Papillary renal neoplasm with reverse polarity has low frequency of alterations in chromosomes 7, 17, and Y.

In papillary renal neoplasm with reverse polarity (PRNRP), the status of chromosomal copy number alterations, especially chromosomes 7/17 gain and chromosome Y loss, has remained controversial. In the literatures, there is a discrepancy among the results of chromosomal alteration in PRNRP depending on the analytical methods. Here, we comprehensively analyzed the status of chromosomal abnormalities in PRNRP. Nineteen PRNRP cases were analyzed by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), five of which were additionally subjected to array-based comparative genomic hybridization (aCGH) analysis. Fifteen cases of PRCC were used as controls. From the aCGH results, no genome copy number abnormalities were found in the five PRNRP cases. By FISH, numbers of nuclei with abnormal chromosomal signals in PRNRP (centromere 7 gain: 11-21% of nuclei, centromere 17 gain: 11% of nuclei, centromere Y loss: 14-31% of nuclei) were similar to those in non-neoplastic tubular cells (centromere 7 gain: 11-15% of nuclei, centromere 17 gain: 12-15% of nuclei, centromere Y loss: 13-45% of nuclei). c-MET immunohistochemical overexpression, a substitute marker for chromosome 7 trisomy, was observed in 0 of 19 PRNRP cases, consistent with the analyses by aCGH and NGS regarding chromosome 7 gain. Taken together, the frequency of chromosomal alterations in PRNRP is similar to that in non-neoplastic tubular cells, and lower than that in PRCC. Our data suggest that PRNRP has a different tumorigenesis and is a distinct entity from PRCC.

Effect of Aging on Vocal Outcomes After Laryngeal Reinnervation Combined With Arytenoid Adduction.

OBJECTIVE: To evaluate the impact of aging on vocal function following laryngeal reinnervation combined with arytenoid adduction (AA) in the treatment of paralytic dysphonia. METHODS: Sixty-eight patients with unilateral vocal fold paralysis who underwent refined nerve-muscle pedicle flap (NMP) implantation and AA were classified into four groups according to age: under 50 years (-50), in their 50s, 60s, and 70 years and older (70+). These groups consisted of 15, 14, 22, and 17 patients, respectively. Their vocal function was followed periodically for 24 months after surgery. RESULTS: Vocal function in all groups showed significant improvement after surgery. Significant improvements in vocal function were observed during a 24-month follow-up period: maximum phonation time in the -50 and 50 seconds groups; pitch range and voice handicap index-10 in the -50, 50s, and 60s groups; "Grade" in the -50, 50s, and 70+ groups; and "Breathiness" and voice-related quality of life in all groups. There were no significant differences in vocal function among the four groups, except for pitch range, at the 24-month postoperative assessment. CONCLUSIONS: Although the younger groups tended to exhibit better vocal function compared to the older groups 24 months postoperatively, the refined NMP+AA proved effective in the treatment of breathy dysphonia resulting from unilateral vocal fold paralysis, not only in the younger population but also in the older population.

Comparison of Akt/mammalian target of rapamycin/4E-binding protein 1 pathway signal activation in round stromal and surface cells in patients with sclerosing pneumocytoma.

Sclerosing pneumocytoma (SP) is a rare benign epithelial tumor of the lung, and approximately 40 % of patients with SP present with AKT1 E17K mutation. SP cells comprise proliferated surface and round stromal cells. To elucidate the role of signal transductions and to identify the difference between surface and stromal cells, the current study aimed to investigate the activation of the Akt/mammalian target of rapamycin (mTOR)/4E-binding protein 1 signaling pathway in SP. METHODS: The molecular and pathological characteristics of SP in 12 patients were analyzed. AKT1 gene analysis revealed AKT1 E17K mutation in four cases. Immunohistochemical analysis revealed that tumor cells were cytoplasmic positive for pAkt, pmTOR, p4EBP1, and pS6RP. The surface cells had a significantly higher expression of pmTOR (p = 0.002) and a significantly lower expression of p4EBP1 (p = 0.017) than stromal cells. SP without AKT1 E17K mutation had a higher positive correlation with pacts, p4EBP1, pmTOR, and pS6RP expression than SP with AKT1 E17K mutation. These findings may be attributed to the aberrant activation of the Akt/mTOR pathway due to AKT1 E17K mutations. Hence, both surface and round stromal cells have tumorigenic characteristics, and differences in these characteristics may contribute to variations in tumor growth and the morphology and angiogenesis of SP.

Robotic radical distal gastrectomy for gastric cancer using the soft coagulation scissors technique.

We have developed a novel technique for safe and precise lymph-node dissection during robotic gastrectomy for gastric cancer using monopolar curved scissors with soft coagulation. This technique is called the soft coagulation scissors technique. The technical details of this technique are as follows: a long bipolar grasper in the first arm and monopolar curved scissors in the third arm are primarily used for lymph-node dissection, maximizing the use of the robotic arm articulation. The monopolar curved scissors were energized in the soft coagulation mode of the Valleylab™ FT10 energy platform or in the forced coagulation mode of the ERBE VIO®dV with an effect 1/power limit of 15 W. This limit was confirmed to be equivalent to the soft coagulation mode in preliminary experiments, and a long bipolar grasper applied adequate tension to the surgical site without strongly grasping the tissue or applying traction. The peak temperatures of our devices were more than 100 °C lower than those of the Harmonic ACE and the Maryland bipolar forceps with the forced coagulation mode. Overall, 80 patients with gastric cancer, including 36 (45.0%) with stage III or IV cancers, underwent robotic distal gastrectomy with this technique. The median estimated blood loss was 10 g. There were only four surgical complications (5.0%): two paralytic ileus, one intra-abdominal abscess, and one duodenal stump leakage. Robotic distal gastrectomy for gastric cancer is made possible by the soft coagulation scissors technique, which allows for safe and precise lymph-node dissection.

Modified side overlap esophagogastrostomy after laparoscopic proximal gastrectomy.

We report a new method of esophagogastrostomy after proximal gastrectomy, side overlap with fundoplication by Yamashita (SOFY) in 2017. Recently, even better treatment results can be obtained by modifying the SOFY method. We describe the technical details of the modified SOFY (mSOFY) after laparoscopic proximal gastrectomy. The stomach was dissected in the short axis direction and the esophagus was dissected in the left and right direction. After the proximal gastrectomy, the bilateral diaphragmatic crus were dissected to enhance gastric elevation. After confirming that the esophagus overlapped more than 5 cm at the center of the remnant stomach (we call it SOFY check), the remnant stomach was suture-fixed to the dissected diaphragmatic crus. The right wall of the esophageal stump and the remnant stomach were anastomosed using the full length of a 45 mm-linear stapler. The entry hole was closed in a direction that did not widen the anastomotic hole. Both sides of the esophagus, remnant stomach, and diaphragmatic crus were suture-fixed on the cranial side 1-2 cm away from the anastomosis. Moreover, the left wall and lower end of the esophagus was suture-fixed to the remnant stomach. The preserved dorsal esophageal wall is pressed and flattened by pressure from the pseudofornix, which is the reflux prevention mechanism. The mSOFY method had favorable treatment outcomes. In conclusion, mSOFY can be one of the safe and feasible reconstruction methods after laparoscopic proximal gastrectomy.

Factors Affecting the Swallowing Dysfunction Following Oral Cancer Surgery.

OBJECTIVE: To investigate the factors affecting the postoperative swallowing dysfunction in patients who underwent oral cancer surgery. METHODS: Retrospective review of clinical records of 70 patients (50 males and 20 females) who underwent oral cancer surgeries from July 2007 to April 2015 were enrolled. Multiple regression analysis was performed using the Food Intake LEVEL Scale (FILS) at discharge as the objective variable and age, tumor size, resection of the tongue base, suprahyoid muscle resection, segmental mandibulectomy, neck dissection and radiation therapy as the explanatory variables in 70 patients. In addition, multiple regression analysis was performed between objective variables, which include maximum hyoid bone movement, laryngeal elevation delay time, pharyngeal constriction ratio (PCR), residue in the vallecular and pear-shaped depression (pyriform sinuses), and Penetration-Aspiration Scale score and one of the main factors representing the characteristics of each case as the explanatory variables, and age was treated as an adjustment factor in 23 patients. RESULTS: The FILS shows significant negative correlation by age and resection of the tongue base. In videofluoroscopic swallowing study, the maximum movement, PCR and residue in the vallecular are significantly correlated with factors demonstrating the characteristic for each case. CONCLUSION: It was suggested that in elderly patients, the presence of more than half of the tongue base resection, suprahyoid muscle resection and neck dissection cause severe dysphagia after surgery.

Swallowing dysfunction in myasthenia gravis patients examined with high-resolution manometry.

OBJECTIVE: To prospectively compare oropharyngeal swallowing dysfunction in myasthenia gravis (MG) patients presenting with difficulty in swallowing between the neutral and chin-down positions, based on the results of high-resolution manometry (HRM) examination. METHODS: We prospectively compared the HRM results of swallowing studies of seven MG patients showing difficulty in swallowing (neutral and chin-down positions) at the Department of Neurology of our institution during the period February-December 2018. The HRM assessment parameters were as follows: maximum swallowing pressure (SP) at the soft palate, meso­hypopharynx, and upper esophageal sphincter (UES), and the duration of relaxation pressure at the UES. These parameters were compared between the two positions and their correlations with the results of neurological evaluations, such as the Quantitative Myasthenia Gravis (QMG) score (total and neck muscles alone), and grip strength, were also analyzed. RESULTS: In comparison with the neutral position, in the chin-down position the maximum SP at the meso­hypopharynx was significantly increased (p < 0.05), the maximum SP at the UES was significantly decreased (p < 0.05), and the duration of relaxing SP at the UES was significantly increased (p < 0.05). Interestingly, there were no correlations between the SP at any location and the results of the neurological evaluations. CONCLUSIONS: The chin-down position appears useful for improving pharyngeal clearance in MG patients, by promoting increased SP at the meso­hypopharynx, relaxing SP at the UES, and increasing the duration of relaxation pressure at the UES.

miR-33a-5p in small extracellular vesicles as non-invasive biomarker for oxaliplatin sensitivity in human colorectal cancer cells.

microRNAs (miRNAs) contained in small extracellular vesicles (sEVs) are candidates for non-invasive biomarkers. Oxaliplatin (L-OHP) has been approved for advanced colorectal cancer (CRC) chemotherapy. However, the response to L-OHP differs among CRC patients. In addition, CRC cells often acquire the resistance to L-OHP. This study aimed at the prediction of L-OHP sensitivity by measuring extracellular miRNAs levels. Firstly, we compared intracellular miRNAs expressions in L-OHP-sensitive CRC cells (SW620 and HCT116 cells) with those in acquired and intrinsic L-OHP-resistant cells. In microarray and real-time RT-PCR analyses, the intracellular miR-33a-5p, miR-210-3p, and miR-224-5p expressions were lower in acquired and intrinsic L-OHP-resistant CRC cells than sensitive cells. Furthermore, in SW620 cells, L-OHP sensitivity was decreased by miR-33a-5p inhibitor. On the other hand, miR-210-3p or miR-224-5p inhibitor did not affect L-OHP sensitivity in SW620 cells. Secondly, the amount of miR-33a-5p, miR-210-3p, and miR-224-5p in sEVs was compared. The amount of miR-33a-5p and miR-210-3p in sEVs secreted from acquired and intrinsic L-OHP-resistant cells tended to be small. miR-224-5p was not detected in sEVs secreted from three types of CRC cells examined. To the best of our knowledge, this is the first study demonstrating that miR-33a-5p and/or miR-210-3p in sEVs would be candidates for biomarkers of L-OHP sensitivity. In particular, miR-33a-5p is a promising candidate because it would be directly involved in L-OHP sensitivity.

Different types of dysphagia alleviated by the chin-down position.

OBJECTIVE: Retrospective videofluoroscopic swallowing study (VFSS) evaluations of pharyngeal swallowing were used to evaluate the types of dysphagia alleviated by the chin-down maneuver. MATERIALS AND METHODS: The study population consisted of 64 patients who underwent VFSS evaluations during neutral and chin-down maneuvers presenting specifically penetration or aspiration. The assessment of the VFSS movie clips of each maneuver was performed using parameters of the Modified Barium Swallow Impairment Profile (MBSImP) and the presence and degree of airway invasion(PDAI) by three blinded raters in the following five subcategorized groups, 1. patietns presenting penetration or aspiration during swallow 2. after swallow, patients of 3. head and neck, 4. digestive and 5. neuromuscular disorders, respectively. The scores registered for the two maneuvers were statistically compared. Additionally, we examined statistically which factors had the impact on the improvement of the PDAI using fisher's exact test. RESULTS: Compared with the neutral position, PDAI, pharyngeal constriction, anterior hyoid movement, pharyngeal constriction, laryngeal elevation, laryngeal closure, upper esophageal sphincter opening, initiation of the pharyngeal swallow, and pharyngeal clearance in pyriform sinus were significantly (p < 0.01-0.05) improved with the chin-down maneuver. In a subcategory comparison with group 1, 3 and 4, the PDAI improved significantly (p < 0.01) with the chin-down maneuver, in which laryngeal elevation and laryngeal closure had statistically the impact (p < 0.01-0.05) on improvement of PDAI. CONCLUSION: The chin-down maneuver was most effective in improving swallow function when the impairment included penetration and aspiration during swallow caused by inadequate laryngeal elevation and laryngeal closure.

Swallowing dysfunction following surgery for well-differentiated thyroid cancer with extrathyroid invasion.

BACKGROUND: Differentiated thyroid carcinoma (DTC) can invade the surrounding aerodigestive tract. Radical surgery for locally advanced DTC will require resection of the trachea, recurrent laryngeal nerve (RLN), inferior pharyngeal constrictor muscles (IPCMs), or a part of the esophagus. The purpose of this study was to demonstrate the effect of resection of these surrounding tissues combined with total thyroidectomy and neck dissection on swallowing function following surgery. METHODS: We performed total thyroidectomy combined with neck dissection and resection of the RLN in 24 patients with DTC with extrathyroidal invasion (19 unilateral, 1 bilateral), IPCMs (n = 5), or muscle layers of esophagus (n = 9). Nine patients received a tracheostomy placement due to a window resection of the trachea for tumor invasion (n = 6) and necessary upper airway management (n = 3). We used the duration of nasogastric tube feeding to evaluate swallowing function following surgery. RESULTS: Patients who underwent tracheostomy or IPCM resection showed significantly longer periods of tube feeding (p = 0.0057 and 0.0017, respectively). In contrast, resection of the unilateral RLN or esophageal muscle layer showed no difference in tube feeding duration. Multiple regression analysis indicated that tracheostomy and IPCM resection were significant independent predictors of longer periods of tube feeding (p = 0.04583 and 0.00087, respectively). CONCLUSION: These results indicate that tracheostomy placement and resection of the IPCMs, together with total thyroidectomy, extends the tube feeding duration in the postoperative period.

The effect of a chin-down maneuver after esophagectomy on oropharyngeal swallowing pressure measured using high-resolution manometry.

OBJECTIVE: To elucidate the effects of a chin-down maneuver using high-resolution manometry (HRM) to measure pharyngeal swallowing pressure (SP) after esophagectomy. METHODS: We evaluated 9 of 16 patients who underwent esophagectomy featuring gastric tube reconstruction and three-field lymph node dissection (3FL) in our Department of Gastroenterological Surgery from September 2015 to June 2016. We compared all parameters of the neutral and chin-down positions using HRM to measure the maximum SP at the velopharynx, meso-hypopharynx, and upper esophageal sphincter (UES) and the duration of lowered SP at the UES, the distance from nostrils to the boundary between hypopharynx and UES and to derive SP and SP propagation curves at various distances from the nostrils. RESULTS: Compared to that at the neutral position, the maximum SP at the velopharynx was significantly lower in the chin-down position (p<0.05); however, SP at the meso-hypopharynx and UES did not differ significantly. The duration of lowered SP at the UES was significantly prolonged in the chin-down position and the distance from nostrils to the boundary between hypopharynx and UES was significantly shortened representing the elevation of the larynx, respectively (p<0.05, p<0.01). On the SP propagation curve for males, the times to SP peaks at 13, 16, 17, and 18cm from the nostrils were significantly prolonged (all p<0.05) in the chin-down position. CONCLUSION: Chin-down positioning after esophagectomy/3FL may improve bolus passage by prolonging the duration of lowered SP at the UES, possibly by enhancing laryngeal elevation.

Phonatory function in patients with well-differentiated thyroid carcinoma following meticulous resection of tumors adhering to the recurrent laryngeal nerve.

BACKGROUND: Well-differentiated thyroid carcinomas (WDTCs) sometimes adhere firmly to the recurrent laryngeal nerve (RLN), while allowing normal mobility of the vocal fold (VF). Meticulous dissection of the adhered tumor from the RLN is known to be effective, preserving VF mobility and oncological safety. However, phonatory function following this preservation procedure has yet to be evaluated sufficiently. The objective of this study was to examine phonatory function following the preservation procedure. METHODS: Ten patients with WDTCs, demonstrating normal preoperative VF mobility with tumors adhering to the RLN, underwent the preservation procedure between 2000 and 2013 (preservation group). During the same period, nine patients with WDTCs demonstrating normal VF mobility underwent resection and reconstruction of the tumor-invaded RLNs (reconstruction group). Phonatory function, including maximum phonation time (MPT), mean flow rate (MFR), jitter, shimmer, harmonics-to-noise ratio, and GRBAS scale score, was evaluated and compared statistically between the two groups. RESULTS: The mean values of MPT and MFR in the preservation group were at normal levels. Both G and B scores of GRBAS scale were at near-normal levels. Additionally, the mean B score of the GRBAS scale was significantly better in the preservation group than in the reconstruction group. CONCLUSIONS: When normal VF mobility is observed preoperatively, meticulous resection for preserving RLN would contribute to maintain not only normal level of MPT and MFR, but also to provide better B score of GRBAS scale than RLN resection followed by immediate reconstruction.

Determining the Efficacy of the Chin-Down Maneuver Following Esophagectomy With Fiberoptic Endoscopic Evaluation of Swallowing.

OBJECTIVES: To clarify the reliability of fiberoptic endoscopic evaluation of swallowing (FEES) compared to videofluoroscopic swallowing studies (VFSSs). Second, we explored the effect of the chin-down maneuver in the presence or absence of vocal fold paralysis (VFP) using FEES in patients with 3-field lymphadenectomy (3FL) postesophagectomy. DESIGN: Retrospective data collection from FEES and VFSS. SETTING: Dysphagic clinics in the ear, nose, and throat department. PARTICIPANTS: Patients (N=15) underwent esophagectomy with 3FL at the Department of Gastroenterologic Surgery, during a period of 12 months. INTERVENTIONS: The patients underwent FEES and VFSS with neutral and chin-down maneuvers 2 weeks postoperatively. Two raters of speech pathology blindly scored aspiration, penetration, delayed initiation, and pharyngeal clearance in the pyriform sinus and vallecula, respectively, from recorded movie clips of both examinations, using the penetration aspiration scale (PAS) and modified Hyodo FEES rating scale. MAIN OUTCOME MEASURES: The intrarater and interrater correlation coefficients of each parameter examined with FEES. Statistical comparison of each parameter between FEES and VFSS and of each parameter evaluated using FEES between 2 maneuvers with or without VFP. RESULTS: The intrarater and interrater correlation coefficients of the PAS and pyriform sinus examined with FEES were both statistically consistent between the 2 raters. The PAS and pyriform sinus evaluated using FEES were significantly correlated with those evaluated in a VFSS (P<.05). The 2 parameters evaluated using FEES were significantly (P<.05) improved with the chin-down maneuver compared to the neutral maneuver, especially in VFP patients. CONCLUSION: FEES performed postesophagectomy with 3FL for evaluation of aspiration is as reliable statistically as VFSSs. The chin-down maneuver is especially useful for reducing the PAS score and pyriform sinus in VFP patients.

Assessment of oropharyngeal swallowing dysfunction in myasthenia gravis patients presenting with difficulty in swallowing.

OBJECTIVE: To examine the correlation between the results of a clinical neurological evaluation and swallowing dysfunction in myasthenia gravis (MG) patients who presented with difficulty in swallowing and underwent videofluorographic (VF) and fiber-optic endoscopic (FE) evaluation. METHODS: The swallowing studies of 13MG patients with difficulty in swallowing seen at the Department of Neurology from June 2016 to April 2018 were reviewed. The assessment parameters on VF and FE examination were as follows: swallowing initiation, bolus stasis at the pyriform sinus (PS) and vallecula (VC), and the degree of aspiration. They were assessed using a 4 or 5-point scale. Associations between these parameters and the clinical neurological evaluation, which included the Myasthenia Gravis Foundation of America (MGFA) clinical classification, the MG Activities of Daily Living score, and a quantitative MG score, were statistically determined. RESULTS: No patients demonstrated aspiration. However, in patients MGFA IIb/IIIb disease, the Hydo's FEES scale and pharyngeal residue examined using VF were significantly (p<0.05) more severe than in patients classified with MGFA IIa/IIIa disease. None of the parameters evaluated with VF and FE correlated significantly with the clinical neurological evaluation except for the grip assessment. CONCLUSION: While not presenting with aspiration but with swallowing difficulty alone, patients classified with MGFA IIb/IIIb disease, regardless of clinical neurological evaluation, require care addressing the reduced pharyngeal clearance. Controlling the severity of the pharyngeal residue may be the key to preventing silent aspiration, especially in patients with MGFA IIb/IIIb disease.

Short- and long-term outcomes after pancreaticoduodenectomy following total gastorectomy: Report of case series and literature review.

PURPOSE: Pancreaticoduodenectomy (PD) following gastrectomy (TG) should be considered challenging even currently although its procedure and clinical value have been being standardized. Short- and long-term outcomes as well as standard reconstruction method following these procedures remain unclear. In order to clarify these issues, we reviewed worldwide English literature and 4 of our own cases of PD for patients with previous TG. METHODS: Clinicopathological variables of 11 cases of PD for patients with previous TG were evaluated. Seven of these 11 were abstracted from a review of worldwide English literature and 4 of 11 were our own cases. RESULTS: 3 cases was reconstructed using Y-limb made in previous TG and afferent loop syndrome (ALS) was observed in 2 of 3, in these cases whereas no cases of ALS were found in cases reconstructed using newly-made Y-limb. In cases where PD was indicated for cancer, early cancer death, defined as death related to cancer recurrence observed within 2 years after PD, was observed in 6 of 9 cases. Notably in cases of pancreatic cancer recurrent cancer was diagnosed within 1year after PD in 5 of 7 cases and 4 of these patients died of pancreatic cancer soon after recurrence. CONCLUSION: In cases of PD following TG, previously-made Y-limb should not be used for reconstruction following PD because of probable cause of previously-made Y-limb for ALS. Long-term outcomes of PD after TG seemed unsatisfactory notably in cases of pancreatic cancer and thus application of PD for patients with previous TG should be carefully decided until reasonable explanation for this dismal outcome is obtained.

Long-term survival after resection of pancreatic ductal adenocarcinoma with para-aortic lymph node metastasis: case report.

Pancreatic cancer patients with para-aortic lymph node metastasis have a poor prognosis and patients living longer than 3 years are rare. We had a patient with pancreatic cancer who survived for more than 10 years after removal of the para-aortic lymph node metastasis. A 57-year-old woman was diagnosed with pancreatic head cancer and underwent a pancreaticoduodenectomy with subtotal gastric resection following Whipple reconstruction in 2000. Para-aortic lymph node metastasis was detected during the operation by intraoperative pathological diagnosis and an extended lymphadenectomy was performed with vascular skeletonization of the celiac and superior mesenteric arteries. In 2004, a low-density area was detected around the superior mesenteric artery (SMA) 5 cm from its root and she was treated with gemcitabine, and the area was undetectable after 3 years of treatment. In 2010, computed tomography showed a low-density area around the same lesion with an increased carcinoembryonic antigen level. After 4 months of gemcitabine treatment, we resected the tumor en bloc with the associated superior mesenteric vein and perineural tissue. Histopathological examination of the resected specimen revealed a well-differentiated tubular adenocarcinoma that closely resembled the original primary pancreatic cancer, indicating perineural recurrence 10 years after the initial resection. She had no recurrence around the SMA for more than one year. Although a meta-analysis has not proved the efficacy of preventive radical dissection, this case indicates that a patient with well-differentiated, chemotherapy-responsive pancreatic cancer with para-aortic lymph node metastasis could have a long survival time through extended dissection of the lymph nodes.