Ectopic Breast Cancer Arising within an Axillary Lymph Node.

We report our experience with the diagnosis and treatment of an ectopic breast cancer arising within an axillary lymph node. The patient was a 65-year-old woman diagnosed breast cancer and axillary lymph node metastasis. We performed a partial mastectomy and axillary lymph node dissection. Postoperative pathology revealed no malignant lesions in the breast; however, a nodule in one of axillary lymph nodes had mixed benign and malignant components, leading to a diagnosis of invasive ductal carcinoma derived from ectopic mammary tissue. This case represents a very rare form of breast cancer, and the malignancy was difficult to distinguish from metastasis.

Treatment of ZC4H2 Variant-Associated Spastic Paraplegia with Selective Dorsal Rhizotomy and Intensive Postoperative Rehabilitation: A Case Report.

Selective dorsal rhizotomy (SDR) has been used to treat children with spastic cerebral palsy (CP), and its beneficial effect on quality of life and ambulation has been confirmed in long-term follow-up studies. However, the role of SDR in the treatment of spasticity in patients with hereditary spastic paraplegia (HSP) and related disorders is not well-established. Here, we report the first patient with the ZC4H2 variant who underwent SDR to treat spastic paraplegia. Abnormal gait was discovered during a regular checkup at the age of 3 years and 9 months, and she was diagnosed with spastic paraplegia. She was heterozygous for the ZC4H2 variant and underwent SDR at the age of 5 years and 11 months, which alleviated the spasticity. The patient underwent inpatient postoperative rehabilitation for 4 months and continued outpatient physiotherapy after discharge. The Gross Motor Function Measure-88 score and maximum walking speed decreased transiently 1 month postoperatively, but gradually recovered, and continuously improved 6 months postoperatively. SDR and postoperative intensive rehabilitation were effective in improving motor and walking functions up to 6 months after surgery, although long-term follow-up is needed to draw conclusions.

Impact of smoking initiation age on nicotine dependency and cardiovascular risk factors: a retrospective cohort study in Japan.

Aims: Initiating smoking in early adolescence results in challenges with smoking cessation and is associated with high risk of cardiovascular disease. Recently, the initiation of smoking has transitioned from adolescence to young adulthood. However, there are few reports on the impact of initiating smoking at a later age. This study investigated the impact of the age of smoking initiation on nicotine dependency, smoking cessation rates, and cardiovascular risk factors, using a cut-off point of 20 years, within the Japanese population. Methods and results: This retrospective cohort study encompassed 1382 smokers who sought smoking cessation treatment at Kyoto Medical Centre Hospital between 2007 and 2019. Clinical indicators were evaluated by adjusting for age at the time of hospital visit and sex. The smoking cessation rate was further adjusted for treatment medication. The group with a smoking initiation age of <20 years reported a higher number of cigarettes/day (P = 0.002), higher respiratory carbon monoxide levels (P < 0.001), a higher Fagerström Test for Nicotine Dependence (FTND) score (P < 0.001), and a higher Self-rating Depression Scale score (P = 0.014). They also reported lower diastolic blood pressure (P = 0.020) and a lower successful smoking cessation rate [odds ratio: 0.736, 95% confidence interval (0.569, 0.951)] than the group with a smoking initiation age of ≥20 years. When smokers were divided into four groups based on the age they started smoking, the FTND score for those who started at 20-21 years was significantly higher than the score for those who started at 22 years or older. Conclusion: In young adulthood, initiating smoking later (beyond 20 years old) was associated with lower nicotine dependency and fewer depressive tendencies, as well as a higher success rate in smoking cessation among Japanese smokers. The results might suggest that raising the legal smoking initiation age from 20 to 22 years old or older could be effective in reducing nicotine dependency in smokers.

Late-onset Wilson Disease in a Patient Followed-up for Nonalcoholic Fatty Liver Disease.

A 73-year-old woman was referred to our hospital for persistent liver dysfunction. When the patient was 45 years old, her youngest sister had been diagnosed with Wilson disease (WD). The patient therefore underwent several family screening tests, all of which were unremarkable. She had an annual medical checkup and was diagnosed with liver dysfunction and fatty liver at 68 years old. A liver biopsy and genetic testing were performed, and she was diagnosed with WD; chelation therapy was then initiated. In patients with hepatic disorders and a family history of WD, multiple medical examinations should be conducted, as the development of WD is possible regardless of age.

Primary Bile Duct Diffuse Large B-cell Lymphoma Diagnosed by Repeated Endoscopic Ultrasound-guided Fine-needle Aspiration and Endoscopic Retrograde Cholangiopancreatography.

A 54-year-old man was admitted with obstructive jaundice. Computed tomography showed common bile duct stricture and a tumor around the celiac artery. Repeated endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endoscopic retrograde cholangiopancreatography (ERCP) as well as a laparotomic biopsy around the celiac artery were diagnostically unsuccessful. Since the bile duct stricture progressed, EUS-FNA and ERCP were performed a third time, finally leading to the diagnosis of diffuse large B-cell lymphoma. The treatment plan and prognosis of obstructive jaundice differ greatly depending on the disease. It is important to conduct careful follow-up and repeated histological examinations with appropriate modifications until a diagnosis is made.

Validation of an on-chip p16ink4a/Ki-67 dual immunostaining cervical cytology system using microfluidic device technology.

More specific screening systems for cervical cancer may become necessary as the human papillomavirus (HPV) vaccine becomes more widespread. Although p16/Ki-67 dual-staining cytology has several advantages, it requires advanced diagnostic skills. Here, we developed an automated on-chip immunostaining method using a microfluidic device. An electroactive microwell array (EMA) microfluidic device with patterned thin-film electrodes at the bottom of each microwell was used for single-cell capture by dielectrophoresis. Immunostaining and dual staining for p16/Ki-67 were performed on diagnosed liquid cytology samples using the EMA device. The numbers of p16/Ki-67 dual-stained cells captured by the EMA device were determined and compared among the cervical intraepithelial neoplasia (CIN) lesion samples. Seven normal, fifteen CIN grade 3, and seven CIN grade 2 samples were examined. The percentage of dual-positive cells was 18.6% in the CIN grade 2 samples and 23.6% in the CIN grade 3 samples. The percentages of dual-positive staining increased significantly as the severity of the cervical lesions increased. p16/Ki67 dual immunostaining using the EMA device is as sensitive as the conventional method of confirming the histopathological diagnosis of cervical samples. This system enables a quantified parallel analysis at the individual cell level.

Prognostic impact of adjuvant endocrine therapy for estrogen receptor-positive and HER2-negative T1a/bN0M0 breast cancer.

PURPOSE: Mammography screening has increased the detection of subcentimeter breast cancers. The prognosis for estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative T1a/bN0M0 breast cancers is excellent; however, the necessity of adjuvant endocrine therapy (ET) is uncertain. METHODS: We evaluated the effectiveness of adjuvant ET in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer who underwent surgery from 2008 to 2012. Standard ET was administrated after surgery. The primary endpoint was the cumulative incidence of distant metastasis. All statistical tests were 2-sided. RESULTS: Adjuvant ET was administered to 3991 (83%) of the 4758 eligible patients (1202 T1a [25.3%] and 3556 T1b [74.7%], diseases). The median follow-up period was 9.2 years. The 9-year cumulative incidence of distant metastasis was 1.5% with ET and 2.6% without ET (adjusted subdistribution hazard ratio [sHR], 0.54; 95% CI, 0.32-0.93). In multivariate analysis, the independent risk factors for distant metastasis were no history of ET, mastectomy, high-grade, and lymphatic invasion. The 9-year overall survival was 97.0% and 94.4% with and without ET, respectively (adjusted HR, 0.57; 95% CI, 0.39-0.83). In addition, adjuvant ET reduced the incidence of ipsilateral and contralateral breast cancer (9-year rates; 1.1% vs. 6.9%; sHR, 0.17, and 1.9% vs. 5.2%; sHR, 0.33). CONCLUSIONS: The prognosis was favorable in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer. Furthermore, adjuvant ET reduced the incidence of distant metastasis with minimal absolute risk difference. These findings support considering the omission of adjuvant ET, especially for patients with low-grade and no lymphatic invasion disease.

The TGF-ß/UCHL5/Smad2 Axis Contributes to the Pathogenesis of Placenta Accreta.

Placenta accreta is a high-risk condition causing obstetric crisis and hemorrhage; however, its pathogenesis remains unknown. We aimed to identify the factors contributing to trophoblast invasiveness and angiogenic potential, which in turn drive the pathogenesis of placenta accreta. We focused on the transforming growth factor (TGF)-ß1-Smad pathway and investigated the intrinsic relationship between the time- and dose-dependent inhibition of the ubiquitinating enzyme UCHL5 using bAP15, a deubiquitinase inhibitor, after TGF-ß1 stimulation and the invasive and angiogenic potential of two cell lines, gestational choriocarcinoma cell line JEG-3 and trophoblast cell line HTR-8/SVneo. UCHL5 inhibition negatively regulated TGF-ß1-induced Smad2 activation, decreasing extravillous trophoblast invasiveness. Smad1/5/9 and extracellular signal-regulated kinase (ERK) were simultaneously activated, and vascular endothelial growth factor was secreted into the trophoblast medium. However, extravillous trophoblast culture supernatant severely impaired the vasculogenic potential of human umbilical vein endothelial cells. These results suggest that the downstream ERK pathway and Smad1/5/9 potentially regulate the TGF-ß1-Smad pathway in extravillous trophoblasts, whereas Smad2 contributes to their invasiveness. The abnormal invasive and angiogenic capacities of extravillous cells, likely driven by the interaction between TGF-ß1-Smad and ERK pathways, underlie the pathogenesis of placenta accreta.

Adult-onset Still's Disease Diagnosed during Puerperium with Liver Dysfunction in Pregnancy and Liver Failure of the Infant.

Most cases of liver dysfunction in pregnancy are pregnancy-related, but the onset of systemic autoimmune diseases is also differentiated. A 24-year-old woman presented with liver dysfunction at 28 weeks' gestation with suspected autoimmune hepatitis and started taking ursodeoxycholic acid. She gave birth prematurely at 35 weeks' gestation, and the infant presented with pancytopenia and liver failure but survived because of liver transplantation. Since the patient had major symptoms during the puerperium, she was diagnosed with adult-onset Still's disease. When encountering a patient with liver dysfunction during pregnancy, we should also consider the onset of autoimmune diseases.

High-grade endometrial stromal sarcoma with YWHAE-NUTM2B fusion gene abnormality identified after 10 years of recurrent pulmonary metastases: A case report.

•Endometrial stromal sarcoma is the second most common type of uterine sarcoma.•Endometrial stromal sarcoma has undergone modifications since its proposal.•This case highlights the importance of accurately diagnosing endometrial stromal sarcoma.•Asymptomatic uterine fibroids may not be treated with therapeutic intervention or prompt regular check-ups.

Development and validation of a symptom illustration scale from the patient-reported outcome common terminology criteria for adverse events for patients with breast cancer.

PURPOSE: Emojis are commonly used for daily communication and may be useful in assessing patient-reported outcomes (PROs) in breast cancer. The purpose of this study is to develop and validate a Symptom Illustration Scale (SIS) as a new PRO measurement. METHODS: Eighteen original SIS items were developed from the PRO-CTCAE. In cohort one, the SIS validity and reliability were examined in patients with breast cancer, using a semi-structured five-question survey to investigate content validity. PROs with PRO-CTCAE and SIS were examined twice to determine criteria validity and test-retest reliability. In cohort two, the responsiveness of the scales were examined in patients treated with anthracycline, docetaxel, paclitaxel, and endocrine therapy. PROs with PRO-CTCAE and SIS were investigated two or three times, depending on the therapy. RESULTS: Patients were enrolled from August 2019 to October 2020. In cohort one (n = 70), most patients had no difficulties with the SIS, but 16 patients indicated that it was difficult to understand severities in the SIS. For criterion validity, Spearman rank correlation coefficients (rs) between PRO-CTCAE and SIS items were ≥ 0.41, except for "Decreased appetite." For test-retest reliability, κ coefficients of the SIS were ≥ 0.41 for 16/18 items (88.9%). Response time was significantly shorter for the SIS than for PRO-CTCAE (p < 0.001). In cohort two (n = 106), score changes between PRO-CTCAE and SIS for relevant symptoms all had correlations with rs ≥ 0.41. CONCLUSION: An original SIS from the PRO-CTCAE for patients with breast cancer were verified the validity, reliability, and responsiveness. Further studies to improve and validate the SIS are needed.

Serum vascular endothelial growth factor associated with the progression of granulosa cell tumor: a report of two cases.

BACKGROUND: Granulosa cell tumors (GCTs) account for approximately 2% of ovarian malignancies and are considered a rare type of ovarian cancer. GCTs are characterized by irregular genital bleeding after menopause due to female hormone production as well as late recurrence around 5-10 years after initial treatment. In this study, we investigated two cases of GCTs to find a biomarker that can be used to evaluate the treatment and predict recurrence. CASE PRESENTATION: Case 1 was a 56-year-old woman who presented to our hospital with abdominal pain and distention. An abdominal tumor was found, and GCTs were diagnosed. Serum vascular endothelial growth factor (VEGF) levels decreased after surgery. Case 2 involved a 51-year-old woman with refractory GCTs. Carboplatin-paclitaxel combination therapy and bevacizumab were administered after the tumor resection. After chemotherapy, a decline in VEGF levels was observed, but serum VEGF levels increased again with disease progression. CONCLUSIONS: VEGF expression may be of clinical importance in GCTs as a clinical biomarker for disease progression, which may be used to determine the efficacy of bevacizumab against GCTs.

Effects of Slide Sheet Use and Bed Position on Muscle Activities in the Low Back and Extremities: A Pilot Experimental Simulation Study.

BACKGROUND: Low-friction slide sheets (SS) are designed to reduce compression loads on the body during manual handling tasks, such as boosting patients. Using SS has been shown to decrease muscle activity in the lower back and upper extremities. However, it is unclear if this effect varies with different bed positions. To investigate this, we studied the effects of SS use, bed height, and their combination on muscle activity during a simulated patient boost. METHODS: Thirty-three Japanese undergraduate students (age 21.0 ± 1.1 years; 14 men, 19 women) participated. Participants were asked to boost a dummy figure on the bed three times each using four conditions. During the repositioning task, electromyography of eight muscles of the lower back and upper and lower extremities, hip and knee joint flexion angles, pelvic forward tilt angle, and position of the center of mass based on the posterior superior iliac spine were evaluated. FINDINGS: Electrophysiological activities of muscles of lower back and upper extremities were significantly lower with SS than without it in both bed positions (30% and 40% of body height); the reduction in muscle activities with SS use was 20% to 40%. Lowering the bed did not affect the SS effect magnitude on reducing muscle activities, although postural changes, including hip and knee joint flexion, were observed. CONCLUSIONS/APPLICATION TO PRACTICE: SS reduced muscle activities in the back, upper, and lower extremities when the bed was in the low position, and this effect persisted at a bed height of ≥30% of the participant's height.

Validity of computed mean compressed fibroglandular tissue thickness and breast composition for stratification of masking risk in Japanese women.

BACKGROUND: The volumetric measurement system for mammographic breast density is a high-precision objective method for evaluating the percentage of fibroglandular tissue volume (FG%). Nonetheless, FG% does not precisely correlate with subjective visual estimation (SVE) and shows poor evaluation performance regarding masking risk in patients with comparatively thin compressed breast thickness (CBT), commonly found in Japanese women. We considered that the mean compressed fibroglandular tissue thickness (mCGT), which incorporates the CBT element into the evaluation of breast density, may better predict masking risk. METHODS: Volumetric measurements and SVEs were performed on mammograms of 108 breast cancer patients from our center. mCGT was calculated as the product of CBT and FG%. SVE was classified using the Breast Imaging-Reporting and Data System classification, 5th edition. Subsequently, the performance of mCGT, SVE, and FG% in predicting masking risk was estimated using the AUC. RESULTS: The AUC values of mCGT and SVE were 0.84 (95% confidence interval, 0.71-0.92) and 0.78 (0.66-0.86), respectively (P = 0.16). The AUC of the FG% was 0.65 (0.52-0.77), which was significantly lower than that of mCGT (P < 0.001). The sensitivity and specificity of mCGT in predicting negative detection were 89% and 71%, respectively; of SVE 83% and 61% (versus 72% and 57% with FG%), suggesting that mCGT was superior to FG% in both sensitivity and specificity, and comparable with SVE. CONCLUSIONS: Objective mCGT calculated from the volumetric measurement system will highly likely be useful in evaluating breast density and supporting visual assessment for masking risk stratification.

Chlamydia Peritonitis Mimicking Juvenile Carcinomatous Peritonitis Diagnosed by Exploratory Laparoscopy: A Case Report.

Chlamydia trachomatis infections may occur in multiple organs, including the lungs, lymph nodes, peritoneal cavity, and genitourinary systems. This disease results in significant ascites, the swelling of lymph nodes, and elevated tumor markers (CA125), sometimes mimicking an ovarian malignancy. At our hospital, we often perform examination laparoscopic surgery in cases of suspected gynecologic cancers before initial treatment. In this paper, we report the case of a 19-year-old woman who came to our hospital because of an ovarian tumor and ascites. There was no history of sexual intercourse (self-reported). We suspected ovarian cancer from image inspections, so we performed laparoscopic surgery for diagnosis. The final pathological diagnosis was acute-to-chronic inflammation of the bilateral fallopian tubes, and a cytologic examination of the ascites was negative for malignant cells. The C. trachomatis antigen was positive on vaginal examination after the operation. Based on this result, we diagnosed this patient with C. trachomatis infection. Chlamydia peritonitis should be a differential diagnosis for cancer peritonitis in juvenile patients with abnormal ascites. Exploratory laparoscopy should help confirm the pathological diagnosis.

Predictive value of immune genomic signatures from breast cancer cohorts containing data for both response to neoadjuvant chemotherapy and prognosis after surgery.

BACKGROUND: Previous studies of immune genomic signatures (IGSs) in breast cancer have attempted to predict the response to chemotherapy or prognosis and were performed using different patient cohorts. The purpose of this study was to evaluate the predictive functions of various IGSs using the same patient cohort that included data for response to chemotherapy as well as the prognosis after surgery. METHODS: We applied five previously described IGS models in a public dataset of 508 breast cancer patients treated with neoadjuvant chemotherapy. The prognostic and predictive values of each model were evaluated, and their correlations were compared. RESULTS: We observed a high proportion of expression concordance among the IGS models (r: 0.56-1). Higher scores of IGSs were detected in aggressive breast cancer subtypes (basal and HER2-enriched) (P < 0.001). Four of the five IGSs could predict chemotherapy responses and two could predict 5-year relapse-free survival in cases with hormone receptor-positive (HR +) tumors. However, the models showed no significant differences in their predictive abilities for hormone receptor-negative (HR-) tumors. CONCLUSIONS: IGSs are, to some extent, useful for predicting prognosis and chemotherapy response; moreover, they show substantial agreement for specific breast cancer subtypes. However, it is necessary to identify more compelling biomarkers for both prognosis and response to chemotherapy in HR- and HER2 + cases.

Liver oligometastatic disease in synchronous metastatic gastric cancer patients: a nationwide population-based cohort study.

INTRODUCTION: This population-based cohort study analysed treatment, overall survival (OS), and independent prognostic factors for OS in gastric cancer patients with liver metastases. METHODS: Between 2015 and 2017, patients with synchronous metastatic gastric or gastroesophageal junction adenocarcinoma limited to the liver were included from the prospectively maintained population-based Netherlands Cancer Registry. Liver oligometastatic disease (OMD) was defined as ≤3 liver metastases. The primary outcome was OS. Independent prognostic factors for OS were analysed using multivariable Cox regression analysis. RESULTS: A total 295 patients with metastases limited to the liver were included. The primary tumour was resected in four patients (1.4%). Treatment for liver metastases consisted of chemotherapy alone (28.1%), trastuzumab plus chemotherapy (4.7%), surgery (1.0%), or best supportive care (67.5%). Median OS across all included patients was 4.0 months (95% confidence interval [CI]: 3.1-4.5). Liver OMD was detected in 77 patients (26%). Treatment for liver OMD consisted of chemotherapy alone (24.6%), trastuzumab plus chemotherapy (5.2%), surgery (3.9%), or best supportive care (67.5%). Median OS among patients with liver OMD was 5.7 months (95% CI: 4.8-7.5). Across all patients, better OS was independently associated with liver OMD (hazard ratio [HR] 0.66, 95% CI: 0.50-0.87), trastuzumab (HR 0.41, 95% CI: 0.23-0.72) but not with triplet compared with doublet chemotherapy (HR 0.94, 95% CI: 0.57-2.87). Worse OS was independently associated with unknown nodal stage versus cN0 (HR 1.74, 95% CI: 1.17-2.60), diffuse-type versus intestinal-type adenocarcinoma (HR 2.06, 95% CI: 1.32-3.20), and monotherapy or best supportive care versus doublet chemotherapy (HR 1.72, 95% CI: 1.03-2.87, and HR 3.61, 95% CI: 2.55-5.10, respectively). CONCLUSION: In this population-based cohort study, liver OMD was detected in 26% of patients. Liver OMD and trastuzumab treatment were independently associated with better OS while triplet as compared with doublet chemotherapy was not. OS among patients with liver OMD nevertheless remained poor. The concept of OMD and the benefit of resection of liver OMD may still have been relatively unknown in this disease type during the study inclusion years.

Practical Utility of a Clinical Pathway for Older Patients with Aspiration Pneumonia: A Single-Center Retrospective Observational Study.

Introduction: Clinical pathways (CPWs) are patient management tools based on a standardized treatment plan aimed at improving quality of care. This study aimed to investigate whether CPW-guided treatment has a favorable impact on the outcomes of hospitalized older patients with aspiration pneumonia. Method: This retrospective study included patients with aspiration pneumonia, aged ≥ 65 years, and hospitalized at a community hospital in Japan. CPW implementation was arbitrarily determined by the attending physician upon admission. Outcomes were compared according to with or without the CPW (CPW-group and non-CPW groups). Propensity score (PS)-based analyses were used to control for confounding factors. Logistic regression analyses were conducted to evaluate the impact of CPW on the clinical course and outcomes. Results: Of 596 included patients, 167 (28%) received the CPW-guided treatment. The mortality rate was 16.4%. In multivariable model, CPW implementation did not increase the risk for total and 30-day mortality, and resulted in shorter antibiotic therapy duration (≤9 days) (PS matching (PSM): odds ratio (OR) 0.50, p = 0.001; inverse provability of treatment weighting (IPTW): OR 0.48, p < 0.001) and length of hospital stay (≤21 days) (PSM: OR 0.67, p = 0.05; IPTW: OR 0.66, p = 0.03). Conclusions: This study support CPW utility in this population.

Randomized double-blind placebo-controlled multicenter trial for the effects of a polyherbal remedy, Yokukansan (YiganSan), in smokers with depressive tendencies.

BACKGROUND: Smoking and depression are closely related and form a vicious cycle. Yokukansan (YiganSan) is a polyherbal remedy that has the effect of calming neuropsychiatric symptoms such as anger and irritation. To examine the efficacy of Yokukansan during smoking cessation (SC) therapy in smokers with depressive tendencies but without major depressive disorders requiring pharmacotherapy. METHODS: A multicenter, double-blind, randomized, placebo-controlled, parallel-group comparison trial was conducted between June 2016 and May 2020 at 12 centers of the National Hospital Organization, Japan. This trial targeted smokers who first visited the SC outpatient clinics, did not receive any pharmacological treatment at the psychiatric or psychosomatic department, and scored 39 or more on the self-rating depression scale (SDS). Participants (n = 198) were randomly assigned to either the Yokukansan or placebo groups. The trial drug was initiated with the start of the SC treatment and continued for 12 weeks. The primary outcome was the high success rate of the SC treatment, and the secondary outcomes included changes in scores of the SDS and the Profile of Mood States (POMS) instrument. RESULTS: The success rate of the SC treatment was similar between the placebo (63%) and Yokukansan (67%) groups (P = .649). The SDS scores (placebo: mean difference [MD] = -3.5, 95% confidence interval [CI][-5.8, -1.2], d = 0.42; Yokukansan: MD = -4.6, 95%CI[-6.8, -2.3], d = 0.55), and the "tension-anxiety" POMS-subscale scores (placebo: MD = -1.6, 95%CI[-2.5, -0.7], d = 0.52; Yokukansan: MD = -1.6, 95%CI[-2.9, -0.3], d = 0.36) showed significant improvement in both groups after the SC treatment. However, "depression-dejection" improved in the Yokukansan group (MD = -1.9, 95%CI[-3.1, -0.7], d = 0.44) but not in the placebo group (MD = -0.1, 95%CI[-1.0, 0.7], d = 0.04). Significant improvement in "fatigue" was noted in the Yokukansan group (MD = -2.1, 95%CI[-3.4, -0.9], d = 0.47) but not in the placebo group (MD = -0.5, 95%CI[-1.8, 0.8], d = 0.11). The time × group interaction on the improvement in "depression-dejection" was significant (P = .019). CONCLUSIONS: Yokukansan does not increase the SC treatment's success rate but has additional positive effects on the psychological states due to the SC treatment in smokers with depressive tendencies but without apparent mental disorders. TRIAL REGISTRATION: ID: UMIN000027036. Retrospectively registered at UMIN on April 18, 2017.