Implications of DNA Methylation Classification in Diagnosing Ependymoma.

BACKGROUND: Ependymoma is a central nervous system (CNS) tumor that arises from the ependymal cells of the brain's ventricles and spinal cord. The histopathology of ependymomas is indistinguishable regardless of the site of origin, and the prognosis varies. Recent studies have revealed that the development site and prognosis reflect the genetic background. In this study, we used genome-wide DNA methylation array analysis to investigate the epigenetic background of ependymomas from different locations treated at our hospital. METHODS: Four cases of posterior fossa ependymomas and 11 cases of spinal ependymomas were analyzed. RESULTS: DNA methylation profiling using the DKFZ methylation classifier showed that the methylation diagnoses of the 2 cases differed from the histopathological diagnoses, and 2 cases could not be classified. Tumor that spread from the brain to the spinal cord was molecularly distinguishable from other primary spinal tumors. CONCLUSIONS: Although adding DNA methylation classification to conventional diagnostic methods may be helpful, the diagnosis in some cases remains undetermined. This may affect decision-making regarding treatment strategies and follow-up. Further investigations are required to improve the diagnostic accuracy of these tumors.

Stromal Ki67 Expression Might be a Useful Marker for Distinguishing Fibroadenoma From Benign Phyllodes Tumor of the Breast.

Background. Fibroadenoma (FA) and benign phyllodes tumor (PT) of the breast often have similar appearances on imaging. While an exact diagnosis of biopsy specimens is required to choose adequate treatment, including surgical procedures, it is sometimes difficult to pathologically differentiate these 2 tumors due to histological resemblances. To elucidate markers for distinguishing FA from benign PT, we analyzed clinical samples immunohistochemically. Methods. We retrospectively investigated 80 breast fibroepithelial lesions. As a discovery set, 60 surgical excision samples (30 FA and 30 benign PT) were examined. Twenty biopsy samples (10 FA and 10 benign PT) were examined as a validation set. To determine targets for immunohistochemistry, we first tested some proteins based on previous reports. As a result, Ki67 was chosen for differentiating FA and PT; thus further examinations were conducted with this protein. Results. Among the proteins examined, stromal Ki67 was significantly higher in PT than in FA. Benign PT had significantly higher stromal Ki67 expression both at random and at hotspots (p < .001 and <.001, respectively). The receiver operating characteristic curve analysis identified 3.5% and 8.5% (at random spots and hotspots, respectively) as the optimal cutoff values of stromal Ki67 for distinguishing between these 2 tumors. In the validation cohort employing needle biopsy specimens, we confirmed that these 2 cutoff values properly classified these 2 tumors (p = .043 and .029, respectively). Conclusion.We revealed that stromal Ki67 might be a potential marker for distinguishing FA from benign PT.

Prospective evaluation of common hepatic duct histopathology at the time of choledochal cyst excision ranging from children to adults.

PURPOSE: To evaluate common hepatic duct just distal to the HE anastomosis (d-CHD) prospectively for mucosal damage, inflammation, fibrosis, dysplasia, carcinoma in situ, malignant transformation, effects of serum amylase, and symptoms at presentation in CC cases ranging from children to adults. METHODS: Cross-sections of d-CHD obtained at cyst excision 2018-2023 from 65 CC patients; 40 children (< 15 years old), 25 adults (≥ 15) were examined with hematoxylin and eosin, Ki-67, S100P, IMP3, p53, and Masson's trichrome to determine an inflammation score (IS), fibrosis score (FS), and damaged mucosa rate (DMR; damaged mucosa expressed as a percentage of the internal circumference). RESULTS: Mean age at cyst excision ("age") was 18.2 years (range: 3 months-74 years). Significant inverse correlations were found for age and DMR (p = 0.002), age and IS (p = 0.011), and age and Ki-67 (p = 0.01). FS did not correlate with age (p = 0.32) despite significantly increased IS in children. Dysplasia was identified in a 4-month-old girl with cystic CC. Serum amylase was elevated in high DMR subjects. CONCLUSIONS: High DMR, high IS, and evidence of dysplasia in pediatric CC suggest children are at risk for serious sequelae best managed by precise histopathology, protocolized follow-up, and awareness that premalignant histopathology can arise in infancy.

A rare case of a toddler with unilateral cryptorchidism-related cranial suspensory ligament remnant.

Key clinical message: Several animal experiment studies have shown that insufficient testicular descent to the scrotum can be caused by persistence of cranial suspensory ligament (CSL). We report a case of right cryptorchidism in a male toddler surgically treated with an orchidopexy possibly associated with CSL persistence based on intraoperative and pathological findings. This case would be a precious source to further investigate the etiopathogenesis of cryptorchidism. Abstract: The CSL anchors embryonic gonads to the dorsal abdominal wall during antenatal mammalian development. Although its persistence appears to cause cryptorchidism in animal models, it has never been proven in humans. A 1-year-old boy with right cryptorchidism underwent right orchidopexy. Intraoperatively, a band-like structure running from the right testis into the retroperitoneum and up to the right side of the liver was noticed and resected. The pathological findings of the specimen showed fibrous connective tissues, smooth muscles, and blood vessels but no tissues suggestive of a testis, a spermatic cord, an epididymis, or liver. Immunohistochemical analysis for an androgen receptor antibody did not detect any signal in the specimen. The right cryptorchidism in this case was possibly caused by CSL persistence, which is the first such human case, to our knowledge.

Possible correlation of apical localization of MUC1 glycoprotein with luminal A-like status of breast cancer.

Adjuvant chemotherapy has played a major role in the treatment of hormone receptor-positive breast cancer for many years. To better determine which patient subsets need adjuvant chemotherapy, various gene expression analyses have been developed, but cost-effective tools to identify such patients remain elusive. In the present report, we retrospectively investigated immunohistochemical expression and subcellular localization of MUC1 in primary tumors and examined their relationship to tumor malignancy, chemotherapy effect and patient outcomes. We retrospectively examined three patient cohorts with hormone receptor-positive/human epidermal growth factor receptor 2-negative invasive breast cancer: 51 patients who underwent 21-gene expression analysis (multi-gene assay-cohort), 96 patients who received neoadjuvant chemotherapy (neoadjuvant chemotherapy-cohort), and 609 patients whose tumor tissue was used in tissue-microarrays (tissue-microarray-cohort). The immunohistochemical staining pattern of the anti-MUC1 monoclonal antibody, Ma695, was examined in cancer tissues, and subcellular localization was determined as apical, cytoplasmic or negative. In the multi-gene assay-cohort, tumors with apical patterns had the lowest recurrence scores, reflecting lower tumor malignancy, and were significantly lower than MUC1-negative tumors (P = 0.038). In the neoadjuvant chemotherapy-cohort, there was no correlation between MUC1 staining patterns and effects of chemotherapy. Finally, in the tissue-microarray-cohort, we found that patients with apical MUC1 staining patterns had significantly longer disease-free-survival and overall survival than other patterns (P = 0.020 and 0.039, respectively). Our data suggest that an apical MUC1 staining pattern indicates luminal A-likeness. Assessment of the subcellular localization of MUC1 glycoprotein may be useful for identifying patients who can avoid adjuvant chemotherapy.

Biopsy Diagnosis of Hirschsprung's Disease Using a Single Excisional Biopsy Based on the Anorectal Line.

INTRODUCTION: A biopsy protocol for diagnosing Hirschsprung's disease (HD) in children using the anorectal line (ARL). MATERIALS AND METHODS: The ARL was adopted for diagnosing HD in 2016 using two excisional submucosal rectal biopsies performed at different levels, sequentially; the first just above the ARL and the second, further proximal (2-ARL). Currently, only the first-level biopsy is performed (1-ARL) and examined intraoperatively. Management was observation if normoganglionic, pull-through if aganglionic, and a second-level biopsy if hypoganglionic. Hypoganglionosis was considered physiologic if the second-level biopsy was normoganglionic and pathologic if hypoganglionic. Colon caliber change and bowel obstructive symptoms reflect the severity of hypoganglionosis. RESULTS: For 2-ARL (n = 54), results were: normoganglionosis (n = 31/54; 57.4%), aganglionosis (n = 19/54; 35.2%), and hypoganglionosis (n = 4/54; 7.4%); physiologic (n = 3/54; 5.6%) and pathologic (n = 1/54; 1.9%). Normoganglionosis and aganglionosis were always duplicated in 2-ARL (kappa = 1.0). For 1-ARL (n = 36), results were: normoganglionosis (n = 17/36; 47.2%), aganglionosis (n = 17/36; 47.2%), and hypoganglionosis (n = 2/36; 5.6%). Second-level biopsies were normoganglionic (physiologic: n = 1) and hypoganglionic (pathologic: n = 1). All normoganglionic cases, except one, resolved conservatively. All aganglionic cases had pull-through with HD confirmed on histopathology. Both pathologic hypoganglionic cases had caliber change and severe obstructive symptoms as definitive indications for pull-through with hypoganglionosis of the entire rectum confirmed on histopathology. Physiologic hypoganglionic cases were observed and currently have regular defecation. CONCLUSION: Because the ARL is an objective functional, neurologic, and anatomic demarcation, normoganglionosis and aganglionosis can be diagnosed accurately with a single excisional biopsy. Only hypoganglionosis requires a second-level biopsy.

Local recurrence of submucosal invasive colorectal cancer after endoscopic submucosal dissection revealed by copy number variation.

We report a case in which analysis of copy number variation revealed local recurrence of submucosal invasive colorectal cancer after curative endoscopic submucosal dissection (ESD). An 86-year-old man with a history of abdominoperineal resection of the rectum for rectal cancer underwent resection with ESD for early-stage sigmoid cancer 5 cm away from the stoma opening. At the same time, ileocecal resection was performed for advanced cecal cancer. Twelve months after ESD, advanced cancer occurred in the area of the ESD lesion. It was unclear if the cancer was a local recurrence after ESD, implantation of cecal cancer, or a new lesion. Copy number variation analysis performed for the three lesions revealed that the new lesion originated from residual tumor cells from ESD and was unlikely to be cecal cancer.

Phase II study of gemcitabine, cisplatin, and bevacizumab for first recurrent and refractory ovarian clear cell carcinoma Kansai Clinical Oncology Group-G1601.

Patients with advanced ovarian clear cell carcinoma (CCC) have a poor prognosis in the absence of an effective standard treatment. Combination therapy with gemcitabine, cisplatin, and bevacizumab (GPBev) is promising for ovarian CCC. Thus, we conducted a multi-institutional, phase II trial in Japan to examine the efficacy and safety of GPBev for CCC. This is the first study on the use of GPBev for CCC. Eighteen patients (median age, 56.5 years) with pathologically confirmed first recurrent or refractory CCC and having evaluable regions, as assessed using RECIST, were recruited between January 2017 and May 2019. Gemcitabine (1000 mg/m 2 ), cisplatin (40 mg/m 2 ), and bevacizumab (10 mg/kg) were administered intravenously on days 1 and 15, every 28 days, for 6-10 cycles, until disease progression or intolerable toxicity. The primary endpoint was overall response rate (ORR). The secondary endpoints included disease control rate (DCR) and adverse events (AEs). Fifteen patients (83.3%) completed 6-10 cycles of treatment; three patients (two with AEs and one with progressive disease) did not. The ORR was 61.1% [complete response (CR) 3 and partial response (PR) 8] and DCR was 88.9% (CR 3, PR 8, and stable disease 5). Grade 3 and 4 hematological AEs were observed in 16.7 and 5.6% of the patients, respectively. Nonhematological AEs of grades 3 and 4 were observed in 27.8 and 5.6% of the patients, respectively. GPBev is a promising therapy for CCC owing to the high ORR and acceptable toxicity for the first recurrence and refractory CCC.

Serum Levels of N- and C-ERC/Mesothelin and Clinicopathological Factors in Mesothelioma Patients and Those without Mesothelioma.

Objectives: ERC/mesothelin is a glycosylphosphatidylinositol (GPI)-anchor protein expressed in mesothelioma. A precursor protein is cleaved by proteases and an N-terminal fragment (N-ERC) is extracellularly secreted. A remaining C-terminal fragment (C-ERC) is tethered on cellular membranes by the GPI-anchor, but C-ERC is also released after cleavage by proteases. We and other groups reported that serum N-/C-ERC levels are associated with stages of mesothelioma and suggested the possibility of their usefulness as diagnostic markers. However, the N-ERC level is also influenced by renal functions that are not directly associated with conditions of mesothelioma. It is not known whether other clinical factors influence serum N-/C-ERC values. Furthermore, their relationship to the amount of ERC/Mesothelin in mesothelioma is not yet validated. The objective of this study is to clarify the relationship of serum N-/C-ERC levels and the status of mesothelioma and several clinical factors. Materials and Methods: We analyzed relations of serum N-/C-ERC levels and ages, gender and other clinical factors in 522 patients without mesothelioma and examined their relation to the amount of ERC/Mesothelin in mesothelioma tissues in 13 mesothelioma cases. Results: Serum N-ERC levels were influenced by renal functions. On the contrary, those of C-ERC were not influenced by any clinical factors examined in this study and were significantly correlated with the amount of ERC/Mesothelin in mesothelioma. Conclusion: Although both markers are good indicators of treatment-responses in individual patients with mesothelioma, only C-ERC reflected the amount of ERC/Mesothelin in mesothelioma among multiple patients, possibly because N-ERC was influenced by renal functions.

Oncologic safety of Carrel patch hepaticojejunostomy for treating cystic-type choledochal cyst in children based on 20-plus years follow-up.

AIM: During choledochal cyst (CC) excision, the hepaticojejunostomy anastomosis (HJA) can be performed conventionally (CHJA) or with a Carrel patch (CPA). CPA can increase CHD diameter to 10-13 mm, preventing anastomotic stenosis and intrahepatic bile duct (IHBD) stones but may be at risk for malignant transformation. METHODS: The medical records of 83 cystic-type CC with CHD ≤ 9 mm followed up for at least 20 years were reviewed retrospectively. Available excised CC specimens (70/83) were re-examined blindly for pre-malignant changes. A questionnaire about suturing narrow lumens was conducted. RESULTS: All 83 had pancreaticobiliary maljunction. Group data were similar. Anastomoses were CPA (n = 43) and CHJA (n = 40). Mean diameter for CPA was 11.4 mm (range: 10-13 mm); for CHJA was 7.4 mm (range: 5-9 mm). Mean follow-up was 27.7 years (range: 20-42). Postoperative anastomotic stenoses were less after CPA: 1/43 (2.3%) versus 5/40 (12.5%) (p = 0.10), but CHJA had significantly more postoperative IHBD stones: 0% versus 4/40 (10.0%) (p < 0.05). All IHBD stone patients had anastomotic stenosis. Excised specimens showed no pre-malignant cytology. Lumen diameter ≤ 9 mm was considered challenging by 10/10 surgical trainees and ≤ 7 mm by 16/22 pediatric surgeons. CONCLUSIONS: CPA appears to be oncologically safe because of the absence of malignant transformation for at least 20 years.

Upper and Lower Respiratory Mucous Membrane Plasmacytosis with a Cobblestone Appearance: a Case Report.

A 53-year-old woman with a recurrent sore throat, xerostomia, nasal obstruction, and nasal discharge came to our hospital. At the first visit, she did not have a fever, but a blood test showed an intense inflammatory response. She had oral mucosal erosion. She developed dyspnea 2 months later. Nasendoscopy, laryngoscopy, and bronchoscopy showed upper and lower respiratory mucosa cobblestone appearance. Microscopy of the nasal and pharyngeal mucosa biopsy found regular mononuclear inflammatory cell dense submucosal infiltrate, mainly plasma cells. A mucous membrane plasmacytosis diagnosis was made. Prednisolone 1 mg/kg/day rapidly improved bronchial symptoms and cobblestone appearance.

High platelet-to-lymphocyte ratios in triple-negative breast cancer associates with immunosuppressive status of TILs.

BACKGROUND: Rating lymphocytes (TILs) are a prognostic marker in breast cancer and high TIL infiltration correlates with better patient outcomes. Meanwhile, parameters involving immune cells in peripheral blood have also been established as prognostic markers. High platelet-to-lymphocyte ratios (PLRs) and neutrophil-to-lymphocyte ratios (NLRs) are related to poor outcomes in breast cancer, but their mechanisms remain unknown. To date, TILs and these parameters have been examined separately. METHODS: We investigated the relationship between TILs and the peripheral blood markers, PLR and NLR, in the same patients, using surgical specimens from 502 patients with invasive breast carcinoma without preoperative chemotherapy. For analysis of triple-negative breast cancer (TNBC) patient outcomes, 59 patients who received preoperative chemotherapy were also examined. For immune cell profiling, multiplexed fluorescent immunohistochemistry (mfIHC) of CD3, CD4, CD8, FOXP3 and T-bet, was conducted. RESULTS: A positive correlation between PLR and TIL was observed in TNBC (P = 0.013). On mfIHC, tumors in patients with high PLR and NLR contained more CD3+CD4+FOXP3+ T-cells (P = 0.049 and 0.019, respectively), while no trend was observed in CD8+ T-cells. TNBC patients had different patterns of outcomes according to TIL and PLR, with the TIL-high/PLR-low group having the lowest rate of disease relapse and death, and the longest distant metastasis-free and overall survivals, while the TIL-low/PLR-high group had the shortest survivals. CONCLUSIONS: Our data suggest that the combination of PLR with TIL assessment may enable more accurate prediction of patient outcomes with TNBC.

Tamoxifen-resistant breast cancer cells exhibit reactivity with Wisteria floribunda agglutinin.

Glycosylation is one of the most important post-translational modifications of cell surface proteins involved in the proliferation, metastasis and treatment resistance of cancer cells. However, little is known about the role of glycosylation as the mechanism of breast cancer cell resistance to endocrine therapy. Herein, we aimed to identify the glycan profiles of tamoxifen-resistant human breast cancer cells, and their potential as predictive biomarkers for endocrine therapy. We established tamoxifen-resistant cells from estrogen receptor-positive human breast cancer cell lines, and their membrane-associated proteins were subjected to lectin microarray analysis. To confirm differential lectin binding to cellular glycoproteins, we performed lectin blotting analyses after electrophoretic separation of the glycoproteins. Mass spectrometry of the tryptic peptides of the lectin-bound glycoproteins was further conducted to identify glycoproteins binding to the above lectins. Finally, expression of the glycans that were recognized by a lectin was investigated using clinical samples from patients who received tamoxifen treatment after curative surgery. Lectin microarray analysis revealed that the membrane fractions of tamoxifen-resistant breast cancer cells showed increased binding to Wisteria floribunda agglutinin (WFA) compared to tamoxifen-sensitive cells. Glycoproteins seemed to be responsible for the differential WFA binding and the results of mass spectrometry revealed several membrane glycoproteins, such as CD166 and integrin beta-1, as candidates contributing to increased WFA binding. In clinical samples, strong WFA staining was more frequently observed in patients who had developed distant metastasis during tamoxifen treatment compared with non-relapsed patients. Therefore, glycans recognized by WFA are potentially useful as predictive markers to identify the tamoxifen-resistant and relapse-prone subset of estrogen receptor-positive breast cancer patients.

[A Case Report for Peritoneal Recurrences by Laparoscopic Surgery after Colorectal Cancer Resection].

We report a cases report of colorectal cancer who underwent repeated resection for peritoneal recurrences by laparoscopic surgery. In 2013, a 70-year-old woman diagnosed with an ascending colon cancer underwent laparoscopic right hemicolectomy. The pathological diagnosis was tub2, pT4aN1M0, Stage Ⅲb. Postoperative adjuvant chemotherapy(uracil and tegafur/Leucovorin)was administered. PET-CT performed at 25 months after the surgery because of CEA elevation. It revealed a peritoneal recurrence in the pouch of Douglas. The following peritoneal recurrences were removed by laparoscopic Hartmann's procedure. Chemotherapy(5-fluorouracil/levofolinate/oxaliplatin/bevacizumab)was administered 11 courses and after that chemotherapy(5-fluorouracil/levofolinate/bevacizumab)was administered 6 courses. PET-CT performed 37 months after the second surgery revealed a peritoneal recurrence near the right ovary in the pouch of Douglas. The following peritoneal recurrences was removed. Chemotherapy(tegafur/gimeracil/oteracil/bevacizumab)was administered 11 courses. The long-term survival has been continued for 7 years and 7 months after first operation. It was considered that laparoscopic surgery for peritoneal recurrence in colorectal cancer is contributed to one of the surgical procedures in selected patients.

Comparison of tumors with HER2 overexpression versus HER2 amplification in HER2-positive breast cancer patients.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-positive tumors are defined by protein overexpression (3+) or gene amplification using immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH), respectively. HER2-positive tumors have historically included both IHC(3+) and IHC(2+, equivocal)/FISH(+) tumors and received the same treatment. Differences in biology between these two tumor types, however, are poorly understood. Considering anti-HER2 drugs bind directly to HER2 protein on the cell surface, we hypothesized anti-HER2 therapies would be less effective in IHC(2+)/FISH(+) tumors than in IHC(3+) tumors, leading to differences in patient outcomes. METHODS: A total of 447 patients with HER2-positive invasive carcinoma who underwent curative surgery were retrospectively investigated. HER2 status was assessed in surgical specimens, except in patients who received neo-adjuvant chemotherapy, where biopsy specimens were employed. RESULTS: Age, tumor size, lymph node status and ER status were independent factors relating to disease-free-survival, but no difference was observed between IHC(3+) and IHC(2+)/FISH(+) tumors. Kaplan-Meier analysis found patient outcomes did not differ, even after stratifying into those that did (n = 314), or did not (n = 129), receive chemotherapy with anti-HER2 drugs. In 134 patients who received NAC, pathological complete response rates in IHC(3+) and IHC(2+)/FISH(+) tumors were 45% and 21%, respectively. Survival after developing metastasis was significantly shorter in the IHC(2+)/FISH(+) group. CONCLUSIONS: The prognosis of patients with IHC(2+)/FISH(+) tumors did not differ from IHC(3+) tumors. However, the significance of HER2 protein overexpression in relation to treatment response remains unclear and warrants further investigations.

Clinicopathological Features Related to the Efficacy of CDK4/6 Inhibitor-Based Treatments in Metastatic Breast Cancer.

BACKGROUND: Resistance to endocrine therapy has been a major obstacle in the management of hormone receptor (HR)-positive metastatic breast cancer (MBC). Meanwhile, a number of treatments are available to such patients, and physicians often encounter difficulties in choosing the most appropriate treatments for individual patients. The combination of CDK 4/6 inhibitors (CDKi) and endocrine therapy has now become a standard treatment for HR-positive and human epidermal growth factor receptor 2 (HER2)-negative MBC. However, no predictive markers for CDKi-based treatments have been established. Considering their side effects and the financial burden on patients, identifying such markers is crucial. METHODS: Clinicopathological features of 107 patients with HR-positive HER2-negative MBC, who received CDKi-based treatments at our institution were retrospectively investigated. HR status in distant metastatic lesions and immunocompetent cells in peripheral blood were also studied. RESULTS: Progression-free survival (PFS) was significantly shorter in patients whose primary tumour was high grade (P = 0.016) or high neutrophil-to-lymphocyte ratio (NLR) at baseline (P = 0.017). Meanwhile, there were no differences in other factors, such as expression levels of hormone receptors. Patients whose metastatic lesions were of low tumour grade or high Ki67 labelling index had longer PFS, and such trends were more obvious than primary lesions. CONCLUSION: Our data indicate that tumour grade in primary lesion and NLR are potential predictive factors for CDKi-based treatments. Moreover, pathological assessment of metastatic lesions might also be useful.

Intraductal Papilloma Arising From the Minor Salivary Glands of the Larynx: A Case Report.

It is rare for intraductal papilloma, a benign papillary tumor, to occur in the salivary glands. To our knowledge, intraductal papilloma occurring in the minor salivary glands of the larynx has not been reported. In this report, we describe a case of intraductal papilloma that occurred in the minor salivary glands of the larynx. A woman in her 30s presented with hoarseness and dyspnea since a year. Fiber-optic laryngoscopy revealed a submucosal tumor involving the left aryepiglottic fold and the left false vocal fold. Computed tomography and magnetic resonance imaging revealed a 17 × 15 × 10 mm3 mass with homogenous isodensity, with regular, well-defined margins located on the left aryepiglottic fold and the left false vocal fold. Surgical resection was performed, and subsequently a diagnosis of intraductal papilloma was made by pathologic evaluation. During the follow-up period of over 3 years, the lesion has not recurred. In conclusion, intraductal papilloma of the minor salivary glands should be considered in the differential diagnosis of laryngeal submucosal tumors.

Outcomes of esophagectomy for patients with esophageal squamous cell carcinoma accompanied by recurrent laryngeal nerve palsy at diagnosis.

BACKGROUND: Hoarseness is one of the classical symptoms in patients with locally advanced thoracic esophageal squamous cell carcinoma (ESCC), and it results from recurrent laryngeal nerve palsy, which is caused by nodal metastasis along the recurrent laryngeal nerve or by main tumors. We reviewed the short-term and long-term results of esophagectomy for patients with locally advanced ESCC and hoarseness at diagnosis. PATIENTS: Patients who initially presented with hoarseness from recurrent laryngeal nerve palsy between 2009 and 2018 and underwent esophagectomy for thoracic ESCC were eligible for this study. Pharyngolaryngectomy or cervical ESCC were exclusionary. RESULTS: A total of 15 patients were eligible, and 14 underwent resection of the recurrent laryngeal nerves. The remaining patient had nerve-sparing surgery. Nine patients (60%) had post-operative complications ≥ Clavien-Dindo class II and, pulmonary complications were most common. Two patients (13%) died in the hospital. The 5-year overall survival rate for all patients was 16%. Age (≤ 65 years), cT1/T2 tumor, and remarkably good response to neoadjuvant treatment were likely related to longer survival; however, these relationships were not statistically significant. CONCLUSIONS: Esophagectomy for ESCC patients who are diagnosed with recurrent laryngeal nerve paralysis at initial presentation could be a treatment option if the patient is relatively young, has a cT1/T2 tumor, or shows a remarkably good response to neoadjuvant treatment. However, clinicians should be aware of the possibility of postoperative pulmonary complications, which were frequently observed with the procedure.

Improvement in the Symptoms and VEGF Levels after Resection of an Extrame Dullary Spinal Tumor and Additional Chemotherapy in a Patient with Multiple Myeloma Complicated with POEMS Syndrome.

We herein report a case of multiple myeloma and polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes (POEMS) syndrome. The patient experienced exacerbated gait disturbance due to weakness and numbness in the lower limbs. Thoracic magnetic resonance imaging revealed an extramedullary tumor with spinal compression that required surgical resection. Plasmacytoma was diagnosed based on a biopsy. Radiation, betamethasone, and chemotherapy were therefore administered. Surgical removal of extramedullary tumors improved his symptoms, motor conduction velocity, and amplitude of the muscle action potential in the peroneal and tibial nerves, as shown by the nerve conduction study. Surgery also decreased the serum vascular endothelial growth factor levels. The patient required additional chemotherapy due to multiple myeloma and showed better outcomes nine months after discharge. The benefits of some treatments remain controversial due to the small number of patients. However, our findings reveal that an early diagnosis and comprehensive treatment may result in better outcomes in such patients.