Efficacy of Chemotherapy After Immune Checkpoint Inhibitor Discontinuation in Head and Neck Cancer.

OBJECTIVE: Immune checkpoint inhibitors (ICI) have become widely used becuse of their effectiveness and relatively low rate of severe adverse events. However, active treatment should be continued after discontinuation of ICI as response rates are lower than that of conventional cytotoxic chemotherapy. The purpose of the present study was to determine the efficacy of treatment after ICI discontinuation. METHODS: This was a retrospective study from hospital charts of 99 consecutive cases treated with ICI at our facility since 2017. Of these, 79 cases of squamous cell carcinoma which had already discontinued ICI were enrolled in the present study. RESULTS: After discontinuation of ICI, 40 cases received active treatment with salvage chemotherapy (SCTx; 33 cases) or surgery or radiotherapy (seven patients) and 39 cases received nonactive treatment. SCTx comprising paclitaxel and cetuximab (PTX-Cmab) was administered to 15 cases and other SCTx regimens to 18 cases. A significant increase in overall survival (OS) was observed with active treatment compared with nonactive treatment. No significant differences in OS or progression-free survival (PFS) were observed between SCTx regimens; however, there was a trend toward increased survival with PTX-Cmab. Univariate analysis of overall response rate (ORR) demonstrated significant differences in the site of disease at ICI and SCTx regimens. A significant difference in disease control rate was observed between SCTx regimens. Multivariate analysis of ORR demonstrated a significant correlation with PTX-Cmab treatment. CONCLUSION: Active treatment after ICI discontinuation and the use of PTX-Cmab as SCTx may increase OS in head and neck squamous cell carcinoma. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:228-235, 2024.

Ultra-high combined positive score and high serum albumin are favorable prognostic biomarkers for immune checkpoint inhibitors in head and neck squamous cell carcinoma.

BACKGROUND: Biomarkers that predict response to immune checkpoint inhibitor (ICI) in recurrent metastatic squamous cell carcinoma of the head and neck (RMHNSCC) are not well known. METHODS: We prospectively measured the combined positive score (CPS) and administered ICI to patients with RMHNSCC. RESULTS: Of 51 patients, 23 patients had a CPS <20 and 12 patients (23.5%) had a CPS ≥90. CPS showed a negative correlation with serum albumin. Survival analysis showed a 2-year survival rate of 24.1%. In multivariate analysis, CPS ≥90 (HR 0.3026, p = 0.02614) and albumin >3.5 (HR 0.3463, p = 0.01354) were the significant factors and plus chemotherapy (HR 0.4648, p = 0.07632) was not significant. Seven patients (14%) with CPS ≥90 and albumin >3.5 showed a 2-year survival rate of 66. 7%. CONCLUSIONS: CPS ≥90 and albumin >3.5 cases are a subgroup of RMHNSCC that respond extremely well to ICI.

Clinical outcomes of head and neck mucosal melanoma treated with surgery: a single-center study in Japan.

BACKGROUND: Head and neck mucosal melanomas are rare malignancies. Although the prognosis is poor owing to the high incidence of distant metastases, locoregional control remains important. It is difficult to obtain results in a large cohort because of its rarity. This study aimed to elucidate the survival outcomes of patients with head and neck mucosal melanoma treated with surgery in Japan. METHODS: Patients with head and neck mucosal melanoma who were surgically treated between 2007 and 2021 at the National Cancer Center Hospital were retrospectively analyzed. RESULTS: A total of 47 patients were included in this study. The 5-year overall survival, disease-specific survival, locoregional control and relapse-free survival rates were 42%, 50%, 79% and 13%, respectively. The disease-specific survival of the oral mucosal melanoma group was significantly better than that of the sinonasal mucosal melanoma group (5-year disease-specific survival rate: 70% versus 37%, respectively; P = 0.04). Multivariate analyses revealed that sinonasal mucosal melanoma were independently significant adverse prognostic factor, for overall survival and disease-specific survival. Patients with oral mucosal melanoma patients had a higher incidence of lymph node metastasis than those with sinonasal mucosal melanoma patients (P < 0.0001). CONCLUSION: This study demonstrated the survival outcomes of the largest cohort of patients with head and neck mucosal melanomas treated surgically at a single institution within the past 20 years in Japan. We found that survival outcomes and incidence of nodal metastases varied by site.

Clinical and pathological features of second primary neoplasms arising in head and neck reconstructive skin flaps.

The incidence of second primary neoplasms arising in the skin reconstructive flap (SNAF) is increasing because of the increase in head and neck flap reconstruction and cancer survival. Prognosis, optimal treatment, and their clinicopathological-genetic features are under debate and are difficult to diagnose. We retrospectively reviewed SNAFs based on a single center's experience over 20 years. Medical records and specimens of 21 patients with SNAF who underwent biopsies between April 2000 and April 2020 at our institute were retrospectively analyzed. Definite squamous cell carcinoma and the remaining neoplastic lesions were subclassified as flap cancer (FC) and precancerous lesions (PLs), respectively. Immunohistochemical studies focused on p53 and p16. TP53 sequencing was conducted using next-generation sequencing. Seven and 14 patients had definite FC and PL, respectively. The mean number of biopsies/latency intervals was 2.0 times/114 months and 2.5 times/108 months for FC and PL, respectively. All lesions were grossly exophytic and accompanied by inflamed stroma. In FC and PL, the incidences of altered p53 types were 43% and 29%, respectively, and those of positive p16 stains were 57% and 64%, respectively. Mutation of TP53 in FC and PL were 17% and 29%, respectively. All except one patient with FC under long-term immunosuppressive therapy survived in this study. SNAFs are grossly exophytic tumors with an inflammatory background and show a relatively low altered p53 and TP53 rate and a high p16 positivity rate. They are slow-growing neoplasms with good prognoses. Diagnosis is often difficult; therefore, repeated or excisional biopsy of the lesion may be desirable.

Comparison of Survival Outcomes Between Larynx-Preserving Open Partial Pharyngectomy and Radiotherapy or Chemoradiotherapy in Patients with Hypopharyngeal Squamous Cell Carcinoma: A Single-Center Retrospective Analysis with Inverse Probability of Treatment Weighting Adjustments.

BACKGROUND: There is a group of hypopharyngeal squamous cell carcinoma (HPSCC) patients for whom larynx-preserving open partial pharyngectomy (PP) and radiotherapy/chemoradiotherapy (RT/CRT) are indicated. We aimed to retrospectively evaluate the survival difference as there is no evidence directly comparing the two therapies. METHODS: This study evaluated HPSCC patients who were initially treated by PP or RT/CRT at our institution between January 2007 and October 2019. Overall survival (OS), disease-specific survival (DSS), laryngectomy-free survival (LFS), and local relapse-free survival (LRFS) were evaluated. The main analyses were performed with inverse probability of treatment weighting (IPTW) adjustments. Sensitivity analyses compared hazard ratios (HRs) obtained with three models: unadjusted, multivariate Cox regression, and propensity score-adjusted. RESULTS: Overall, 198 patients were enrolled; 63 and 135 underwent PP and RT/CRT, respectively. IPTW-adjusted 5-year OS, DSS, LFS, and LRFS rates in the PP and RT/CRT groups were 84.3% and 61.9% (p = 0.019), 84.9% and 75.8% (p = 0.168), 94.8% and 90.0% (p = 0.010), and 75.9% and 74.1% (p = 0.789), respectively. In the IPTW-adjusted regression analysis, PP was associated with a significant benefit regarding OS (HR 0.48, 95% confidence interval [CI] 0.26-0.90) and LFS (HR 0.17, 95% CI 0.04-0.77). The results obtained with the three models in the sensitivity analyses were qualitatively similar to those of the IPTW-adjusted models. CONCLUSION: Despite the risk of bias related to unadjusted factors, our results suggest that PP is associated with significantly better OS and LFS compared with RT/CRT for HPSCC.

BCOR-CCNB3 sarcoma arising in the pharynx.

Reports on BCOR-CCNB3 sarcoma in the head and neck region are scarce, given their unknown etiology. An 18-year-old male patient presented a rapidly enlarging tumor extending from the right nasopharynx to the oropharynx. Histological examination showed a spindle cell sarcoma with BCOR-CCNB3 fusion detected by fluorescence in situ hybridization, and BCOR-CCNB3 was diagnosed. After three courses of alternating VDC-IE therapy, the patient underwent tumor resection based on the original tumor range with a minimal margin, using the mandibular swing technique. Radiation therapy (50.4 Gy) was administered postoperatively, followed by three additional courses of alternating VDC-IE therapy. The patient survived and showed no evidence of disease at 12 months postoperatively. BCOR-CCNB3 sarcoma is a chemotherapy-sensitive sarcoma, and conservative resection with a minimal margin that does not interfere with the treatment flow is preferable.

Transnasal photoimmunotherapy with cetuximab sarotalocan sodium: Outcomes on the local recurrence of nasopharyngeal squamous cell carcinoma.

Photoimmunotherapy for head and neck cancer (HNC-PIT) is a newly developed locoregional treatment targeting the epidermal growth factor. This treatment consists in administering cetuximab sarotalocan sodium that conjugates cetuximab with the dye IRdye700DX, which is activated by near-infrared ray illumination at 690 nm. HNC-PIT has been conditionally approved in Japan in September 2020 for the treatment of unresectable locally advanced or unresectable locoregionally recurrent HNC. However, its outcomes on the local recurrence of the nasopharyngeal squamous cell carcinoma (NPSCC) remain undetermined. In this report, we assessed the effects of HNC-PIT assisted by transnasal endoscopy on the local recurrence of NPSCC. A 77-year-old male presented with a local recurrence of NPSCC. The initial diagnosis revealed a squamous cell carcinoma, T2N2M0 stage III, positive for Epstein-Barr virus-encoded small RNA by in situ hybridization, which was treated with concurrent chemoradiotherapy (CRT). However, local recurrence was detected 14 months after CRT. We performed HNC-PIT under transnasal endoscopy. Seven months have passed since the HNC-PIT treatment, and the patient is alive without delayed adverse events and evidence of recurrence. Local recurrence of NPSCC, which is difficult to treat with minimally invasive surgery, is considered a potential candidate for HNC-PIT.

Tumor-stroma ratio can predict lymph-node metastasis in cT1/2N0 oral tongue squamous cell carcinoma independent of tumor budding grade.

BACKGROUND: cT1/2 oral tongue squamous cell carcinoma (OTSCC) often metastasizes to cervical lymph nodes. However, predicting neck lymph-node metastasis (NLM) remains challenging. Pathomorphological evaluation of tumor budding grade (TBG) and tumor-stroma ratio (TSR) reportedly can predict lymph-node metastases. Hence, this study aimed to evaluate TBG and TSR in OTSCC and investigate their relationship to occult NLM and cancer relapse. METHODS: Clinicopathological data of patients with cT1/2N0 OTSCC treated at the University of Tokyo Hospital between 2007 and 2017 were collected. TBG and TSR were evaluated using hematoxylin-eosin staining and cytokeratin AE1/AE3 immunostaining. RESULTS: Out of 70 patients, 16 underwent elective neck dissection in addition to primary-tumor resection, whereas 54 did not. During follow-up, NLM was found in 35 patients. NLM correlated with the pathological depth of invasion (pDOI) (p < 0.001), TBG (p = 0.008), and TSR (p < 0.001) in univariate analysis and pDOI (p = 0.01) and TSR (p = 0.02) in multivariate analysis. The 5-year recurrence-free survival rate (RFS) was 78% for patients with a pDOI ≤ 5 mm and stroma-poor tumors and 33% for patients with a pDOI > 5 mm and stroma-rich tumors. CONCLUSION: Patients with a pDOI > 5 mm and stroma-rich tumors have a high risk for cancer relapse. TSR and pDOI may be promising NLM predictors in cT1/2N0 OTSCC.

Usefulness of circulating tumor DNA by targeting human papilloma virus-derived sequences as a biomarker in p16-positive oropharyngeal cancer.

In head and neck cancer, early detection of recurrence after treatment is important. The contemporary development of therapeutic agents have improved the prognosis after recurrence; however, no biomarker has been established for evaluating therapeutic effects or detecting recurrence. Recently, circulating tumor DNA (ctDNA), which comprises DNA derived from tumor cells and exists in the form of cell-free DNA in the blood, has attracted attention as a minimally invasive and repeatable biomarker for detecting cancer. We validated the usefulness of ctDNA of human papilloma virus (HPV)-derived sequences as a biomarker in HPV-related p16-positive oropharyngeal cancer by assessing 25 patients with p16-positive oropharyngeal cancer. Blood samples were collected from each patient at multiple time points during the treatment, and the plasma was preserved. The ctDNA was extracted from the plasma and analyzed using digital polymerase chain reaction. HPV-derived ctDNA was detected in 14 (56%) of the 25 patients. In all the patients, the samples were found to be ctDNA-negative after initial treatment. Cancer recurrence was observed in 2 of the 14 patients; HPV-derived ctDNA was detected at the time of recurrence. Our results indicate that HPV-derived ctDNA can be a prospective biomarker for predicting the recurrence of p16-positive oropharyngeal cancer.

Statistical Analysis of Ultrasonic Scattered Echoes Enables the Non-invasive Measurement of Temperature Elevations inside Tumor Tissue during Oncological Hyperthermia.

Non-invasive monitoring of temperature elevations inside tumor tissue is imperative for the oncological thermotherapy known as hyperthermia. In the present study, two cancer patients, one with a developing right renal cell carcinoma and the other with pseudomyxoma peritonei, underwent hyperthermia. The two patients were irradiated with radiofrequency current for 40 min during hyperthermia. We report the results of our clinical trial study in which the temperature increases inside the tumor tissues of patients with right renal cell carcinoma and pseudomyxoma peritonei induced by radiofrequency current irradiation for 40 min could be detected by statistical analysis of ultrasonic scattered echoes. The Nakagami shape parameter m varies depending on the temperature of the medium. We calculated the Nakagami shape parameter m by statistical analysis of the ultrasonic echoes scattered from the tumor tissues. The temperature elevations inside the tumor tissues were expressed as increases in brightness on 2-D hot-scale maps of the specific parameter αmod, indicating the absolute values of the percentage changes in m values. In the αmod map for each tumor tissue, the brightness clearly increased with treatment time. In quantitative analysis, the mean values of αmod were calculated. The mean value of αmod for the right renal cell carcinoma increased to 1.35 dB with increasing treatment time, and the mean value of αmod for pseudomyxoma peritonei increased to 1.74 with treatment time. The increase in both αmod brightness and the mean value of αmod implied temperature elevations inside the tumor tissues induced by the radiofrequency current; thus, the acoustic method is promising for monitoring temperature elevations inside tumor tissues during hyperthermia.

Temperature elevation in tissue detected in vivo based on statistical analysis of ultrasonic scattered echoes.

It is demanded to monitor temperature in tissue during oncological hyperthermia therapy. In the present study, we non-invasively measured the temperature elevation inside the abdominal cavity and tumour tissue of a living rat induced by capacitive-coupled radiofrequency heating. In the analysis of ultrasound scattered echoes, the Nakagami shape parameter m in each region of interest was estimated at each temperature. The Nakagami shape parameter m has temperature dependence; hence, the temperature increase inside tissue specimens can be detected with the m values. By carrying out in vivo experiments, we visualized the temperature increase inside the abdominal cavity and tumour tissue of living rats using two-dimensional hot-scale images indicating the absolute values of the ratio changes of the m values. In both the abdominal cavity and tumour tissue, the brightness in the hot-scale images clearly increased with increasing temperature. The increases in brightness in the hot-scale images imply the temperature elevations inside the abdominal cavity and tumour tissue of the living rats. The study results prove that the acoustic method we proposed is a promising method for monitoring changes in the internal temperature of the human body under hyperthermia treatment.

Active Surveillance for T1bN0M0 Papillary Thyroid Carcinoma.

BACKGROUND: Prospective trials of active surveillance for asymptomatic papillary microcarcinoma (T1aN0M0) since the 1990s have shown progression rates of only 5-10%. Late rescue surgery after progression had no deleterious effects on mortality and morbidity. The 2015 American Thyroid Association guidelines approved active surveillance for very low-risk papillary thyroid carcinoma (PTC) as an alternative method to immediate surgery. However, there is no study that evaluates long-term active surveillance for T1b tumors. METHODS: A prospective trial of active surveillance with 360 very low-risk PTC (T1aN0M0) patients has been conducted since 1995. Of the 392 T1bN0M0 patients, 61 selected active surveillance over surgery and eventually participated in this trial, while the remaining 331 patients underwent surgery. To find an appropriate management strategy for patients with T1bN0M0 PTC, the outcomes of active surveillance for T1bN0M0 to T1aN0M0 PTC were investigated and compared, and the outcomes of surgery for T1bN0M0 PTC were studied. RESULTS: After a mean of 7.4 years of active surveillance, 29 (8%) T1aN0M0 tumors and four (7%) T1bN0M0 tumors had increased in size (p = 0.69). Development of lymph node metastasis was seen in three (0.8%) patients and two (3%) patients, respectively (p = 0.10). No significant difference in progression rate was seen between groups. Among T1bN0M0 tumors, weak calcification and rich vascularity were risk factors for tumor-size increase, and younger age was a predictor for the development of lymph node metastasis. Mean initial tumor size was significantly greater in T1bN0M0 patients who underwent immediate surgery (14.5 ± 2.8 mm) than it was in patients who chose observation (11.7 ± 1.1 mm; p < 0.0001). No postoperative recurrence was seen in patients with tumor <15 mm in diameter. CONCLUSIONS: Active surveillance is an option for selected patients with T1bN0M0 PTC.

[Fourteen Cases of Implanted Central Venous Access Port-Related Bloodstream Infection].

We conducted a clinical study involving cases of central venous(CV)port-related infection in Tokyo Rosai Hospital. Fourteen patients with suspected CV port-related infection at Tokyo Rosai Hospital between April 2015 and January 2017 were observed. Identical bacterial types were detected from 2 sets of blood cultures and cultures from the catheter tip, and a definitive diagnosis was made. Data on patient background, causative bacteria, quick sequentialorgan failure assessment (qSOFA)score, CV port placement period, presence or absence of local inflammatory findings, and prognosis were analysed. The causative bacteria were coagulase-negative Staphylococcus(CNS)in 7 cases(50%), Staphylococcus aureus in 3(21%), and Candida in 4(29%). Most CNS-infected cases(71%)exhibited a qSOFA score of 1 or less at the examination time, which indicated that even if bacteremia occurred in CNS cases, organopathy might not occur easily. Local inflammatory findings were found in only 3 CNS cases. Cases without local inflammatory findings showed methicillin-resistant Staphylococcus aureus(MRSA)(18%)or Candida(36%)at high proportions, indicating that treatments might be difficult.

[A Case of Brain Abscess Caused by Nocardia farcinica in which the Test Results for Drug Susceptibility Conflicted with the Actual Clinical Course].

Sulfamethoxazloe-trimethoprim is one of the most frequently used antibiotics in the treatment of Nocardia infection. However, in vitro studies have shown an increase in sulfonamide resistance among Nocardia species. Here, we present a case with a brain abscess caused by Nocardia farcinica in which the test results for drug susceptibility to sulfonamide conflicted with the actual clinical course. A 74-year-old woman with autoimmune hepatitis who has being treated with oral prednisolone (16 mg/day) was admitted because of headaches and fever. A CT scan and MRI revealed a brain abscess that had ruptured into the lateral ventricle. She was empirically treated with antibiotics, but her condition did not resolve. Therefore, the abscess was drained surgically. Gram and Kinyoun stains for pus revealed a modified acid-fast branching filamentous bacterium consistent with Nocardia species. The pathogen was identified as Nocardia farcinica based on its 16S rRNA sequence. Consequently, the patient was treated with sulfamethoxazole -trimethoprim and amikacin. However, susceptibility testing (broth microdilution method) showed that the strain was completely resistant to sulfamethoxazole-trimethoprim. We therefore changed the therapeutic regimen to imipenem-cilastatin and amikacin, but her symptoms worsened and the treatment was thought to have failed. She was then re-treated with sulfamethoxazole- trimethoprim, and her symptoms resolved. Some reports have suggested that interpreting the results of Nocardia susceptibility testing may be difficult especially the susceptibility of Nocardia to sulfamethoxazole-trimethoprim. The present case suggests a confliction between susceptibility testing and the clinical course of a patient with Nocardia infection.

Wandering pneumonia caused by dabigatran.

We herein describe the case of a 74-year-old man who experienced pulmonary consolidation and chest pain following administration of dabigatran, a novel oral anticoagulant. The consolidation settled spontaneously in another lung area, a condition sometimes referred to as "wandering pneumonia." Although we did not find specific pathological evidence of interstitial lung disease on transbronchial lung biopsy, a lung opacity spontaneously disappeared following discontinuance of dabigatran, and there was no recurrence. There are no other reports of dabigatran-induced lung injury, except alveolar hemorrhage and eosinophilic pneumonia. We should consider that any novel drug could cause various types of pulmonary injuries.

[A case of Wegener granulomatosis after treatment for non-tuberculous mycobacteriosis].

A 67-year-old woman with a history of non-tuberculous mycobacteriosis due to Mycobacterium avium in 2002 and 2006 was admitted because of low-grade fever and cavitary lesions in both lungs on chest computed tomography (CT). Bronchial brushing cytology by bronchoscopy did not yield mycobacterium. Her serum antineutrophil cytoplasmic antibodies (MPO-ANCA) level was elevated and PR3 ANCA was negative. A surgical lung biopsy revealed basophilic necrosis with cavitary lesions and necrotizing vasculitis compatible with Wegener granulomatosis (WG). In the resected specimen, several hyalinizing nodules with caseous necrosis, probably associated with previous mycobacterium infection, were also seen. Because her disease was limited to the lungs, we successfully treated her with corticosteroids and methotrexate. WG is considered to be a type of ANCA-associated vasculitis, and microbial infections have been associated with initiation and relapse of WG. This case clearly demonstrated that lesions of WG occurred after mycobacterial infection in the lung. We believe that this case was ANCA production in association with bacterial infection.

[Sputum smear-positive tuberculosis diagnosed after hospitalization].

A tuberculosis infection-control program is based on a 3-level hierarchy of measures, including administrative, environmental, and respiratory protection. The most important level of tuberculosis controls is the use of administrative measures to reduce the risk of exposure to patients who might have infectious tuberculosis. In 126 patients tuberculosis was given diagnosed in our hospital over 10 years, and 51 patients among them had bacilli-positive sputum smears, of whom 26 were given diagnoses after admission, and 15 patients of these, in whom tuberculosis was not strongly suspected on admission, were considered to be at risk of nosocomial infection. The mean age of these 15 patients was 66.3 years, and 9 of them were given diagnoses of pneumonia. Duration until tuberculosis diagnosis was within 3 days in 11 patients, 4 to 7 days in 2, and more than 8 days in 2 patients. Twelve patients were admitted from the emergency room or belonged to other departments than respiratory medicine. We believe that it is important to consider tuberculosis when deciding about admission, in order not to delay diagnosis. Furthermore, ventilation of general rooms must be sufficient when dealing with the unexpected admission of patients with tuberculosis, and ability of health-care workers to use N95 respirators should be confirmed.

[Patient with MPO-ANCA-associated disease with interstitial pneumonia and lower cranial nerves palsy who was previously exposed to asbestos].

A 65-year-old man who was occupationally exposed to asbestos for 40 years was admitted to our hospital with fever and cough. Chest CT revealed paraseptal emphysema, subpleural fibrosis in both lungs, and pleural plaques. On bronchoalveolar lavage fluid contained elevated levels of lymphocytes and neutrophils (15% and 17%, respectively), and asbestos bodies were also found. Because serum MPO-ANCA titer was elevated to 188 EU, we suspected ANCA-associated disease with interstitial pneumonia. Prednisolone was begun at 30 mg/day and his lung opacities partially disappeared. Six weeks later, he complained of headache, dysphagia and hoarseness, and was admitted to the neurology department of the hospital. Under a diagnosis of either hypertrophic pachymeningitis or neuritis due to angiitis of the lower cranial nerves, steroid pulse therapy was performed. Asbestos exposure may have been a contributing factor for ANCA generation in this case. Furthermore, the fact that cranial nerves palsy occurred in spite of steroid therapy may also be important.

Pulmonary tuberculosis accompanied by a transient increase in serum carcinoembryonic antigen level with tuberculous empyema drainage.

We present a case of pleural effusion with encapsulation that was observed in the right thorax of a patient. PCR analysis of the patient's pleural effusion showed positivity for Mycobacterium tuberculosis. After six months, his chest CT showed the development of niveau and pulmonary consolidation. We definitively diagnosed him as having chronic pulmonary tuberculosis with tuberculous empyema drainage. At the time of his hospital admission, his serum carcinoembryonic antigen (CEA) level was elevated. After we started treatment using antituberculosis drugs, the infiltration shadow in his lung fields disappeared, and the serum CEA level decreased. The results suggest that the serum CEA level reflects the extent of the development of pulmonary tuberculosis lesions.

Bleeding from the bone marrow enhances remodeling of the in situ frozen-thawed anterior cruciate ligament.

BACKGROUND: The purpose of this study is to biomechanically and histologically evaluate the effect of bleeding from bone marrow on remodeling of the in situ frozen-thawed anterior cruciate ligament. METHODS: Forty-four rabbits were used. Eight rabbits were used to evaluate the amount of bleeding at days 1-4. Thirty-six rabbits were divided into two groups, after the right anterior cruciate ligament underwent the freeze-thaw treatment. In Group I, no treatments were applied. In Group II, a tunnel was drilled into the bone marrow the femoral intercondylar notch. Each rabbit was sacrificed at 6 or 12 weeks. We examined the mechanical properties, and the histology of the anterior cruciate ligament. FINDINGS: A small amount of blood clot was observed only on the first day in Group I, while a large amount of blood clot was seen around the anterior cruciate ligament for 3 days after surgery in Group II. In the midsubstance, a number of cells were scattered in Group II, no cells were seen in Group I at 6 weeks. The tangent modulus showed some tendency of difference between Groups I and II at each period. INTERPRETATION: Bleeding from the bone marrow obviously enhanced extrinsic cell infiltration into the in situ frozen-thawed anterior cruciate ligament at 6 weeks, and showed some effects on its mechanical properties. This study implied that, in anterior cruciate ligament reconstruction, the blood from a bone tunnel play an important role in graft remodeling.