A case of refractory chylothorax due to an unenclosed esophageal hiatus after subtotal esophagectomy treated with lipiodol lymphangiography.

BACKGROUND: Chylothorax, a rare but serious complication following esophagectomy, can lead to dehydration, malnutrition, and even mortality. Surgical intervention is considered when conservative treatment is ineffective; however, in some refractory cases, the cause of chylothorax remains unclear. We report a case of refractory chylothorax caused by abdominal chyle leakage into the pleural space via an unenclosed esophageal hiatus. CASE PRESENTATION: A 66-year-old man was diagnosed with advanced esophageal squamous cell carcinoma. The patient underwent robot-assisted thoracoscopic subtotal esophagectomy in the prone position with retrosternal gastric tube reconstruction following neoadjuvant chemotherapy. The thoracic duct was ligated and resected because of tumor invasion. Chylothorax and chylous ascites were observed 2 weeks after surgery but did not improve despite conservative management with medications and drainage. Lymphoscintigraphy through the inguinal lymph node showed tracer accumulation in the fluid in both the abdominal and pleural spaces. Lipiodol lymphangiography revealed abdominal lymphoid leakage, but no leakage was detected from the thoracic duct or mediastinum. We considered that the chylothorax was caused by chylous ascites flowing into the pleural space via an unenclosed esophageal hiatus, and we performed surgical intervention. Laparotomy revealed abdominal chyle leakage and a fistula at the esophageal hiatus with the inflow of ascites into the thoracic cavity. Lipiodol lymphangiography was additionally performed for treating abdominal lymphorrhea after surgery, and resulted in the improvement of the chylothorax and ascites. The patient was discharged with no recurrence of chylothorax or chylous ascites. CONCLUSIONS: Refractory chylothorax can occur due to chylous ascites flowing into the pleural space via an unenclosed esophageal hiatus. When the site of chylothorax leakage is unclear, the possibility of inflowing chylous ascites via the unenclosed esophageal hiatus should be explored. Esophageal hiatus closure and lipiodol lymphangiography could be effective in treating refractory chylothorax of unknown cause after esophagectomy.

Esophagectomy for esophageal cancer in patients with a history of total pharyngolaryngectomy: a Japanese nationwide retrospective cohort study.

BACKGROUND: Second primary esophageal cancer often develops in patients with head and neck cancer, and esophagectomy in patients with a history of total pharyngolaryngectomy (TPL) is challenging. However, the clinical outcomes of these patients have yet to be examined in a multicenter setting. METHODS: We evaluated the surgical outcomes of a nationwide cohort of 62 patients who underwent esophagectomy for esophageal cancer with a history of TPL. RESULTS: Ivor-Lewis and McKeown esophagectomies were performed in 32 (51.6%) and 30 (48.4%) patients, respectively. Postoperatively, 23 patients (37.1%) developed severe complications, and 7 patients (11.3%) required reoperation within 30 days. Pneumonia and anastomotic leakage occurred in 13 (21.0%) and 16 (25.8%) patients, respectively. Anastomotic leakage occurred more frequently in the McKeown group than in the Ivor-Lewis group (46.7% vs. 6.2%, P < 0.001). The adjusted odds ratio for anastomotic leakage in the McKeown group was 9.64 (95% confidence intervals (CI), 2.11-70.82, P = 0.008). Meanwhile, the 5-year overall survival rates were comparable between the groups (41.8% for Ivor-Lewis and 42.7% for McKeown), and the adjusted hazard ratio of overall survival was 1.44 (95% CI, 0.64-3.29; P = 0.381; Ivor-Lewis as the reference). CONCLUSIONS: In our cohort, anastomotic leakage occurred more frequently after McKeown than Ivor-Lewis esophagectomy, and almost half of patients in the McKeown group experienced leakage. Ivor-Lewis esophagectomy is preferred for decreasing anastomotic leakage when oncologically and technically feasible.

Targeting Pancreatic Cancer with Novel Nicolaioidesin C Derivatives: Molecular Mechanism, In Vitro, and In Vivo Evaluations.

Pancreatic cancer, one of the deadliest cancers with the lowest 5-year survival rate, often develops resistance to gemcitabine-based chemotherapies. The hypovascular nature of pancreatic tumors forces cancer cells to adapt to nutrient-depleted tumor microenvironments. Conventional anticancer agents targeting rapidly dividing cancer cells under nutrient-rich conditions are largely ineffective against adapted pancreatic cancer cells. Thus, targeting cancer cells under nutrient starvation, termed the "antiausterity strategy", may be effective for pancreatic cancer. This study examined nicolaioidesin C (Nic-C) derivatives as antiausterity agents. Among the 32 derivatives, Nic-15 (4n) exhibited superior cytotoxicity against MIA PaCa-2 and PANC-1 pancreatic cancer cells, inhibited MIA PaCa-2 cell migration and colony formation, and modulated the PI3K/Akt/mTOR pathway, while reducing the ER stress markers induced by gemcitabine. Nic-15 was found to inhibit tumor growth and enhance the efficacy of gemcitabine in an in vivo xenograft model. Nic-15 in combination with gemcitabine may be an effective strategy for the treatment of pancreatic cancer.

Thoracoscopic enucleation of an esophageal glomus tumor in the prone position: a case report and literature review.

BACKGROUND: Glomus tumors (GT) generally occur in the skin. However, esophageal GT, an extremely rare condition, has no established standardized treatment guidelines. Herein, we report the case of an esophageal GT successfully removed by thoracoscopic enucleation in the prone position using intra-esophageal balloon compression. CASE PRESENTATION: A 45-year-old man underwent an annual endoscopic examination and was found to have a submucosal tumor in the lower esophagus. Endoscopic ultrasound (EUS) revealed a hyperechoic mass originating from the muscular layer. Contrast-enhanced computed tomography identified a 2 cm mass lesion with high contrast enhancement in the right side of the lower esophagus. Pathologic findings of EUS-guided fine needle aspiration biopsy (EUS-FNA) revealed round to spindle shaped atypical cells without mitotic activity. Immunohistochemically, the tumor was positive for alpha-smooth muscle actin, but negative for CD34, desmin, keratin 18, S-100 protein, melan A, c-kit, and STAT6. He was diagnosed with an esophageal GT and a thoracoscopic approach to tumor resection was planned. Under general anesthesia, a Sengstaken-Blakemore (SB) tube was inserted into the esophagus. The patient was placed in the prone position and a right thoracoscopic approach was achieved. The esophagus around the tumor was mobilized and the SB tube balloon inflated to compress the tumor toward the thoracic cavity. The muscle layer was divided and the tumor was successfully enucleated without mucosal penetration. Oral intake was initiated on postoperative day (POD) 3 and the patient discharged on POD 9. No surgical complications or tumor metastasis were observed during the 1-year postoperative follow-up. CONCLUSIONS: As malignancy criteria for esophageal GT are not yet established, the least invasive procedure for complete resection should be selected on a case-by-case basis. Thoracoscopic enucleation in the prone position using intra-esophageal balloon compression is useful to treat esophageal GT on the right side of the esophagus.

A case of squamous cell carcinoma of the breast achieved a pathological complete response after dose-dense AC + dose-dense PTX.

BACKGROUND: Squamous cell carcinoma (SCC) of the breast is a rare form of breast cancer, accounting for approximately 0.1% of all breast cancers. It is known for its rapid tumor growth and poor prognosis with no established treatment. CASE PRESENTATION: A 56-year-old woman was diagnosed with breast SCC with axillary, supraclavicular and internal thoracic lymph node metastases. She received neoadjuvant chemotherapy (NAC) with dose-dense doxorubicin and cyclophosphamide (AC) followed by dose-dense paclitaxel (PTX). This treatment resulted in a pathological complete response (pCR) after breast-conserving surgery. The patient was then treated with radiotherapy. She remained free of recurrence for three years postoperatively. CONCLUSIONS: We report a rare case of breast SCC treated with preoperative dose-dense chemotherapy, resulting in pCR and allowing breast-conserving surgery.

MicroRNAs associated with postoperative outcomes in patients with limited stage neuroendocrine carcinoma of the esophagus.

Esophageal neuroendocrine carcinoma (E-NEC) is an aggressive disease with a poor prognosis. The present study aimed to assess the role of surgery in the treatment of patients with resectable E-NEC, and identify a microRNA (miRNA/miR) signature in association with positive postoperative outcomes. Between February 2017 and August 2019, 36 patients with E-NEC who underwent curative surgery at the Japan Neuroendocrine Tumor Society partner hospitals were enrolled in the study. A total of 16 (44.4%) patients achieved disease-free survival (non-relapse group), whereas 20 (55.6%) patients developed tumor relapse (relapse group) during the median follow-up time of 36.5 months (range, 1-242) after surgery with a 5-year overall survival rate of 100 and 10.8%, respectively (P<0.01). No clinicopathological parameters, such as histological type or TNM staging, were associated with tumor relapse. Microarray analysis of 2,630 miRNAs in 11 patients with sufficient quality RNA revealed 12 miRNAs (miR-1260a, -1260b, -1246, -4284, -612, -1249-3p, -296-5p, -575, -6805-3p, -12136, -6822-5p and -4454) that were differentially expressed between the relapse (n=6) and non-relapse (n=5) groups. Furthermore, the top three miRNAs (miR-1246, -1260a and -1260b) were associated with overall survival (P<0.01). These results demonstrated that surgery-based multidisciplinary treatment is effective in a distinct subpopulation of limited stage E-NEC. A specific miRNA gene set is suggested to be associated with treatment outcome.

The use of an artificial intelligence algorithm for circulating tumor cell detection in patients with esophageal cancer.

Despite recent advances in multidisciplinary treatments of esophageal squamous cell carcinoma (ESCC), patients frequently suffer from distant metastasis after surgery. For numerous types of cancer, circulating tumor cells (CTCs) are considered predictors of distant metastasis, therapeutic response and prognosis. However, as more markers of cytopathological heterogeneity are discovered, the overall detection process for the expression of these markers in CTCs becomes increasingly complex and time consuming. In the present study, the use of a convolutional neural network (CNN)-based artificial intelligence (AI) for CTC detection was assessed using KYSE ESCC cell lines and blood samples from patients with ESCC. The AI algorithm distinguished KYSE cells from peripheral blood-derived mononuclear cells (PBMCs) from healthy volunteers, accompanied with epithelial cell adhesion molecule (EpCAM) and nuclear DAPI staining, with an accuracy of >99.8% when the AI was trained on the same KYSE cell line. In addition, AI trained on KYSE520 distinguished KYSE30 from PBMCs with an accuracy of 99.8%, despite the marked differences in EpCAM expression between the two KYSE cell lines. The average accuracy of distinguishing KYSE cells from PBMCs for the AI and four researchers was 100 and 91.8%, respectively (P=0.011). The average time to complete cell classification for 100 images by the AI and researchers was 0.74 and 630.4 sec, respectively (P=0.012). The average number of EpCAM-positive/DAPI-positive cells detected in blood samples by the AI was 44.5 over 10 patients with ESCC and 2.4 over 5 healthy volunteers (P=0.019). These results indicated that the CNN-based image processing algorithm for CTC detection provides a higher accuracy and shorter analysis time compared to humans, suggesting its applicability for clinical use in patients with ESCC. Moreover, the finding that AI accurately identified even EpCAM-negative KYSEs suggested that the AI algorithm may distinguish CTCs based on as yet unknown features, independent of known marker expression.

Repair using the pectoralis major musculocutaneous flap for refractory anastomotic leakage after total esophagectomy.

BACKGROUND: The pectoralis major musculocutaneous flap (PMMF) is a pedicled flap often used as a reconstruction option in head and neck surgery, especially in cases with poor wound healing. However, applying PMMF after esophageal surgery is uncommon. We report here, the case of a successfully repaired refractory anastomotic fistula (RF) after total esophagectomy, by PMMF. CASE PRESENTATION: A 73-year-old man had a history of hypopharyngolaryngectomy, cervical esophagectomy, and reconstruction using a free jejunal graft for hypopharyngeal carcinosarcoma at the age of 54. He also received conservative treatment for pharyngo-jejunal anastomotic leakage (AL), then postoperative radiation therapy. This time, he was diagnosed with carcinosarcoma in the upper thoracic esophagus; cT3rN0M0, cStageII, according to the Japanese Classification of Esophageal Cancer 12th Edition. As a salvage surgery, thoracoscopic total resection of the esophageal remnant and reconstruction using gastric tube via posterior mediastinal route was performed. The distal side of the jejunal graft was cut and re-anastomosed with the top of the gastric tube. An AL was observed on the 6th postoperative day (POD), and after 2 months of conservative treatment was then diagnosed as RF. The 3/4 circumference of the anterior wall of the gastric tube was ruptured for 6 cm in length, and surgical repair using PMMF was performed on POD71. The edge of the defect was exposed and the PMMF (10 × 5 cm) fed by thoracoacromial vessels was prepared. Then, the skin of the flap and the wedge of the leakage were hand sutured via double layers with the skin of the flap facing the intestinal lumen. Although a minor AL was observed on POD19, it healed with conservative treatment. No complications, such as stenosis, reflux, re-leakage, were observed over 3 years of postoperative follow-up. CONCLUSIONS: The PMMF is a useful option for repairing intractable AL after esophagectomy, especially in cases with large defect, as well as difficulties for microvascular anastomosis due to previous operation, radiation, or wound inflammation.

Targeting Pancreatic Cancer with Novel Plumbagin Derivatives: Design, Synthesis, Molecular Mechanism, In Vitro and In Vivo Evaluation.

Pancreatic tumors grow in an "austerity" tumor microenvironment characterized by nutrient deprivation and hypoxia. This leads to the activation of adaptive pathways in pancreatic cancer cells, promoting tolerance to nutrition starvation and aggressive malignancy. Conventional anticancer drugs are often ineffective against tumors that grow in such austerity condition. Plumbagin, a plant-derived naphthoquinone, has shown potent preferential cytotoxicity against pancreatic cancer cells under nutrient-deprived conditions. Therefore, we synthesized a series of plumbagin derivatives and found that 2-(cyclohexylmethyl)-plumbagin (3f) was the most promising compound with a PC50 value of 0.11 µM. Mechanistically, 3f was found to inhibit the PI3K/Akt/mTOR signaling pathways, leading to cancer cell death under nutrient-deprived conditions. In vivo studies using pancreatic cancer xenograft mouse models confirmed the efficacy of 3f, demonstrating significant inhibition of tumor growth in a dose-dependent manner. Compound 3f represents a highly promising lead for anticancer drug development based on an antiausterity strategy.

Parkinson's disease-associated ATP13A2/PARK9 functions as a lysosomal H+,K+-ATPase.

Mutations in the human ATP13A2 (PARK9), a lysosomal ATPase, cause Kufor-Rakeb Syndrome, an early-onset form of Parkinson's disease (PD). Here, we demonstrate that ATP13A2 functions as a lysosomal H+,K+-ATPase. The K+-dependent ATPase activity and the lysosomal K+-transport activity of ATP13A2 are inhibited by an inhibitor of sarco/endoplasmic reticulum Ca2+-ATPase, thapsigargin, and K+-competitive inhibitors of gastric H+,K+-ATPase, such as vonoprazan and SCH28080. Interestingly, these H+,K+-ATPase inhibitors cause lysosomal alkalinization and α-synuclein accumulation, which are pathological hallmarks of PD. Furthermore, PD-associated mutants of ATP13A2 show abnormal expression and function. Our results suggest that the H+/K+-transporting function of ATP13A2 contributes to acidification and α-synuclein degradation in lysosomes.

Nicolaioidesin C: An Antiausterity Agent Shows Promising Antitumor Activity in a Pancreatic Cancer Xenograft Mouse Model.

Human pancreatic tumors are hypovascular in nature, and their tumor microenvironment is often characterized by hypoxia and severe nutrient deprivation due to uncontrolled heterogeneous growth, a phenomenon known as "austerity". However, pancreatic tumor cells have the inherent ability to adapt and thrive even in such low nutrient and hypoxic microenvironments. Anticancer drugs such as gemcitabine and paclitaxel, which target rapidly proliferating cells, are often ineffective against nutrient-deprived pancreatic cancer cells. In order to overcome this limitation, the search for novel agents that can eliminate cancer cells' adaptations to nutrition starvation, also known as "antiausterity" agents, represents a promising strategy to make the cancer cells susceptible to treatment. The natural product (+)-nicolaioidesin C (Nic-C) was found to have potent antiausterity activity against the PANC-1 human pancreatic cancer cell line in a nutrient-deprived condition. However, its efficacy in vivo remained untested. To address this, we synthesized Nic-C in its racemic form and evaluated its antitumor potential in a human pancreatic cancer xenograft model. Nic-C inhibited pancreatic cancer cell migration and colony formation and significantly inhibited tumor growth in MIA PaCa-2 xenografts in a dose-dependent manner. Furthermore, Nic-C inhibited the Akt/mTOR and autophagy signaling pathways in both in vitro and in vivo studies. Metabolomic profiling of in vivo tumor samples suggests that Nic-C downregulates amino acid metabolism while upregulating sphingolipid metabolism.

The malignant potential of pancreatic intraductal papillary mucinous neoplasm is reflected in expression levels of fucosylated glycans in α1 -acid glycoprotein.

BACKGROUND: Pancreatic intraductal papillary mucinous neoplasm (IPMN) involves multiple histopathological stages from benign to malignant lesions. Further, a biomarker to diagnose the malignant IPMN (IPMC) is clinically relevant. Recently, we found that serum fucosylated α1 -acid glycoprotein (fAGP) level markedly elevated along with disease progression in large cohorts of patients with various cancers. METHODS: The fAGP level was retrospectively analyzed in preoperative sera from 109 patients with IPMN, and the clinical relevance of fAGP was compared with currently available predictors as standard. RESULTS: The fAGP level in IPMC was found to be significantly higher than in benign IPMN (P = .0012). At a cutoff value of 27.04 U/µg, its sensitivity, specificity, and accuracy for IPMC were determined to be 83.61%, 65.96%, and 75.93%, respectively. Multivariate analyses revealed that the fAGP level was the only independent risk factor for predicting IPMC. Additionally, a combination of the fAGP level and 18 F-fluorodeoxyglucose uptake on the PET/CT imaging in the lesions seemed to offer the best diagnosis of IPMN. Accordingly, 27 of the 28 patients who were positive in both tests had IPMC, while patients who are negative had benign IPMN. CONCLUSIONS: The fAGP level appeared to be a relevant biomarker for malignant potential of IPMN.

miR-877-3p as a Potential Tumour Suppressor of Oesophageal Squamous Cell Carcinoma.

BACKGROUND/AIM: MicroRNAs (miRNAs) are abnormally expressed and involved in the pathogenesis of various carcinomas. The present study aimed to identify novel miRNA genes associated with the pathogenesis and prognosis of oesophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: The miRNA profiling of 873 genes was performed using surgically resected oesophageal tissues from 35 patients with ESCC to identify candidate miRNAs. To examine the biological activities of candidate miRNAs, their proliferative, invasive, and migratory abilities were evaluated in ESCC cells subjected to miRNA mimic-mediated over-expression. The miRNA expression levels of the selected candidate miRNAs were analysed in the resected oesophageal tissues of 76 patients with ESCC from the two cohorts and correlated with the clinicopathological parameters. RESULTS: Among the four candidate miRNAs identified by miRNA profiling, miR-877-3p was selected for subsequent analyses. In vitro analyses showed that the over-expression of miR-877-3p significantly suppressed the proliferation, invasion, and migration of ESCC cell lines compared with those of control cells. In the analyses of clinical specimens, the expression of miR-877-3p was down-regulated in ESCC tissues compared with that in adjacent normal oesophageal tissues. The down-regulation of miR-877-3p expression in ESCC tissues was significantly associated with advanced local progression and lymphatic involvement. The miR-877-3p down-regulation was also significantly associated with poor disease-free and disease-specific survival. CONCLUSION: miR-877-3p acts as a tumour suppressor gene in ESCC cells, and its down-regulation in ESCC tissues is associated with a poor prognosis. Thus, miR-877-3p may serve as a novel prognostic marker and promising therapeutic target.

MicroRNA as a Biomarker in Gastroenterological Cancers.

This Special Issue aims to highlight the usefulness of microRNA (miRNA) as diagnostic and prognostic markers of gastroenterological cancer (GC) [...].

Comprehensive Genomic Profiling of Neuroendocrine Carcinomas of the Gastrointestinal System.

The neuroendocrine carcinoma of the gastrointestinal system (GIS-NEC) is a rare but highly malignant neoplasm. We analyzed 115 cases using whole-genome/exome sequencing, transcriptome sequencing, DNA methylation assays, and/or ATAC-seq and found GIS-NECs to be genetically distinct from neuroendocrine tumors (GIS-NET) in the same location. Clear genomic differences were also evident between pancreatic NECs (Panc-NEC) and nonpancreatic GIS-NECs (Nonpanc-NEC). Panc-NECs could be classified into two subgroups (i.e., "ductal-type" and "acinar-type") based on genomic features. Alterations in TP53 and RB1 proved common in GIS-NECs, and most Nonpanc-NECs with intact RB1 demonstrated mutually exclusive amplification of CCNE1 or MYC. Alterations of the Notch gene family were characteristic of Nonpanc-NECs. Transcription factors for neuroendocrine differentiation, especially the SOX2 gene, appeared overexpressed in most GIS-NECs due to hypermethylation of the promoter region. This first comprehensive study of genomic alterations in GIS-NECs uncovered several key biological processes underlying genesis of this very lethal form of cancer. SIGNIFICANCE: GIS-NECs are genetically distinct from GIS-NETs. GIS-NECs arising in different organs show similar histopathologic features and share some genomic features, but considerable differences exist between Panc-NECs and Nonpanc-NECs. In addition, Panc-NECs could be classified into two subgroups (i.e., "ductal-type" and "acinar-type") based on genomic and epigenomic features. This article is highlighted in the In This Issue feature, p. 587.

JNETS clinical practice guidelines for gastroenteropancreatic neuroendocrine neoplasms: diagnosis, treatment, and follow-up: a synopsis.

Neuroendocrine neoplasms (NENs) are rare neoplasms that occur in various organs and present with diverse clinical manifestations. Pathological classification is important in the diagnosis of NENs. Treatment strategies must be selected according to the status of differentiation and malignancy by accurately determining whether the neoplasm is functioning or nonfunctioning, degree of disease progression, and presence of metastasis. The newly revised Clinical Practice Guidelines for Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs) comprises 5 chapters-diagnosis, pathology, surgical treatment, medical and multidisciplinary treatment, and multiple endocrine neoplasia type 1 (MEN1)/von Hippel-Lindau (VHL) disease-and includes 51 clinical questions and 19 columns. These guidelines aim to provide direction and practical clinical content for the management of GEP-NEN preferentially based on clinically useful reports. These revised guidelines also refer to the new concept of "neuroendocrine tumor" (NET) grade 3, which is based on the 2017 and 2019 WHO criteria; this includes health insurance coverage of somatostatin receptor scintigraphy for NEN, everolimus for lung and gastrointestinal NET, and lanreotide for GEP-NET. The guidelines also newly refer to the diagnosis, treatment, and surveillance of NEN associated with VHL disease and MEN1. The accuracy of these guidelines has been improved by examining and adopting new evidence obtained after the first edition was published.

Paratracheal air cyst and bronchogenic cyst in patients with esophageal cancer who received thoracoscopic esophagectomy: A case series of three patients.

INTRODUCTION AND IMPORTANCE: Mediastinal cystic lesions, such as paratracheal air cyst (PTAC) and bronchogenic cyst (BC), are rare anomaly usually found incidentally in thoracic imaging. Special attention is needed in the case of thoracic surgery. CASE PRESENTATION: All three patients were male, 71, 73, and 76 years old. Preoperative CT showed each had a lobular cystic lesion at the right posterolateral side of trachea in the thoracic outlet 11, 14, and 19 mm in size, respectively, with air density and tracheal communication, leading to a diagnosis of PTACs. An oval cystic lesion, 7 mm in size, was found in one patient at the right lateral side of the upper esophagus with low density and without tracheal communication, leading to a diagnosis of paraesophageal BC. Intraoperative findings of the three PTACs demonstrated a soft bulge from the membranous portion of trachea that was left intact. The BC had an oval elastic structure, mimicking a metastatic lymph node, and was removed with the mediastinal lymph nodes. Histological examination showed ciliated columnar epithelium, confirming a diagnosis of BC. CLINICAL DISCUSSION: PTACs are associated with increased intraluminal pressure due to chronic lung disease. BCs are congenital anomalies that originate from abnormal budding of the embryonic foregut. CONCLUSION: PTACs and BCs need to be considered in preoperative image diagnosis in patients with esophageal cancer. PTACs should be left intact to avoid tracheal injury, while removal of isolated BCs is recommended as a diagnostic and therapeutic measure.

Immediate one-stage breast reconstruction for an 85-year-old breast cancer patient using deep inferior epigastric perforator flap surgery.

The deep inferior epigastric perforator (DIEP) flap is widely recognized as safe for use as a first-choice option in autologous tissue breast reconstruction; however, DIEP is often not performed for breast reconstruction in the elderly. We report a case of an 85-year-old woman who underwent DIEP flap reconstruction. Immediate reconstruction was performed after mastectomy. The patient successfully underwent DIEP flap reconstruction with no complications. Other options for reconstruction include a latissimus dorsi flap, a transverse rectus abdominis flap and implant-based reconstruction. DIEP flap reconstruction was performed, which does not cause muscle damage and provides sufficient volume. To our knowledge, this study is the first to report DIEP breast reconstruction in a patient over 85 years of age. This case demonstrates the usefulness of DIEP flap reconstruction for elderly patients.

Survival of detached cancer cells is regulated by movement of intracellular Na+,K+-ATPase.

Beginning of metastasis, cancer cells detach from the primary tumor and they can survive even under loss of anchorage; however, the detachment-elicited mechanisms have remained unknown. Here, we found that Na+,K+-ATPase α3-isoform (α3NaK) in human cancer cells is dynamically translocated from intracellular vesicles to the plasma membrane when the attached cells are detached and that this mechanism contributes to the survival of the detached (floating) cancer cells. α3NaK was detected in the plasma membrane of floating cancer cells in peritoneal fluids of patients, while it was in the cytoplasm of the cells in primary tumor tissues. On cancer cell detachment, we also found the focal-adhesion-kinase-dependent Ca2+ response that induces the α3NaK translocation via nicotinic acid adenine dinucleotide phosphate pathway. Activation of AMP-activated protein kinase was associated with the translocated α3NaK in the plasma membrane. Collectively, our study identifies a unique mechanism for survival of detached cancer cells, opening up new opportunities for development of cancer medicines.

Prognosis of Immune-related Adverse Events in Patients With Advanced Gastric Cancer Treated With Nivolumab or Pembrolizumab: A Multicenter Retrospective Analysis.

BACKGROUND: Immune-checkpoint inhibitors (ICI), including nivolumab and pembrolizumab, are among the standard treatments for previously treated advanced gastric cancer (AGC). This study aimed to evaluate the frequency of immune-related adverse events (irAEs) and the correlation between irAEs and their efficacy in AGC cases. PATIENTS AND METHODS: Patients were divided into two groups according to irAE occurrence. The frequency of irAEs and the treatment outcome (response rate [RR], progression-free survival [PFS], and overall survival [OS]) were evaluated. The survival rates were evaluated by landmark analysis considering lead-time bias. RESULTS: Among 108 patients who received nivolumab or pembrolizumab, 17 (15.7%) had irAEs. In a 4-week landmark analysis, the RR, median PFS, and median OS were 28.5%, 3.9 months (95% CI=2.8-9.3), and 12.2 months (95% CI=3.8-NA) in patients with irAEs, while 3.0% (2/65), 1.8 months (95% CI=1.4-2.1), and 3.5 months (95% CI, 2.9-5.1) in patients without irAEs, respectively. In multivariate analysis, irAEs were associated with better PFS (HR=2.08, 95% CI=1.34-3.21). CONCLUSION: The occurrence of irAEs was associated with a better clinical outcome of ICIs in patients with AGC.