Mixed adenoneuroendocrine carcinoma of the esophagogastric junction: a case report

Abstract Background Mixed adenoneuroendocrine carcinoma (MANEC) is a tumor of the gastrointestinal tract that contains both exocrine and endocrine components, with each component exceeding 30% of the total tumor area. Because MANECs are exceedingly rare, no therapeutic strategies have been established yet. Case presentation An 81-year-old man was referred to our hospital with a 5-month history of dysphagia. Esophagogastroduodenoscopy revealed an ulcerated mass in the lower thoracic esophagus, extending up to the esophagogastric junction (33 to 40 cm from the incisors). The initial biopsy diagnosis was adenocarcinoma. Computed tomography revealed no evidence of lymph node or distant metastasis. The patient was treated by thoracoscopic esophagectomy with three-field lymph node dissection and gastric tube reconstruction via a posterior mediastinal approach, under the diagnosis of esophagogastric junctional cancer (T3N0M0, stage IIA). Histopathological examination revealed two distinct components, namely, a neuroendocrine carcinoma component and an adenocarcinoma component, and the patient was diagnosed as having mixed adenoneuroendocrine carcinoma (MANEC). He presented with liver metastasis 6 months after the surgery. Thereafter, the tumor became even more aggressive, and the patient died 8 months after the surgery. Conclusions We report a patient with MANEC of the esophagogastric junction. Close attention should be paid to such patients, as MANEC can be a highly aggressive tumor, showing rapid progression. In the treatment of MANEC, it is necessary to carefully consider the pathological features in each individual case

Voluntary Exercise Positively Affects the Recovery of Long-Nerve Gap Injury Following Tube-Bridging with Human Skeletal Muscle-Derived Stem Cell Transplantation

The therapeutic effects of voluntary exercise on the recovery of long-gap nerve injury following the bridging of an acellular conduit filled with human skeletal muscle-derived stem cells (Sk-SCs) have been described. Human Sk-SCs were sorted as CD34+/45− (Sk-34) cells, then cultured/expanded under optimal conditions for 2 weeks. Surgery to generate a long-gap sciatic nerve injury was performed in athymic nude mice, after which the mice were divided into exercise (E) and non-exercise (NE) groups. The mice were housed in standard individual cages, and voluntary exercise wheels were introduced to the cages of the E group one week after surgery. After 8 weeks, the human Sk-34 cells were actively engrafted, and showed differentiation into Schwann cells and perineurial cells, in both groups. The recovery in the number of axons and myelin in the conduit and downstream tibial nerve branches, and the lower hindlimb muscle mass and their tension output, was consistently higher by 15–25% in the E group. Moreover, a significantly higher innervation ratio of muscle spindles, reduced pathological muscle fiber area, and acceleration of blood vessel formation in the conduit were each observed in the E group. These results showed that the combined therapy of tube-bridging, Sk-34 cell transplantation, and voluntary exercise is a potentially practical approach for recovery following long-gap nerve injury

Regeneration of Transected Recurrent Laryngeal Nerve Using Hybrid-Transplantation of Skeletal Muscle-Derived Stem Cells and Bioabsorbable Scaffold

Hybrid transplantation of skeletal muscle-derived multipotent stem cells (Sk-MSCs) and bioabsorbable polyglyconate (PGA) felt was studied as a novel regeneration therapy for the transected recurrent laryngeal nerve (RLN). Sk-MSCs were isolated from green fluorescence protein transgenic mice and then expanded and transplanted with PGA felt for the hybrid transplantation (HY group) into the RLN transected mouse model. Transplantation of culture medium (M group) and PGA + medium (PGA group) were examined as controls. After eight weeks, trans-oral video laryngoscopy demonstrated 80% recovery of spontaneous vocal-fold movement during breathing in the HY group, whereas the M and PGA groups showed wholly no recoveries. The Sk-MSCs showed active engraftment confined to the damaged RLN portion, representing favorable prevention of cell diffusion on PGA, with an enhanced expression of nerve growth factor mRNAs. Axonal re-connection in the HY group was confirmed by histological serial sections. Immunohistochemical analysis revealed the differentiation of Sk-MSCs into Schwann cells and perineurial/endoneurial cells and axonal growth supportive of perineurium/endoneurium. The number of axons recovered was over 86%. These results showed that the stem cell and cytokine delivery system using hybrid transplantation of Sk-MSCs/PGA-felt is a potentially practical and useful approach for the recovery of transected RLN

Usefulness of three‐dimensional thoracoscope for prone position thoracoscopic esophagectomy improves mediastinal lymph node dissection and prognosis for esophageal cancer

Abstract Objectives This study aimed to assess the superiority of 3D flexible thoracoscope against 2D thoracoscope for lymph node dissection (LND) and prognosis for prone‐position thoracoscopic esophagectomy (TE) in esophageal cancer. Methods Three hundred and sixty‐seven esophageal cancer patients who underwent prone‐position TE with 3‐field LND between 2009 and 2018 were evaluated. 2D and 3D thoracoscope was used in 182 (2D group) and 185 cases (3D group), respectively. Short‐term surgical outcomes, numbers of retrieved mediastinal lymph node (LN), and rates of LN recurrence were compared. Risk factors for mediastinal LN recurrence and long‐time prognosis were also evaluated. Results No differences in postoperative complications were observed between the groups. The numbers of retrieved mediastinal LN were significantly higher, and the rates of LN recurrence were significantly lower in the 3D group compared to 2D group. Use of 2D thoracoscope was a significant independent factor of middle mediastinal LN recurrence by multivariable analysis. Survival was compared by cox regression analysis, and the 3D group had a significantly better prognosis than the 2D group. Conclusions Prone position TE using 3D thoracoscope may improve the accuracy of mediastinal LND and prognosis without increasing postoperative complications for esophageal cancer

Multimodal Treatment Strategies to Improve the Prognosis of Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma: A Narrative Review

Esophageal cancer is the seventh most common malignancy and sixth most common cause of cancer-related death globally. Esophageal squamous cell carcinoma (ESCC) with aortic or tracheal invasion is considered unresectable, and has an extremely poor prognosis; its standard treatment is definitive chemoradiotherapy (dCRT). In recent years, induction chemotherapy (ICT) has been reported to yield high response rates for locally advanced ESCC, and the efficacy and safety of ICT followed by conversion surgery (CS) have been investigated. Multimodal treatment, combining surgery with induction chemoradiotherapy (ICRT) or ICT, is necessary to improve ESCC prognosis. CS is generally performed for locally advanced ECC after ICRT or ICT when tumor downstaging is achieved, although its prognostic benefit remains controversial. The Japan Clinical Oncology Group (JCOG) has conducted a three-arm phase III randomized controlled trial (JCOG1510) to confirm the superiority of DCF (docetaxel, cisplatin, and 5-fluorouracil) ICT, over conventional dCRT, among patients with initially unresectable ESCC. In recent years, researchers have reported favorable outcomes of induction therapy followed by CS and salvage surgery, after dCRT or systemic immunochemotherapy. In this review, we will describe the latest developments in the multimodal treatment including chemotherapy, CRT, surgery, and immunotherapy, which may improve oncological and survival outcomes for patients with cT4 ESCC

Summary of the facial nerve-blood vessel large deficit model, sheet-pellet transplantation, and functional measurement.

<p>(A-C) Schematic drawing and (D-G) stereomicroscopic photographs showing the large facial nerve-blood vessel network deficit model and sheet-pellet transplantation methods. Panel (A) shows the complex nerve-blood vessels networks in the face. (B) Large removal was performed near the convergent point of nerve-vascular networks. (C) Note that the sheet-pellets can be picked up with forceps. (D) Overview of surgical field. (E) Removal of tissues. (F) Patch transplantation of sheet-pellets. (G) Fluorescence microscopy of panel (F). Ruled markings indicate 1 mm. (H) Schematic drawing of contractility measurement in the whisker movement muscles. Amp = amplifier.</p

Detection of engrafted GFP⁺ tissue and cells in mouse experiment.

<p>(A, B) Macroscopic detection of multiple branches of facial nerves under fluorescence stereomicroscopy. GFP⁺ nerve branches in multiple directions were evident, and several vascular branches were also observed on the surface of GFP⁺ nerves (arrows). (C) Histological profile taken from the dotted line in panel B. Five aggregated conduit nerves were detected (arrows). (D and E) Axon staining by N200. GFP⁺ tissues encircled individual and/or several axons (E, merge). (F and G) myelin staining by MBP. Re-myelination was also established. (H-J) GFP⁺ tissues/cells show close relationships with N200⁺ axons (arrows in F and G) and were present in the SkMA⁺ muscle fiber area (arrows in H). (K-M) GFP⁺ tissue/cells can be seen close to the neuromuscular junction, as detected by αBungarotoxin (arrow in K and L), showing extension into the motor nerve end (arrow in M). Bars in A = 3 mm; B = 1 mm; C = 200 μm; D-E, F-H = 50 μm; and I-K = 20 μm.</p

Detailed contributions of engrafted GFP⁺ cells in mouse experiment.

<p>(A) Axon staining by N200. (B) Perineurium/endoneurium staining by GULT-1. (C) Myelin staining by MBP. Regenerated axons and myelin were encircled by GFP⁺ tissues, which were positive for the perineurium marker GULT-1. (E) Schwann cell staining by p75. (H) Vascular endothelial cell staining by CD31. (K) Vascular smooth muscle staining by αSMA. Panels (F, I, L) show merged view of each staining. Engrafted GFP⁺ cells also differentiate into Schwann cells (arrows in D-F), vascular endothelial cells (arrows in G-I) and smooth muscle cells (arrows in J-L). Bars in A and B = 100 μm; C, D-F, G-I, J-L = 20 μm.</p