Cooling positronium to ultralow velocities with a chirped laser pulse train.

When laser radiation is skilfully applied, atoms and molecules can be cooled1-3, allowing the precise measurements and control of quantum systems. This is essential for the fundamental studies of physics as well as practical applications such as precision spectroscopy4-7, ultracold gases with quantum statistical properties8-10 and quantum computing. In laser cooling, atoms are slowed to otherwise unattainable velocities through repeated cycles of laser photon absorption and spontaneous emission in random directions. Simple systems can serve as rigorous testing grounds for fundamental physics-one such case is the purely leptonic positronium11,12, an exotic atom comprising an electron and its antiparticle, the positron. Laser cooling of positronium, however, has hitherto remained unrealized. Here we demonstrate the one-dimensional laser cooling of positronium. An innovative laser system emitting a train of broadband pulses with successively increasing central frequencies was used to overcome major challenges posed by the short positronium lifetime and the effects of Doppler broadening and recoil. One-dimensional chirp cooling was used to cool a portion of the dilute positronium gas to a velocity distribution of approximately 1 K in 100 ns. A major advancement in the field of low-temperature fundamental physics of antimatter, this study on a purely leptonic system complements work on antihydrogen13, a hadron-containing exotic atom. The successful application of laser cooling to positronium affords unique opportunities to rigorously test bound-state quantum electrodynamics and to potentially realize Bose-Einstein condensation14-18 in this matter-antimatter system.

Feasibility of transperineal minimal invasive surgery when performing sacrectomy for advanced primary and recurrent pelvic malignancies.

BACKGROUND: This study aimed to clarify the efficacy and safety of minimally invasive transabdominal surgery (MIS) with transperineal minimal invasive surgery (tpMIS) for sacrectomy in advanced primary and recurrent pelvic malignancies. METHODS: Using a prospectively collected database, we retrospectively analyzed the clinical, surgical, and pathological outcomes of MIS with tpMIS for sacrectomies. Surgery was performed between February 2019 and May 2023. The median follow-up period was 27 months (5-46 months). RESULTS: Fifteen consecutive patients were included in this analysis. The diagnoses were as follows: recurrent rectal cancer, n = 11 (73%); primary rectal cancer, n = 3 (20%); and recurrent ovarian cancer, n = 1 (7%). Seven patients (47%) underwent pelvic exenteration with sacrectomy, six patients (40%) underwent abdominoperineal resection (APR) with sacrectomy, and two patients (13%) underwent tumor resection with sacrectomy. The median intraoperative blood loss was 235 ml (range 45-1320 ml). The postoperative complications (Clavien-Dindo grade ≥ 3a) were graded as follows: 3a, n = 6 (40%); 3b, n = 1 (7%); and ≥ 4, n = 0 (0%). Pathological examinations demonstrated that R0 was achieved in 13 patients (87%). During the follow-up period, two patients (13%) developed local re-recurrence due to recurrent cancer. The remaining 13 patients (87%) had no local disease. Fourteen patients (93%) survived. CONCLUSIONS: Although the patient cohort in this study is heterogeneous, MIS with tpMIS was associated with a very small amount of blood loss, a low incidence of severe postoperative complications, and an acceptable R0 resection rate. Further studies are needed to clarify the long-term oncological feasibility.

Ex vivo intervertebral disc cultures: degeneration-induction methods and their implications for clinical translation.

Because low back pain is frequently a result of intervertebral disc degeneration (IVDD), strategies to regenerate or repair the IVD are currently being investigated. Often, ex vivo disc cultures of non-human IVD organs or tissue explants are used that usually do not exhibit natural IVDD. Therefore, degenerative changes mimicking those reported in human IVDD need to be induced. To support researchers in selecting ex vivo disc cultures, a systematic search was performed for them and their potential use for studying human IVDD reviewed. Five degeneration induction categories (proinflammatory cytokines, injury/damage, degenerative loading, enzyme, and other) were identified in 129 studies across 7 species. Methods to induce degeneration are diverse and can induce mild to severe degenerative changes that progress over time, as described for human IVDD. The induced degenerative changes are model-specific and there is no "one-fits-all" IVDD induction method. Nevertheless, specific aspects of human IVDD can be well mimicked. Currently, spontaneously degenerated disc cultures from large animals capture human IVDD in most aspects. Combinatorial approaches of several induction methods using discs derived from large animals are promising to recapitulate pathological changes on several levels, such as cellular behaviour, extracellular matrix composition, and biomechanical function, and therefore better mimic human IVDD. Future disc culture setups might increase in complexity, and mimic human IVDD even better. As ex vivo disc cultures have the potential to reduce and even replace animal trials, especially during preclinical development, advancement of such models is highly relevant for more efficient and cost-effective clinical translation from bench-to-bedside.

Feasibility of transanal minimally invasive surgery for total pelvic exenteration for advanced primary and recurrent pelvic malignancies.

BACKGROUND: The purpose of this study was to clarify the efficacy and safety of transanal minimally invasive surgery (TAMIS) for total pelvic exenteration (TPE) in advanced primary and recurrent pelvic malignancies. METHODS: Using a prospectively collected database, we retrospectively analyzed the clinical, surgical, and pathological outcomes of TAMIS for TPE. Surgery was performed between September 2019 and April 2023. The median follow-up period was 22 months (2-45 months). RESULTS: Fifteen consecutive patients were included in this analysis M:F = 14:1 and median (range) age was 63 (36-74). Their diagnoses were as follows: primary rectal cancer (n = 5; 33%), recurrent rectal cancer (n = 4; 27%), primary anorectal cancer (n = 5; 33%), and gastrointestinal stromal tumor (n = 1; 7%). Bladder-sparing TPE was selected for two patients (13%). In nine of 15 patients (60%) the anal sphincter could be successfully preserved, five patients (33%) required combined resection of the internal iliac vessels, and two (13%) required rectus muscle flap reconstruction. The median operative time was 723 min (561-1082), and the median intraoperative blood loss was 195 ml (30-1520). The Clavien-Dindo classifications of the postoperative complications were as follows: grade 0-2 (n = 11; 73%); 3a (n = 3; 20%); 3b (n = 1; 7%); and ≥ 4 (n = 0; 0%). No cases of conversion to laparotomy or mortality were observed. The pathological results demonstrated that R0 was achieved in 14 patients (93%). CONCLUSIONS: The short-term outcomes of this initial experience proved that this novel approach is feasible for TPE, with low blood loss, acceptable postoperative complications, and a satisfactory R0 resection rate.

Difamilast, a selective phosphodiesterase 4 inhibitor, ointment in paediatric patients with atopic dermatitis: a phase III randomized double-blind, vehicle-controlled trial.

BACKGROUND: In atopic dermatitis (AD), phosphodiesterase 4 (PDE4) inhibition reduces proinflammatory mediators and cytokines. Difamilast is a new selective PDE4 inhibitor. OBJECTIVES: To demonstrate the superiority of topical difamilast to vehicle in Japanese paediatric patients with AD. METHODS: This was a phase III randomized, double-blind, vehicle-controlled trial. Patients aged 2-14 years with an Investigator Global Assessment (IGA) score of 2 or 3 received difamilast 0·3% (n = 83), difamilast 1% (n = 85) or vehicle (n = 83) ointment twice daily for 4 weeks. RESULTS: The primary endpoint was the percentage of patients with an IGA score of 0 or 1 with improvement by at least two grades at week 4. The success rates in IGA score at week 4 were 44·6%, 47·1% and 18·1% in the difamilast 0·3%, difamilast 1% and vehicle groups, respectively. Both difamilast groups demonstrated significantly higher success rates in IGA score compared with vehicle at week 4 [difamilast 0·3% (P < 0·001); difamilast 1% (P < 0·001)]. Regarding secondary endpoints, improvements in Eczema Area and Severity Index (EASI; improvement of ≥ 50%, ≥ 75% and ≥ 90% in overall score) at week 4 were significantly higher in patients in the difamilast 0·3% and 1% groups than those in the vehicle group. EASI score in the difamilast 0·3% and 1% groups was significantly reduced compared with that of patients in the vehicle group at week 1. The significant difference between both the difamilast groups and the vehicle groups was maintained from week 1 through to week 4. Most treatment-emergent adverse events were mild or moderate, and no serious events or deaths were reported. CONCLUSIONS: Difamilast 0·3% and 1% ointments are superior to vehicle and well tolerated in Japanese paediatric patients with AD.

Influence of using history of immune checkpoint inhibitor therapy for neutropenia caused by combination therapy of ramucirumab and docetaxel.

Recently, pretreatment with immune checkpoint inhibitors (ICIs) has been shown to enhance the therapeutic effects of the combination therapy of ramucirumab (RAM) and docetaxel (DTX); however, its influence on the drug's side effects remains unclear. This study investigated the influence of pretreatment with ICIs on the incidence of neutropenia caused by RAM + DTX therapy in patients with non-small cell lung cancer (NSCLC). Patients with NSCLC who received RAM + DTX therapy at Gifu Prefectural General Medical Center between April 2016 and December 2020 were enrolled. Retrospective data regarding age, sex, performance status and detailed treatment history, among others, at treatment initiation were collected from the patients' electronic medical records. Additionally, data on the course number of RAM + DTX therapy, supportive therapy and blood biochemical parameters, including leukocyte and neutrocyte counts, during the treatment period were collected. We identified 41 patients receiving RAM + DTX therapy. Among the more than grade 3 adverse events caused by this therapy, neutropenia was the most common (78.1%). Despite the fact that all previous risk factors influencing this incidence rate had corresponded, the only factor influencing the incidence rate of neutropenia more than grade 3 was ICI treatment history. A difference in the incidence of neutropenia more than grade 3 in the Kaplan-Meier curve was observed between patients with and without ICI pretreatment history (p = 0.037). The pretreatment history of ICI therapy affects the incidence of neutropenia caused by RAM + DTX therapy in patients with NSCLC.

Proteoglycan 4 reduces friction more than other synovial fluid components for both cartilage-cartilage and cartilage-metal articulation.

OBJECTIVE: The clinical success of focal metallic resurfacing implants depends largely on the friction between implant and opposing cartilage. Therefore, the present study determines the lubricating ability of the synovial fluid components hyaluronic acid (HA), proteoglycan 4 (PRG4) and a surface-active phospholipid (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, POPC), on the articulation between cartilage and a Cobalt Chromium Molybdenum (CoCrMo) implant surface, compared with two cartilage surfaces. METHODS: A ring-on-disk geometry was used to perform repeated friction measurements at physiologically relevant velocities (6 and 60 mm/s) using lubricants with an increasing number of components present. Shear measurements were performed in order to evaluate the viscosity. To ensure that it is clinically relevant to explore the effect of these components, the presence of PRG4 in synovial fluid obtained from primary and revision knee and hip implant surgeries was examined. RESULTS: PRG4 in the presence of HA was found to significantly reduce the coefficient of friction for both cartilage-cartilage and cartilage-CoCrMo interface. This is relevant, as it was also demonstrated that PRG4 is still present at the time of revision surgeries. The addition of POPC had no effect for either configurations. HA increased the viscosity of the lubricating fluid by one order of magnitude, while PRG4 and POPC had no effect. CONCLUSION: The present study demonstrates the importance of selecting the appropriate lubrication solution to evaluate implant materials with biotribology tests. Because PRG4 is a key component for reducing friction between cartilage and an opposing surface, developing coatings which bind PRG4 is recommended for cartilage resurfacing implants.

Spectroscopic photoacoustic imaging of cartilage damage.

OBJECTIVE: Osteoarthritis (OA) is a chronic joint disease characterized by progressive degradation of cartilage. It affects more than 10% of the people aged over 60 years-old worldwide with a rising prevalence due to the increasingly aging population. OA is a major source of pain, disability, and socioeconomic cost. Currently, the lack of effective diagnosis and affordable imaging options for early detection and monitoring of OA presents the clinic with many challenges. Spectroscopic Photoacoustic (sPA) imaging has the potential to reveal changes in cartilage composition with different degrees of damage, based on optical absorption contrast. DESIGN: In this study, the capabilities of sPA imaging and its potential to characterize cartilage damage were explored. To this end, 15 pieces of cartilage samples from patients undergoing a total joint replacement were collected and were imaged ex vivo with sPA imaging at a wide optical spectral range (between 500 nm and 1,300 nm) to investigate the photoacoustic properties of cartilage tissue. All the PA spectra of the cartilage samples were analyzed and compared to the corresponding histological results. RESULTS: The collagen related PA spectral changes were clearly visible in our imaging data and were related to different degrees of cartilage damage. The results are in good agreement with histology and the current gold standard, i.e., the Mankin score. CONCLUSIONS: This study demonstrates the potential and possible clinical application of sPA imaging in OA.

Observation of Coulomb-Assisted Nuclear Bound State of Ξ

In an emulsion-counter hybrid experiment performed at J-PARC, a Ξ^{-} absorption event was observed which decayed into twin single-Λ hypernuclei. Kinematic calculations enabled a unique identification of the reaction process as Ξ^{-}+^{14}N→_{Λ}^{10}Be+_{Λ}^{5}He. For the binding energy of the Ξ^{-} hyperon in the Ξ^{-}-^{14}N system a value of 1.27±0.21 MeV was deduced. The energy level of Ξ^{-} is likely a nuclear 1p state which indicates a weak ΞN-ΛΛ coupling.

Ex vivo Bone Models and Their Potential in Preclinical Evaluation.

PURPOSE OF REVIEW: Novel therapies for damaged and diseased bone are being developed in a preclinical testing process consisting of in vitro cell experiments followed by in vivo animal studies. The in vitro results are often not representative of the results observed in vivo. This could be caused by the complexity of the natural bone environment that is missing in vitro. Ex vivo bone explant cultures provide a model in which cells are preserved in their native three-dimensional environment. Herein, it is aimed to review the current status of bone explant culture models in relation to their potential in complementing the preclinical evaluation process with specific attention paid to the incorporation of mechanical loading within ex vivo culture systems. RECENT FINDINGS: Bone explant cultures are often performed with physiologically less relevant bone, immature bone, and explants derived from rodents, which complicates translatability into clinical practice. Mature bone explants encounter difficulties with maintaining viability, especially in static culture. The integration of mechanical stimuli was able to extend the lifespan of explants and to induce new bone formation. Bone explant cultures provide unique platforms for bone research and mechanical loading was demonstrated to be an important component in achieving osteogenesis ex vivo. However, more research is needed to establish a representative, reliable, and reproducible bone explant culture system that includes both components of bone remodeling, i.e., formation and resorption, in order to bridge the gap between in vitro and in vivo research in preclinical testing.

Measuring mineralised tissue formation and resorption in a human 3D osteoblast-osteoclast co-culture model.

In vitro tissue engineered bone constructs have been developed, but models which mimic both formation and resorption in parallel are still lacking. To be used as a model for the bone remodeling process, the formation and resorption of mineralised tissue volume over time needs to be visualised, localised and quantified. The goal of this study was to develop a human 3D osteoblast-osteoclast co-culture in which 1) osteoblasts deposit mineralised matrix, 2) monocytes differentiate into resorbing osteoclasts, and 3) the formation and resorption of mineralised matrix could be quantified over time using micro-computed tomography (µCT). Mesenchymal stromal cells were seeded on silk fibroin scaffolds and differentiated towards osteoblasts to create mineralised constructs. Thereafter, monocytes were added and differentiated towards osteoclasts. The presence of osteoblasts and osteoclasts was confirmed using immunohistochemistry. Osteoclastic activity was confirmed by measuring the increased release of osteoclast marker tartrate resistant acid phosphatase (TRAP), suggesting that osteoclasts were actively resorbing mineralised tissue. Resorption pits were visualised using scanning electron microscopy. Mineralised matrix formation and resorption were quantified using µCT and subsequent scans were registered to visualise remodelling. Both formation and resorption occurred in parallel in the co-culture. The resorbed tissue volume exceeded the formed tissue volume after day 12. In conclusion, the current model was able to visualise, localise and quantify mineralised matrix formation and resorption. Such a model could be used to facilitate fundamental research on bone remodeling, facilitate drug testing and may have clinical implications in personalised medicine by allowing the use of patient cells.

Wire-loop lesion is associated with serological immune abnormality, but not renal prognosis, in lupus nephritis.

BACKGROUND: Wire-loop lesion (WL) is one of the active lesions of lupus nephritis (LN). However, few reports have focused on the clinicopathological relationships of WL to serological immune abnormality and renal prognosis. METHODS: We enrolled 126 Japanese LN patients subjected to renal biopsy in 11 hospitals from 2000 to 2018. In patients with class III or IV of the International Society of Nephrology/Renal Pathology Society classification, we retrospectively compared clinicopathological findings between those with WL (WL+ group) and without WL (WL- group) to detect factors associated with WL. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate of <60 mL/min/1.73m2 for more than three months. We also compared these findings between those with CKD (CKD+ group) and without CKD (CKD- group) at the last visit to investigate factors associated with renal prognosis. RESULTS: Of 126 patients, 100 (79.4%) were classified as class III or IV. WL was found in 36 (36.0%) of them. Although the renal function did not differ, the WL+ group had a higher titre of serum anti-dsDNA antibodies and lower serum complement 3 levels than the WL- group. Linear regression analysis revealed a significant association only between anti-dsDNA antibodies and WL (ß = 0.27, 95% confidence interval (CI) 0.001-0.100, p = 0.01). Of these patients, 69 were tracked for 59.6 ± 55.1 months. Kaplan-Meier analysis showed no difference in renal prognosis between these groups. Next, the CKD+ group included 15 (22.1%) patients. They were older and had higher frequencies of hypertension and hyperuricaemia, serum creatinine (Cr) level, glomerulosclerosis, interstitial inflammation, interstitial fibrosis and tubular atrophy than the CKD- group at the time of renal biopsy. The frequency of WL was not significantly different. Cox regression analysis revealed significant associations of CKD with hypertension, hyperuricaemia, serum Cr level at the time of renal biopsy clinically and with tubular atrophy histologically. CONCLUSIONS: WL was associated with serum anti-dsDNA antibodies but not with renal prognosis, suggesting that WL reflects immune abnormality but is not an independent factor predictive of renal prognosis in LN.

Uncompromised MRI of knee cartilage while incorporating sensitive sodium MRI.

Sodium imaging is able to assess changes in ion content, linked to glycosaminoglycan content, which is important to guide orthopeadic procedures such as articular cartilage repair. Sodium imaging is ideally performed using double tuned RF coils, to combine high resolution morphological imaging with biochemical information from sodium imaging to assess ion content. The proton image quality of such coils is often harshly degraded, with up to 50% of SNR or severe acceleration loss as compared to single tuned coils. Reasons are that the number of proton receive channels often severely reduced and double tuning will degrade the intrinsic sensitivity of the RF coil on at least one of the nuclei. However, the aim of this work was to implement a double-tuned sodium/proton knee coil setup without deterioration of the proton signal whilst being able to achieve acquisition of high SNR sodium images. A double-tuned knee coil was constructed as a shielded birdcage optimized for sodium and compromised for proton. To exclude any compromise, the proton part of the birdcage is used for transmit only and interfaced to RF amplifiers that can fully mitigate the reduced efficiency. In addition, a 15 channel single tuned proton receiver coil was embedded within the double-resonant birdcage to maintain optimal SNR and acceleration for proton imaging. To validate the efficiency of our coil, the designed coil was compared with the state-of-the-art single-tuned alternative at 7 T. B1+ corrected SNR maps were used to compare both coils on proton performance and g-factor maps were used to compare both coils on acceleration possibilities. The newly constructed double-tuned coil was shown to have comparable proton quality and acceleration possibilities to the single-tuned alternative while also being able to acquire high SNR sodium images.

Validation of distal radius failure load predictions by homogenized- and micro-finite element analyses based on second-generation high-resolution peripheral quantitative CT images.

This study developed a well-standardized and reproducible approach for micro-finite element (mFE) and homogenized-FE (hFE) analyses that can accurately predict the distal radius failure load using either mFE or hFE models when using the approaches and parameters developed in this study. INTRODUCTION: Micro-FE analyses based on high-resolution peripheral quantitative CT (HR-pQCT) images are frequently used to predict distal radius failure load. With the introduction of a second-generation HR-pQCT device, however, the default modelling approach no longer provides accurate results. The aim of this study was to develop a well-standardized and reproducible approach for mFE and hFE analyses that can provide precise and accurate results for distal radius failure load predictions based on second-generation HR-pQCT images. METHODS: Second-generation HR-pQCT was used to scan the distal 20-mm section of 22 cadaver radii. The sections were excised and mechanically tested afterwards. For these sections, mFE and hFE models were made that were used to identify required material parameters by comparing predicted and measured results. Using these parameters, the models were cropped to represent the 10-mm region recommended for clinical studies to test their performance for failure load prediction. RESULTS: After identification of material parameters, the measured failure load of the 20-mm segments was in good agreement with the results of mFE models (R2 = 0.969, slope = 1.035) and hFE models (R2 = 0.966, slope = 0.890). When the models were restricted to the clinical region, mFE still accurately predicted the measured failure load (R2 = 0.955, slope = 1.021), while hFE predictions were precise but tended to overpredict the failure load (R2 = 0.952, slope = 0.780). CONCLUSIONS: It was concluded that it is possible to accurately predict the distal radius failure load using either mFE or hFE models when using the approaches and parameters developed in this study.

Double-core ionization photoelectron spectroscopy of C6H6: Breakdown of the "intuitive" ortho-meta-para binding energy ordering of K-1K-1 states.

Single-site Double-Core Hole (ss-DCH or K-2) and two-site Double-Core Hole (ts-DCH or K-1K-1) photoelectron spectra including satellite lines were experimentally recorded for the aromatic C6H6 molecule using the synchrotron radiation and multielectron coincidence technique. Density functional theory and post-Hartree-Fock simulations providing binding energies and relative intensities allow us to clearly assign the main K-2 line and its satellites. K-1K-1 states' positions and assignments are further identified using a core-equivalent model. We predict that, contrary to what has been observed in the C2H2n series of molecules, the K-1K-1 energy-level ordering in C6H6 does not reflect the core-hole distances between the two holes.

Tailored Raman-resonant four-wave-mixing processes.

Nonlinear optical processes are strongly dominated by phase relationships among electromagnetic fields involved. In this paper, we theoretically and experimentally show that in a Raman-resonant four-wave-mixing process, the first anti-Stokes and Stokes generations can be tailored in a variety of ways by manipulating the phase relationships among the relevant electromagnetic fields.

Localisation of mineralised tissue in a complex spinner flask environment correlates with predicted wall shear stress level localisation.

Spinner flask bioreactors have often been employed for bone tissue engineering. However, the reasons for their success in facilitating bone growth remain inconclusive. It was hypothesised that engineered bone tissue formation can be attributed to mechanical stimuli, which can be predicted in the tissue engineered construct. To test the hypothesis and draw conclusions as to how mechanical stimulation affects cell behaviour, a multi- disciplinary approach using cell culture experiments and computational fluid dynamics (CFD) to simulate the complex flow within the spinner flask and scaffold was employed. Micro-computed tomography and histology showed that statically cultured human bone marrow derived stromal cells on silk fibroin scaffolds did not form extracellular matrix (ECM) or deposit minerals. However, constructs cultured at 60 rpm resulted in ECM formation and mineralisation, mainly at the bottom of the scaffold (bottom: 78 ± 7 %, middle: 17 ± 5 %, top: 5 ± 2 % of total mineralised volume). Culturing at 300 rpm led to a more homogeneously distributed ECM (bottom: 40 ± 14 %, middle: 33 ± 1 %, top: 27 ± 14 % of total mineralised volume). These observations were in agreement (Pearson correlation coefficient: 97 %) with the computational simulations that predicted maximal scaffold mineralisation, based on wall shear stress stimulation, in the bottom at 60 rpm and in the main body at 300 rpm. Such combinations of CFD modelling and experimentation could advance our knowledge of the mechanical stimuli that cells experience in vitro and link them to biological responses.

Residual carcinoma cells after chemoradiotherapy for esophageal squamous cell carcinoma patients: striving toward appropriate judgment of biopsy.

In esophageal squamous cell carcinoma (ESCC) patients who are treated with chemoradiotherapy (CRT), identification of the presence or absence of residual or recurrent carcinoma is usually pivotal in their clinical management. In addition, the extent of carcinoma invasion into the esophageal wall could determine the clinical outcome of these patients following CRT. Therefore, in this study, we evaluated the response to CRT both macroscopically and histologically in a consecutive series of 42 ESCC patients receiving neoadjuvant chemoradiotherapy following curative esophageal resection at Tohoku University Hospital between August 2011 and December 2012. The histological grading of tumor regression was as follows: grade 3, markedly effective (no viable residual tumor cells); grade 2, moderately effective (residual tumor cells in less than one-third of the tumor); grade 1, slightly effective (1b, residual tumor cells in one-third to two-thirds of the tumor; 1a, residual tumor cells in more than two-thirds of the tumor); and grade 0, ineffective. In this study, we selected grade 2 and 1b cases because they might show a complete response with definitive CRT. We evaluated the presence of any residual in situ lesions and tumor depth in detail. The grading of tumor regression in primary sites was as follows: grade 3 (7 cases), grade 2 (16 cases), grade 1b (13 cases), and grade 1a (6 cases). The concordance rate between macroscopic and histopathological evaluation on the depth of the tumor was 40% (17/42). Among 29 cases (grade 2 and grade 1b), intraepithelial lesions were not detected in 17 cases, and tumor nests were not detected in the lamina propria mucosae in 9 cases. The results of this study highlight the difficulties of detecting residual carcinoma cells using conventional endoscopic biopsy in patients who have received CRT. Therefore, when residual cancer is clinically suspected in patients who have received CRT, the biopsy specimen should be obtained from the deep layer of the esophagus whenever possible. Additionally, close follow-up is required using positron emission tomography/computed tomography, endoscopy, and other radiological evaluations.