Distinct and opposite effects of leukemogenic Idh and Tet2 mutations in hematopoietic stem and progenitor cells.

Mutations in IDH1, IDH2, and TET2 are recurrently observed in myeloid neoplasms. IDH1 and IDH2 encode isocitrate dehydrogenase isoforms, which normally catalyze the conversion of isocitrate to α-ketoglutarate (α-KG). Oncogenic IDH1/2 mutations confer neomorphic activity, leading to the production of D-2-hydroxyglutarate (D-2-HG), a potent inhibitor of α-KG-dependent enzymes which include the TET methylcytosine dioxygenases. Given their mutual exclusivity in myeloid neoplasms, IDH1, IDH2, and TET2 mutations may converge on a common oncogenic mechanism. Contrary to this expectation, we observed that they have distinct, and even opposite, effects on hematopoietic stem and progenitor cells in genetically engineered mice. Epigenetic and single-cell transcriptomic analyses revealed that Idh2R172K and Tet2 loss-of-function have divergent consequences on the expression and activity of key hematopoietic and leukemogenic regulators. Notably, chromatin accessibility and transcriptional deregulation in Idh2R172K cells were partially disconnected from DNA methylation alterations. These results highlight unanticipated divergent effects of IDH1/2 and TET2 mutations, providing support for the optimization of genotype-specific therapies.

Management challenges and the role of adjuvant chemotherapy in remnant gastric cancer: an analysis of 313 patients from the KEGG multicenter observational study.

BACKGROUND: Clinical findings and postoperative follow-up data on remnant gastric cancer (RGC) are limited due to its rarity. Additionally, the preoperative staging, radical surgery, and managing recurrence in RGC present significant clinical challenges. METHODS: We analyzed the clinicopathological findings, adjuvant chemotherapy, and patterns of postoperative recurrence of 313 consecutive patients who underwent curative surgery for RGC at 17 Japanese institutions. This study investigated the optimal management of RGC and the impact of adjuvant chemotherapy (AC) on recurrence-free survival (RFS). RESULTS: Pathological stages I, II, and III were observed in 55.9% (N = 175), 24.9% (N = 78), and 19.2% (N = 60) of the patients, respectively. The overall concordance rate between clinical and pathological T staging was 58.3%, with a clinical T4 sensitivity of 41.4% for diagnosing pathological T4. During the median follow-up period of 4.6 years, disease recurrence occurred in 24.3% of patients. Most recurrences (over 80%) occurred within 2.5 years, and 96.1% within 5 years after RGC surgery. Peritoneal recurrence was the most common in patients with advanced RGC, accounting for 14.1% in stage II and 28.3% in stage III. Multivariable regression analysis showed that AC was significantly associated with a longer RFS, with a hazard ratio of 0.45 (95% confidence interval: 0.26-0.76). CONCLUSIONS: Our study underscores the importance of early detection, accurate preoperative staging, and postoperative surveillance in managing advanced RGC cases. Despite some limitations, our findings indicate that AC may provide survival benefits comparable to those seen in primary gastric cancer.

A Y-linked anti-Müllerian hormone type-II receptor is the sex-determining gene in ayu, Plecoglossus altivelis.

Whole-genome duplication and genome compaction are thought to have played important roles in teleost fish evolution. Ayu (or sweetfish), Plecoglossus altivelis, belongs to the superorder Stomiati, order Osmeriformes. Stomiati is phylogenetically classified as sister taxa of Neoteleostei. Thus, ayu holds an important position in the fish tree of life. Although ayu is economically important for the food industry and recreational fishing in Japan, few genomic resources are available for this species. To address this problem, we produced a draft genome sequence of ayu by whole-genome shotgun sequencing and constructed linkage maps using a genotyping-by-sequencing approach. Syntenic analyses of ayu and other teleost fish provided information about chromosomal rearrangements during the divergence of Stomiati, Protacanthopterygii and Neoteleostei. The size of the ayu genome indicates that genome compaction occurred after the divergence of the family Osmeridae. Ayu has an XX/XY sex-determination system for which we identified sex-associated loci by a genome-wide association study by genotyping-by-sequencing and whole-genome resequencing using wild populations. Genome-wide association mapping using wild ayu populations revealed three sex-linked scaffolds (total, 2.03 Mb). Comparison of whole-genome resequencing mapping coverage between males and females identified male-specific regions in sex-linked scaffolds. A duplicate copy of the anti-Müllerian hormone type-II receptor gene (amhr2bY) was found within these male-specific regions, distinct from the autosomal copy of amhr2. Expression of the Y-linked amhr2 gene was male-specific in sox9b-positive somatic cells surrounding germ cells in undifferentiated gonads, whereas autosomal amhr2 transcripts were detected in somatic cells in sexually undifferentiated gonads of both genetic males and females. Loss-of-function mutation for amhr2bY induced male to female sex reversal. Taken together with the known role of Amh and Amhr2 in sex differentiation, these results indicate that the paralog of amhr2 on the ayu Y chromosome determines genetic sex, and the male-specific amh-amhr2 pathway is critical for testicular differentiation in ayu.

Prospective external validation of radiomics-based predictive model of distant metastasis after dynamic tumor tracking stereotactic body radiation therapy in patients with non-small-cell lung cancer: A multi-institutional analysis.

BACKGROUND AND PURPOSE: This study aims to externally validate a predictive model for distant metastasis (DM) with computed tomography (CT)-based radiomics features in prospectively enrolled non-small-cell lung cancer patients undergoing dynamic tumor-tracking stereotactic body radiation therapy (DTT-SBRT). MATERIALS AND METHODS: The study collected retrospective data from 567 patients across 11 institutions as the training dataset and prospectively enrolled 42 patients from four institutions as the external test dataset. Four clinical features were collected, and 944 CT-based radiomic features were extracted from gross tumor volumes. After standardization and feature selection, DM predictive models were developed using fine and gray regression (FG) and random survival forest (RSF), incorporating clinical and radiomic features, and their combinations within the training dataset. Then, the model was applied to the test dataset, dividing patients into high- and low-risk groups based on medians of risk scores. Model performance was assessed using the concordance index (C-index), and the statistical significance between groups was evaluated using Gray's test. RESULTS: In the training dataset, 122 of 567 patients (21.5%) developed DM, compared to 9 of 42 patients (21.4%) in the test dataset. In the test dataset, the C-indices of the clinical, radiomics, and hybrid models with FG were 0.559, 0.544, and 0.560, respectively, whereas those with RSF were 0.576, 0.604, and 0.627, respectively. The hybrid model with RSF, which exhibited the best predictive performance of all models, identified 7 of 23 patients (30.4%) as high risk and 2 of 19 patients (10.5%) as low risk for DM incidence in the test dataset (p = 0.116). CONCLUSION: Although predictive models for DM lack significance when applied to prospectively enrolled cases undergoing DTT-lung SBRT, the model with RSF exhibits a consistent capacity to effectively classify patients at a high risk of developing DM.

Gender equity in surgical instruments: ergonomics of ring-handled forceps.

INTRODUCTION: Female surgeons have ergonomic issues with commercialized instruments tailored for male surgeons. The purpose of this study was to identify satisfaction levels and ergonomic problems of female surgeons while using laparoscopic forceps with ring-handles and suggest improvement measures. MATERIAL AND METHODS: A questionnaire was sent to 19,405 members of the Japanese Society of Gastroenterological Surgery via email between 1 August 2022 and 30 September 2022. It included demographic information and specific questions regarding the use of laparoscopic forceps with ring- handles (ergonomic evaluation, influence of the negative aspects of laparoscopic forceps during surgery, physical discomfort in the hands and fingers, degree of satisfaction, and handle size). RESULTS: Valid responses were received from 1,030 respondents (131 female and 899 male surgeons). The ergonomics of the laparoscopic forceps with ring-handles were rated lower by female surgeons in all ten categories (all p value < 0.05). They also reported a negative impact on surgical manipulation and discomfort to their hands and fingers. CONCLUSIONS: Female surgeons had a wide variety of ergonomic problems when using laparoscopic forceps with ring-handles, and showed lower levels of satisfaction. Developing a different model tailored to female surgeons with smaller hands and a weaker grip could be a viable solution.

[A Case of Hormone Receptor-Positive Recurrent Breast Cancer Successfully Treated with Low-Dose Ethinyl Estradiol].

The patient, an 83-year-old woman, was diagnosed with ER- and PgR-positive left breast cancer(T2N0M0, Stage ⅡA) at the age of 68. At the time, she underwent preoperative chemotherapy followed by Bp+Ax and postoperative radiotherapy to the conserved breast. She also received endocrine therapy as adjuvant therapy. At the age of 73, she underwent radiotherapy for multiple bone metastases and left axillary lymphadenectomy due to left axillary lymph node recurrence. After surgery, she received 4 regimens of endocrine therapy over a period of 5 years and 1 month for bone metastases. At the age of 79, S-1 was administered for pulmonary metastasis which continued for the next 2 years and 8 months. At the age of 81, palbociclib+letrozole were administered for 1 year and 8 months owing to the progression of bone metastases. At the age of 83, she developed liver metastases and was administered ethinyl estradiol, starting at 1.5 mg/day and continued at a reduced dose of 0.5 mg/day for 9 months. The reduction in tumor markers after treatment initiation was rapid, and there were no serious adverse events. Ethinyl estradiol was useful for maintaining QOL in this elderly patient with recurrent breast cancer.

[A Case Report of Adenomyoepithelioma Coexisting with Apocrine Carcinoma in Contralateral Breasts].

Adenomyoepithelioma(AME)of the breast is a rare condition, and comorbidity with carcinoma is even more unusual. Herein, we report a case of both AME and apocrine carcinoma in different breasts of a single patient. A 48-year-old woman presented to our clinic with a right breast tumor. Fine needle aspiration cytology(FNAC)was indeterminate and suspicious for both papilloma and non-invasive ductal carcinoma, but excisional biopsy indicated an AME. Immuno-histochemical staining showed EMA(+), AE1/3(+), and CK7(+)mammary duct cells and αSMA(+), CK5/6(+), and p63(+) myoepithelial cells. Six months later, the patient noticed a left breast tumor, and although FNAC indicated no malignancy, after 6 additional months, the tumor size had increased and a mammography revealed tumor microcalcification, suggesting malignancy. Vacuum-assisted biopsy revealed an apocrine carcinoma. The patient underwent partial mastectomy and sentinel node biopsy, followed by radiotherapy and chemotherapy. The post-surgical pathology was pT1pN0M0, Stage Ⅰ, triple- negative, and the patient was disease-free for 12 years postoperatively. To our knowledge, this is only the second case of AME and breast cancer in different breasts reported in Japan.

Near-Infrared Fluorescent Switch-On Probe for Guanine-Quadruplex Imaging with Extremely Large Stokes Shift.

To visualize the guanine-quadruplex (G4) nucleic acids in cells or in biological tissues, near-infrared (NIR) fluorescent probes that can respond specifically to G4 nucleic acids are required. Herein, an NIR fluorescence switch-on probe for G4 imaging having higher selectivity and extremely large Stokes shift (ca. 220 nm) was successfully developed by the modification of our original tripodal quinone-cyanine fluorescent dye. The target binding-induced intramolecular stacking interaction of the probe might cause red shifting of the fluorescence emission. The NIR fluorescence switch-on probe developed here might contribute largely to revealing the behaviors of G4 nucleic acids not only in cells but also in biological tissues.

HTLV-1 bZIP factor impairs DNA mismatch repair system.

Adult T-cell leukemia (ATL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1). Microsatellite instability (MSI) has been observed in ATL cells. Although MSI results from impaired mismatch repair (MMR) pathway, no null mutations in the genes encoding MMR factors are detectable in ATL cells. Thus, it is unclear whether or not impairment of MMR causes the MSI in ATL cells. HTLV-1 bZIP factor (HBZ) protein interacts with numerous host transcription factors and significantly contributes to disease pathogenesis and progression. Here we investigated the effect of HBZ on MMR in normal cells. The ectopic expression of HBZ in MMR-proficient cells induced MSI, and also suppressed the expression of several MMR factors. We then hypothesized that the HBZ compromises MMR by interfering with a transcription factor, nuclear respiratory factor 1 (NRF-1), and identified the consensus NRF-1 binding site at the promoter of the gene encoding MutS homologue 2 (MSH2), an essential MMR factor. The luciferase reporter assay revealed that NRF-1 overexpression enhanced MSH2 promoter activity, while co-expression of HBZ reversed this enhancement. These results supported the idea that HBZ suppresses the transcription of MSH2 by inhibiting NRF-1. Our data demonstrate that HBZ causes impaired MMR, and may imply a novel oncogenesis driven by HTLV-1.

Adding Induction Chemotherapy Before Chemoradiotherapy with Total Mesorectal Excision and Selective Lateral Lymph Node Dissection for Patients with Poor-Risk, Locally Advanced, Mid-to-Low Rectal Cancer May Improve Oncologic Outcomes: A Propensity Score-Matched Analysis.

BACKGROUND: This study aimed to investigate whether the addition of induction chemotherapy before chemoradiotherapy (CRT) and total mesorectal excision (TME) with selective lateral lymph node dissection improves disease-free survival for patients with poor-risk, mid-to-low rectal cancer. METHODS: The authors' institutional prospective database was queried for consecutive patients with clinical stage II or III, primary, poor-risk, mid-to-low rectal cancer who received neoadjuvant treatment followed by TME from 2004 to 2019. The outcomes for the patients who received induction chemotherapy before neoadjuvant CRT (induction-CRT group) were compared (via log-rank tests) with those for a propensity score-matched cohort of patients who received neoadjuvant CRT without induction chemotherapy (CRT group). RESULTS: From 715 eligible patients, the study selected two matched cohorts with 130 patients each. The median follow-up duration was 5.4 years for the CRT group and 4.1 years for the induction-CRT group. The induction-CRT group had significantly higher rates of 3-year disease-free survival (83.5 % vs 71.4 %; p = 0.015), distant metastasis-free survival (84.3 % vs 75.2 %; p = 0.049), and local recurrence-free survival (98.4 % vs 94.4 %; p = 0.048) than the CRT group. The pathologically complete response rate also was higher in the induction-CRT group than in the CRT group (26.2 % vs 10.0 %; p < 0.001). Postoperative major complications (Clavien-Dindo classification ≥III) did not differ significantly between the two groups (12.3 % vs 10.8 %; p = 0.698). CONCLUSIONS: The addition of induction chemotherapy to neoadjuvant CRT appeared to improve oncologic outcomes significantly, including disease-free survival, for the patients with poor-risk, mid-to-low rectal cancer who underwent TME using selective lateral lymph node dissection.

Integrated genetic and clinical prognostic factors for aggressive adult T-cell leukemia/lymphoma.

The prognosis of aggressive adult T-cell leukemia/lymphoma (ATL) is poor, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment. In order to identify favorable prognostic patients after intensive chemotherapy, and who therefore might not require upfront allo-HSCT, we aimed to improve risk stratification of aggressive ATL patients aged <70 years. The clinical risk factors and genetic mutations were incorporated into risk modeling for overall survival (OS). We generated the m7-ATLPI, a clinicogenetic risk model for OS, that included the ATL prognostic index (PI) (ATL-PI) risk category, and non-silent mutations in seven genes, namely TP53, IRF4, RHOA, PRKCB, CARD11, CCR7, and GATA3. In the training cohort of 99 patients, the m7-ATLPI identified a low-, intermediate-, and highrisk group with 2-year OS of 100%, 43%, and 19%, respectively (hazard ratio [HR] =5.46; P<0.0001). The m7-ATLPI achieved superior risk stratification compared to the current ATL-PI (C-index 0.92 vs. 0.85, respectively). In the validation cohort of 84 patients, the m7-ATLPI defined low-, intermediate-, and high-risk groups with a 2-year OS of 81%, 30%, and 0%, respectively (HR=2.33; P=0.0094), and the model again outperformed the ATL-PI (C-index 0.72 vs. 0.70, respectively). The simplified m7-ATLPI, which is easier to use in clinical practice, achieved superior risk stratification compared to the ATLPI, as did the original m7-ATLPI; the simplified version was calculated by summing the following: high-risk ATL-PI category (+10), low-risk ATL-PI category (-4), and non-silent mutations in TP53 (+4), IRF4 (+3), RHOA (+1), PRKCB (+1), CARD11 (+0.5), CCR7 (-2), and GATA3 (-3).

Employment Status of Patients With Colorectal Cancer After Surgery: A Multicenter Prospective Cohort Study in Japan.

BACKGROUND: Because of improved survival rates, patients with colorectal cancer may try to return to work. Many countries, however, have limited knowledge of the employment status of these patients. OBJECTIVE: To explore the employment status of patients with colorectal cancer after surgery in Japan and the risk factors affecting the same. DESIGN: This is a prospective multicenter cohort study that used self-administered questionnaires. Patients were recruited from June 2019 to August 2020 and were followed up for 12 months after surgery. SETTING: Six community hospitals and 1 university hospital in Japan. PATIENTS: Patients with clinical stages I to III colorectal cancer, employed at the time of diagnosis. INTERVENTIONS: Patients who underwent surgical resection between June 2019 and August 2020. MAIN OUTCOME MEASUREMENTS: The time it takes patients to return to work after surgery and the proportion of working patients 12 months after surgery were collected using self-administered questionnaires. RESULTS: A total of 129 patients were included in the analyses. The median time to return-to-work was 1.1 months, and the proportion of working patients at 12 months after surgery was 79%. Risk factors for delayed return-to-work after surgery were an advanced tumor stage, stoma, severe postoperative complications, shorter years of service at the workplace, and lower willingness to return-to-work. Risk factors for not working 12 months after surgery were stoma, lower willingness to return-to-work, nonregular employee status, lower income, national health insurance, and no private medical insurance. LIMITATIONS: This study is limited by its short-term follow-up and small sample size. CONCLUSIONS: This study revealed that Japanese patients with stages I to III colorectal cancer found favorable employment outcomes in the 12 months after surgery. These results may help health care providers better understand the employment status of patients with colorectal cancer and encourage them to consider returning to work after surgery. SITUACIN LABORAL DE LOS PACIENTES CON CNCER COLORRECTAL DESPUS DE LA CIRUGA UN ESTUDIO DE COHORTE PROSPECTIVO MULTICNTRICO EN JAPN: ANTECEDENTES:Debido a las mejores tasas de supervivencia, los pacientes con cáncer colorrectal pueden intentar volver al trabajo. Muchos países, sin embargo, tienen un conocimiento limitado de su situación laboral.OBJETIVO:Explorar la situación laboral de los pacientes con cáncer colorrectal después de la cirugía en Japón y los factores de riesgo que afectan a la misma.DISEÑO:Este es un estudio prospectivo de cohortes multicéntrico que utiliza cuestionarios autoadministrados. Los pacientes fueron reclutados desde junio de 2019 hasta agosto de 2020 y fueron seguidos durante 12 meses después de la cirugía.ENTORNO CLINICO:Seis hospitales comunitarios y un hospital universitario en Japón.PACIENTES:Pacientes con estadios clínicos I-III de cáncer colorrectal, trabajando en el momento del diagnóstico.INTERVENCIONES:Pacientes que recibieron resección quirúrgica desde junio de 2019 hasta agosto de 2020.PRINCIPALES MEDIDAS DE RESULTADO:El tiempo que tardan los pacientes en volver al trabajo después de la cirugía y la proporción de pacientes que trabajan 12 meses después de la cirugía se recogieron mediante cuestionarios autoadministrados.RESULTADOS:Un total de 129 pacientes fueron incluidos en los análisis. La mediana de tiempo de reincorporación al trabajo fue de 1,1 meses y la proporción de pacientes que trabajaban a los 12 meses de la cirugía fue del 79%. Los factores de riesgo para el retraso en el regreso al trabajo después de la cirugía fueron un estadio avanzado del tumor, estoma, complicaciones postoperatorias graves, menos años de servicio en el lugar de trabajo y menor disposición para volver al trabajo. Los factores de riesgo para no trabajar 12 meses después de la cirugía fueron estoma, menor voluntad de volver al trabajo, condición de empleado no regular, ingresos más bajos, seguro nacional de salud y la falta de seguro médico privado.LIMITACIONES:Este estudio está limitado por su seguimiento a corto plazo y tamaño de muestra pequeño.CONCLUSIONES:Este estudio reveló que los pacientes japoneses con cáncer colorrectal en estadios I-III obtuvieron resultados laborales favorables en los 12 meses posteriores a la cirugía. Estos resultados pueden ayudar a los proveedores de atención médica a comprender mejor la situación laboral de los pacientes con cáncer colorrectal y alentarlos a considerar regresar al trabajo después de la cirugía. (Traducción- Dr. Francisco M. Abarca-Rendon ).

Inferior versus medial approach in laparoscopic colectomy with complete mesocolic excision and D3 lymphadenectomy for right-sided colon cancer: A propensity-score-matched analysis.

AIM: In laparoscopic colectomy with complete mesocolic excision and D3 lymphadenectomy for right-sided colon cancer, either an inferior approach (IA) or a medial approach (MA) is selected in our institution based on the surgeon's preference. The present study compared the treatment outcomes between IA and MA. METHOD: This retrospective, single-centre study using propensity score matching analysed the short- and long-term outcomes of laparoscopic surgery in patients with right-sided colon cancer from 2010 to 2019 at Cancer Institute Hospital. RESULTS: After patient selection, 1011 patients remained for the analysis, of which 67% underwent IA surgery and 33% underwent MA surgery. After propensity score matching (1:1), 325 patients in each group were analysed. Regarding the short-term outcomes, there were no significant differences in the operation time, rate of conversion to open surgery or postoperative complication rate (Clavien-Dindo Grade ≥ III) between the two groups, although the intra-operative median blood loss was significantly less in the IA group than in the MA group (IA, 13 ml vs. MA, 20 ml, P < 0.0001). Regarding the long-term outcomes, the relapse-free survival, liver-relapse-free survival, cancer-specific survival and overall survival were all similar between groups. CONCLUSION: Both the IA and MA in laparoscopic colectomy with complete mesocolic excision and D3 lymphadenectomy for right-sided colon cancer are safe and feasible approaches; the IA may have an advantage over the MA in terms of reduced intra-operative blood loss. Based on their similar oncological outcomes, either the IA or MA can be selected, based on one's preference.

What can surgeons do to prevent job leave soon after cancer diagnosis? A brief report on colorectal cancer survivors in Japan.

PURPOSE: Colorectal cancer is one of the most diagnosed cancers in Japan and the number of cancer survivors has increased. Work-related issues of cancer survivors have been investigated in relation to occupational health, and sufficient evidence in clinical practice is needed to support this. This study aimed to obtain the relevant information, intending to support the employment of patients with colorectal cancer for clinical settings. METHODS: We conducted a prospective, multicenter cohort study, which included patients who underwent surgery with clinical stage I-III colorectal cancer. An electronic survey was used at the time of hospital admission to collect the patients' occupational information, including job resignation soon after cancer diagnosis. A cross-sectional analysis was performed to evaluate the patients' employment situations. RESULTS: Of 129 eligible patients, 46 (36%) were female. Thirty-nine (30%) were self-employed and 72 (56%) worked at small-sized workplaces, which are not obliged to have occupational physicians. Most patients (89%) expressed their desire to return to work, but eight patients (6%) left their jobs soon after being diagnosed with colorectal cancer before undergoing surgery for several reasons stemming from worries about future treatment and its consequences. Multivariable analyses indicated that nonregular employees and the self-employed might be at a disadvantage in keeping their job at diagnosis. CONCLUSION: Surgeons should address work-related issues for survivorship, which begins at cancer diagnosis and, when available, collaborate with occupational physicians while being mindful that patients working at smaller companies do not have immediate access to occupational physicians.

Long-term results of a phase 2 study of neoadjuvant chemotherapy with molecularly targeted agents for locally advanced rectal cancer.

BACKGROUND: We previously reported the feasibility and efficacy of neoadjuvant chemotherapy without radiotherapy for locally advanced rectal cancer. Here, we report the results of a long-term follow-up study. METHODS: This was a multi-institutional, prospective phase 2 study of patients with locally advanced rectal cancer. Patients received neoadjuvant chemotherapy with molecularly targeted agents before undergoing total mesorectal excision. Six cycles of modified FOLFOX (mFOLFOX6) with bevacizumab were administered to KRAS-mutant patients, and mFOLFOX6 with cetuximab was administered to KRAS-wild-type patients. Here, we report the secondary end points of overall survival, relapse-free survival, and local recurrence rate. RESULTS: Sixty patients were enrolled in this study. R0 resection was achieved in 98.3% (59/60) patients, and pathological complete response was achieved in 16.7% (10/60) patients. After a median follow-up of 5.4 years, the 5 year overall survival was 81.6%, the 5 year relapse-free survival was 71.7%, and the 5 year local recurrence rate was 12.6%. None of the patients who achieved pathological complete response developed recurrence within 5 years. CONCLUSIONS: The use of molecularly targeted agents in the neoadjuvant setting for locally advanced rectal cancer has an acceptable prognosis.

Novel mobilization of the medial approach without changing the position for robotic right hemicolectomy.

Conventional laparoscopic or robotic surgery for right-sided colon cancer often requires intraoperative repositioning and removal of the bowel. Changing positions during robotic surgery can be troublesome and robotic removal of the small intestine carries a risk of unexpected injury because robotic devices have a strong grasping force and no sense of touch. Herein, we introduce a novel mobilization of the medial approach without changing the position for robotic right hemicolectomy. Using this technique, mobilization is performed in counterclockwise succession, allowing all mobilizations and bowel removal to be completed sequentially, without positional change.

[A Case of Breast Carcinoma That Changed Subtype to Squamous Cell Carcinoma after Chemotherapy].

Metaplastic carcinoma is a rare histological malignancy, often triple-negative, and has a poor prognosis. Here, we report a case of breast cancer in which the primary lesion degenerated into squamous cell carcinoma(triple negative)after drug treatment for invasive ductal carcinoma(Luminal type). The patient was a 41-year-old woman who was diagnosed with Stage Ⅳ left breast cancer T2N2bM1(HEP)(ER 90%, PR 70%, HER2 2+, FISH-)at another hospital and participated in the PATHWAY study(tamoxifen plus goserelin plus palbociclib/placebo). Since the primary lesion and liver metastasis increased in size, the study was discontinued after 8 weeks. She was treated at our hospital thereafter, with capecitabine plus cyclophosphamide, palbociclib plus fulvestrant plus leuprorelin, paclitaxel plus bevacizumab, eribulin, EC therapy, and docetaxel. However, both the primary lesion and liver metastasis increased. In particular, the increase in primary lesion size was remarkable, and the QOL significantly reduced due to bleeding and exudation. Biopsy performed during docetaxel treatment revealed metaplastic/squamous cell carcinoma(ER-, PR-, HER2 0, Ki-67 90-100%)histopathological findings. BRCA and microsatellite instability tests were negative, and PDL1 expression was less than 1%. Although Mohs ointment was used, tumor bleeding, exudate, and stink were poorly controlled, and the patient experienced painful symptoms due to the weight of the tumor. Therefore, left mastectomy plus pectoralis major muscle resection was performed. The patient died one month after the operation.

[Five Cases of Breast Cancer Developed after Silicone Breast Implant].

We report 5 cases of breast cancer that developed after cosmetic augmentation using silicone breast implants. The chief complaints were breast tumor in 3 cases, skin change in 1 case, and nipple bleeding in 1 case. Intervals between silicone breast implants and breast cancer surgeries ranged from 10 to 31 years. The pTNM stages included were Stage 0, Ⅰ, ⅡA, ⅢB, and Ⅳ, respectively, and the subtypes included were 3 Luminal types and 2 Luminal-HER2 types. Silicone bag rupture was noted in 1 case, and all bags were removed during surgery. The breast cancer surgeries performed were four breast- conserving surgeries and one mastectomy. The follow-up period ranged between 1.8 and 14 years(mean 5.1 years). All cases survived, but 2 cases had recurrences; the Stage ⅢB case experienced lung metastasis 2 years postoperatively and Stage Ⅳ case had induced pCR by chemotherapy postoperatively, but therapeutic self-interruption led to recurrences at the contralateral axillary nodes and contralateral breast and lung metastases 3 years postoperatively. Judging from limited reports of breast cancer after silicone breast implant in Japan, their incidence seems to be extremely low, and the incidence in our clinic during these 15 years(5 out of 1,851 primary breast cancers)is 0.27%.

Dual-Color Fluorescence Switch-On Probe for Imaging G-Quadruplex and Double-Stranded DNA in Living Cells.

A tripodal quinone-cyanine dye having one donor and three acceptors, that is, one quinone and three N-methylbenzothiazolium moieties, QCy(MeBT)3, was synthesized by simple Knoevenagel condensation between 2-hydroxybenzene-1,3,5-tricarbaldehyde and N-methyl-2-methylbenzothiazolium iodide. The 700 nm (λex, 570 nm) and 600 nm (λex, 470 nm) fluorescence emission of QCy(MeBT)3 was significantly and individually enhanced with the addition of G-quadruplex (G4) DNA and double-stranded DNA (dsDNA), respectively. The results of docking simulations and the response against the viscosity change revealed that the dual-fluorescence response was caused by the difference in the binding mode of QCy(MeBT)3 depending on the DNA structure. The results of fluorescence microscopy imaging experiments using QCy(MeBT)3 suggested that G4 DNAs and dsDNAs in the cell nucleus can be imaged with near-infrared (NIR, 700 nm) and red (600 nm) fluorescence emissions. Furthermore, pyridostatin-induced G4 formation in the living cells can be imaged with NIR fluorescence. The results indicated that QCy(MeBT)3 has huge potential to be a NIR-fluorescent molecular probe for analyzing the structural dynamics of nucleic acids in living cells with a normal fluorescence microscope.

Aberrant Cerebello-Cortical Connectivity in Pianists With Focal Task-Specific Dystonia.

Musician's dystonia is a type of focal task-specific dystonia (FTSD) characterized by abnormal muscle hypercontraction and loss of fine motor control specifically during instrument playing. Although the neuropathophysiology of musician's dystonia remains unclear, it has been suggested that maladaptive functional abnormalities in subcortical and cortical regions may be involved. Here, we hypothesized that aberrant effective connectivity between the cerebellum (subcortical) and motor/somatosensory cortex may underlie the neuropathophysiology of musician's dystonia. Using functional magnetic resonance imaging, we measured the brain activity of 30 pianists with or without FTSD as they played a magnetic resonance imaging-compatible piano-like keyboard, which elicited dystonic symptoms in many but not all pianists with FTSD. Pianists with FTSD showed greater activation of the right cerebellum during the task than healthy pianists. Furthermore, patients who reported dystonic symptoms during the task demonstrated greater cerebellar activation than those who did not, establishing a link between cerebellar activity and overt dystonic symptoms. Using multivoxel pattern analysis, moreover, we found that dystonic and healthy pianists differed in the task-related effective connectivity between the right cerebellum and left premotor/somatosensory cortex. The present study indicates that abnormal cerebellar activity and cerebello-cortical connectivity may underlie the pathophysiology of FTSD in musicians.