Secondary osteosarcoma associated with osteofibrous dysplasia: a case report.

Secondary osteosarcoma is a rare complication of primary malignancies and benign bone lesions. There are various types of diseases that cause secondary osteosarcoma. A 15-year-old male presented at our medical center complaining of pain and redness in the right lower leg. He had been diagnosed with osteofibrous dysplasia in the right tibia when he was 2 years old and since then had been followed up. Although he had a pathological fracture of the right tibia at the age of 7, his fracture healed with a plaster cast and did not require surgery. At the time of the patient's last visit, a radiograph revealed a periosteal reaction as well as erosion of the bone cortex. Magnetic resonance imaging revealed an infiltrative area in the soft tissue surrounding the osteofibrous dysplasia lesion in the tibia. Consequent to pathological examination (through bone biopsy), the patient was diagnosed with secondary osteosarcoma. The patient underwent chemotherapy and extensive resection with liquid nitrogen. He has been progressing satisfactorily after the operation. The present case is the first report of secondary osteosarcoma associated with osteofibrous dysplasia. During the long-term follow-up of osteofibrous dysplasia, oncologists should be aware of the possibility of secondary osteosarcoma.

Inflammatory Undifferentiated Pleomorphic Sarcoma Mimicking Bacteremia in an Elderly Patient: A Case Report.

Undifferentiated pleomorphic sarcoma (UPS) is major type of soft tissue sarcomas. UPS presenting with inflammation is rare, and its pathophysiology remains unclear. Herein, we report a rare case of UPS with prolonged fever. A 91-year-old female complaining of high fever was referred to our hospital because of a high C-reactive protein (CRP) level of 12.51 mg/dL. She had been experiencing intermittent fevers for approximately 10 years. The fever of unknown origin worsened with time and went into remission with repeated antimicrobial therapy. She also had a mass on her central lower back over the sacral region for 6 years, which showed a gradual increase in size. The blood tests showed that the leukocyte count and neutrophils were 6.51 × 103 /µL and 70.3%, respectively. She had a 10 × 10 cm mass on her buttock that showed 2-[fluorine-18] fluoro-2-deoxy-d-glucose (FDG) accumulation on FDG-positron emission tomography-computed tomography examination (standardized uptake value-max value: 5.4). A blood culture examination was performed to rule out bacteremia, however, no bacteria were identified. We then performed a needle biopsy and confirmed the diagnosis of UPS; subsequently, the patient underwent a wide-margin resection. A few days after the surgery, her CRP, leukocyte, and neutrophil levels decreased to 0.305 mg/dL, 2.83 × 103/uL, and 50.1%, respectively. This case demonstrated that UPS with inflammation should be treated surgically as soon as possible after ruling out other sources of infection to achieve a favorable prognosis.

Characterization of the intramolecular transfer state of marine carotenoid fucoxanthin by femtosecond pump-probe spectroscopy.

Fucoxanthin, containing a carbonyl group in conjugation with its polyene backbone, is a naturally occurring pigment in marine organisms and is essential to the photosynthetic light-harvesting function in brown alga and diatom. Fucoxanthin exhibits optical characteristics attributed to an intramolecular charge transfer (ICT) state that arises in polar environments due to the presence of the carbonyl group. In this study, we report the spectroscopic properties of fucoxanthin in methanol (polar and protic solvent) observed by femtosecond pump-probe measurements in the near-infrared region, where transient absorption associated with the optically allowed S2 (1(1)B u (+) ) state and stimulated emission from the strongly coupled S1/ICT state were observed following one-photon excitation to the S2 state. The results showed that the amplitude of the stimulated emission of the S1/ICT state increased with decreasing excitation energy, demonstrating that the fucoxanthin form associated with the lower energy of the steady-state absorption exhibits stronger ICT character.

Light-dependent conformational change of neoxanthin in a siphonous green alga, Codium intricatum, revealed by Raman spectroscopy.

Siphonous green algae, a type of deep-sea green algae, appear olive drab and utilize blue-green light for photosynthesis. A siphonous green alga, Codium (C.) intricatum, was isolated from Okinawa prefecture in Japan, and a clonal algal culture in filamentous form was established. The major light-harvesting antenna was analogous to the trimeric LHCII found in higher plants, but the C. intricatum complex contained an unusual carbonyl carotenoid siphonaxanthin. Culture conditions were optimized to achieve high siphonaxanthin content in intact lyophilized filamentous bodies. Interestingly, the carotenoid composition was different when cultured under high irradiance: all-trans neoxanthin was accumulated in addition to the normal 9'-cis form in whole cell extract. Resonance Raman spectra of intact filamentous bodies, cultured under high- and low-light conditions, confirmed the accumulation of all-trans neoxanthin under high irradiance conditions. A plausible function of the presence of all-trans neoxanthin will be discussed in relation to the regulation against high light stress.

Aggressive intraosseous lipoma of the scapula: A case report.

The details of the pathogenesis of intraosseous lipomas are not fully elucidated, although most cases do not require surgical treatment. The present report describes the case of a 79-year-old female patient diagnosed with intracapsular lipoma who also exhibited an extraosseous extension. Chest computed tomography revealed an abnormal shadow or a mass in the right scapula and destruction of the glenoid bone. Magnetic resonance imaging revealed a high-intensity mass on T1-weighted and T2-weighted images in the same area. Marginal resection of the mass was performed. The histopathology confirmed that the mass was a lipoma. No postoperative recurrence was observed. Oncologists must be aware that lipoma arising within the scapula may extend outside the bone.

Isolation and purification of the major photosynthetic antenna, fucoxanthin-Chl a/c protein, from cultured discoid germilings of the brown Alga, Cladosiphon okamuranus TOKIDA (Okinawa Mozuku).

A chlorophyll c binding membrane intrinsic light-harvesting complex, the fucoxanthin-chlorophyll a/c protein (FCP), was isolated from cultured discoid germilings of an edible Japanese brown alga, Cladosiphon (C.) okamuranus TOKIDA (Okinawa Mozuku in Japanese). The discoid germiling is an ideal source of brown algal photosynthetic pigment-protein complexes in terms of its size and easiness of cultivation on a large scale. Ion-exchange chromatography was crucial for the purification of FCP from solubilized thylakoid proteins. The molecular weight of the purified FCP assembly was estimated to be ~56 kDa using blue native-PAGE. Further subunit analyses using 2D-PAGE revealed that the FCP assembled as a trimer consisting of two distinguishable subunits having molecular weights of 18.2 (H) and 17.5 (L) kDa. Fluorescence and fluorescence-excitation spectra confirmed that the purified FCP assembly was functionally intact.

The pigment stoichiometry in a chlorophyll a/c type photosynthetic antenna.

The trimeric fucoxanthin-chlorophyll a/c protein (FCP) was purified from a Japanese brown alga, Cladosiphon okamuranus TOKIDA. Its pigment stoichiometry was determined to be chlorophyll (Chl) a:Chl c (1):Chl c (2):fucoxanthin = 4.6:1.1:1.0:5.5 by a combination of binary HPLC and (1)H NMR spectroscopy. No violaxanthin found bound to the FCP. The ratio of Chl c/Chl a in this FCP is amongst the highest so far reported.

Discovery of a novel siphonaxanthin biosynthetic precursor in Codium fragile that accumulates only by exposure to blue-green light.

Photosynthetic organisms adapt to a variety of light conditions. Codium fragile, a macrosiphonous green alga, binds a unique carbonyl carotenoid, siphonaxanthin, to its major photosynthetic light-harvesting complexes, allowing it to utilize dim blue-green light for photosynthesis. Here, we describe the absolute chemical structure of a novel siphonaxanthin biosynthetic precursor, 19-deoxysiphonaxanthin, that accumulates specifically in the photosynthetic antenna only when cultivated under blue-green light. The action spectra of pigment accumulation suggest that siphonaxanthin biosynthesis is regulated by a specific wavelength profile. The results provide clues to a new acclimation mechanism to withstand hours of intense light at low tide and why siphonous algae have been growing invasively on the world's coasts for more than a century.

Clinicopathological assessment of cancer/testis antigens NY­ESO­1 and MAGE­A4 in osteosarcoma.

The cancer/testis antigens (CTAs), New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and melanoma antigen gene (MAGE)-A4 are normally restricted to male germ cells but are aberrantly expressed in several cancers. Considering the limited information regarding their significance in osteosarcoma (OS), the purpose of this study was to determine the clinical significance of NY-ESO-1 and MAGE-A4 expression in OS. Nine patients with OS treated at Kindai University Hospital were included in the study. The median age was 27 years, and median follow-up period was 40 months. The specimens obtained at the time of biopsy were used to perform immunostaining for NY-ESO, MAGE-A4, p53, and Ki-67. The positive cell rates and positive case rates of NY-ESO, MAGE-A4, p53, and Ki-67 were calculated. The correlation between the positive cell rate of immunohistochemical markers was also calculated. The correlation between the positive cell rate of NY-ESO-1 or MAGE-A4 and tumor size or maximum standardized uptake (SUV-max) was also determined. The positive cell rates of NY-ESO-1 or MAGE-A4 in continuous disease-free (CDF) cases were also compared with those in alive with disease (AWD) or dead of disease (DOD) cases. The average positive cell rates of NY-ESO, MAGEA4, p53, and Ki-67 were 71.7%, 85.1%, 16.2%, and 14.7%, and their positive case rates were 33.3%, 100%, 44.4%, and 100%, respectively. The positivity rates of NY-ESO-1 and p53 were strongly correlated, whereas those of NY-ESO-1 and Ki-67 were moderately correlated. The MAGE-A4 and p53 positivity rates and the MAGE-A4 and Ki-67 positive cell rates were both strongly correlated. The NY-ESO-1 and MAGE-A4 positivity rates were moderately correlated. The positive correlation between the NY-ESO-1 positive cell rate and tumor size was medium, and that between the MAGE-A4 positivity rate and SUV-max was very strong. There was no significant difference in the positive cell rates of NY-ESO-1 or MAGE-A4 between CDF cases and AWD or DOD cases. Overall, our results suggest that NY-ESO-1 and MAGE-A4 may be involved in the aggressiveness of OS.

SARS-CoV-2 RNA in Wastewater Was Highly Correlated With the Number of COVID-19 Cases During the Fourth and Fifth Pandemic Wave in Kobe City, Japan.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the current coronavirus disease 2019 (COVID-19) pandemic and associated respiratory infections, has been detected in the feces of patients. Therefore, determining SARS-CoV-2 RNA levels in sewage may help to predict the number of infected people within the area. In this study, we quantified SARS-CoV-2 RNA copy number using reverse transcription quantitative real-time PCR with primers and probes targeting the N gene, which allows the detection of both wild-type and variant strain of SARS-CoV-2 in sewage samples from two wastewater treatment plants (WWTPs) in Kobe City, Japan, during the fourth and fifth pandemic waves of COVID-19 between February 2021 and October 2021. The wastewater samples were concentrated via centrifugation, yielding a pelleted solid fraction and a supernatant, which was subjected to polyethylene glycol (PEG) precipitation. The SARS-CoV-2 RNA was significantly and frequently detected in the solid fraction than in the PEG-precipitated fraction. In addition, the copy number in the solid fraction was highly correlated with the number of COVID-19 cases in the WWTP basin (WWTP-A: r = 0.8205, p < 0.001; WWTP-B: r = 0.8482, p < 0.001). The limit of capturing COVID-19 cases per 100,000 people was 0.75 cases in WWTP-A and 1.20 cases in WWTP-B, respectively. Quantitative studies of RNA in sewage can be useful for administrative purposes related to public health, including issuing warnings and implementing preventive measures within sewage basins.

Ultrafast excited state dynamics of fucoxanthin: excitation energy dependent intramolecular charge transfer dynamics.

Carotenoids containing a carbonyl group in conjugation with their polyene backbone are naturally-occurring pigments in marine organisms and are essential to the photosynthetic light-harvesting function in aquatic algae. These carotenoids exhibit spectral characteristics attributed to an intramolecular charge transfer (ICT) state that arise in polar solvents due to the presence of the carbonyl group. Here, we report the spectroscopic properties of the carbonyl carotenoid fucoxanthin in polar (methanol) and nonpolar (cyclohexane) solvents studied by steady-state absorption and femtosecond pump-probe measurements. Transient absorption associated with the optically forbidden S(1) (2(1)A) state and/or the ICT state were observed following one-photon excitation to the optically allowed S(2) (1(1)B) state in methanol. The transient absorption measurements carried out in methanol showed that the ratio of the ICT-to-S(1) state formation increased with decreasing excitation energy. We also showed that the ICT character was clearly visible in the steady-state absorption in methanol based on a Franck-Condon analysis. The results suggest that two spectroscopic forms of fucoxanthin, blue and red, exist in the polar environment.

Limitations and usefulness of biopsy techniques for the diagnosis of metastatic bone and soft tissue tumors.

BACKGROUND: Biopsies are widely used for diagnosing metastatic tumors in the bone and soft tissues; however, their usefulness and limitations remain unclear. PATIENTS AND METHODS: Biopsies of patients (13 men, 8 women, mean age 76 years) with metastatic tumors in the bone (19 patients) and soft tissues (2 patients) were reviewed retrospectively. Investigators surveyed the lesion sites, medical histories, Eastern Cooperative Oncology Group (ECOG) Performance Status (PS), biopsy sites, methods, comorbidities, diagnoses, treatments, and outcomes. RESULTS: Five patients had multiple lesions, and 16 patients had one lesion. The ECOG PS scores were PS0 (11 patients), PS1 (7 patients), PS2 (2 patients), and PS3 (1 patient). Biopsy sites included pelvic bone (6 cases), rib bone (5 cases), spinal vertebra (7 cases), soft tissue of the shoulder (2 cases), and inner retroperitoneum (1 case). Diagnostic methods included open biopsy (8 patients), core needle biopsy under general (7 patients) or local (3 patients) anesthesia, and computed tomography-guided core needle biopsy under local anesthesia (3 patients). Histology indicated hematological malignancies (9 cases); breast cancer (3 patients); lung cancer, renal cell cancer, cancer of unknown primary (2 cases each); prostate cancer, endometrial (uterine) cancer, and myxoid liposarcoma (1 case each). The primary site identification rate was 90.5%. Outcomes included three patients "dead of disease." CONCLUSION: Biopsies are useful for early diagnosis and for the scrutiny of primary lesions of metastatic bone and soft tissue tumors. If the primary tumor is still unknown after biopsy, evidence-based treatment should be initiated promptly.

Clinical features and outcomes of primary bone and soft tissue sarcomas in adolescents and young adults.

The aim of the present study was to investigate the clinical outcomes of adolescents and young adults with bone and soft tissue sarcomas. Records of seven male and six female patients aged 17-39 years with bone or soft tissue sarcomas were reviewed retrospectively; data on histology, size, location, grade/stage, treatment, recurrence, presence of metastasis, and prognosis were retrieved. Five-year survival rates were estimated using the Kaplan-Meier method and were compared according to age, sarcoma type, histological grade, and location. Seven and six patients had bone and soft tissue sarcomas, respectively. In terms of histology, patients with bone sarcomas included four with osteosarcoma, two with chondrosarcoma, and one with Ewing sarcoma of the bone. Of those with soft tissue sarcomas, three had liposarcomas, two had synovial sarcomas, and one each had Ewing sarcoma and leiomyosarcoma. The five-year survival rate of the cohort was 57.1%. Younger patients with sarcoma had poorer survival than older patients. Patients with high-grade sarcomas also had poorer survival than those with low-grade tumors. In addition, patients with trunk-located tumors had poorer survival than those with tumors in the extremities. These findings suggest that, younger adolescents and young adults with high-grade or trunk-located sarcomas require more aggressive treatment.

Surgical management of sarcoma in adolescent and young adult patients.

OBJECTIVE: To examine the clinical features and outcomes of adolescent and young adult sarcoma patients who underwent surgical management and clarify important factors associated with prognosis. We reviewed 18 young adult sarcoma patients sarcoma patients treated surgically in our hospital. The tumor site, histology, grade, stage, and American Society of Anesthesiologists-Physical Status before surgery, operation time, intraoperative blood loss, complications, surgical margin, local recurrence, metastasis, and outcomes were investigated. The 3-year survival rate was also calculated. We compared survival based on age, grade, and surveyed features of poor outcome cases. RESULTS: The 3-year survival rate was 61.3%. There was no significant difference in survival based on age, grade, operation time, or intraoperative blood loss. Three of five patients who died of the disease had stage ≥ IV at diagnosis. All patients with R1 surgical margins developed recurrence and all those with an American Society of Anesthesiologists-Physical Status ≥ 2 died. Patients with late-stage sarcomas, R1 tumor margin, or high American Society of Anesthesiologists-Physical Status score had poor prognoses. To achieve a favorable outcome in adolescent and young adult sarcoma patients, early detection and obtaining R0 ≥ surgical margin are essential.

Outcomes of comprehensive treatment for primary osteosarcoma.

PURPOSE: This study aimed to evaluate the clinical features and outcomes of osteosarcoma to identify prognostic factors and determine new strategies to improve overall survival. PATIENTS AND METHODS: We retrospectively analyzed 12 cases of osteosarcoma treated at our hospital from 2012 to 2017. Tumor site, tissue type, stage, treatments, adverse effects, postoperative limb function, surgical margin, and final outcomes were evaluated. RESULTS: All patients received chemotherapy, and 10 underwent wide resection. The Musculoskeletal Tumor Society scores were more than good in all cases, and the 3-year survival rate was 73.3%. Two patients are alive with disease, eight have remained disease-free, and two died of the disease. Three of the four recurrent cases involved the pelvis. CONCLUSION: The treatment of primary osteosarcoma with wide resection in our department, therefore, yielded favorable outcomes. However, improved treatment strategies are needed for pelvic and advanced cases.

Ascorbate sensitizes human osteosarcoma cells to the cytostatic effects of cisplatin.

Osteosarcoma (OS) is the most common malignant bone tumor and a leading cause of cancer-related deaths in children and adolescents. Current standard treatments for OS are a combination of preoperative chemotherapy, surgical resection, and adjuvant chemotherapy. Cisplatin is used as the standard chemotherapeutic for OS treatment, but it induces various adverse effects, limiting its clinical application. Improving treatment efficacy without increasing the cisplatin dosage is desirable. In the present study, we assessed the combined effect of ascorbate on cisplatin treatment using cultured human OS cells. Co-treatment with ascorbate induced greater suppression of OS cell but not nonmalignant cell proliferation. The chemosensitizing effect of ascorbate on cisplatin treatment was tightly linked to ROS production. Altered cellular redox state due to increased ROS production modified glycolysis and mitochondrial function in OS cells. In addition, OS cell sphere formation was markedly decreased, suggesting that ascorbate increased the treatment efficacy of cisplatin against stem-like cells in the cancer cell population. We also found that enhanced MYC signaling, ribosomal biogenesis, glycolysis, and mitochondrial respiration are key signatures in OS cells with cisplatin resistance. Furthermore, cisplatin resistance was reversed by ascorbate. Taken together, our findings provide a rationale for combining cisplatin with ascorbate in therapeutic strategies against OS.

Angiolymphoid hyperplasia with eosinophilia in a hand treated with a reverse digital island flap and artificial skin: a case report.

BACKGROUND: Angiolymphoid hyperplasia with eosinophilia is a rare nodular skin tumor characterized by eosinophilic invasion and vascular proliferation. Previous reports suggested that irritation and inflammation are the causative factors of this disease. Most cases of angiolymphoid hyperplasia with eosinophilia occur around the auricle, forehead, and scalp; the hand is rarely affected. Moreover, the tumor seldom presents as multiple nodules. CASE PRESENTATION: A 67-year-old Japanese woman presented with a complaint of skin masses on her left thumb and index finger, which had gradually grown in size over the past few months. A biopsy was performed confirming a diagnosis of angiolymphoid hyperplasia with eosinophilia. The aponeurosis on her index finger was resected and tissue was reconstructed using a reverse palmar digital island flap harvested from the base of her index finger. The thumb lesion was also resected and covered with collagen-based artificial skin. Gradual progression of skin epithelialization followed by healing was noted 2 months after the surgery. CONCLUSION: Angiolymphoid hyperplasia with eosinophilia is a rare tumor; it is seldom seen in the hands. It is generally treated by surgical resection. It is important to resect a sufficiently large area of the tissue due to the possibility of relapse in some cases. Furthermore, appropriate reconstruction is mandatory after wide margin tumor resection.

Clinical outcomes of patients with primary malignant bone and soft tissue tumor aged 65 years or older.

The number of elderly patients with sarcoma (65 years or older) has increased with the rise in the aging of society. As it is difficult to treat elderly sarcoma patients in the same manner as younger patients, the present study sought to compare treatment options currently available for elderly patients. The present study was comprised 34 Japanese patients (21 men and 13 women) with malignant bone or soft tissue tumors who underwent surgery in our department from September 2004 to March 2014. The median patient age was 72 years (range, 65-86 years). Histologically, 23 cases were categorized as high-grade and 11 as low-grade. Treatments included surgery with adequate margins (25 cases), surgery with inadequate margins and radiotherapy (4 cases), surgery with inadequate margins and chemotherapy (3 cases) and intralesional resection (2 cases). The postoperative follow-up period ranged from 7 to 112 months (average, 49 months). The 5-year survival rates were determined and compared using the Kaplan-Meier method and log-rank test, respectively. Eastern Cooperative Oncology Group Performance Status (ECOG-PS) and Anesthesiologists-Physical Status (ASA-PS) scores were also determined. The overall 5-year survival rate was 86.02%; it differed significantly between patients with high-grade (100%) vs. low-grade (74.3%) neoplasms P<0.001), but not between patients aged 65-69 (76.9%) vs. ≥70 (90.2%) years-old (P=0.65). Tumor status was classified as follows: i) Continuously disease-free, n=24 cases; ii) alive with disease, n=3 cases; iii) and dead of disease, n=7 cases. The ECOG-PS status scores were 0 in 9 cases, 1 in 21 cases, and 2 in 4 cases. ASA-PS scores were also I in 9 cases and II in 23 cases. Thus, the primary treatment for elderly patients with sarcoma should be surgery alone as no additional benefits were obtained when radiotherapy or chemotherapy was also performed. Adequate margins should be confirmed along with the histology of surgical specimens.

Aggressive superficial acral fibromyxoma of the great toe: A case report and mini-review of the literature.

Superficial acral fibromyxoma is a very rare soft tissue tumor. Fetsch et al first described the condition in 2001. It often occurs in the fingers and toes and has slow-progressive features. Since being described, a few cases occurring in the great toe have been reported. The present study indicated a case of a 37-year-old male kickboxer with a history of a rapid-growing lump under the nail of his left great toe with bone erosion. The patient was suspected to have a soft tissue tumor under the nail, such as a glomus tumor, as a differential diagnosis. However, a malignant soft tissue tumor as a differential diagnosis could not be ruled out because of the observed bone erosion. The patient underwent surgical excision, and pathologic analysis revealed superficial acral fibromyxoma. Twenty-four months after the treatment, he had no complaints or functional disorder and no recurrence was noted. Although an unusual diagnosis, surgeons should be aware of this tumor, which requires complete surgical excision and follow-up to detect recurrence. To the best of our knowledge, this is the first reported case of superficial acral fibromyxoma with bone erosion in a great toe.

Tuberculoma with phlegmon-like symptoms mimicking soft tissue sarcoma in the wrist: A case report.

Despite the increasing incidence of tuberculosis, even in developed countries like Japan, tuberculoma is a relatively uncommon disease. Furthermore, given the rarity of tuberculoma, a definitive diagnosis is often delayed. We herein present the case of a 79-year-old man who presented with an erythematous and warm mass in the left forearm. Radiography revealed calcification of the wrist's volar side, and magnetic resonance imaging revealed a mosaic pattern at the lesion. Soft tissue sarcoma of the wrist was suspected, and an incisional biopsy was performed, which revealed numerous yellow rice bodies. A rapid pathological evaluation revealed caseous necrosis and Langhans giant cells, and a histological evaluation confirmed the diagnosis of tuberculoma. All the rice bodies were resected and the patient received postoperative antibiotic treatment with pyrazinamide, isoniazid, rifampicin and ethambutol. However, the patient developed hepatic insufficiency during treatment, and the regimen was discontinued. The patient had not experienced recurrence 1 year after the treatment. In conclusion, tuberculoma should be considered in the differential diagnosis of a wrist mass mimicking an inflamed soft tissue tumor.