Smell loss associated with SARS-CoV-2 is not clinically different from other viruses: a multicenter cohort study.

BACKGROUND: Although the COVID-19 pandemic has increased the prevalence of cases with olfactory loss, other respiratory viruses can also cause this condition. We aimed to compare the prevalence of acute SARS-CoV-2 infection and other respiratory viruses in patients with sudden smell loss, and to assess the impact of SARS-CoV-2 viral load and co-infection on olfactory symptoms. METHODS: Patients with sudden smell loss were recruited in a multicenter prospective cohort study in 15 hospitals in Brazil. Clinical questionnaire, Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory test and nasopharyngeal swab to perform a PCR-based respiratory viral panel were collected at first visit (day 0) and 30 and 60 days after recruitment. RESULTS: 188 of 213 patients presented positive test result for SARS-CoV-2, among which 65 were co-infected with other respiratory viruses (e.g., rhinovirus, enterovirus, and parainfluenza). 25 had negative test results for SARS-CoV-2. Patients in both SARSCoV-2 and non-SARS-CoV-2 groups had objective anosmia (less than 2 points according to the psychophysical olfactory CCCRC) at day 0, with no significant difference between them. Both groups had significant smell scores improvement after 30 and 60 days, with no difference between them. Co-infection with other respiratory viruses, and SARS-CoV-2 viral load did not impact olfactory scores. CONCLUSION: Patients with sudden smell loss associated with SARS-CoV-2 and other respiratory viruses had similar presentation, with most participants initiating with anosmia, and total or near total recovery after 60 days. SARS-CoV-2 viral load and co-infections with other respiratory viruses were not associated with poorer olfactory outcomes.

New evidence for the Ontong Java Nui hypothesis.

The formation of the Ontong Java Nui super oceanic plateau (OJN), which is based on the model that the submarine Ontong Java Plateau (OJP), Manihiki Plateau (MP), and Hikurangi Plateau (HP) were once its contiguous fragments, could have been the largest globally consequential volcanic event in Earth's history. This OJN hypothesis has been debated given the paucity of evidence, for example, the differences in crustal thickness, the compositional gap between MP and OJP basalts and the apparent older age of both plateaus relative to HP remain unresolved. Here we investigate the geochemical and 40Ar-39Ar ages of dredged rocks recovered from the OJP's eastern margin. Volcanic rocks having compositions that match the low-Ti MP basalts are reported for the first time on the OJP and new ~ 96-116 Ma and 67-68 Ma 40Ar-39Ar age data bridge the temporal gap between OJP and HP. These results provide new evidence for the Ontong Java Nui hypothesis and a framework for an integrated tectonomagmatic evolution of the OJP, MP, and HP. The isotopic data imply four mantle components in the source of OJN that are also expressed in present-day Pacific hotspots sources, indicating origin from (and longevity of) the Pacific Large Low Shear-wave Velocity Province.

Discovery of ONO-8590580: A novel, potent and selective GABAA α5 negative allosteric modulator for the treatment of cognitive disorders.

The identification and SAR development of a series of negative allosteric modulators of the GABAA α5 receptor is described. This novel series of compounds was optimised to provide analogues with high GABAA α5 binding affinity, high α5 negative allosteric modulatory activity, good functional subtype selectivity and low microsomal turnover, culminating in identification of ONO-8590580.

Functional Analysis of PTH1R Variants Found in Primary Failure of Eruption.

Although many variants of the parathyroid hormone 1 receptor (PTH1R) gene are known to be associated with primary failure of eruption (PFE), the mechanisms underlying the link remains poorly understood. We here performed functional analyses of PTH1R variants reported in PFE patients-namely, 356C>T (P119L), 395C>T (P132L), 439C>T (R147C), and 1148G>A (R383Q)-using HeLa cells with a lentiviral vector-mediated genetic modification. Two particular variants, P119L and P132L, had severe reduction in a level of N-linked glycosylation when compared with wild-type PTH1R, whereas the other 2 showed modest alteration. PTH1R having P119L or P132L showed marked decrease in the affinity to PTH1-34, which likely led to severely impaired cAMP accumulation upon stimulation in cells expressing these mutants, highlighting the importance of these 2 amino acid residues for ligand-mediated proper functioning of PTH1R. To further gain insights into PTH1R functions, we established the induced pluripotent stem cell (iPSC) lines from a patient with PFE and the heterozygous P132L mutation. When differentiated into osteoblastic-lineage cells, PFE-iPSCs showed no abnormality in mineralization. The mRNA expression of RUNX2, SP7, and BGLAP, the osteoblastic differentiation-related genes, and that of PTH1R were augmented in both PFE-iPSC-derived cells and control iPSC-derived cells in the presence of bone morphogenetic protein 2. Also, active vitamin D3 induced the expression of RANKL, a major key factor for osteoclastogenesis, equally in osteoblastic cells derived from control and PFE-iPSCs. In sharp contrast, exposure to PTH1-34 resulted in no induction of RANKL mRNA expression in the cells expressing P132L variant PTH1R, consistent with the idea that a type of heterozygous PTH1R gene mutation would spoil PTH-dependent response in osteoblasts. Collectively, this study demonstrates a link between PFE-associated genetic alteration and causative functional impairment of PTH1R, as well as a utility of iPSC-based disease modeling for future elucidation of pathogenesis in genetic disorders, including PFE.

Cathepsin K inhibitor causes changes in crystallinity and crystal structure of newly-formed mandibular bone in rats.

Cathepsin K inhibitors are new drugs with the potential for the treatment of osteoporosis because they sustain bony remodelling better than bone resorption inhibitors such as bisphosphonates. The treatment of osteoporosis with inhibitors of bony resorption is associated with osteonecrosis of the jaw, as the deterioration in bony quality that they induce is thought to be one of its causes. The quality of bone is delineated by structural and material characteristics (which include the degree and quality of mineralisation, and depends on the content of proteoglycan and the structural integrity of the bony collagen).1,2 Animal and clinical studies have shown that cathepsin K inhibitors improve the mineral density and structural characteristics of bone, but their effect on the rest remains unknown. We therefore hypothesised that these inhibitors will affect the material characteristics of newly-formed mandibular bone. To verify our hypothesis, we used Raman microspectroscopy to examine such bone in rats that were given a cathepsin K inhibitor, and found unusual crystallinity and an increased substitution of carbonate (CO32-) in its crystal structure.

Molecular alterations of newly formed mandibular bone caused by zoledronate.

Bone quality is defined by structural and material characteristics. Most studies on the mandible have focused on the analysis of structural characteristics, with insufficient investigation of material characteristics. This study tested whether zoledronate affects the material characteristics of newly formed mandibular bone. Thirty-six female Wistar rats were assigned to three groups: sham-ovariectomized rats (SHAM, n=12), ovariectomized rats (OVX, n=12), and ovariectomized rats treated with zoledronate (ZOL, n=12). The left side of the mandibular ramus of all rats was drilled bicortically. Twenty-eight days after surgery, all surviving rats were euthanized and all mandibles were removed. Raman microspectroscopy was performed, and five spectra per specimen of newly formed mandibular bone were analysed. Compared with OVX rats, the mineral/matrix ratio in ZOL rats was significantly increased (5.43±1.88 vs. 7.86±2.05), while crystallinity (0.055±0.002 vs. 0.050±0.002), relative proteoglycan content (0.43±0.10 vs. 0.31±0.05), and collagen structural integrity (1.16±0.21 vs. 0.72±0.06) were significantly decreased. These changes in material characteristics may explain why rats that received zoledronate exhibited peculiar biological phenomena such as bisphosphonate-related osteonecrosis of the jaw.

Stim1 Regulates Enamel Mineralization and Ameloblast Modulation.

Loss-of-function mutations in the Ca2+ release-activated Ca2+ channel genes ORAI1 and STIM1 abolish store-operated Ca2+ entry (SOCE) and result in ectodermal dysplasia with amelogenesis imperfecta. However, because of the limited availability of patient tissue, analyses of enamel mineralization or possible changes in ameloblast function or morphology have not been possible. Here, we generated mice with ectodermal tissue-specific deletion of Stim1 ( Stim1 cKO [conditional knockout]), Stim2 ( Stim2 cKO), and Stim1 and Stim2 ( Stim1/2 cKO) and analyzed their enamel phenotypes as compared with those of control ( Stim1/2fl/fl) animals. Ablation of Stim1 and Stim1/2 but not Stim2 expression resulted in chalky enamel and severe attrition at the incisor tips and molar cusps. Stim1 and Stim1/2 cKO, but not Stim2 cKO, demonstrated inferior enamel mineralization with impaired structural integrity, whereas the shape of the teeth and enamel thickness appeared to be normal in all animals. The gene expression levels of the enamel matrix proteins Amelx and Ambn and the enamel matrix proteases Mmp20 and Klk4 were not altered by the abrogation of SOCE in Stim1/2 cKO mice. The morphology of ameloblasts during the secretory and maturation stages was not significantly altered in either the incisors or molars of the cKO animals. However, in Stim1 and Stim1/2 cKO incisors, the alternating modulation of maturation-stage ameloblasts between the smooth- and ruffle-ended cell types continued beyond the regular cycle and extended to the areas corresponding to the zone of postmodulation ameloblasts in the teeth of control animals. These results indicate that SOCE is essential for proper enamel mineralization, in which Stim1 plays a critical role during the maturation process.

Clonal structure in Ichthyobacterium seriolicida, the causative agent of bacterial haemolytic jaundice in yellowtail, Seriola quinqueradiata, inferred from molecular epidemiological analysis.

Bacterial haemolytic jaundice caused by Ichthyobacterium seriolicida has been responsible for mortality in farmed yellowtail, Seriola quinqueradiata, in western Japan since the 1980s. In this study, polymorphic analysis of I. seriolicida was performed using three molecular methods: amplified fragment length polymorphism (AFLP) analysis, multilocus sequence typing (MLST) and multiple-locus variable-number tandem repeat analysis (MLVA). Twenty-eight isolates were analysed using AFLP, while 31 isolates were examined by MLST and MLVA. No polymorphisms were identified by AFLP analysis using EcoRI and MseI, or by MLST of internal fragments of eight housekeeping genes. However, MLVA revealed variation in repeat numbers of three elements, allowing separation of the isolates into 16 sequence types. The unweighted pair group method using arithmetic averages cluster analysis of the MLVA data identified four major clusters, and all isolates belonged to clonal complexes. It is likely that I. seriolicida populations share a common ancestor, which may be a recently introduced strain.

Challenges following discharge from acute psychiatric inpatient care in Japan: patients' perspectives.

WHAT IS KNOWN ON THE SUBJECT?: A lack of transitional care covering the period from psychiatric hospital discharge to community mental health care can increase the likelihood of illness recurrence or readmission of discharged patients. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: The participants expressed the view that discontinuity between inpatient and community life was a post-discharge challenge after being involuntarily admitted to a psychiatric emergency ward. These challenges arose from the dissatisfaction with inpatient treatment, inability to coordinate post-discharge life WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Patients should be able to disclose their feelings about their own experiences in inpatient care settings and the current challenges in community care settings in an open manner. An advocate should be appointed in acute psychiatric inpatient care settings to reflect patients' own feelings and individual needs to transitional care without bias to inpatient and community care providers. ABSTRACT: Introduction Psychiatric care in Japan usually comprises inpatient care provided during lengthy hospital stays. Recently, policies for shortening psychiatric hospital stays have been aggressively pursued. However, appropriate transitional care is not always provided for acute psychiatric inpatient care. Aim We elucidated patients' challenges immediately after hospital discharge following acute psychiatric inpatient care to clarify how to improve inpatient care and post-discharge follow-ups. Method This study utilized a qualitative descriptive study design and incorporated patient interviews. Participants comprised 18 patients who experienced involuntary admission following a diagnosis of schizophrenia spectrum disorder. Inductive qualitative content analysis was used to create codes and categories from interview transcripts. Findings The core category of post-discharge challenges that emerged was 'separating life as an inpatient from community life'. This comprised two subcategories: 'dissatisfaction with the inpatient care received' and 'lack of abilities to coordinate lifestyle following discharge'. Discussion Patients should be able to disclose their feelings about their experiences in inpatient care settings and the current challenges in community care settings openly. Implications for practice Advocate (e.g. peer staff) should be appointed in acute psychiatric inpatient care settings to reflect patients' feelings and individual needs to transitional care without bias to inpatient and community care providers.

Correlation between temperature variations of static and dynamic properties in glass-forming liquids.

Detailed analysis of the static structure factor S(Q) in several glass-forming liquids reveals that the temperature variations of the width of the main diffraction peak ΔQ(T) correlate with the fragility of these liquids. This observation suggests a direct connection between rather subtle structural changes and sharp slowing down of structural relaxation in glass-forming liquids. We show that this observation can be rationalized using the Adam-Gibbs approach, through a connection between temperature variations of structural correlation length, l_{c}∼2π/ΔQ, and the size of cooperatively rearranging regions.

Hand-assisted laparoscopic transhiatal esophagectomy with a systematic procedure for en bloc infracarinal lymph node dissection.

Laparoscopic transhiatal esophagectomy is a minimally invasive approach for esophageal cancer. However, a transhiatal procedure has not yet been established for en bloc mediastinal dissection. The purpose of this study was to present our novel procedure, hand-assisted laparoscopic transhiatal esophagectomy, with a systematic procedure for en bloc mediastinal dissection. The perioperative outcomes of patients who underwent this procedure were retrospectively analyzed. Transhiatal subtotal mobilization of the thoracic esophagus with en bloc lymph node dissection distally from the carina was performed according to a standardized procedure using a hand-assisted laparoscopic technique, in which the operator used a long sealing device under appropriate expansion of the operative field by hand assistance and long retractors. The thoracoscopic procedure was performed for upper mediastinal dissection following esophageal resection and retrosternal stomach roll reconstruction, and was avoided based on the nodal status and operative risk. A total of 57 patients underwent surgery between January 2012 and June 2013, and the transthoracic procedure was performed on 34 of these patients. In groups with and without the transthoracic procedure, total operation times were 370 and 216 minutes, blood losses were 238 and 139 mL, and the numbers of retrieved nodes were 39 and 24, respectively. R0 resection rates were similar between the groups. The incidence of recurrent laryngeal nerve palsy was significantly higher in the group with the transthoracic procedure, whereas no significant differences were observed in that of pneumonia between these groups. The hand-assisted laparoscopic transhiatal method, which is characterized by a systematic procedure for en bloc mediastinal dissection supported by hand and long device use, was safe and feasible for minimally invasive esophagectomy.

Structural and Chemical Analysis of the Zirconia-Veneering Ceramic Interface.

The interfacial interaction of veneering ceramic with zirconia is still not fully understood. This study aimed to characterize morphologically and chemically the zirconia-veneering ceramic interface. Three zirconia-veneering conditions were investigated: 1) zirconia-veneering ceramic fired on sandblasted zirconia, 2) zirconia-veneering ceramic on as-sintered zirconia, and 3) alumina-veneering ceramic (lower coefficient of thermal expansion [CTE]) on as-sintered zirconia. Polished cross-sectioned ceramic-veneered zirconia specimens were examined using field emission gun scanning electron microscopy (Feg-SEM). In addition, argon-ion thinned zirconia-veneering ceramic interface cross sections were examined using scanning transmission electron microscopy (STEM)-energy dispersive X-ray spectrometry (EDS) at high resolution. Finally, the zirconia-veneering ceramic interface was quantitatively analyzed for tetragonal-to-monoclinic phase transformation and residual stress using micro-Raman spectroscopy (µRaman). Feg-SEM revealed tight interfaces for all 3 veneering conditions. High-resolution transmission electron microscopy (HRTEM) disclosed an approximately 1.0-µm transformed zone at sandblasted zirconia, in which distinct zirconia grains were no longer observable. Straight grain boundaries and angular grain corners were detected up to the interface of zirconia- and alumina-veneering ceramic with as-sintered zirconia. EDS mapping disclosed within the zirconia-veneering ceramic a few nanometers thick calcium/aluminum-rich layer, touching the as-sintered zirconia base, with an equally thick silicon-rich/aluminum-poor layer on top. µRaman revealed t-ZrO2-to-m-ZrO2 phase transformation and residual compressive stress at the sandblasted zirconia surface. The difference in CTE between zirconia- and the alumina-veneering ceramic resulted in residual tensile stress within the zirconia immediately adjacent to its interface with the veneering ceramic. The rather minor chemical elemental shifts recorded in the veneering ceramic did not suffice to draw definitive conclusions regarding potential chemical interaction of the veneering ceramic with zirconia. Sandblasting damaged the zirconia surface and induced phase transformation that also resulted in residual compressive stress. Difference in CTE of zirconia versus that of the veneering ceramic resulted in an unfavorable residual tensile stress at the zirconia-veneering ceramic interface.

Abnormal neutrophil scattergram obtained using Pentra MS CRP in the patients with myelodysplastic syndrome showing dysgranulopoiesis.

INTRODUCTION: Pentra MS CRP is an automated hematology analyzer capable of cytochemistry using Chlorazol black E, a lipid-staining agent, for white blood cell (WBC) differentials. Pentra MS CRP displays a WBC scattergram according to the cell volume obtained using flow impedance and light absorbance reflecting the Chlorazol black E (CBE)-positive lipid content. METHOD: Neutrophil scattergrams obtained using Pentra MS CRP were compared between 5 patients with myelodysplastic syndrome (MDS) and normal controls. Sudan black B (SBB)-staining patterns of peripheral blood neutrophils were subdivided into four types (types I, II, III, and VI) based on their staining intensity and scored by counting 200 cells. Such SBB scores were also compared between the two groups. RESULTS: Neutrophil scattergrams deviated downward in the MDS group, suggesting the decreased CBE positivity that seemed reflect the reduction of the lipid content in dysplastic neutrophils. SBB scores determined in this study were also decreased in the MDS group when compared with those in normal controls. CONCLUSION: Pentra MS CRP might rapidly generate useful information on dysplastic neutrophils in patients with MDS based on its cytochemistry for WBC differentials during routine laboratory hematology.

Reprogramming human B cells into induced pluripotent stem cells and its enhancement by C/EBPα.

B cells have been shown to be refractory to reprogramming and B-cell-derived induced pluripotent stem cells (iPSC) have only been generated from murine B cells engineered to carry doxycycline-inducible Oct4, Sox2, Klf4 and Myc (OSKM) cassette in every tissue and from EBV/SV40LT-immortalized lymphoblastoid cell lines. Here, we show for the first time that freshly isolated non-cultured human cord blood (CB)- and peripheral blood (PB)-derived CD19+CD20+ B cells can be reprogrammed to iPSCs carrying complete VDJH immunoglobulin (Ig) gene monoclonal rearrangements using non-integrative tetracistronic, but not monocistronic, OSKM-expressing Sendai Virus. Co-expression of C/EBPα with OSKM facilitates iPSC generation from both CB- and PB-derived B cells. We also demonstrate that myeloid cells are much easier to reprogram than B and T lymphocytes. Differentiation potential back into the cell type of their origin of B-cell-, T-cell-, myeloid- and fibroblast-iPSCs is not skewed, suggesting that their differentiation does not seem influenced by 'epigenetic memory'. Our data reflect the actual cell-autonomous reprogramming capacity of human primary B cells because biased reprogramming was avoided by using freshly isolated primary cells, not exposed to cytokine cocktails favoring proliferation, differentiation or survival. The ability to reprogram CB/PB-derived primary human B cells offers an unprecedented opportunity for studying developmental B lymphopoiesis and modeling B-cell malignancies.

A comparison of systemic inflammatory responses between immunocompetent and immunocompromised patients presenting with otorrhea due to chronic suppurative middle ear disease.

OBJECTIVES: To study the occurrence of fever and the behaviours of inflammatory blood markers (C-reactive protein - CRP and procalcitonin - PCT) during episodes of otorrhea due to uncomplicated chronic otitis media in immunocompetent and immunocompromised patients. DESIGN: Prospective study of patients presenting with otorrhea over a 36-month period. SETTING: All patients were treated at Bonsucesso General Hospital, a tertiary referral hospital in Rio de Janeiro, Brazil. PARTICIPANTS: A total of 84 participants, of which 50 were immunocompetent and 34 were immunocompromised. Immunocompetent patients had a total of 106 episodes of otorrhea, and immunocompromised patients had 117 episodes of otorrhea. MAIN OUTCOME MEASURES: Occurrence of fever (axillary temperature over 38(°) C) and elevation of C-reactive protein and procalcitonin levels above the normal ranges. RESULTS: In the immunocompetent group, the levels of procalcitonin were elevated in five of 106 episodes of otorrhea. The C-reactive protein levels were above the normal range in nine of 106 episodes, the same number of episodes in which fever was observed. In the immunocompromised group, procalcitonin was elevated in 38 of 117 episodes of otorrhea, C-reactive protein levels were abnormal in 40 episodes, and fever was detected in 37 episodes. Cases of otorrhea with systemic inflammatory response were significantly more common in immunocompromised patients with associated rhinosinusitis. CONCLUSIONS: Otorrhea due to uncomplicated chronic otitis media rarely causes a systemic inflammatory response in immunocompetent patients. Its occurrence in immunocompromised patients seems to be more related to concurrent rhinosinusitis than to the chronic middle ear inflammation itself.

Basic evaluation of Pentra MS CRP, a new automated hematology analyzer for rapid 5-part WBC differential and CRP using a small volume of whole blood.

INTRODUCTION: Pentra MS CRP is a new automated hematology analyzer that can rapidly and reliably provide 5-part differential of leukocytes (5-Diff) and C-reactive protein (CRP) within approximately 3.5 min using a small volume of whole blood (35 µL). METHODS: We evaluated the basic performance of Pentra MS CRP and correlations with Sysmex XN-3000, manual microscopic count, and Hitachi LABOSPECT. RESULTS: Pentra MS CRP demonstrated good repeatability and linearity without any significant carryover for all parameters examined (WBC, RBC, HGB, Hct, PLT, 5-Diff, and CRP). Complete blood cell count (CBC) data examined by Pentra MS CRP correlated well with those evaluated by Sysmex XN-3000 (R ≥ 0.9880). Absolute number of NEU, LYM, and EOS also showed the good correlation (R ≥ 0.9866) between the two analyzers. The correlation with the manual microscopic count was within acceptable criteria. Furthermore, when CRP was examined in hemolyzed whole blood by Pentra MS CRP and converted to plasma concentrations according to Hct, it correlated well (R = 0.9964) with serum CRP examined by Hitachi LABOSPECT. CONCLUSION: Pentra MS CRP is a convenient and reliable analyzer especially in the emergency unit of hospitals in which the prompt and simultaneous measurement of CBC including 5-Diff and CRP is often necessary.

Percutaneous endoscopic gastrostomy (PEG) tubes are placed in elderly adults in Japan with advanced dementia regardless of expectation of improvement in quality of life.

BACKGROUND: The Japan Geriatrics Society published a guideline on the decision-making process for health care for the elderly in June 2012, noting that withholding or withdrawing feeding tubes are treatment options that should be discussed during the decision-making process. Arguments against the guideline posit that the insertion of a percutaneous endoscopic gastrostomy (PEG) tube feeding may improve quality of life (QOL) for elderly adults and their relatives. OBJECTIVES: The aim of the present study was to explore (a) expected outcomes with PEG tube placement and (b) outcomes from PEG tube feeding in long-term care settings among elderly adults with advanced dementia in Japan. DESIGN: This study was conducted using a cross-sectional study design. SETTING: A total of 381 hospitals and 985 long-term care facilities provided sets of completed questionnaires. PARTICIPANTS: There were 1 199 hospital patients and 2 160 long-term care patients aged 65 years or older with PEG tube placement included in the analysis. MEASUREMENTS: The nurses or physicians at each hospital provided information on the level of dementia at the time of PEG tube placement and on the expected outcomes of PEG tube feeding for elderly hospital patients. The nurses or other direct care workers at each facility provided information on the level of dementia and outcomes from PEG tube feeding for the long-term care patients. RESULTS: In the hospital patient group, 62.9% of patients had advanced dementia. PEG tube feeding was expected to prolong survival for 51.1% of hospital patients with advanced dementia. Improved QOL was expected for 39.1% of them. In the long-term care patient group, 61.7% of patients had advanced dementia. The rate of patients enjoying their own lives was lower in long-term care patients who had advanced dementia (4.2%) than in the other patients (16.4%). Approximately 60% of relatives reported satisfaction with the QOL of the patients, both in the long-term care patients with advanced dementia and the other patients. CONCLUSION: Our results question the assumption that PEG tube feeding may improve QOL among elderly adults with advanced dementia. The national health policy should explore an approach to help patients, relatives, and practitioners make decisions about feeding options.

Perioperative outcomes of esophagectomy preceded by the laparoscopic transhiatal approach for esophageal cancer.

This study was designed to determine the efficacy of esophagectomy preceded by the laparoscopic transhiatal approach (LTHA) with regard to the perioperative outcomes of esophageal cancer. The esophageal hiatus was opened by hand-assisted laparoscopic surgery, and carbon dioxide was introduced into the mediastinum. Dissection of the distal esophagus was performed up to the level of the tracheal bifurcation. En bloc dissection of the posterior mediastinal lymph nodes was performed using LTHA. Next, cervical lymphadenectomy, reconstruction via a retrosternal route with a gastric tube and anastomosis from a cervical approach were performed. Finally, a small thoracotomy (around 10 cm in size) was made to extract the thoracic esophagus and allow upper mediastinal lymphadenectomy to be performed. The treatment outcomes of 27 esophageal cancer patients who underwent LTHA-preceding esophagectomy were compared with those of 33 patients who underwent the transthoracic approach preceding esophagectomy without LTHA (thoracotomy; around 20 cm in size). The intrathoracic operative time and operative bleeding were significantly decreased by LTHA. The total operative time did not differ between the two groups, suggesting that the abdominal procedure was longer in the LTHA group. The number of resected lymph nodes did not differ between the two groups. Postoperative respiratory complications occurred in 18.5% of patients treated with LTHA and 30.3% of those treated without it. The increase in the number of peripheral white blood cells and the duration of thoracic drainage were significantly decreased by this method. Our surgical procedure provides a good surgical view of the posterior mediastinum, markedly shortens the intrathoracic operative time, and decreases the operative bleeding without increasing major postoperative complications.