A case of hyperammonemia occurring during treatment of metastatic renal cell carcinoma with axitinib.

Introduction: Although the incidence of hyperammonemia as an adverse event of tyrosine kinase inhibitors is quite low, several cases of tyrosine kinase inhibitor associated hyperammonemia have been reported. We report a case of hyperammonemia, that occurred during combined treatment with axitinib and pembrolizumab in a metastatic renal cell carcinoma patient without hepatic disorder or liver metastases. Case presentation: A 77-year-old Japanese woman was diagnosed with metastatic renal cell carcinoma and was treated with pembrolizumab and axitinib. Both agents were subsequently discontinued due to hyperammonemia with hypothyroidism. After recovery, the patient resumed single-agent therapy with axitinib. However, hyperammonemia and hypothyroidism occurred again, suggesting axitinib-inducible adverse event. After nephrectomy, a lower dose of axitinib was restarted and continued safely for residual metastases under prophylactic treatment with aminoleban, lactulose, and levothyroxine. Conclusion: The rare occurrence of hyperammonemia should be considered during treatment with VEGFR- targeted tyrosine kinase inhibitor including axitinib, and supportive prophylactic medication may be useful.

Possible role of combined therapy targeting MET and pro-HGF activation for renal cell carcinoma: analysis by human HGF-producing SCID mice.

MET is a high-affinity receptor tyrosine kinase of HGF (hepatocyte growth factor). HGF is secreted as an inactive single-chain precursor (pro-HGF), which requires proteolytic activation for conversion to an active form. HGF activator inhibitor (HAI)-2 is a transmembrane Kunitz-type serine protease inhibitor, which inhibits all pro-HGF-activating enzymes. In RCC, increased expression of MET and decreased expression of HAI-2 were reported to be poor prognostic factors. In the current study, we tried to inhibit the growth of RCC cells by dual inhibition of both MET phosphorylation and pro-HGF-activation using MET inhibitor and HAI-2 overexpression. A transgenic mouse model which expressed human HGF (HGF mouse) was used for in vivo analysis to evaluate the HGF/MET signaling axis accurately. Initially, doxycycline-induced HAI-2 overexpression RCC cells (786-O-HAI2) were prepared. The cells were cultured with pro-HGF, and inhibitory effect of MET inhibitor (SCC244) and HAI-2 was evaluated by phosphorylation of MET and cell proliferation. Next, the cells were subcutaneously implanted to HGF mice and the growth inhibition was determined by SCC244 and HAI-2. Single use of each inhibitor showed significant inhibition in MET phosphorylation, migration and proliferation of 786-O-HAI2 cells; however, the strongest effect was observed by combined use of both inhibitors. Although in vivo analysis also showed apparent downregulation of MET phosphorylation and growth inhibition in combined treatment, statistical significance was not observed compared with single use of MET inhibitor. Combined treatment with MET-TKI and HAI-2 suggested to consider as a candidate for new strong therapy for RCC.

Clinicopathological findings, prognosis, and Epstein-Barr virus infection in rheumatoid arthritis patients with other iatrogenic immunodeficiency-associated T- and NK-cell lymphoproliferative disorders.

BACKGROUND: Other iatrogenic immunodeficiency-associated (OIIA) T- and natural killer (NK)-cell lymphoproliferative disorders (TNK-LPDs) are rare in patients with rheumatoid arthritis (RA). METHODS: We investigated the clinicopathological characteristics, Epstein-Barr virus (EBV) infection, genetic findings, therapeutic response, and prognostic factors in 21 RA patients with OIIA TNK-LPDs and compared these with those of 39 with OIIA B-cell LPDs (B-LPDs) and 22 with non-OIIA B-LPDs. RESULTS: Immunohistologically, 11 patients (52%) showed CD4+ T-LPDs, and 7 had a T follicular helper (TFH) phenotype. The other nine patients (43%) showed CD8+ T-LPDs, and the remaining one (5%) had features of CD3+ CD4- CD8- nasal type TNK-cell lymphoma. CD30+, p53+, and CMYC+ atypical lymphocytes were identified in seven (33%), eight (38%), and five (24%) patients, respectively. In situ hybridisation detected EBV-encoded RNA (EBER) + large atypical lymphocytes in five patients (24%). Nine of 17 patients (53%) showed clonal peaks of TCRγ by polymerase chain reaction. Withdrawal of MTX and biologic drugs was effective in 12 patients (57%), and 8 (38%) received chemotherapies. Two patients with TFH+ or EBV+ CD4+ CD30+ large cell peripheral T-cell lymphoma, one with CD8+ systemic anaplastic large cell lymphoma, and two with systemic EBV+ CD8+ T-cell lymphoma of childhood showed a lethal progressive clinical course within 13 months. Moreover, > 500 U/L LDH, large atypical lymphocytes, expression of CD30, p53, and CMYC, and EBER+ atypical lymphocytes were significantly poor prognostic factors for overall survival (p < 0.05). Median interval from RA onset to OIIA TNK-LPDs was 72 months, which was shorter than 166 months in OIIA B-LPDs (p = 0.003). EBV+ atypical and reactive lymphocytes were frequently found in 15 patients with OIIA TNK-LPDs (71%), in 27 with OIIA B-LPDs (69%), and only in 3 with non-OIIA B-LPDs (14%). CONCLUSIONS: OIIA TNK-LPDs occurred in early phase of RA, compared with OIIA B-LPDs, and occasionally showed a lethal progressive clinical course. Detection of OIIA TNK-LPD patients with poor prognostic factors is necessary. EBV infection in immunosuppressed patients due to persistent RA, MTX, and biologic drugs may play a role in forming the tumour microenvironment and lymphomagenesis of TNK-LPDs.

A Rare Case of Tracheal Crystal-Storing Histiocytosis Associated with Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue.

Crystal-storing histiocytosis (CSH) is a rare non-neoplastic histiocytic lesion with abnormal accumulation of immunoglobulin (Ig) light chain. CSH is associated with Ig overproduction by B-lymphoproliferative disorders (B-LPDs) or by persistent inflammatory diseases. Eighteen cases of pulmonary CSH have been reported. However, no case reports of tracheal CSH have been published. In this patient, we found a solitary tracheal tumor in an asymptomatic 60-year-old man on chest computed tomography scan. Histologically, the tumor comprised two different lesions. One lesion showed diffuse proliferation of spindle-shaped histiocytes with abundant eosinophilic granular cytoplasm. With immunohistochemistry, the histiocytic cells were positive for CD68, CD163 and Ig kappa light chain, and the cytoplasm was weakly positive for anaplastic lymphoma kinase (ALK) protein. Fluorescence in situ hybridization indicated no split signals for the ALK gene. Electron microscopy demonstrated many elongated or rhomboid-shaped dense crystals in the cytoplasm of histiocytes. The second lesion showed proliferation of CD20-positive small atypical lymphocytes mixed with Ig kappa chain-positive plasma cells. A diagnosis of CSH and concomitant mucosa-associated lymphoid tissue lymphoma was made. In this patient, unexpected ALK protein was detected in infiltrating histiocytes. Therefore, careful assessment of the ALK protein and gene was necessary to differentiate from other histiocytic disorders.

Programmed cell death-ligand 1 (PD-L1)+ tumour cells and low-reacting programmed cell death 1 (PD1)+ tumour-infiltrating lymphocytes predict poor prognosis in Epstein-Barr virus+ diffuse large B-cell lymphoma.

Epstein-Barr virus (EBV)+ diffuse large B-cell lymphoma (DLBCL) has specific tumour cell characteristics, and these patients have worse outcomes than EBV-negative DLBCL patients. We compared 38 EBV+ DLBCL patients with 43 methotrexate-associated EBV+ B-cell lymphoproliferative disorders (MTX+/EBV+ BLPDs) and 30 non-germinal centre (GC) subtype DLBCL. Lymphoma cells of the EBV+ DLBCL group were positive for BCL2 in 17 patients (44.7%), CMYC in 23 patients (60.5%), and p53 in 33 patients (86.8%), which was significantly higher than in the MTX+/EBV+ BLPD group (P < 0.05), and were positive for CD30 in 29 patients (76.3%), compared with two in non-GC subtype DLBCL (6.7%) (P < 0.0001). Significantly more EBV+ DLBCL patients (n = 16, 42.1%) had programmed cell death-ligand 1 (PD-L1)+ tumour cells than patients with non-GC subtype DLBCL (n = 5, 16.7%; P = 0.024), and PD-L1+ tumour cells were more common in advanced stages than in early stages (P = 0.048). Twenty-five EBV+ DLBCL patients (69.4%) had few reactive PD1+ tumour-infiltrating lymphocytes (TILs), compared with 12 patients with MTX+/EBV+ BLPDs (37.5%) (P = 0.008). In the EBV+ DLBCL group, CD30, BCL2, CMYC, and p53 expression was not related to patient prognosis. Poor outcomes were associated with PD-L1+ tumour cells (P = 0.001) and low-reacting PD1+ TILs (P = 0.02), while their combination conferred a worse outcome (P < 0.0001). Immune evasion by PD-L1+ tumour cells and exhaustion of PD1+ TILs may occur in EBV+ DLBCL patients, and PD-L1/PD1 interactions may influence tumour progression and poor prognosis.

Large cell morphology, CMYC+ tumour cells, and PD-1+ tumour cell/intense PD-L1+ cell reactions are important prognostic factors in nodal peripheral T-cell lymphomas with T follicular helper markers.

BACKGROUND: The clinicopathological characteristics and prognostic factors in nodal peripheral T-cell lymphomas (PTCLs) with two or more T follicular helper markers (TFH+) are not adequately investigated. METHODS: Immunohistologically, we selected 22 patients with TFH+ lymphoma (PTCL-TFH) in 47 of PTCL-not otherwise specified (NOS), and subclassified into large and small cell groups. We compared the two groups with 39 angioimmunoblastic T-cell lymphoma (AITL) and seven follicular T-cell lymphoma (F-TCL) patients. Prognostic factors were analysed by overall survival in patients with three types of TFH+ PTCLs. RESULTS: Thirteen large cell and nine small cell PTCL-TFH patients had more than two TFH markers including programmed cell death-1 (PD-1). Large cell PTCL-TFH showed frequent CMYC expression in 10 patients (77%), and four of 11 large cell group (36%) had somatic RHOA G17V gene mutation by Sanger sequencing. Large cell PTCL-TFH patients showed significantly worse prognosis than those of the small cell group, AITL, and F-TCL (p < 0.05). In TFH+ PTCLs, CMYC+ tumour cells, and combined PD-1 ligand 1 (PD-L1) + tumour cells and intense reaction of PD-L1+ non-neoplastic cells (high PD-L1+ cell group) were significantly poor prognostic factors (p < 0.05). Combinations of CMYC+ or PD-1+ tumour cells and high PD-L1+ cell group indicated significantly poor prognosis (p < 0.01). CONCLUSION: Large cell PTCL-TFH indicated poor prognosis in TFH+ PTCLs. These data suggested that CMYC+ tumour cells and intense PD-L1+ cell reaction influenced tumour cell progression in TFH+ PTCLs, and PD-1+ tumour cell/intense PD-L1+ cell reactions may play a role in immune evasion.

[A Cohort Study on the Prognosis of Patients with Urothelial Carcinoma Using the Miyazaki Urological Cancer Database (MUCD)].

Miyazaki Urological Cancer Database (MUCD) is a web-based database containing background, treatment, and prognosis of patients with prostate, renal, and urothelial cancers diagnosed in Miyazaki. We entered information on patients diagnosed with urothelial carcinoma from 2014 to 2018 at 4 of the 17 facilities that diagnose urothelial carcinoma in Miyazaki Prefecture. We analyzed the overall survival for bladder cancer and upper urinary tract cancer, and examined its correlation with the presence of symptoms, urine cytology, and clinical TNM classification. There were 487 patients with urothelial carcinoma, comprising 372 (76%) with bladder cancer and 115 (24%) with upper tract urinary cancer. In the bladder cancer group, 301 (81%) patients had symptomatic disease and 119 (32%) had positive urine cytology. The stage according to the TNM classification was Ta-1N0, T2-4N0, N1-2M0 and M1 in 248 (67%), 94 (26%), 19 (5%) and 11 (3%) patients, respectively. In the upper urinary tract cancers group, 89 (76%) had symptomatic disease and 41 (36%) had positive urine cytology. The stage according to the TNM classification was Ta-1N0, T2-4N0, N1-2M0 and M1 in 45 (39%), 37 (32%), 11 (10%) and 22 (19%) patients, respectively. The 3-year survival rates for bladder and upper urinary tract cancer were 83.4% and 67.8%, respectively. TNM classification (≤T1 vs ≥T2≥) was significantly associated with overall survival (bladder cancer : HR＝7.07, 95% CI＝3.13-16.0, p＜0.0001 ; upper tract urinary cancer : HR＝6.33, 95% CI＝2.13-18.8, p＝0.0009). The prognosis of patients with urothelial carcinoma diagnosed in multiple institutions could be evaluated using MUCD. The clinical T stage was significantly associated with overall survival in patients with bladder cancer and patients with upper urinary tract cancer.

Clinicopathological findings of systemic Epstein-Barr virus-positive T-lymphoproliferative diseases in younger and older adults.

BACKGROUND: Systemic Epstein-Barr virus+ T-cell lymphoma (sEBV+ TCL) occurs in childhood and young adults, and is exceptionally rare in older adults. METHODS: We investigated clinicopathological features in 16 patients of various ages with systemic EBV+ CD8+ T-lymphoproliferative diseases. RESULTS: Eight younger patients and four of eight older adults had sEBV+ CD8+ TCL, with invasion by medium-sized to/or large atypical lymphocytes primarily in bone marrow and lymph nodes, hemophagocytic lymphohistiocytosis (HLH), and progressive clinicopathological course. A further two patients demonstrated EBV+ node-based CD8+ large TCL without HLH, while the remaining two had the systemic form of chronic active EBV infection (sCAEBV) with CD8+ small lymphocytes. Past history of sCAEBV-like lesions was observed in one sEBV+ TCL patient (8.3%). Immunohistologically, in 12 sEBV+ TCL patients, atypical lymphocytes were positive for phosphate signal transducer and activator of transcription 3 (66.7%), CMYC (83.3%), and p53 (75%). Strong reactions of programmed cell death-ligand (PD-L)1+ tumor or non-neoplastic cells were detected in nine sEBV+ TCL patients (75%). Clonal peaks of the T-cell receptor (TCR) γ gene were detected in eight sEBV+ TCL patients by polymerase chain reaction. Four younger patients in sEBV+ TCL (33.3%) are in remission with chemotherapies including etoposide, and three of the four underwent allogeneic stem cell transplantation (SCT). CONCLUSION: sEBV+ CD8+ TCL was observed in younger and older adults with less history of sCAEBV. HLH, tumor cell atypia, immunohistological findings, and progressive clinical course were characteristic of sEBV+ CD8+ TCL. Prompt chemotherapy and SCT induced tumor regression in sEBV+ CD8+ TCL patients.

Testicular sarcoidosis with bilateral scrotal swelling.

INTRODUCTION: Sarcoidosis is a disease in which noncaseating granulomas form in several organs, particularly in the lungs and skin. Male genitourinary involvement in sarcoidosis is uncommon. CASE PRESENTATION: A 32-year-old male with painless bilateral scrotal swelling who was diagnosed with lung sarcoidosis presented to our hospital. Serum tumor marker levels were normal. Scattered hypoechoic mass lesions in both testes were noted on ultrasound examination. Biopsy of both testes revealed pathologically noncaseating epithelioid cell granuloma, and perihilar lymphadenopathy and a granulomatous lung nodule were found on chest computed tomography. Semen examination was performed after the biopsy, demonstrating oligospermia. A corticosteroid regimen was administered. After treatment, no abnormal accumulation in both testes was observed on gallium-67 scintigraphy, and semen examination demonstrated the mild improvement of the sperm count. CONCLUSION: Treatments for testicular sarcoidosis vary, and malignancy and fertility must be considered.

Clinical and cytopathological characteristics of HTLV-1+ hodgkin lymphoma.

BACKGROUND: Human T-lymphotropic virus-1 (HTLV-1)+ Hodgkin lymphoma (HL) is difficult to differentiate from adult T-cell leukemia/lymphoma (ATLL) with HL-like histology (HL-like ATLL). METHODS: Cytological and immunohistological features, HTLV-1 proviral DNA integration, and rearrangements of the T-cell receptor (TCR) Cß1 gene were examined in 11 HTLV-1+ patients with HL-like disease. RESULTS: Six patients were classified as HTLV-1+ HL and five as HL-like ATLL in accordance with genetic findings of HTLV-1 proviral DNA integration and rearrangements of the TCR Cß1 gene. Small ordinary looking lymphocytes with round nuclei were detected in the background of six patients with HTLV-1+ HL, which were immunohistochemically negative for CD25 and CC chemokine receptor (CCR)4 and had a low MIB1 labeling index (mean: 28.3%). In the HL-like ATLL specimens, small- and medium-sized atypical lymphocytes with indented and irregular-shaped nuclei were found, and were diffusely positive for CD25 and CCR4, with high MIB1 labeling (mean: 76%). Both groups had scattered CD30+ and CD15+ Hodgkin and Reed Sternberg (RS) giant cells, with or without CD20 expression and Epstein-Barr virus infection. The 50% overall survival period was significantly longer for the HTLV-1+ HL group (180 months) than for the HL-like ATLL group (7.8 months; P = .004). CONCLUSIONS: HTLV-1+ HL showed typical small lymphoid cells with a low MIB1 labeling index in a background of Hodgkin and RS cells, with some scattered CD25+ and CCR4+ lymphocytes. In HTLV-1 endemic areas, distinguishing HTLV-1+ HL from HL-like ATLL is important because of their differing treatment strategies and prognoses.

[A Case of Neuroendcrine Carcinoma of the Prostate Diagnosed by Prostate Re-Biopsy during Hormonal Treatment and Effectively Treated by Multidisciplinary Therapy].

A 73-year-old Japanese man visited the urology clinic with the chief complaint of gross hematuria in June 2015. His prostate specific antigen (PSA) level was 146.7 ng/ml and he was diagnosed with prostate adenocarcinoma with a Gleason Score of 5+4. With bone metastasis in the right femur (cT3aN0M1), he was treated by orchiectomy and bicalutamide. He had gross hematuria in October 2017 and a prostate tumor was detected by computed tomography (CT) and magnetic resonance imaging without increasing PSA levels. Prostate re-biopsy showed prostate neuroendocrine carcinoma and local radiation therapy (74 Gy) was performed. Follow-up CT revealed a left adrenal tumor with a positive positron emission tomographic scan in October 2018. Under the diagnosis of metastatic neuroendocrine carcinoma, chemotherapy using cisplatinum and etoposide was performed. The tumor shrunk after five courses of treatment, followed by regrowth in April 2019. Radiation therapy (50 Gy) was added to the left adrenal tumor and it shrunk again. However, a left retroperitoneal tumor was detected in July 2019 and it was resected under laparoscopic surgery and diagnosed as metastatic neuroendocrine carcinoma. Since then, no recurrence has been observed.

Malignant lymphoma of the bladder with bilateral hydronephrosis.

Lymphoma of the urinary bladder is uncommon, and upper urinary tract obstruction due to lymphoma is rare. Herein, we report a case of malignant lymphoma of the bladder with bilateral hydronephrosis in a 67-year-old female who presented with oliguria. Ultrasonography and computed tomography demonstrated a thickened posterior bladder wall and bilateral hydronephrosis. Whole-body positron emission tomography-computed tomography revealed abnormal accumulation in the right iliac internal lymph nodes. Trans-urethral bladder biopsy led to a histopathological diagnosis of non-Hodgkin diffuse large B-cell malignant lymphoma of the bladder. After bilateral nephrostomy, the patient was treated with six cycles of combination chemotherapy including rituximab, cyclophosphamide, daunorubicin, vincristine, and prednisolone (R-CHOP) and two cycles of rituximab alone. Complete remission was maintained during the 3 years of follow-up.

Female urethral diverticulum containing large calculi.

Urinary stones in female urethral diverticulum are rarely seen. We report a 79-year-old woman who presented with irritative lower urinary tract symptoms and vaginal cystocele with incontinence. The urethral stones in the diverticulum were successfully extracted through the trans-urethral route and anterior tension-free vaginal mesh was applied one month later. The patient has been well, with no lower urinary symptoms or incontinence for 4 months.

Use of a pneumatic tourniquet in total knee arthroplasty increases the risk of distal deep vein thrombosis: A prospective, randomized study.

BACKGROUND: There has been controversy regarding the incidence of deep vein thrombosis (DVT) after total knee arthroplasty (TKA) with or without the use of a tourniquet. The aim of this randomized, prospective study was to clarify the effects of tourniquet use on DVT in TKA. METHODS: The subjects were 109 patients scheduled to undergo TKA from April 2008 to March 2009 before the establishment of the American Association of Orthopedic Surgeons (AAOS) practice guidelines. They were randomized into two groups: 51 patients in the tourniquet group (group T) and 52 patients in the control group without a tourniquet (group C). We investigated the thrombotic presence using ultrasonography one week after surgery and compared both groups. RESULTS: There was no difference in the rate of proximal DVTs (P=0.63). However, the risk of distal DVT was significantly higher in group T than in group C (52.9% vs. 23.1%; P=0.002). CONCLUSIONS: Use of the tourniquet in TKA increased the risk of distal DVT.

What are the causes of revision total knee arthroplasty in Japan?

BACKGROUND: There is limited information regarding the cause of revision TKA in Asia, especially Japan. Owing to differences in patient backgrounds and lifestyles, the modes of TKA failures in Asia may differ from those in Western countries. QUESTIONS/PURPOSES: We therefore determined (1) causes of revision TKA in a cohort of Japanese patients with revision TKA and (2) whether patient demographic features and underlying diagnosis of primary TKA are associated with the causes of revision TKA. METHODS: We assessed all revision TKA procedures performed at five major centers in Hokkaido from 2006 to 2011 for the causes of failures. Demographic data and underlying diagnosis for index primary TKA of the revision cases were compared to those of randomly selected primary TKAs during the same period. RESULTS: One hundred forty revision TKAs and 4047 primary TKAs were performed at the five centers, indicating a revision burden of 3.3%. The most common cause of revision TKA was mechanical loosening (40%) followed by infection (24%), wear/osteolysis (9%), instability (9%), implant failure (6%), periprosthetic fracture (4%), and other reasons (8%). The mean age of patients with periprosthetic fracture was older (77 versus 72 years) and the male proportion in patients with infection was higher (33% versus 19%) than those of patients in the primary TKA group. There was no difference in BMI between primary TKAs and any type of revision TKA except other causes. CONCLUSIONS: The revision burden at the five referral centers in Hokkaido was 3.3%, and the most common cause of revision TKA was mechanical loosening followed by infection. Demographic data such as age and sex might be associated with particular causes of revision TKA.

Implantation sites and fiber diameters affect the rate of degradation in absorbable polydioxanone fibers.

PURPOSE: The purpose of this study is to test the question of whether implantation sites and fiber diameters affect the rate of degradation in absorbable polydioxanone fibers. TYPE OF STUDY: Randomized trial. METHODS: Forty-eight mature rabbits were used. In the first study, using 24 rabbits, a 0.3-mm diameter polydioxanone fiber was implanted into the subcutaneous, intra-articular, and intramedullary sites. Six rabbits each were killed at 1, 2, 3, and 6 weeks after surgery. In the second study, the remaining 24 rabbits were divided into 2 groups of 12 animals each. In group I, a 0.3-mm diameter fiber was implanted into the intramedullary and subcutaneous sites. In group II, a 0.6-mm diameter fiber was implanted in the same manner. In each group, 6 rabbits were killed at 3 and 6 weeks. In each study, all fiber specimens underwent tensile testing to determine the material properties. We defined the percentage of the maximum load of each fiber specimen compared with the normal control value as the I/N ratio. RESULTS: In the first study, the maximum load and the stiffness of the fibers implanted into the intramedullary site were significantly lower than those of the fibers implanted into the other 2 sites at each period (P <.0001). In the second study, the I/N ratio of group I was significantly less than that of group II at each implanted site (P <.0001). CONCLUSIONS: Polydioxanone fiber implanted into the intramedullary site deteriorates more rapidly than that implanted into the subcutaneous and the intra-articular sites. Thin fibers deteriorate more rapidly than thick fibers. Therefore, the degradation of absorbable synthetic fibers intended for use in ligament reconstruction should be evaluated not only in the subcutaneous site but also in the intramedullary site using various diameter fibers.

Effects of stress deprivation on mechanical properties of the in situ frozen-thawed semitendinosus tendon in rabbits.

OBJECTIVE: To clarify the effect of complete stress deprivation on the mechanical properties of the in situ frozen-thawed semitendinosus tendon, an idealized autograft model. DESIGN: Ninety-six rabbits were divided into three groups. In the frozen group (n=36), we applied the freeze-thaw treatment to the semitendinosus tendon to necrotize fibroblasts in the tendon. In the frozen and stress-shielded group (n=30), after we applied the same freeze-thaw treatment to the tendon, we completely released the tendon from stress. In the sham group (n=30), a sham operation was applied. In each group, 6 rabbits were sacrificed at 0 (only in the frozen group), 1, 2, 3, 6 and 12 weeks after surgery. BACKGROUND: Previous studies have not clarified remodeling of the semitendinosus autograft in ligament reconstruction or its idealized model. METHODS: The tendon was frozen with liquid nitrogen. The tendon was released from stress with the originally developed technique using a polyester tape. In each period, 5 out of the 6 rabbits were evaluated with tensile testing, and the remaining rabbit was histologically observed. RESULTS: Complete stress shielding significantly increased the cross-sectional area of the frozen-thawed tendon at 1 and 2 weeks, while it significantly inhibited the increase of the area due to the freeze-thaw treatment at 3 and 6 weeks. Complete stress shielding significantly reduced material properties of the frozen-thawed tendon after 2 weeks. CONCLUSIONS: The frozen-thawed semitendinosus tendon has unique remodeling characteristics under a stress-shielded condition, which were not the same as those of the frozen-thawed patellar tendon. RELEVANCE: Remodeling of the semitendinosus tendon autograft under stress-shielded conditions may be different from that of the patellar tendon autograft.