Disinfection and monitoring of Mycobacterium avium complex in the environment: A novel approach to the management of hot tub lung.

A 45-year-old man visited our hospital with a chronic cough and breathing difficulties. Chest computed tomography revealed diffuse granular shadows. Mycobacterium avium (M. avium) was cultured from bronchoalveolar lavage fluid (BALF). Surgical lung biopsy revealed non-necrotizing granulomas, and M. avium-specific PCR was positive in the tissue. M. avium was also cultured in a sample from the inlet of the patient's bathtub. Mycobacterium avium tandem repeat variable-number tandem-repeat loci (MATR-VNTR) analysis confirmed that the M. avium cultured from BALF and the bathtub inlet had identical allele profiles. The patient's symptoms and oxygenation improved while the patient was in hospital, presumably because of lack of ongoing exposure to M. avium. He was diagnosed with hot tub lung. We advised the patient to avoid bathing to avoid re-exposure. However, the patient was unwilling to follow this advice. Therefore, his bathtub and pipework were disinfected by heating them to over 70 °C. We confirmed that the disinfection has been successful by repeated culture of environmental samples. Three months after resuming bathtub use, the patient's symptoms resolved, and the pulmonary shadows seen on the initial radiography did not recur. For the treatment of hot tub lung, disinfection of M. avium complex in the environment should be considered and the environment should be monitored to confirm eradication.

Galectin-3 in bone tumor microenvironment: a beacon for individual skeletal metastasis management.

The skeleton is frequently a secondary growth site of disseminated cancers, often leading to painful and devastating clinical outcomes. Metastatic cancer distorts bone marrow homeostasis through tumor-derived factors, which shapes different bone tumor microenvironments depending on the tumor cells' origin. Here, we propose a novel insight on tumor-secreted Galectin-3 (Gal-3) that controls the induction of an inflammatory cascade, differentiation of osteoblasts, osteoclasts, and bone marrow cells, resulting in bone destruction and therapeutic failure. In the approaching era of personalized medicine, the current treatment modalities targeting bone metastatic environments are provided to the patient with limited consideration of the cancer cells' origin. Our new outlook suggests delivering individual tumor microenvironment treatments based on the expression level/activity/functionality of tumor-derived factors, rather than utilizing a commonly shared therapeutic umbrella. The notion of "Gal-3-associated bone remodeling" could be the first step toward a specific personalized therapy for each cancer type generating a different bone niche in patients afflicted with non-curable bone metastasis.

Angiomatoid fibrous histiocytoma: a series of seven cases including genetically confirmed aggressive cases and a literature review.

BACKGROUND: Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor of intermediate biologic potential. Because of its rarity and nonspecific radiological and diverse pathological findings, AFH is often clinically misdiagnosed. However, few clinical reports have described this tumor. As reported herein, we analyzed the clinical and radiological features and clinical outcomes of AFH. METHODS: We retrospectively reviewed the medical records of seven cases histopathologically diagnosed as AFH. We examined clinical features, MRI findings, histopathological diagnoses, treatments, and outcomes. RESULTS: These seven cases comprised five male and two female patients with ages ranging from 8 to 50 years old. The primary locations included upper extremities in 2, lower extremities in 4, and the inguinal region in one patient. Of the tumors, 4 occurred in subcutaneous tissues and 3 occurred in deep tissues. No cases were diagnosed as AFH from MRI and needle biopsy results. All cases were diagnosed histopathologically after excision. After treatment, 2 patients (29%) had tumor recurrence and metastasis, one of whom died from disease progression. These 2 aggressive cases involved both EWSR1 and CREB1 gene rearrangements as determined by FISH. The other patients were alive and well without recurrence or metastasis. CONCLUSION: AFH is a rare tumor that is difficult to diagnose. Therefore, it tends to be misdiagnosed and to be treated inadequately by referring physicians. Surgeons must therefore be mindful of the presence of AFH, learn about appropriate treatment necessary for this tumor, and conduct careful follow-up because AFH can engender poor outcomes.

L-type amino acid transporter-1 and CD98 expression in bone and soft tissue tumors.

L-type amino acid transporter-1 (LAT1) is expressed in many cancers. We examined LAT1 and CD98 expression immunohistochemically in surgically resected specimens of various bone and soft tissue tumors. Out of 226 cases, 79 (35%) were LAT1(+) and 95 (42%) were CD98(+) . In bone tumors, LAT1 was highly expressed in osteoblastoma (89%), chondrosarcoma (50%), and osteosarcoma (60%); in soft tissue tumors, LAT1 was highly expressed in rhabdomyosarcoma (80%), synovial sarcoma (63%), Ewing's sarcoma (60%), epithelioid sarcoma (100%) and angiosarcoma (100%). In malignant soft tissue tumors, LAT1 expression was associated with higher histological grade. High CD98 expression was seen in many bone tumors of intermediate and high malignancy. Among soft tissue tumors, CD98 was expressed in tendon sheath giant cell tumor and malignant peripheral nerve sheath tumor (57%), Ewing's sarcoma (50%) and undifferentiated sarcoma (64%). Some of the malignant soft tissue tumors expressed both LAT1 and CD98. This study showed that LAT1 and CD98 was expressed in many malignant and intermediate bone tumors, and some malignant soft tissue tumors.

Lung squamous cell carcinoma responding to nivolumab retreatment six years after initial treatment: A case report.

A 61-year-old man presented to our hospital with a chief complaint of chronic cough. He was diagnosed with lung squamous cell carcinoma at clinical stage cT2aN3M1a. He received chemotherapy up to the fourth line, but both the primary tumor and lymph node metastases increased in size. Nivolumab, administered as the fifth line, resulted in a complete response (CR) that continued for 2 years and 8 months. Treatment was stopped due to the appearance of common terminology criteria for adverse events grade 1 pneumonitis. He was followed up without treatment for 3 years and 8 months, but a left supraclavicular fossa lymph node metastasis appeared. Retreatment with nivolumab was initiated, and the patient achieved CR again. One year and 6 months after retreatment, CR was maintained with nivolumab. This case represents a rare instance in which nivolumab yielded a significant response after a prolonged immune checkpoint inhibitor (ICI)-free interval. Our experience has shown that the long-term response to ICIs may deteriorate in the future. Therefore, retreatment with ICIs may be effective when the initial therapy is successful.

Vascular endothelial growth factor-D is a key molecule that enhances lymphatic metastasis of soft tissue sarcomas.

Studies on lymph node metastasis of soft tissue sarcomas are insufficient because of its rarity. In this study, we examined the expressions of vascular endothelial growth factor (VEGF)-C and VEGF-D in soft tissue sarcomas metastasized to lymph nodes. In addition, the effects of the two molecules on the barrier function of a lymphatic endothelial cell monolayer against sarcoma cells were analyzed. We examined 7 patients who had soft tissue sarcomas with lymph node metastases and who had undergone neither chemotherapy nor radiotherapy before lymphadenectomy. Immunohistochemistry revealed that 2 of 7 sarcomas that metastasized to lymph nodes expressed VEGF-C both in primary and metastatic lesions. On the other hand, VEGF-D expression was detected in 4 of 7 primary and 7 of 7 metastatic lesions, respectively. Interestingly, 3 cases that showed no VEGF-D expression at primary sites expressed VEGF-D in metastatic lesions. Recombinant VEGF-C at 10(-8) and VEGF-D at 10(-7)and 10(-8)g/ml significantly increased the random motility of lymphatic endothelial cells compared with controls. VEGF-D significantly increased the migration of sarcoma cells through lymphatic endothelial monolayers. The fact that VEGF-D induced the migration of fibrosarcomas through the lymphatic endothelial monolayer is the probable reason for the strong relationship between VEGF-D expression and lymph node metastasis in soft tissue sarcomas. The important propensities of this molecule for the increase of lymph node metastases are not only lymphangiogenesis but also down-regulation of the barrier function of lymphatic endothelial monolayers, which facilitates sarcoma cells entering the lymphatic circulation.

Randomized controlled trial comparing antioxidant-enriched enteral nutrition with immune-enhancing enteral nutrition after esophagectomy for cancer: a pilot study.

PURPOSE: The objective of this study was to compare the effects of two types of enteral supplements, an antioxidant-enriched enteral nutrition (AeEN) and an immune-enhancing enteral nutrition (IeEN), on the nutrition, immunoinflammatory response, antioxidant capacity and clinical outcomes in patients after esophagectomy for cancer. METHODS: Patients (n = 20) undergoing esophagectomy for cancer were randomized in this single-center, open-label study. Two types of enteral supplements were used for 5 days before surgery and 7 days after surgery. The circulating levels of nutritional markers, immunoinflammatory markers, oxidative stress markers, and the antioxidant capacity were compared throughout the perioperative period, and the patients' clinical outcomes were also compared. RESULTS: The circulating levels of nutritional markers decreased after surgery, but the changes were not significantly different between the AeEN group and the IeEN group throughout the perioperative period. Surgery increased the immunoinflammatory markers, and the levels were not significantly different between the groups after surgery. Surgery also increased the levels of oxidative stress markers, but there were no significant differences between the groups throughout the study period. CONCLUSIONS: The results of this pilot study suggest that AeEN and IeEN have a similar effect on nutrition, the immunoinflammatory response, antioxidant capacity and clinical outcomes after esophagectomy for cancer. These findings, therefore, warrant further studies on a larger scale.

Lumbar corsets can decrease lumbar motion in golf swing.

Swinging a golf club includes the rotation and extension of the lumbar spine. Golf-related low back pain has been associated with degeneration of the lumbar facet and intervertebral discs, and with spondylolysis. Reflective markers were placed directly onto the skin of 11young male amateur golfers without a previous history of back pain. Using a VICON system (Oxford Metrics, U.K.), full golf swings were monitored without a corset (WOC), with a soft corset (SC), and with a hard corset (HC), with each subject taking 3 swings. Changes in the angle between the pelvis and the thorax (maximum range of motion and angular velocity) in 3 dimensions (lumbar rotation, flexion-extension, and lateral tilt) were analyzed, as was rotation of the hip joint. Peak changes in lumbar extension and rotation occurred just after impact with the ball. The extension angle of the lumbar spine at finish was significantly lower under SC (38°) or HC (28°) than under WOC (44°) conditions (p < 0.05). The maximum angular velocity after impact was significantly smaller under HC (94°/sec) than under SC (177°/sec) and WOC (191° /sec) conditions, as were the lumbar rotation angles at top and finish. In contrast, right hip rotation angles at top showed a compensatory increase under HC conditions. Wearing a lumbar corset while swinging a golf club can effectively decrease lumbar extension and rotation angles from impact until the end of the swing. These effects were significantly enhanced while wearing an HC. Key pointsRotational and extension forces on the lumbar spine may cause golf-related low back painWearing lumbar corsets during a golf swing can effectively decrease lumbar extension and rotation angles and angular velocity.Wearing lumbar corsets increased the rotational motion of the hip joint while reducing the rotation of the lumbar spine.

A New Procedure for Reconstructing the Knee Extension Mechanism After Resection of the Knee Joint and Patella: A Case Report.

CASE: We reconstructed the knee extension mechanism using a novel procedure for a 16-year-old adolescent girl with osteosarcoma that invaded her femur, patella, and patellar tendon. The knee joint was replaced with a megaprosthesis, and the extension mechanism was reconstructed using artificial ligaments sandwiched with bone cement forming a patella. At the one-year follow-up, she could walk using a knee orthosis without crutches. CONCLUSIONS: Reconstruction of the knee extension mechanism after patellectomy remains challenging. Our new method achieved an acceptable knee function and is, therefore, useful for patients undergoing excision of the knee joint and extension mechanism.

Pure Red Cell Aplasia Induced by Atezolizumab in a Patient with Small-Cell Lung Cancer Successfully Treated with Steroid Therapy: A Case Report.

Introduction: Combination therapy of atezolizumab and chemotherapy has become the standard treatment for small-cell lung cancer. Immune-related adverse events (irAEs) can occur during immune checkpoint inhibitor administration. A few reports exist on pure red cell aplasia (PRCA) as an irAE after atezolizumab treatment. PRCA is characterized by normocytic-normochromic anemia, a marked decrease in reticulocytes, and a decrease in bone marrow erythroblasts. Here, we report a case of atezolizumab-induced PRCA. Case Presentation: A 69-year-old male patient was brought to the emergency department with the chief complaint of seizures. Multiple metastatic brain tumors and a mass suspected to be the primary lesion in the right hilar region were observed. After a brain biopsy, he was diagnosed with small-cell lung cancer (cT1cN0M1c stage IVB). He received four courses of carboplatin, etoposide, and atezolizumab in combination with whole-brain irradiation, which led to a partial response. After six courses of atezolizumab maintenance therapy, severe anemia (hemoglobin, 3.4 g/dL) was observed. PRCA induced by atezolizumab was diagnosed using a bone marrow biopsy performed during red blood cell transfusion. Treatment was started with prednisolone 25 mg/day (0.5 mg/kg/day). Anemia improved, and the dose was gradually reduced to 5 mg/day. Conclusion: Reports of PRCA as an irAE are rare but important; hence, we reported this case.

Target concentration achievement for efficacy and safety of patients with osteosarcoma treated with high-dose methotrexate based on individual pharmacokinetics: A retrospective study.

In the high-dose methotrexate (HD-MTX) treatment of patients with osteosarcoma, a dose-adjustment method using individual pharmacokinetic parameters (PK method) to optimize the concentration was developed in 2010. However, to the best of our knowledge, the clinical usefulness of the PK method has not been verified until now. In the present retrospective study, to assess the usefulness of the PK method, the achievement rate of an effective and safe concentration range was evaluated. A total of 43 patients with osteosarcoma who were administered HD-MTX therapy (43 first courses and 200 subsequent courses) were enrolled. The MTX dose in the first course was determined using a common method based on body surface area (BSA method); a total of 8-12 g/m2 was administered as an initial dose for 1 h and a maintenance dose for 5 h. In the subsequent courses, loading and maintenance doses were calculated by the PK method based on the serum MTX concentration profile of the previous course. The effective target concentration during 1-6 h after the start of MTX administration was 700-1,000 µmol/l, whereas the target safe MTX level was less than 10, 1 and 0.1 µmol/l at 24, 48 and 72 h, respectively. Notably, the rate of achieving the effective target concentration was significantly higher when using the PK method as compared to that when using the BSA method. The achievement rate of the safe target concentration at 24, 48 and 72 h when using the PK method was significantly higher. Additionally, the incidence of abnormal laboratory values of aspartate aminotransferase and alanine aminotransferase was significantly lower when using the PK method. Therefore, the PK method was suggested to be very useful in HD-MTX therapy for patients with osteosarcoma.

An 83-year-old patient with RET fusion-positive non-small cell lung cancer experiencing severe hepatic disorder due to selpercatinib administration.

An 83-year-old woman with RET fusion-positive advanced lung adenocarcinoma was administered selpercatinib 320 mg/day. Despite the shrinking of the tumour, fever, fatigue, and anorexia developed on day 17. Selpercatinib administration was interrupted. On day 21, elevated blood aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were observed. On day 28, AST and ALT levels increased to demonstrate Grade 4 in CTCAE Ver.5. The patient received a glycyrrhizin-compounding agent and steroid treatment, and AST and ALT levels gradually decreased. On day 63, selpercatinib 160 mg/day was restarted after improvement of the hepatic disorder. Since then, selpercatinib was continued without any severe adverse events. Selpercatinib is a reasonable treatment option for RET fusion-positive advanced non-small cell lung cancer even in older patients. However, old age may be a risk factor for adverse events including hepatic disorders. For safe treatment in such patients, careful follow-up is required.

Changes in Acidity Levels in the Gastric Tube After Esophagectomy for Esophageal Cancer.

Reflux esophagitis and gastric tube ulcer sometimes cause severe clinical problems in patients undergoing esophagectomy with gastric tube reconstruction. We previously reported that acidity in the gastric tube was decreased for 1 year after esophagectomy, and that lower acidity levels were associated with Helicobacter pylori (H. pylori) infection. However, the long-term changes in gastric acidity remain unknown. We aimed to investigate the long-term changes in gastric acidity after surgery. Eighty-nine patients who underwent esophagectomy with gastric tube reconstruction for esophageal cancer were analyzed. They underwent 24-hour pH monitoring, serum gastrin measurement, and H. pylori infection examination before surgery, at 1 month, 1 year, and 2 years after surgery. The gastric acidity at 1 month and 1 year after surgery was significantly lower than that before surgery (p=0.003, p=0.003). However, there was no difference in gastric acidity before and 2 years after surgery. The gas tric acidity in H. pylori-infected patients was significantly lower in comparison to non-infected patients at each time point (p=0.0003, p<0.0001, p<0.0001, p<0.0001, respectively). In H. pylori-infected patients, gastric acid ity was decreased for 1 year after surgery, and recovered within 2 years after surgery. However, no significant differences were observed in the acidity levels of non-infected patients during the 2-year follow-up period. The serum gastrin level increased after esophagectomy. The acidity levels in the gastric tube recovered within 2 years after surgery. Periodic endoscopy examination is recommended for early detection of acid-related disease, such as reflux esophagitis or gastric tube ulcer, after esophagectomy with gastric tube reconstruction.

Effectiveness of the Gerdq Questionnaire for Diagnosing Gastroesophageal Reflux Disease After Esophagectomy for Esophageal Cancer.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common complication after esophagectomy with gastric tube reconstruction. The GerdQ questionnaire was developed for diagnosing GERD in primary care patients. Its effectiveness in patients after esophagectomy remains unknown. In this study, we evaluated the usefulness of the GerdQ questionnaire for diagnosing GERD after esophagectomy for esophageal cancer. MATERIALS AND METHODS: A total of 124 patients with esophageal cancer underwent right transthoracic esophagectomy with gastric tube reconstruction between January 2010 and December 2016. Esophagogastroduodenoscopy and 24-hour esophageal pH-metry were performed at 1 month, 1 year, and 2 years postoperatively. The GerdQ questionnaire was administered at the same postoperative time points. We assessed any correlation between the GerdQ scores and the endoscopy and pH-metry findings. RESULTS: The incidence rates of GERD at 1 month, 1 year and 2 years post-surgery were 31.6%, 46.9%, and 49.2%, respectively. The GerdQ questionnaire showed 77% sensitivity and 56% specificity for diagnosing GERD at 2 years after esophagectomy when the cutoff point was 7. However, the optimal cutoff points were different at each postoperative time, and the scores showed some imbalance between sensitivity and specificity. Regurgitation may be a useful indicator, as the frequency of regurgitation was significantly higher in patients with GERD than in patients without GERD at 1 year (P = 0.046) and 2 years postoperatively (P = 0.048). CONCLUSION: The GerdQ questionnaire is not a useful diagnostic tool for GERD in patients who have undergone esophagectomy for esophageal cancer.

Solid variant of aneurysmal bone cyst in the tibia treated with simple curettage without bone graft: a case report.

The solid variant of aneurysmal bone cyst (solid ABC) is rarely encountered in long bones and appropriate treatment for this disease remains unclear. We experienced a 13-year-old boy suffering from pain in his left knee caused by solid ABC. Simple curettage of the bone lesion without any adjuvant therapy and a bone graft gave immediate pain relief. Histological examination of the surgical specimen showed typical features of solid ABC, and cycloxygenase-2 (COX-2) expression was confirmed in giant cells with a background of spindle cells by immunohistochemistry. Magnetic resonance imaging showed that soft tissue edema surrounding the lesion was improved two months after surgery and there was no indication of recurrence two years after surgery. If COX-2 secreted from the tumor induces soft tissue edema, simple curettage of the bone lesion seems to be a reasonable treatment for solid ABC and is able to minimize invasive treatment of the patients.

A risk factor analysis for local recurrence of bone and soft tissue sarcoma treated with carbon ion radiotherapy: A retrospective cohort study at a single institution.

AIM: Carbon ion radiotherapy is well-recognized as an excellent radiation modality that is suitable for treating unresectable bone and soft-tissue sarcoma of the trunk, spine, and pelvis; however, further study is needed to improve the local control rate. The current study examined the risk factors of the local recurrence of sarcomas after carbon ion radiotherapy. METHODS: Patients with inoperable bone and soft-tissue sarcomas treated with carbon ion radiotherapy in our institute from 2010 to 2018 were retrospectively analyzed. Among them, 87 patients were eligible for this study. We divided the instances of local recurrence into two types, in-field and out-field recurrence, and evaluated the predictors for the risk of local recurrence such as the age at the treatment, sex, histopathological diagnosis, standard uptake value on fluorodeoxyglucose positron emission tomography, and the clinical target volume for each recurrence using a Cox proportional hazards model. RESULTS: A multivariate analysis revealed that the tumors with a post-treatment standard uptake value of more than 3.84 on positron emission tomography had a significantly high risk of in-field recurrence (hazard ratio, 3.42; p = .03). Furthermore, postoperative lesions were a risk factor for out-field recurrence (hazard ratio, 3.82; p < .01). CONCLUSION: The current study revealed that sarcomas maintaining a high glucose metabolic activity after carbon ion radiotherapy carried a risk of in-field recurrence, and the most significant risk factor of out-field recurrence was identified to be surgery before CIRT.

Proliferative flexor tenosynovitis in the index finger of a 10-year-old baseball player gloved hand: A case report.

Flexor tenosynovitis is rare in young children. This case report describes that of a 10-year-old boy with diffuse swelling of the left index finger, pain when catching a ball, and progressive inability for full flexing of the finger 2 months after starting baseball play. Magnetic resonance imaging showed a defined lesion with iso-signal intensity to muscle on T1-weighted imaging, and with high signal intensity to muscle on T2-weighted imaging. It was enhanced in T1-weighted fat suppression imaging with gadolinium enhancement. Surgical excision relieved the symptom. Histopathological findings mainly indicated proliferation of synoviocytes and plasma cell and lymphocyte infiltration. We speculated that the physical impact of the ball on the left index finger of his gloved hand during catching activated some immunological mechanism and thereby caused nonspecific tenosynovitis in this young baseball player. Awareness of this pathophysiology might raise confidence in proper diagnosis for assessing the swelling of fingers in young baseball players.

Long-term survival of two patients with inoperable post-irradiation osteosarcoma treated with carbon-ion radiotherapy: a case report.

BACKGROUND: Curative treatment of inoperable post-irradiation sarcoma is often challenging, especially using radiotherapy, wherein curative dose administration is difficult because the organs around the tumor have already been irradiated during the first cancer treatment. Carbon-ion radiotherapy (C-ion RT) might be useful in the treatment of post-irradiation sarcomas because it allows re-irradiation with high-dose localization properties and also demonstrates higher cytotoxic effects on radioresistant tumors compared with X-rays. This study presents the long-term survival of two patients with inoperable post-irradiation pelvic osteosarcoma treated with C-ion RT after uterine cervical cancer treatment. CASE PRESENTATION: The durations from prior radiotherapy to the diagnosis of post-irradiation osteosarcoma were 112.8 and 172.2 months, respectively. Both patients received 70.4 Gy (relative biological effectiveness) in 16 fractions of C-ion RT, and chemotherapy was performed before and after C-ion RT. Both patients achieved a complete response 1 year after the initiation of C-ion RT. However, one patient developed single lung metastasis 12.6 months after the initiation of C-ion RT and underwent thoracoscopic lobectomy. After 63.7 and 89.0 months from the initiation of C-ion RT, respectively, the patients were alive with no evidence of local recurrence, other distant metastasis, or fatal toxicities. CONCLUSIONS: The study findings suggest that C-ion RT is a suitable treatment option for inoperable post-irradiation osteosarcoma.

Evidence for cell density affecting C2C12 myogenesis: possible regulation of myogenesis by cell-cell communication.

INTRODUCTION: Community effect is a phenomenon caused by cell-cell communication during myogenesis. In myogenic C2C12 cells in vitro, the confluent phase is needed for myogenesis induction. METHODS: To examine the cell-density effect, growth kinetics and myogenic differentiation were investigated in cells plated at four different cell densities. RESULTS: We found that expression of a myogenic differentiation marker was high in a density-dependent manner. At high density, where cell-cell contact was obvious, contact inhibition after the proliferation stage was accompanied by microarray findings demonstrating upregulation of negative regulating cell-cycle markers, including CDKI p21 and the muscle differentiation markers MyoD and myogenin. Interestingly, developmentally regulated protein expression (drebrin) protein expression was also upregulated in a density-dependent manner. CONCLUSIONS: These results suggest that contact inhibition after the proliferation stage may induce growth arrest via cell-cell communication through the expression of CDKI p21 and may be responsible for progressing cell fusion.