Single-center experience of thoracoscopic sympathectomy for palmar hyperhidrosis with long-term postoperative questionnaire survey.

OBJECTIVES: Thoracoscopic sympathectomy is an effective treatment for palmar hyperhidrosis. However, compensatory hyperhidrosis occurs frequently as a postoperative complication of the procedure. The goal of this study was to elucidate the clinical significance of thoracoscopic sympathectomy using our surgical procedure. METHODS: Consecutive 151 patients who underwent thoracoscopic sympathectomy for palmar hyperhidrosis were studied. In addition, to investigate patients' satisfaction and long-term quality of life, 111 patients were asked to complete a mailing questionnaire survey, and 84 responded (response rate of 75.7%). RESULTS: All of the 151 patients reported a reduction in palmar sweating during the immediate postoperative period. None of the patients had pneumothorax, hemothorax, Horner's syndrome, or worsening of bradycardia. Based on the questionnaire, the surgical success rate was 98.8%. None of the patients had a recurrence of palmar hyperhidrosis during the long-term postoperative period. However, compensatory hyperhidrosis was reported in 82 patients (97.6%). In total, 94.0% of patients had high levels of postoperative satisfaction. CONCLUSIONS: Thoracoscopic sympathectomy is an effective surgical treatment for palmar hyperhidrosis. By contrast, the careful preoperative explanation of compensatory hyperhidrosis is considered to be very important.

Wnt2b and Wnt5a expression is highly associated with M2 TAMs in non­small cell lung cancer.

Tumor­associated macrophages (TAMs), particularly M2 macrophages, promote tumor progression, while Wnt genes encode a family of multi­functional glycoproteins that serve an important role in tumorigenesis. Immunohistochemical studies were performed to evaluate Wnt2b and Wnt5a expression in tumor and stromal cells in M2 and M1 TAMs and Ki­67 proliferation index in 160 consecutive patients with resected non­small cell lung cancer (NSCLC). Overall, 52 tumors (32.5%) were classified as tumoral Wnt2b­high (Wnt2b­positive tumor cells >30%) and 95 (59.4%) as stromal Wnt2b­high (Wnt2b­positive stromal cells >30%), while 75 (46.9%) were classified as tumoral Wnt5a­high (Wnt5a­positive tumor cells >30%) and 63 (39.4%) as stromal Wnt5a­high (Wnt5a­positive stromal cells >28%). The density of M2 TAMs was significantly higher in the tumoral (P=0.0024) and stromal Wnt2b­high groups (P=0.0054). The density of M2 TAMs was also significantly higher in the tumoral (P=0.0005) and stromal Wnt5a­high groups (P=0.0486). By contrast, no difference in stromal or islet M1 TAM density was observed in relation to tumoral or stromal Wnt2b or Wnt5a status. Furthermore, Ki­67 proliferation index was significantly higher in the tumoral (P=0.0121) and stromal Wnt2b­high (P=0.0019) and tumoral Wnt5a­high (P=0.0088) groups. Overall survival rate was significantly lower in the Wnt2b­high (P=0.0437), Wnt5a­high (P=0.0106) and M2 TAM­high (P=0.0060) groups. Wnt2b and Wnt5a expression in tumor and stromal cells may induce M2 TAMs to produce more aggressive behavior during tumor progression in NSCLC.

Evaluation of the postoperative course of East Asian eyelid reconstruction with free tarsoconjunctival graft transplantation: A Japanese single-centre retrospective study.

Although eyelid reconstruction by transplanting an autologous free tarsoconjunctival graft (FTG) is a well-established technique, few studies have examined the postoperative course of FTG transplantation for East Asian eyelids, including those of Japanese patients. Therefore, this study investigated complication and reoperation rates after FTG transplantation in the reconstruction of East Asian (Japanese) eyelids. This study included 42 eyelids wherein posterior lobe reconstruction after resection of a malignant tumour of the eyelid was performed by FTG transplantation between 2007 and 2019 at Niigata University Medical and Dental Hospital. We investigated complications and need for revision surgery during the patients' postoperative courses. The relationship between postoperative complications, tumour diameter, and eyelid defect width was statistically examined. Of 42 cases reconstructed with FTG, the upper eyelid was reconstructed in 23. Postoperative complications were observed in 12 cases (52%): entropion in eight and corneal epithelial disorder in four. Revision surgery was required in three of those cases (13%). There were 19 cases of lower eyelid reconstruction. Postoperative complications were observed in seven cases (32%): ectropion in three and corneal epithelial disorder in two and one lower eyelid ptosis. Two of these cases (11%) required revision surgery. There was no statistically significant difference in tumour diameter between cases with and without postoperative complications. There was also no significant association between the width of the eyelid defect and the presence/absence of complications. Entropion and ectropion were more likely to occur in the upper and lower eyelids, respectively. For Japanese eyelids, complication rates after FTG transplantation were approximately 50% and 30% for the upper and lower eyelids, respectively. The revision surgery rate was approximately 10% for both upper and lower eyelids. As these revision surgery rates are low, FTG transplantation may be an option for the reconstruction of Japanese eyelids.

Differential expression of PD­L1 and PD­L2 is associated with the tumor microenvironment of TILs and M2 TAMs and tumor differentiation in non­small cell lung cancer.

To improve the treatment strategy of immune­checkpoint inhibitors for non­small cell lung cancer (NSCLC), a comprehensive analysis of programmed death­ligand (PD­L)1 and PD­L2 expression is clinically important. The expression of PD­L1 and PD­L2 on both tumor cells (TCs) and tumor­infiltrating immune cells (ICs) was investigated, with respect to tumor­infiltrating lymphocytes (TILs) and M2 tumor­associated macrophages (TAMs), which are key components of the tumor microenvironment, in 175 patients with resected NSCLC. The TIL and M2 TAM densities were associated with the expression of PD­L1 on the two TCs (both P<0.0001) and ICs (both P<0.0001). The TIL and M2 TAM densities were also associated with the expression of PD­L2 on both TCs (P=0.0494 and P=0.0452, respectively) and ICs (P=0.0048 and P=0.0125, respectively). However, there was no correlation between the percentage of PD­L1­positive TCs and the percentage of PD­L2­positive TCs (r=0.019; P=0.8049). Meanwhile, tumor differentiation was significantly associated with the PD­L1 expression on TCs and ICs (P=0.0002 and P<0.0001, respectively). By contrast, tumor differentiation was inversely associated with the PD­L2 expression on both TCs and ICs (P=0.0260 and P=0.0326, respectively). In conclusion, the combined evaluation of PD­L1 and PD­L2 expression could be clinically important in the treatment strategy of immune­checkpoint inhibitors in patients with NSCLC. In particular, the evaluation of PD­L2 expression may be necessary for patients with PD­L1­negative NSCLC.

Choroid structure analysis following initiation of hemodialysis by using swept-source optical coherence tomography in patients with and without diabetes.

We aimed to evaluate choroid structural changes using swept-source optical coherence tomography (SS-OCT) following hemodialysis initiation in diabetic and nondiabetic patients with end-stage kidney disease (ESKD). In this multicenter, prospective, cross-sectional study, diabetic (DM group; 30 eyes; 16 patients) and nondiabetic patients (NDM group; 30 eyes; 15 patients) with ESKD were evaluated after hemodialysis initiation. SS-OCT findings were analyzed using a manual delineation technique and binarization method before the first and last hemodialysis sessions, conducted approximately 2 weeks apart. Subfoveal choroidal thickness changes and mean large choroidal vessel layer thickness were significantly greater in the DM group (-13.3% ± 2.5% and -14.5% ± 5.2%, respectively) than the NDM group (-9.5% ± 3.1% and -9.2% ± 3.4%, respectively; p = 0.049 and p = 0.02, respectively). Binarized SS-OCT analysis revealed that the mean subfoveal choroidal area was significantly larger in the DM group (-21.9% ± 6.5%) than the NDM group (-17.2% ± 5.9%; p = 0.032). The change ratio in mean luminal area values was significantly greater in the DM group (-27.7% ± 8.7%) than the NDM group (-17.7% ± 5.8%; p = 0.007). The DM group exhibited substantial changes in the choroidal layer, possibly reflecting choroidal vascular disorders caused by diabetes.

The natural course of IgG4-related ophthalmic disease after debulking surgery: a single-centre retrospective study.

OBJECTIVE: This study aimed to examine the natural course and relapse rate of IgG4-related ophthalmic disease (IgG4-ROD) after debulking surgery in Japanese patients. METHODS AND ANALYSIS: This retrospective review included patients with IgG4-ROD who did not undergo further treatment following debulking surgery. The patients were diagnosed between January 2009 and December 2018 at the Department of Ophthalmology and Pathology, Niigata University Medical and Dental Hospital. The main outcome measures included postoperative IgG4-ROD recurrence rate and differences between patients with and without recurrent disease. RESULTS: Fifteen patients (six male, 9 female; 61.8±16.2 years) were included. Twelve patients (80.0%) had dacryoadenitis disease and three patients (20.0%) had orbital fat tissue disease. About 70%-100% of the lesion was resected in the debulking surgery and the pathological diagnosis was rendered. A definitive diagnosis was made in 13 cases (86.7%) and a probable diagnosis in 2 cases (13.3%). Patients were followed up for 39.0±25.5 months following operation. All patients had lesion volume reduction and patients with dacryoadenitis had eyelid swelling improvement after surgery. Two patients (13.3%) had disease recurrence and six patients (40.0%) had extraophthalmic lesions. There was no statistically significant difference in clinical features between relapsed and non-recurring cases. CONCLUSION: We observed a 13.3% relapse rate following debulking surgery in patients with IgG4-ROD who did not undergo further treatment. This rate is lower than the documented relapse rate of 30%-70% following oral prednisolone therapy. Therefore, debulking surgery may be a treatment option for IgG4-ROD.

The Role of Mutation Rates of GNAQ or GNA11 in Cases of Uveal Melanoma in Japan.

GNAQ and GNA11 mutations are thought to be important for the tumorigenesis of uveal melanoma. Although previous studies have reported on mutation rates in cases of uveal melanoma, presently, no such report for the Japanese population exists. In this study, we examined the frequency of GNAQ and GNA11 somatic mutations in cases of uveal melanoma in Japan and their relationship with clinicopathologic features or Ki-67-positive cell rates (Ki-67 labeling index: Ki-67 LI) using immunofluorescence methods. The study involved 19 cases of uveal melanoma. We extracted the template DNA from formalin-fixed, paraffin-embedded specimens using a DNA extraction kit. We amplified the DNA sequences of GNAQ and GNA11 using polymerase chain reaction and analyzed mutations by direct sequencing. We evaluated Ki-67 LI using immunofluorescence methods. The frequencies of GNAQ and GNA11 somatic mutations were 26.3% (5/19) and 31.6% (6/19), respectively. The GNAQ and GNA11 mutations were mutually exclusive, as indicated in previous reports. The frequency of GNA11 mutations was significantly higher in epithelioid cells; however, no significant association between GNAQ mutations and cell type was evident, and there was no significant difference in Ki-67 LI between the mutation-positive and mutation-negative tumors. GNAQ and GNA11 mutations were identified in cases of uveal melanoma in Japan, although at lower frequencies than in white counterparts. The mutation frequency of GNA11 was significantly higher in epithelioid cells.

Trametinib plus 4-Methylumbelliferone Exhibits Antitumor Effects by ERK Blockade and CD44 Downregulation and Affects PD-1 and PD-L1 in Malignant Pleural Mesothelioma.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is a highly aggressive malignancy in which the mitogen-activated protein kinase pathway plays a critical role in the regulation of tumorigenesis. Hyaluronic acid (HA) is a major component of the extracellular matrix, and elevated HA levels with a concurrent increase in malignant properties are associated with MPM. METHODS: We evaluated the effects of trametinib, a mitogen-activated protein kinase (MEK) inhibitor, and 4-methylumbelliferone (4-MU), an HA synthesis inhibitor, alone and in combination on MPM cells in vitro and in vivo. We studied the effects of trametinib, 4-MU, and their combination on MPM cells by using cell viability assays, Western blot analysis, and a mouse xenograft model. RESULTS: Trametinib and 4-MU exhibited antiproliferative activity in MPM cells. Trametinib blocked MEK-dependent extracellular signal-regulated kinase (ERK) phosphorylation and decreased CD44 expression in a concentration-dependent manner. Trametinib inhibited the expression of Fra-1 (the activator protein 1 [AP1] component), inhibited ERK phosphorylation, and decreased CD44 expression. 4-MU inhibited ERK phosphorylation but not CD44 expression. In a mouse xenograft model, trametinib and 4-MU alone suppressed tumor growth compared with a control. The combination had a greater inhibitory effect than either monotherapy. Immunohistochemical analysis showed that trametinib treatment alone significantly reduced expression of programmed cell death 1 ligand 1. Furthermore, the combination of trametinib and 4-MU resulted in higher expression of programmed cell death 1 and programmed cell death 1 ligand 1 than did the 4-MU treatment alone. CONCLUSIONS: Our results suggest that trametinib and 4-MU are promising therapeutic agents in MPM and that further study of the combination is warranted.

Is volumetric 3-dimensional computed tomography useful to predict histological tumour invasiveness? Analysis of 211 lesions of cT1N0M0 lung adenocarcinoma.

OBJECTIVES: The purpose of this study was to use Hounsfield unit (HU) thresholds of computed tomography (CT) images to predict pathological lymph node metastasis and tumour invasiveness of cT1N0M0 lung adenocarcinoma on 3D evaluations. METHODS: Preoperative CT images of 211 lesions of surgically resected cT1N0M0 lung adenocarcinoma were retrospectively examined. The tumour size was calculated in 1D, 2D and 3D views. Tumours with -300 HU and over were defined as 'solid tumours', and those between -800 and -301 HU were defined as 'ground glass opacity tumours'. Tumours with -800 HU and over were assumed to be the whole tumour entity. The proportion of 'solid tumour' within the whole tumour entity was also calculated as the 'solid tumour ratio'. These were compared with pathological information. RESULTS: Solid tumour size and ratio were positively correlated with microscopic invasion to pleura, vessels and lymphatics in all dimensional evaluations. Pathological lymph node metastases were also well predicted by solid tumour size and ratio in all dimensional evaluations. The P-values for the receiver operating characteristic (ROC) curves of 1D, 1D ×2, 2D and 3D evaluations were: solid tumour size P = 0.013, 0.014 and 0.032; and solid tumour ratio 0.016, 0.0032 and <0.0001. In comparisons of 1D, 2D and 3D evaluations, 'solid tumour size' of the area under the curve (AUC) of ROC to detect pathological lymph node metastases was not significant. However, strikingly, the 3D solid tumour ratio was found to be significantly more accurate for the prediction of pathological lymph node metastases than the 1D and 2D solid tumour ratios on ROC evaluation (AUC: 1D 0.736, 2D 0.803 and 3D 0.882; P-values for the AUC comparisons were P = 0.013 for 3D versus 1D and P = 0.022 for 3D versus 2D). The correlations of subtypes of adenocarcinoma and the 3D solid tumour ratio were also investigated. Subtypes of adenocarcinoma were well correlated with the 3D solid tumour ratio. CONCLUSIONS: Preoperative 3D CT using threshold values of -800 and -300 HU was useful for predicting pathological lymph node metastases and tumour invasiveness of cT1N0M0 lung adenocarcinoma.

A case of a resected thymoma in the middle mediastinum.

We experienced an extremely rare case of a thymoma in the middle mediastinum. A 42-year-old woman presented with a 4-cm-sized abnormal mass in the middle mediastinum by chest computed tomography. To resect this tumor, we performed surgery using the thoracoscopic lateral approach from the right side subsequently followed by a median sternotomy. After the resection of this tumor, the intraoperative quick pathological examination diagnosed this tumor as a thymoma. An extended thymectomy was performed additionally.

Second relapse of solitary fibrous tumor within 20 years of initial resection.

A 64-year-old woman presented with a sessile solitary fibrous tumor in the right thoracic cavity. She had undergone 2 solitary fibrous tumor resections 7 and 20 years previously. The latest histological findings were identical to the previous, and pathologically benign. However, we clinically classified the tumors as malignant because of repeated relapse. The tumor and extrapulmonary structures should be resected at the time of recurrence.

Thymic Neuroblastoma within a Thymic Cyst in an Adult.

CASE PRESENTATION: A 65-year-old female patient with no clinical manifestations was hospitalized for examination and treatment of an anterior mediastinal tumor found at the time of a regular health checkup. Enhanced computed tomography (CT) and magnetic resonance imaging revealed a cystic lesion containing a solid tumor. Positron emission tomography-CT demonstrated increased uptake in the solid lesion. Tumor resection with total thymectomy was performed. A pathological diagnosis of thymic neuroblastoma within a thymic cyst was made. Micorscopic examination revealed that tumor cells of the solid component were lined with thymic epithelial cells of the inner cyst wall. Furthermore, some tumor cells of the solid component had melanin granules. These findings suggest that this tumor arose from progenitors of the thymic epithelial cells with the potential to differentiate along neural lines. CONCLUSIONS: Neuroblastoma commonly occurs in children. However, the diagnosis of neuroblastoma in adults has been reported in several case reports. We report an adult case of histogenetically informative thymic neuroblastoma within a thymic cyst. There are no standard treatment strategies and chemotherapy protocols. Complete surgical resection might be important for a better outcome.

[A variety of orbital lymphangioma treatments: one case treated with orbital decompression therapy and the other case with intralesional injection of OK-432 therapy].

BACKGROUND: Orbital lymphangioma can result in ocular emergencies due to acute enlargement, leading to painful proptosis, compressive optic neuropathy, exposure keratopathy, restrictive ocular motility and increased intraocular pressure. Treatment methods and clinical courses of two cases with orbital lymphangioma are reported, one with orbital decompression therapy and the other with intralesional injection of OK-432 therapy. CASE 1: An 8-year-old girl had multilocular cystic orbital intracornal lymphangioma. Emergency operation was deemed necessary because the patient presented with the painful proptosis, the compressive optic neuropathy, and increased intraocular pressure due to acute enlargement, we put the orbital inferior wall was decompressed by inserting an intact inframedial orbital strut. The proptosis vanished completely and visual acuity loss improved. CASE 2: A 2-year-old girl had multilocular cystic orbital intra and extracornal lymphangioma. She had severe proptosis and exposure keratopathy. The extracornal cystic lesion was treated with an intralesional injection of OK-432. On the 7th day after injection, the patient presented with painful severe proptosis. Aspiration of the fluid in the cystic lesion was performed, and the drain was preserved. After the treatment, both the severe proptosis and the exposure keratopathy improved. CONCLUSIONS: Inferior wall decompression was performed on case 1 while keeping the inframedial orbital strut. Although the eye movement disorder was low at the time, the medial and lateral wall decompression improved. In case 2, the extracornal cystic lesion was treated with an intralesional injection of OK-432 Judging from the results of that clinical course, the injection of OK-432 to the intracornal lesion could prove dangerous to the visual performance. Although OK-432 is predictably-effective against lymphangioma, it should not perform be applied without careful consideration.

Changes of scleral sulfated proteoglycans in three cases of nanophthalmos.

PURPOSE: To examine the composition of scleral sulfated proteoglycans in three nanophthalmic eyes by electron microscopic histochemistry. METHODS: Scleral tissues from three cases of nanophthalmos were collected from the Niigata University Hospital for transmission electron microscopic examination. Sulfated proteoglycans were studied using the cuprolinic blue (CB) dye binding method in conjunction with enzymatic digestion. RESULTS: Compared with the controls, the nanophthalmic sclerae were much thicker, and the collagen fibrils showed a less orderly arrangement. Twisting or fraying of collagen fibrils was noted in some areas, and fine fibrous materials surrounded the abnormal fibrils. CB-positive proteoglycan filaments were found around the collagen fibrils and in the fine fibrous materials in the nanophthalmic specimens. The number of proteoglycan filaments was smaller than that in the normal specimens. After enzymatic digestion, the CB-positive filaments were identified as dermatan/chondroitin sulfate proteoglycans. Although the number of dermatan sulfate filaments in nanophthalmos sclerae was similar to that in the controls, there were many fewer chondroitin sulfate filaments. CONCLUSION: A loss of chondroitin sulfate proteoglycan was observed in nanophthalmic sclerae. The alteration may be related to the abnormal organization of collagen fibrils and the onset of uveal effusion.

Phospholipase C delta-type consists of three isozymes: bovine PLCdelta2 is a homologue of human/mouse PLCdelta4.

To date, 12 phospholipase C (PLC) isozymes have been identified in mammals, and they are divided into five classes, beta-, gamma-, delta-, epsilon-, and zeta-type. PLCdelta-type is reported to be composed of four isozymes, PLCdelta1-delta4. Here we report that a screening for mouse PLCdelta2 from a BAC library with primers that amplify a specific region of bovine PLCdelta2 resulted in isolation of one clone containing the mouse PLCdelta4 gene. Furthermore, a database search revealed that there is only one gene corresponding to PLCdelta2 and PLCdelta4 in the mouse and human genomes, indicating that bovine PLCdelta2 is a homologue of human and mouse PLCdelta4. However, PLCdelta2 Western blot analysis with a widely used commercial anti-PLCdelta2 antibody showed an expression pattern distinct from that of PLCdelta4 in wild-type mice. In addition, an 80-kDa band, which was recognized by antibody against PLCdelta2, was smaller than an 85-kDa band detected by anti-PLCdelta4 antibody, and the 80-kDa band was detectable in lysates of brain, testis, and spleen from PLCdelta4-deficient mice. We also found that immunoprecipitates from brain lysates with this PLCdelta2 antibody contained no PLC activity. From these data, we conclude that bovine PLCdelta2 is a homologue of human and mouse PLCdelta4, and that three isozymes (delta1, delta3, and delta4) exist in the PLCdelta family.

Recurrent meningitis associated with complete Currarino triad in an adult--case report.

A 58-year-old woman presented with Currarino triad manifesting as recurrent meningitis. Currarino triad is a combination of a presacral mass, a congenital sacral bony abnormality, and an anorectal malformation, which is caused by dorsal-ventral patterning defects during embryonic development. She had a history of treatment for anal stenosis in her childhood. Radiographic examinations demonstrated the characteristic findings of Currarino triad and a complicated mass lesion. The diagnosis was recurrent meningitis related to the anterior sacral meningocele. Neck ligation of the meningocele was performed via a posterior transsacral approach after treatment with antibiotics. At surgery, an epidermoid cyst was observed inside the meningocele. The cyst content was aspirated. She suffered no further episodes of meningitis. The meningitis was probably part of the clinical course of Currarino triad. Radiography of the sacrum and magnetic resonance imaging are recommended for patients with meningitis of unknown origin. The early diagnosis and treatment of this condition are important.