The Japanese Breast Cancer Society Clinical Practice Guidelines for systemic treatment of breast cancer, 2022 edition.

The Japanese Breast Cancer Society (JBCS) Clinical Practice Guidelines for systemic treatment of breast cancer were updated to the 2022 edition through a process started in 2018. The updated guidelines consist of 12 background questions (BQs), 33 clinical questions (CQs), and 20 future research questions (FRQs). Multiple outcomes including efficacy and safety were selected in each CQ, and then quantitative and qualitative systematic reviews were conducted to determine the strength of evidence and strength of recommendation, which was finally determined through a voting process among designated committee members. Here, we describe eight selected CQs as important updates from the previous guidelines, including novel practice-changing updates, and recommendations based on evidence that has emerged specifically from Japanese clinical trials.

A case of superficial spreading type of poorly differentiated adenocarcinoma of the stomach with invasion to the esophagus.

BACKGROUND: Invasion is more likely to occur in gastric cancer affecting larger areas. Poorly differentiated adenocarcinoma tends to invade deep. The cardiac region prefers submucosal invasion because the submucosa is coarser than the other regions. CASE PRESENTATION: A 75-year-old man presented with a chief complaint of abdominal discomfort and weight loss. Esophagogastroduodenoscopy revealed an irregular ulcerative lesion with partial redness of the upper body and lesser curve of the stomach. A continuous shallow depressed lesion invaded the abdominal esophagus by approximately 40 mm. Poorly differentiated adenocarcinomas (por, sig) were observed on biopsy. Grossly, the cancer appeared to extend into the muscle layer; however, we could not confirm invasion into the muscle layer in our biopsy tissue. We diagnosed the lesion as a superficial spreading type of advanced gastric cancer and performed a total gastrectomy, D2-lymph node dissection (spleen preservation), Roux-en-Y reconstruction, and cholecystectomy. Postoperative histopathological examination revealed extensive infiltration of poorly differentiated adenocarcinoma (90 mm × 55 mm), and all were intramucosal lesions. The final pathological diagnosis was T1a, N0, M0, and Stage IA. The postoperative course was uneventful and the patient was discharged on postoperative day (POD) 11. Five years have passed since the operation, and the patient is alive without recurrence. CONCLUSION: We encountered a case of gastric carcinoma in which poorly differentiated adenocarcinomas expanded extensively. All lesions were intramucosal.

[Effect of Biweekly-DCF Neoadjuvant Chemotherapy on Skeletal Muscle Mass of Esophageal Cancer Patients].

INTRODUCTION: Several studies reported that skeletal muscle mass affects the clinical response and quality of life of cancer patients during chemotherapy. Here we examined the adverse events and effects of anticancer drugs on the skeletal muscle mass of patients with esophageal cancer who received biweekly docetaxel, cisplatin, and 5-fluorouracil(DCF)neoadjuvant chemotherapy in our department. SUBJECTS AND METHODS: We retrospectively analyzed 105 patients with esophageal cancer who received biweekly-DCF neoadjuvant chemotherapy in 2009-2019. The cross-sectional area of the psoas muscle at the level of the third lumbar vertebra on computed tomography was assessed to calculate the psoas muscle index(PMI). Patients were divided into the high PMI group(high-group)and low PMI group(low-group)by cut-off value(male: 6.36 cm2/m2; female: 3.92 cm2/m2). Hematological toxicity, non-hematological toxicity, and therapeutic effect were retrospectively examined. RESULTS: Male in the high-group had significantly less ≥Grade 3 hematological toxicity than those in the low-group. Univariate and multivariate analyses showed that PMI(odds ratio: 1, p<0.05)was significantly related to decreased hematological toxicity. CONCLUSION: In preoperative chemotherapy for esophageal cancer, the incidence of hematological toxicity was significantly higher in patients with low skeletal muscle mass. Thus, skeletal muscle mass may be a marker for determining optimal anticancer drug dosage.

Relapsing polychondritis occurring after esophageal cancer surgery: a case report with a literature review.

INTRODUCTION: Relapsing polychondritis is a relatively rare chronic inflammatory disease of unknown etiology. In this case the treatment for esophageal cancer may have triggered relapsing polychondritis. CASE PRESENTATION: A 70-year-old man complained of dysphagia and weight loss. An upper gastrointestinal endoscopy revealed type 2 advanced esophageal cancer. A subtotal esophagectomy and three-region lymph node dissection were performed after chemotherapy. One month later, the patient developed respiratory distress accompanied by wheezing, dizziness, and hearing loss. The symptoms improved within a few days. The frequency of respiratory distress increased and the patient visited our department. Pharyngeal endoscopy revealed narrowing of the glottic space and a subglottic tumor. No malignant findings were found histopathologically on the biopsy specimens, but infiltration of inflammatory cells was observed. We diagnosed relapsing polychondritis based on the histopathological findings of the pharyngeal cartilage, in addition to the osteolytic changes of the cricoid cartilage on CT. The symptoms were relieved after the administration of oral steroids. Despite tapering of the steroids, no recurrence of relapsing polychondritis occurred. There was no evidence of esophageal cancer recurrence. CONCLUSION: Early diagnosis and treatment for relapsing polychondritis are necessary because this condition is often associated with airway lesions. Esophageal cancer treatment may trigger relapsing polychondritis.

The Role of Adjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma Patients with Pathological Positive Lymph Nodes After Neoadjuvant Chemotherapy Followed by Esophagectomy: a Single Institute Retrospective Analysis.

The need for adjuvant therapy after radical resection for patients with stage II-III thoracic esophageal squamous cell carcinoma (TESCC) who have undergone neoadjuvant chemotherapy (NAC) has not been determined. Since recurrence can occur after radical resection and since the prognosis is still poor, it is necessary to consider additional treatment strategies, including adjuvant chemotherapy. We retrospectively investigated the significance of adjuvant therapy after NAC followed by radical resection for TESCC. Between 2008 and 2018, 115 patients with clinical stage II-III underwent radical subtotal esophagectomy after neoadjuvant therapy. Among them, 62 were analyzed, excluding patients with T4 tumors and patients who had undergone R plus resection or who were receiving preoperative chemoradiotherapy. We compared patients who received adjuvant chemotherapy with those who only received observation; we examined overall survival (OS) and recurrence rates. Twenty-nine patients (46.7%) had lymph node metastasis, 12 of whom received adjuvant chemotherapy (41.3%). The recurrence rates for patients with and without lymph node metastasis were 55.1 % and 15.1%, respectively (p = 0.0022). Among patients with lymph node metastasis, there was no significant difference in the recurrence rate (p = 0.9270) or OS (p = 0.5416) based on the administration of adjuvant chemotherapy. However, in 15 patients with two or more positive lymph nodes, adjuvant chemotherapy increased OS (p = 0.0404). Adjuvant chemotherapy was associated with improved OS in clinical stage II-III TESCC patients with two or more pathological positive lymph nodes after NAC followed by radical surgery. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13193-021-01419-0.

Right-sided Zenker's diverticulum resected using intraoperative neuromonitoring.

Right-sided Zenker's diverticulum is a rare pharyngoesophageal diverticulum. The risk of intraoperative injury of the recurrent laryngeal nerve is high during transcervical diverticulectomy because this nerve presents many variations of extralaryngeal bifurcation before entry into the larynx. We present a case of right-sided Zenker's diverticulum that was safely resected with the use of intraoperative neuromonitoring to prevent right recurrent laryngeal nerve injury. A 55-year-old man complaining of chronic cough and regurgitation of ingested food was diagnosed as having right-sided Zenker's diverticulum and underwent open transcervical diverticulectomy and cricopharyngeal myotomy. The location of the right recurrent laryngeal nerve was accurately determined during dissection by intermittent stimulation using a monopolar stimulation probe of an intraoperative neuromonitoring system to avoid injury. The postoperative course was uneventful, and postoperative evaluation showed no vocal cord paralysis. Intraoperative neuromonitoring may be beneficial during transcervical diverticulectomy for right-sided Zenker's diverticulum nearby the right recurrent laryngeal nerve, which can present with many variations of extralaryngeal bifurcation.

Successful treatment of superior mesenteric artery thrombosis via preoperative interventional radiology and surgery using indocyanine green fluorescence.

We report a successful case that offered a symbolic therapeutic experience of interventional radiology and surgery collaboration for superior mesenteric artery thrombosis. A 70-year-old man presented with a chief complaint of sudden abdominal pain. Contrast-enhanced computed tomography revealed superior mesenteric artery thrombosis. Interventional radiology was performed, and thrombotic occlusion was observed in the superior mesenteric artery trunk. The abdominal pain disappeared; however, after a while, the thrombus re-formed and the abdominal pain reappeared. Thus, emergency surgery was performed. Before surgery, thrombus aspiration was performed via interventional radiology as much as possible. During surgery, when the blood flow was evaluated using fluorescence with indocyanine green, a region of markedly poor blood flow was detected in the ileum, and the area was excised. The postoperative course was favorable. In this patient, it is possible that preoperative removal of the thrombus via interventional radiology minimized the ischemic area of the intestinal tract, and blood flow evaluation using indocyanine green allowed reliable excision of only the ischemic area. We believe that our case involved a treatment that exploited the advantages of both interventional radiology and surgery using indocyanine green fluorescence.

MIEAP, a p53-downstream gene, is associated with suppression of breast cancer cell proliferation and better survival.

Mitochondria-eating protein (MIEAP; also known as SPATA18), a p53-downstream gene, is involved in mitochondrial quality control (MQC). Enforced MIEAP expression induces caspase-dependent cell death in vitro, and impairment of the p53/MIEAP-regulated MQC pathway is frequently observed in breast cancer (BC), resulting in poor disease-free survival (DFS). To investigate the clinical significance of MIEAP in BC, we identified 2,980 patients from two global, large-scale primary BC cohorts: the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC; n=1,904) and the Cancer Genome Atlas (TCGA; n=1,076). We divided patients in each cohort into high and low groups based on median gene expression levels and analyzed the association between MIEAP expression and clinical outcomes. Compared with normal tumors, MIEAP expression was significantly downregulated in all patients with p53-mutant BC regardless of subtype. MIEAP expression was negatively correlated with KI67 expression. Gene set enrichment analysis demonstrated that cell cycle- and proliferation-associated gene sets were significantly enriched in MIEAP-low tumors compared to MIEAP-high tumors. Patients with MIEAP-high luminal subtype were associated with significantly longer DFS than those with MIEAP-low luminal tumors in both cohorts, whereas significantly longer overall survival was observed only in the METABRIC cohort, which has roughly double the number of samples. These results indicated that the mechanistic role of MIEAP is clinically relevant in the two independent cohorts. This is the first study to use large cohorts to demonstrate the association between MIEAP expression and survival in patients with luminal subtype BC.

Treatment Strategy for Cancer-associated Venous Thromboembolism During Chemotherapy: The Keep ACT2 Concept.

Background/Aim: The frequency of detecting cancer-associated venous thromboembolism (CAT) during chemotherapy is increasing. It is not desirable to discontinue chemotherapy for CAT. In this study, we investigated the feasibility of simultaneous progression of anticoagulant and anticancer therapy, focusing on drug interactions. Patients and Methods: We retrospectively evaluated patients with gastroenterological CAT from February 2017 to December 2020 at the Gifu University Hospital. When both chemotherapy and CAT treatments using edoxaban were performed in parallel and the thrombus disappeared, patients were defined as being Keep-ACT 2 (keeping anticancer therapy and anticoagulant therapy) successful. The effect and safety of treatment strategy focusing on cytochrome P450 (CYP) metabolism using edoxaban were evaluated. Results: A total of 114 patients with CAT during chemotherapy were treated with edoxaban. Keep-ACT 2 was successful in 101 (88.6%) cases. Clinically relevant non-major bleeding was observed in 5 cases (4.4%). All 114 patients were using some drug affected by CYP metabolism, and the median number of affected cases was 5. Conclusion: Combined use of edoxaban for CAT may lead to sustainable therapy for gastroenterological cancer patients who are administered several drugs.

[A Case of Malignant Lymphoma of the Breast after Treatment of the Contralateral Breast Cancer].

A 57-year-old female was referred to our hospital due to a palpable tumor of the left breast; she was diagnosed with cancer in the left breast 3 years prior, in 201X. After the administration of FEC and docetaxel plus trastuzumab as preoperative chemotherapy, left mastectomy with axillary lymph node dissection was performed, and irradiation and trastuzumab were administered postoperatively for 1 year. During the observation, there was skin thickening around the right nipple. A skin biopsy was then performed in 201X, and the patient was diagnosed with diffuse large B-cell lymphoma(DLBCL). PET-CT revealed a slight accumulation in the peripheries of the right nipple and mammary glands. Core needle biopsy of the tumor in the mammary gland showed DLBCL similar to that observed in the skin biopsy. Imaging revealed complete response after chemotherapy, whole-body irradiation, and intrathecal administration. Currently, both breast cancer and DLBCL of the breast have not relapsed.