100%, respectively. Obtaining at least 5 biopsy cores based on tumor size ≤ 0.5 cm and an L-to-B SER of ≤ 1.6 on MRI (27 patients) resulted in 100% NPV and accuracy. No differences in accuracy were noted between CNB and VAB (90% vs. 90%). CONCLUSIONS: Investigation using stringent MRI criteria and ultrasound-guided biopsy could accurately predict patients with pCR after NAC. A larger prospective clinical trial evaluating the clinical safety of breast surgery omission after NAC in selected patients will be conducted based on these findings.

Determinants of Functional Outcomes Using Clinical Pathways for Rehabilitation After Hip Fracture Surgery.

BACKGROUND: This study evaluated functional outcomes using newly established clinical pathways after hip fracture surgery in older adults and analyzed the major determinants of successful functional outcomes in rehabilitation programs using standardized clinical pathways. METHODS: This was a retrospective cohort study performed in a tertiary rehabilitation facility. A total of 220 patients who had received unilateral hip fracture surgery were followed up from immediately after surgery to 6 months postoperatively. Clinical pathways for rehabilitation included early, individualized rehabilitation, education for activities of daily living, review of general medical conditions, and arrangement of discharge settings. One rehabilitation specialist consecutively checked ambulatory function using 3-level grading, and patients were classified into good recovery and poor recovery groups based on ambulatory function at 6 months postoperatively. Logistic regression analysis was performed using 7 representative variables (age, sex, bone mineral density, Mini-Mental Status Examination [MMSE], Berg Balance Scale [BBS], premorbid ambulatory function, and length of hospital stay). RESULTS: A total of 86.8% of patients could walk with or without assistance at 6 months after surgery and 75.5% of patients involved in the rehabilitation program were classified into the good recovery group in this study. the good recovery group showed higher mmse and bbs scores compared with the poor recovery group. the factors in the model most strongly correlated with recovery were mmse and bbs. CONCLUSION: This study showed that a well-designed rehabilitation program could improve ambulatory function in older patients after hip fracture surgery and that cognitive impairment and poor balance control may inhibit the recovery of ambulatory function.

Myotonic dystrophy mimicking postpolio syndrome in a polio survivor.

We describe a 38-yr-old polio survivor with newly developed weakness from myotonic dystrophy. He suffered muscle atrophy and weakness in his legs as a result of poliomyelitis at the age of 3 yrs. After a stable interval of about 30 yrs, he felt new weakness and fatigue in his legs. Electromyography revealed generalized myotonic discharges, early recruitment, and findings of chronic denervation in his left leg. Genetic testing was consistent with myotonic dystrophy type 1. A biopsy from the right gastrocnemius revealed findings of both myotonic dystrophy and chronic denervation. This case report shows the importance of considering other uncommon conditions in the differential diagnoses of postpolio syndrome.

Effect of dendritic cells treated with CpG ODN on atopic dermatitis of Nc/Nga mice.

Atopic dermatitis (AD) is a chronic inflammatory skin disease and the pathogenesis of AD is associated with the release of various cytokines/chemokines due to activated Th(2) immune responses. Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG dinucleotide in the context of particular base sequence (CpG motifs) are known to have the immunostimulatory activities in mice and to convert from Th(2) to Th(1) immune responses in AD. We aimed to investigate that CpG ODN, especially phosphodiester form, can stimulate the protective immunity in NC/Nga mice with AD. We isolated BMDCs from NC/Nga mice and then, cultured with GM-CSF and IL-4 for 6 days, and treated for 2 days by either phosphorothioate ODN or phosphodiester ODN. CpG ODN-treated DCs resulted in more production of IL-12. When CpG ODN-treated DCs were intravenously injected into the NC/Nga mice, the NC/Nga mice with CpG ODN-treated DCs showed significant improvement of AD symptoms and decrease of IgE level. Histopathologically, the NC/Nga mice skin with CpG ODN-treated DCs showed the decreased IL-4 and TARC expression comparing with non-injected mice. These results may suggest that phosphodiester CpG ODN-treated DCs might function as a potent adjuvant for AD in a mouse model.

EC-SOD suppresses contact hypersensitivity in mouse skin by impairing Langerhans cell migration.

Extracellular superoxide dismutase (EC-SOD) is primarily a tissue enzyme and has been implicated in the modulation of inflammatory response. The biological role of EC-SOD in skin, however, has rarely been investigated. In this study, we aim to explore the effects of EC-SOD on the inflammatory response in skin by evaluating the contact hypersensitivity response (CHS) in EC-SOD transgenic mice. Transgenic mice with skin-specific expression of EC-SOD were sensitized and challenged with 2,4,6-trinitro-1-chlorobenzene (TNCB), followed by measurement of ear swelling. EC-SOD transgenic mice showed significantly reduced CHS responses compared with wild-type mice. Histological evaluation of the challenged ears of EC-SOD transgenic mice revealed diminished infiltration of inflammatory cells with a failure to induce expression of inflammatory cytokines, such as tumor necrosis factor-alpha and IFN-gamma, on sensitization and challenge with TNCB. Furthermore, Langerhans cell migration to lymph nodes was impaired in EC-SOD transgenic mice. These results indicate that EC-SOD downregulates CHS through inhibition of the inflammatory response, suggesting a possible therapeutic regimen in inflammatory skin diseases.

Regulation of Bcl-3 through interaction with the Lck tyrosine kinase.

bcl-3 is a protooncogene which undergoes chromosomal translocation in a subset of chronic B-cell lymphocytic leukemia cells. Bcl-3 is a unique IkappaB family protein that regulates transcription of a number of NF-kappaB target genes through interactions with NF-kappaB dimers. Based on previous studies, suggesting that Bcl-3 interacts with the Fyn tyrosine kinase in platelets, we investigated possible interactions of Bcl-3 with Lck, a related tyrosine kinase important in lymphoid cells. Protein-protein interactions between Bcl-3 and the Lck tyrosine kinase were identified both in vitro and in vivo. Lck enhanced Bcl-3-mediated activation of a p52/Bcl-3-responsive promoter in reporter gene assays independent of its tyrosine kinase activity, but requiring the Lck SH3 protein interaction domain. These studies suggest that Bcl-3 might participate in oncogenic pathways involving Lck.

Regulatory effect of SOCS on NF-kappaB activity in murine monocytes/macrophages.

The suppressor of cytokine signaling (SOCS) group of proteins has been implicated in regulation of various cytokine signaling and in a negative crosstalk between distinct signaling pathways. Interleukin-10 (IL-10) and LPS were known to induce expression of SOCS-3 in neutrophils and monocytes/macrophages. IL-10 was also reported to inhibit a proinflammatory signal-induced NF-kappaB activation in monocytes and peripheral T lymphocytes. The effects of increased SOCS-3 expression upon IL-10 regulation of NF-kappaB activation have not yet been demonstrated. Here we examined the effects of SOCS-3 on NF-kappaB activity. SOCS-3 did not induce any alterations in NF-kappaB activity induced by LPS or TNF-alpha. However, it enhanced RelA-dependent kappaB promoter activity when cotransfected with RelA. Similar results were observed with SOCS-1. In contrast, SOCS-2 did not show any regulatory effects on RelA activity. Analysis of C-terminal truncation mutants of SOCS-1 and SOCS-3 demonstrated that the SOCS box and its N-terminal region, a less well-conserved linker region were important for SOCS-3 activation of RelA. In contrast, the SOCS box itself was critical for SOCS-1 to activate RelA. These results suggest that SOCS proteins can enhance the effects of NF-kappaB/Rel proteins, and therefore, further modulate immune and inflammatory responses.