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.

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.

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.

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.

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.

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.

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.

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.

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.

Cross-sectional Study of the Hip Joint Condition in Young Baseball Players.

OBJECTIVE: The hip joint is a crucial part of the kinetic chain for throwing baseball pitches. Nevertheless, few reports have described assessments of the functional development of the hip joint in young baseball players. METHODS: We examined 315 young baseball players, 7-14 years old, all of whom had completed a self-administered questionnaire including items related to the dominant side and throwing-related hip joint pain sustained during the previous year. We measured the hip ranges of motion (ROMs: external and internal rotation and flexion) and hip muscle strengths (external and internal rotation) on the dominant and non-dominant sides. The differences of hip ROMs and muscle strengths between the dominant and non-dominant sides and between age groups were investigated. Correlations were calculated between the players ages and hip ROMs and muscle strengths. RESULTS: No baseball player reported hip pain. The hip external rotation on the dominant side was smaller than that on the non-dominant side, whereas the hip internal rotation on the dominant side was greater than that on the non-dominant side. However, no significant difference was found between the dominant and non-dominant sides in terms of the hip muscle strength. Significant positive associations were found between the player's age and hip muscle strengths, whereas significant negative associations were found between the age and hip ROMs. CONCLUSIONS: Our data concerning the relationship between age and hip joint development could be useful for supporting strategies for the prevention and rehabilitation of throwing injuries; however, hip injuries might be rare among young baseball players.

Prospective Evaluation of Quality of Life and Functional Outcomes after Carbon Ion Radiotherapy for Inoperable Bone and Soft Tissue Sarcomas.

Carbon-ion radiotherapy (CIRT) represents a definitive treatment for inoperable bone and soft tissue sarcoma (BSTS). This prospective study analyzed 61 patients with inoperable BSTS who were treated with CIRT to evaluate QOL, functional outcomes, and predictive factors in patients with inoperable BSTS treated with definitive CIRT. The Musculoskeletal Tumor Society (MSTS) scoring system and the Short Form (SF)-8 questionnaire were completed before and at 1, 3, 6, 12, and 24 months after CIRT. The median follow-up period was 38 months. The main site of primary disease was the pelvis (70.5%), and the most common pathologic diagnosis was chordoma (45.9%). The 3-year overall survival and local control rates were 87.8% and 83.8%, respectively. The MSTS score and physical component score (PCS) of SF-8 did not change significantly between the baseline and subsequent values. The mental component score of SF-8 significantly improved after CIRT. Multivariate analysis showed that the normalized MSTS and normalized PCS of SF-8 at the final follow-up were significantly affected by performance status at diagnosis and sex. CIRT showed clinical efficacy, preserving the physical component of QOL and functional outcomes and improving the mental component of QOL, suggesting its potential value for the treatment of patients with inoperable BSTS.

Impact of Carbon Ion Radiotherapy on Inoperable Bone Sarcoma.

Management of patients with bone sarcoma who are unsuitable for surgery is challenging. We aimed to analyze the clinical outcomes among such patients who were treated with carbon ion radiotherapy (C-ion RT). We reviewed the medical records of the patients treated with C-ion RT between April 2011 and February 2019 and analyzed the data of 53 patients. Toxicities were classified using the National Cancer Institute's Common Terminology Criteria for Adverse Events (Version 4.0). The median follow-up duration for all patients was 36.9 months. Histologically, 32 patients had chordoma, 9 had chondrosarcoma, 8 had osteosarcoma, 3 had undifferentiated pleomorphic sarcoma, and 1 had sclerosing epithelioid fibrosarcoma. The estimated 3-year overall survival (OS), local control (LC), and progression-free survival (PFS) rates were 79.7%, 88.6%, and 68.9%, respectively. No patients developed grade 3 or higher acute toxicities. Three patients developed both grade 3 radiation dermatitis and osteomyelitis, one developed both grade 3 radiation dermatitis and soft tissue infection, and one developed rectum-sacrum-cutaneous fistula. C-ion RT showed favorable clinical outcomes in terms of OS, LC, and PFS and low rates of toxicity in bone sarcoma patients. These results suggest a potential role for C-ion RT in the management of this population.

Rectal dose-sparing effect with bioabsorbable spacer placement in carbon ion radiotherapy for sacral chordoma: dosimetric comparison of a simulation study.

It is difficult to treat patients with an inoperable sarcoma adjacent to the gastrointestinal (GI) tract using carbon ion radiotherapy (C-ion RT), owing to the possible development of serious GI toxicities. In such cases, spacer placement may be useful in physically separating the tumor and the GI tract. We aimed to evaluate the usefulness of spacer placement by conducting a simulation study of dosimetric comparison in a patient with sacral chordoma adjacent to the rectum treated with C-ion RT. The sacral chordoma was located in the third to fourth sacral spinal segments, in extensive contact with and compressing the rectum. Conventional C-ion RT was not indicated because the rectal dose would exceed the tolerance dose. Because we chose spacer placement surgery to physically separate the tumor and the rectum before C-ion RT, bioabsorbable spacer sheets were inserted by open surgery. After spacer placement, 67.2 Gy [relative biological effectiveness (RBE)] of C-ion RT was administered. The thickness of the spacer was stable at 13-14 mm during C-ion RT. Comparing the dose-volume histogram (DVH) parameters, Dmax for the rectum was reduced from 67 Gy (RBE) in the no spacer plan (simulation plan) to 45 Gy (RBE) in the spacer placement plan (actual plan) when a prescribed dose was administered to the tumor. Spacer placement was advantageous for irradiating the tumor and the rectum, demonstrated using the DVH parameter analysis.

Nutritional status and activities of daily living in patients with Parkinson's disease.

Patients with Parkinson's disease are often frail and likely to be malnourished. Several studies have reported the adverse effects of malnutrition on functional outcomes; however, the association between nutritional status and activities of daily living is unclear among patients with Parkinson's disease. This study aimed to investigate the relationship between nutritional status and activities of daily living in patients with Parkinson's disease. We conducted a retrospective cohort study with the data of 124 patients who were consecutively admitted to a rehabilitation hospital in Japan, among whom the data of 61 patients were included in the analyses. The Controlling Nutritional Status score was used to measure the nutritional status of the participants, and the motor subdomain of the Functional Independence Measure was used to assess the activities of daily living. Piecewise linear mixed-effects models were fitted to the data after adjusting for confounding factors. A poor nutritional status (i.e., Controlling Nutritional Status score >3) was significantly associated with a poor Functional Independence Measure gain, which was defined as difference in the score values of the Functional Independence Measures between discharge and admission. Our findings could aid in developing nutritional intervention programs for patients with Parkinson's disease by employing the Controlling Nutritional Status score to improve their activities of daily living.

A case of rheumatoid arthritis with multiple lung rheumatoid nodules successfully treated with tofacitinib.

Sporadic cases of rheumatoid nodules (RNs) in the lung during treatment with tumour necrosis factor (TNF) inhibitors have been reported, but no treatment has been established. Here, we report a case of symptomatic lung RNs refractory to abatacept (ABT) and intravenous cyclophosphamide (IVCY) that improved with tofacitinib (TOF) treatment. A 75-year-old Japanese woman with a 10-year history of rheumatoid arthritis (RA) presented with a cough and haemoptysis during treatment with etanercept (ETN). Radiographic examinations revealed multiple nodules that were diagnosed as lung RNs via biopsy. The ETN was discontinued and ABT followed by IVCY was introduced; however, neither was sufficiently effective against the lung RNs. Thereafter, TOF was started and the lung RNs improved rapidly. The precise mechanisms that induce RNs during treatment with TNF inhibitors are unknown. Cytokines (IL-23 and IL-6) are suspected to be involved. TOF may be a reasonable strategy for treating symptomatic lung RNs.

Evaluating dose of cisplatin responsible for causing nephrotoxicity.

Nephrotoxicity is a well-known side effect of cisplatin for cancer treatment. Various regimens have been developed to treat cancer based on the type and severity of the tumor. We focus on the docetaxel, cisplatin, and 5-fluorouracil regimen, which is called the TPF regimen, where the standard dose of cisplatin is 60 mg/m2. The aim of this study is to examine the relationship of the dosage of cisplatin that causes nephrotoxicity and back ground factors of patients using information about the dose of cisplatin actually administered to patients. It is shown that nephrotoxicity may be caused by a substantially smaller dosage than the standard dose of cisplatin in the TPF regimen, indicating the need for dose adjustment, taking into account the patient's background factors in the treatment of a cancer.

Phase I clinical trial of percutaneous cryoablation for osteoid osteoma.

PURPOSE: This prospective phase I trial was conducted to evaluate the safety of percutaneous cryoablation for osteoid osteoma (OO). MATERIALS AND METHODS: Nine patients with OO (mean tumor size: 5.9 mm; tibia, n = 5; femur, n = 2; lumbar spine, n = 2) were enrolled and treated with percutaneous cryoablation. The primary endpoint was the evaluation of the treatment safety as determined using step-by-step registration. The secondary endpoints were the incidence and grade of adverse events by CTCAE version 4.0, and the short-term efficacy of this treatment. Based on a decrease in the numerical rating scale (NRS) score, efficacy was classified as significantly effective (SE ≥ 5 or reached 0-2), moderately effective (ME 2-4), or not effective (NE < 2 or increase). RESULTS: Cryoablation procedures were completed in all patients. Major adverse events (≥ grade 3) related to the procedure were not observed. Minor adverse events (≤ grade2) were observed in 22-67%. The mean NRS score was 7 before treatment, 0.6 at 4-week, 0.1 at 6-month, and 0 at 1-year post-treatment. All procedures were classified as SE. CONCLUSION: Percutaneous cryoablation is a safe treatment for OO. Future phase II trials with large patient cohorts are warranted.