Risk-adjusted hazard analysis of survival after pulmonary metastasectomy for uterine malignancies in 319 cases.

Objective: There is little evidence of the outcome of pulmonary metastasectomy for uterine tumors when comparing different histologies. This study aimed to delineate the primary histology that leads to more favorable outcomes after pulmonary metastasectomy. Methods: The database of the Metastatic Lung Tumor Study Group of Japan for 1984 to 2016 was used to analyze the outcomes of patients with gynecologic malignancies who underwent pulmonary metastasectomy. Prognostic factors and long-term outcomes were compared according to the histology of the primary uterine tumors, specifically adenocarcinoma, squamous cell carcinoma, and sarcoma. The adjusted hazard risks according to disease-free intervals (DFIs) and the number and maximum size of resected tumors were also analyzed to delineate the pattern of risk trends. Results: A total of 319 patients were included in the analysis (122 with adenocarcinomas, 113 with squamous cell carcinomas, 46 with sarcomas, and 38 with other types). The 5-year survival rate was 66.5% for the entire cohort, 71.6% for the patients with adenocarcinoma, 61.3% for those with squamous cell carcinoma, and 55.4% for those with sarcoma. Multivariate analyses identified the positive prognostic factors as DFI ≥12 months in adenocarcinoma and sarcoma and the primary site (corpus) of uterine tumors in adenocarcinoma. The nonlinear adjusted hazard risks indicated that a shorter DFI was associated with an elevated risk of death in patients with adenocarcinoma and sarcoma. Conclusions: The survival outcome after pulmonary metastasectomy varies according to primary tumor histology, and the prognostic factors differ among histologic subtypes. Surgical indications should be determined based on the prognostic factors for each histology.

Withdrawal from Hemodialysis in a Patient with IgD Type Multiple Myeloma: A Case-based Review.

Several previous case reports have shown that patients with immunoglobulin D (IgD) multiple myeloma (MM) can be withdrawn from hemodialysis, however, the characteristics that can predict withdrawal in these patients have not yet been elucidated. A 57-year-old Japanese woman required hemodialysis because of renal dysfunction due to IgD-λ and Bence Jones protein-λ MM. Bortezomib-based chemotherapy nine days after admission led to her withdrawal from hemodialysis on Day 50. In our case-based review, younger age and early initiation of bortezomib-based chemotherapy emerged as possible predictors of successful hemodialysis withdrawal.

Survival after Lung Metastasectomy from Esophageal Cancer: Results from a Multi-Institutional Database.

To clarify the clinical impact and to identify prognostic predictors of surgical intervention for pulmonary metastasis from esophageal cancer, a registry database analysis was performed. From January 2000 to March 2020, patients who underwent resection of pulmonary metastases from primary esophageal cancer at 18 institutions were registered in a database developed by the Metastatic Lung Tumor Study Group of Japan. An amount of 109 cases were reviewed and examined for the prognostic factors for pulmonary metastasectomy of metastases from esophageal cancer. As a result, five-year overall survival after pulmonary metastasectomy was 34.4% and five-year disease-free survival was 22.1%. The multivariate analysis for overall survival revealed that initial recurrence site, maximum tumor size, and duration from primary tumor treatment to lung surgery were selected as the significant prognostic factors (p = 0.043, p = 0.048, and p = 0.037, respectively). In addition, from the results of the multivariate analysis for disease free survival, number of lung metastases, initial recurrence site, duration from primary tumor treatment to lung surgery, and preoperative chemotherapy for lung metastasis were selected as the significant prognostic factors (p = 0.037, p = 0.008, p = 0.010, and p = 0.020, respectively). In conclusion, eligible patients with pulmonary metastasis from esophageal cancer selected based on the identified prognostic predictors would be good candidates for pulmonary metastasectomy.

Solitary pulmonary capillary hemangioma mimicking a preinvasive malignant lesion in an asymptomatic middle-aged female patient.

Pulmonary capillary hemangiomatosis (PCH) is a rare disease characterized by a proliferation of capillaries in the alveolar septa, bronchial and venous walls, pleura, and regional lymph nodes. However, the etiology of the disease remains unknown due to its rarity. Therefore, we present a case of a solitary PCH lesion without symptoms in a 38-year-old female patient. According to computed tomography, she was diagnosed with lung carcinoma, indicated by a tiny nodule with ground-glass opacity detected in her right upper lung. However, no other lesions were detected on systemic examination. Consequently, partial lung resection was conducted, since the lesion was suspected of lung adenocarcinoma. Pathologic results showed that the thick alveolar septa were caused by capillary growth without cellular atypia and hardly any infiltration of inflammatory cells. Finally, we diagnosed the pulmonary lesion as PCH, although solitary PCH has previously been reported in a few case reports. Therefore, further case studies are essential to clarify the causes of PCH.

Hazard Function Analysis of Recurrence in Patients with Curatively Resected Lung Cancer: Results from the Japanese Lung Cancer Registry in 2010.

To optimize postoperative surveillance of lung cancer patients, we investigated the hazard function of tumor recurrence in patients with completely resected lung cancer. We analyzed the records of 12,897 patients in the 2010 Japanese Joint Committee of Lung Cancer Registry who underwent lobectomy to completely resect pathological stage I-III lung cancer. The risk of postoperative recurrence was determined using a cause-specific hazard function. The hazard function for recurrence exhibited a peak at approximately 9 months after surgery, followed by a tapered plateau-like tail extending to 60 months. The peak risk for intrathoracic recurrence was approximately two-fold higher compared with that of extrathoracic recurrence. Subgroup analysis showed that patients with stage IIIA adenocarcinoma had a continuously higher risk of recurrence compared with patients with earlier-stage disease. However, the risk of recurrence in patients with squamous cell carcinoma was not significantly different compared with that more than 24 months after surgery, regardless of pathological stage. In conclusion, the characteristics of postoperative tumor recurrence hazard in a large cohort of lung cancer patients may be useful for determining the time after surgery at which patients are at the highest risk of tumor recurrence. This information may improve stage-related management of postoperative surveillance.

Survival Outcomes of Complete Pulmonary Metastasectomy for Head and Neck Squamous Cell Carcinomas.

Purpose: Metastatic head and neck squamous cell carcinoma (HNSCC) is relatively poor; however, depending on the selected cases, pulmonary metastasectomy can be a practical therapeutic option. This study aimed to identify the outcomes of complete metastasectomy based on each primary site and to investigate unfavorable prognostic factors. Patients and Methods: We used the database from the Metastatic Lung Tumour Study Group of Japan. Between November 1980 and April 2017, 231 patients were deemed eligible. According to anatomy and the current epidemiology of HNSCC, the patients were divided into three groups: nasopharynx, oropharynx, and salivary gland (n = 40, Group 1), oral cavity, tongue, and paranasal sinuses (n = 69, Group 2), and larynx and hypopharynx (n = 122, Group 3). Results: The 5-year overall survival after complete pulmonary metastasectomy was 58.5%, 25.0%, and 46.9% in G1, 2, and 3, respectively (p < 0.01). Multivariate analyses revealed unfavourable prognostic factors to be G2, and pathological maximum diameter was >20 mm. Therefore, on dividing group 1 and 3 with or without diameter, the 5-year overall survival was significantly worse in HNSCC with a diameter >20 mm (n = 74) than that in the remnant (n = 88; 61.9% vs 35.5%; p < 0.01). Conclusion: According to the multi-institutional Japanese data, pulmonary metastasectomy from HNSCC indicates a potential survival benefit. Oral cavity, tongue, and paranasal sinuses cancer, and tumour size (>20 mm) were poor prognostic factors for pulmonary metastasectomy from head and neck cancer.

A pilot study of intraoperative localization of peripheral small pulmonary tumors by cone-beam computed tomography: sandwich marking technique.

Background: Intraoperative identification of small pulmonary nodules has been an important technical issue. We aimed to develop a new localization method which is much safer and simple procedure compared with conventional methods. Methods: This was a retrospective study including patients with resected peripheral pulmonary nodules between November 2017 and April 2021 at Teikyo University School of Medicine, and Saitama Cardiovascular and Respiratory Center. All surgical procedure was wedge resection, and the tumor size was equal to or less than 20 mm which were detected by cone-beam computed tomography (CBCT; Philips Allura Xper FD 20, Philips). Some metal clips were put on several places of visceral pleura, where the target lesion was sandwiched by marking clips (sandwich marking technique). CBCT detected both the target lesion and metal clips, and video-assisted thoracoscopic surgery (VATS) was performed. Radiological and pathological findings were analyzed, and the correlation coefficient of tumor size was examined among pre-, intra-, and post-operative tumor sizes. Results: The average age of 90 patients was 65.2 years, and 47 were male (52.2%). All procedure was wedge resection including twelve bi-wedge resections, and one hundred nine peripheral pulmonary lesions were obtained by sandwich marking technique. The detection rate was 100%, and there was no marking-related complication. Conclusions: All small peripheral pulmonary lesions were successfully detected and resected by using CBCT with no marking-related complication. Sandwich marking technique was demonstrated to provide safe, reliable, and simple localization procedure for small peripheral pulmonary lesions.

Plasma exosomal DOK3 reflects immunological states in lung tumor and predicts prognosis of gefitinib treatment.

To identify liquid biomarkers that predict clinical outcomes of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), we enrolled patients with EGFR gene mutation-positive non-small-cell lung cancer who were intended to receive gefitinib treatment. Using plasma samples obtained prior to gefitinib treatment from 12 enrolled patients, we performed comprehensive proteomic analysis of plasma exosomes to explore proteins correlating with tumor reduction rate (TRR), progression-free survival (PFS), or overall survival (OS). Of the detected 1769 proteins, 119, 130, or 119 proteins demonstrated a strong correlation (|r| > 0.5) with TRR, PFS, or OS, respectively. Interestingly, 34 (29%), 41 (32%), or 27 (23%) of them, respectively, were functionally involved in the regulation of the immune response. CD8α chain was consistently listed as a molecule positively correlated with PFS and OS, suggesting that the long-lasting effects of gefitinib may be due to the antitumor effects of CD8+ T cells, as well as the induction of immunogenic apoptosis of tumor cells by blocking the EGFR signaling pathway. Notably, Doking Protein 3 (DOK3), a molecule involved in B-cell receptor signaling, and some immunoglobulin and complement molecules exhibited a clear correlation with PFS longevity of gefitinib treatment. Indeed, the strong expression of DOK3 in B cells was confirmed within tertiary lymphoid structures of lung cancer tissues derived from patients with long PFS. These findings suggest that the patients with active B-cell and T-cell immunity as a host immunological feature are more likely to benefit from gefitinib therapy. Circulating exosomal DOK3 has the potential as a predictive marker of response to gefitinib indicating this immunological feature.

Positive Intrapleural Pressure with Carbon Dioxide May Limit Intraoperative Pulmonary Arterial Bleeding: Verification by Animal Model.

PURPOSE: Intraoperative complications, especially unexpected bleeding, are of great concern in the safety of thoracoscopic surgery. We investigated the hemostatic efficacy and safety of positive intrapleural pressure (PIP) with carbon dioxide insufflation by assessing the amount of blood loss in a pulmonary arterial hemorrhage model. METHODS: An ex vivo experimental model of saline flow into a swine vessel was created in a container simulating a chest cavity. From the results, in vivo experiments (swine model) were conducted to compare the pulmonary arterial bleeding volume while applying PIP. RESULTS: In the ex vivo experiment, regardless of the incision type, the outflow volumes did not significantly differ at flow pressures of 20, 30, and 40 mmHg. At each flow pressure, the outflow volumes at 10, 15, and 20 mmHg of positive pressure in the container were significantly smaller than those of the control (p = 0.027, p = 0.002, and p = 0.005, respectively). Similarly, the in vivo experiments showed that bleeding decreased as intrapleural pressure increased (slope = -0.22, F = 55.13, p <0.0001). CONCLUSION: It may be possible to temporarily suppress pulmonary arterial bleeding by increasing the intrapleural pressure to 10 to 20 mmHg using carbon dioxide insufflation. This method may be an adjunctive hemostatic maneuver for intraoperative bleeding.

Loop-Mediated Isothermal Amplification as Point-of-Care Testing for EGFR-Mutated Lung Adenocarcinoma.

Liquid biopsy has been adapted as a diagnostic test for EGFR mutations in patients with advanced or metastatic non-small cell lung cancer (NSCLC). Loop-mediated isothermal amplification (LAMP) has been widely used for the rapid detection of pathogens through DNA amplification. This study investigated the efficacy of an EGFR-LAMP assay using plasma samples of patients with resected NSCLC tumors. The EGFR status was investigated using both LAMP and next-generation sequencing (NGS) assays in cases that met the following criteria: (1) pulmonary adenocarcinoma with EGFR mutation detected by the Therascreen EGFR PCR Kit and (2) preoperative plasma samples contained enough DNA for the LAMP and NGS experiments. Among 51 specimens from patients with EGFR-mutated tumors or metastatic lymph nodes, the LAMP assay detected 1 EGFR mutation that was also detected in the NGS assay. However, a plasma sample that demonstrated EGFR wild type in the LAMP assay showed an EGFR mutant status in NGS. The detection rates (1.9% in LAMP and 3.9% in NGS) were very low in both assays, demonstrating a similar performance in detecting EGFR mutations in NSCLC tumors; therefore, it could be a more suitable test for the advanced stage, not the early stage. Notably, the LAMP assay was more time-saving, cost-effective, and straightforward. However, further investigation is required to develop a more sensitive assay.

Time to Incurable Recurrence for Patients Treated With Pulmonary Metastasectomy for Colorectal Cancer.

BACKGROUND: Probability of cure is important for patients with lung metastasis who must decide whether to undergo metastasectomy. Although progression-free survival (PFS) is thought to reflect this, it does not include curative effects by repeat metastasectomy. Thus, the authors developed a new indicator, time to incurable recurrence (TTIR), in which only incurable recurrence was set as an event that included death, with incurable recurrence defined as recurrence not treated by definitive local therapy (DLT), recurrence treated by DLT but with PFS maintained less than 2 years, or recurrence followed by re-recurrence. METHODS: This multi-institutional study included 339 patients who underwent lung metastasectomy for colorectal cancer between 1990 and 2008. RESULTS: Among the 339 patients, 191 experienced recurrence, 77 received DLT for recurrence, 38 had a PFS of 2 years or longer after the treatment, and 33 had maintained a PFS at the last follow-up date. The patients had PFS ranging from 39 to 212 months (median, 101 months). The 5-year OS, PFS, and TTIR rates were respectively 63.4%, 42.2%, and 51.9%. The TTIR curve was similar to the OS curve 7 years after the initial metastasectomy. The difference between TTIR and PFS at 7 years was 9.7%, indicating probability of cure by repeat DLT. Multivariable analysis showed different prognostic factors among OS, PFS, and TTIR. CONCLUSION: At the initial metastasectomy, TTIR may reflect probability of a cure, including cure by repeat DLT, and can be used to analyze prognostic factors associated with cure.

Bicarbonate concentration as a predictor of prognosis in moderately severe COVID-19 patients: A multicenter retrospective study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) patients reportedly have high bicarbonate concentration. However, its relationship to the disease progression are obscure. METHODS: In this two-center retrospective study, we included COVID-19 patients with moderate severity between March 2020 and May 2021. We classified patients into three groups according to bicarbonate concentrations: high (>27 mEq/L), normal (21 to 27 mEq/L), and low (<21 mEq/L). The primary outcome was the time to clinical worsening defined by the requirement of intubation or death during 90 days. We evaluated high or low bicarbonate concentration during the clinical course related to the primary outcome using multivariable Cox proportional hazard models. RESULTS: Of the 60 participants (median age 72 years), 60% were men. Participants were classified into high (13 patients), normal (30 patients), and low (17 patients) groups. Clinical worsening occurred in 54% of patients in the high group, 23% in the normal group, and 65% in the low group. Both high and low groups were associated with a higher clinical worsening rate: HR, 3.02 (95% CI, 1.05 to 8.63) in the high group; 3.49 (95% CI: 1.33 to 9.12) in the low group. CONCLUSION: Monitoring of bicarbonate concentrations may be useful to predict the prognosis.

Effects of Glycyrrhizic Acid in Licorice on Prolongation of Murine Cardiac Allograft Survival.

Recent evidence has pointed to the promising benefits of using specific immunosuppressive herbal compounds to prolong transplant allograft survival. In this study, we investigated the effects of glycyrrhizic acid (GA), a major component of licorice, in a model of murine heart transplantation. CBA (H2k) mice were transplanted with a fully-MHC mismatched C57BL/6 (H2b) heart allograft and subsequently received daily intraperitoneal administration of normal saline or 0.02, 0.2, or 2.0 mg/d of GA for 7 consecutive days. Untreated CBA recipients, with a median survival time (MST) of 7 days, and groups receiving 0.02mg/d (MST, 8 days) or 0.2mg/d (MST, 9 days) of GA acutely rejected C57BL/6 cardiac allografts. But mice treated with 2.0 mg/d of GA demonstrated significant prolongation of allografts (MST, 23 days). Histologic studies showed that cardiac allografts from GA-treated CBA recipients had preserved graft and vessel structure. Moreover, flow cytometric study showed that the percentage of CD4+CD25+Foxp3+ cell (regulatory T cell [Treg]) populations were increased in GA-treated CBA recipients. In a mixed leukocyte culture, splenocytes from GA-treated mice demonstrated suppressed allo-proliferation, in which interleukin (IL)-2 and interferon gamma production were downregulated and IL-10 secretion was upregulated. In conclusion, GA may be a novel promising therapeutic agent to prolong cardiac allograft survival through direct anti-inflammatory effects and induction of Treg populations.

Suspected Transmission of Severe Fever with Thrombocytopenia Syndrome Virus from a Cat to a Veterinarian by a Single Contact: A Case Report.

A 67-year-old male veterinarian presented with fatigue, anorexia, and diarrhea. Although there were no tick bite marks, we suspected severe fever with thrombocytopenia syndrome (SFTS) due to bicytopenia, mild disturbance of consciousness, and a history of outdoor activities. Thus, we started immunoglobulin therapy immediately. A serum reverse transcription-polymerase chain reaction (RT-PCR) test for SFTS virus (SFTSV) was positive. The patient had treated a cat with thrombocytopenia 10 days prior to admission. The cat's serum SFTSV RT-PCR test result was positive, and the whole genome sequences of the patient's and cat's SFTSV were identical, suggesting the possibility of transmission from the cat to the patient. Other cases of direct cat-to-human SFTV transmission have been reported recently. Mucous membranes should be protected, including eye protection, in addition to standard precautions, when in contact with any cat with suspected SFTS.

A novel method of tracheal anastomosis healing using a single submucosal injection of basic fibroblast growth factor: initial report.

OBJECTIVES: For the technical management of tracheal anastomosis, developing new and simple methods is required to relieve anastomotic tension. This study aimed to investigate whether basic fibroblast growth factor (bFGF) only once injected immediately before anastomosis promotes cartilage regeneration at the tracheal anastomosis and whether the regenerated cartilage has the effect of reinforcing the anastomosis in a rabbit model. METHODS: New Zealand white rabbits were anaesthetized, and the cervical trachea was exposed through a cervical midline incision, followed by resection of the 10th tracheal cartilage. The rabbits were categorized into 2 groups: the bFGF group (n = 6) and the control group (n = 6). In the former group, bFGF (25 µg) was administered into the submucosal layer of the cartilage using a 27-G needle immediately before tracheal anastomosis. The animals were sacrificed 4 weeks later. Histological, mechanical and biochemical evaluations were performed on this anastomosed trachea. RESULTS: At 4 weeks of age, the anastomoses were spindle-shaped and displayed maximum diameter at the injection site compared with those in the control group. Histological evaluation showed that cartilage tissue had regenerated between the 9th and 11th tracheal cartilage rings. Tensile test showed that the anastomoses displayed a significantly high strain/stress ratio (P = 0.035). The collagen type II and glycosaminoglycan levels were significantly increased, and the collagen type I level was significantly decreased (P = 0.019, P = 0.013 and P = 0.045, respectively). CONCLUSIONS: A new wound-healing concept of airway anastomosis could be provided by the results that single injection of bFGF regenerated tracheal cartilage in rabbits and strengthened the anastomosis by bridging the regenerated and well-matured cartilage. Further investigation of this method will lead to potential clinical applications for reinforcement of tracheal anastomoses.

Successful Radiograph-guided Bronchial Occlusion With Silicon Spigots for Bronchobiliary Fistula.

Bronchobiliary fistulas (BBFs), defined as abnormal connections between a bronchus and the bile duct, are rare. Bronchial occlusion with silicon spigots under radiographic guidance is a good alternative means of treating a BBF when surgical intervention is considered too risky. A 60-year-old man had a diagnosis of intrahepatic cholangiocarcinoma and underwent chemotherapy. Obstructive jaundice developed and was treated with percutaneous transhepatic cholangiography drainage (PTCD). Subsequent bronchoscopy with contrast medium through the PTCD tube enabled identification of a BBF and the responsible bronchus, which was occluded with silicon spigots. There were no complications after this procedure.

Added Diagnostic Value of Cerebrospinal Fluid Carcinoembryonic Antigen in a Patient with Leptomeningeal Carcinomatosis as the Initial Manifestation of Gastric Cancer.

A 77-year-old woman with no history of malignancy presented with anorexia and bilateral lower extremity weakness. Her consciousness level worsened daily, so we performed a lumbar puncture. Cerebrospinal fluid (CSF) analysis indicated meningitis, but three rounds of CSF cytology showed no malignant cells. The patient's carcinoembryonic antigen (CEA) level was highly elevated in CSF, but normal in serum. Through gadolinium-enhanced brain/spinal magnetic resonance imaging and gastrointestinal endoscopy, she was diagnosed with leptomeningeal carcinomatosis (LC) from gastric cancer. CEA level in CSF facilitated the diagnosis of LC from gastric cancer because there were no malignant cells on CSF cytology.

Recurrent atelectasis and brain infarction in a patient with anti-neutrophil antibody negative eosinophilic granulomatosis with polyangiitis: a case report.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is an anti-neutrophil antibody (ANCA)-associated necrotizing vasculitis, which predominantly affects small to medium vessels, and is associated with asthma and eosinophilia. EGPA has two different pathogenic aspects: eosinophilic granulomatous inflammation and ANCA-associated inflammation. A recent histological study of peripheral nerves showed that not only ANCA-associated inflammation but also eosinophil-associated vascular occlusion leads to ischemia. Endobronchial involvement is relatively common especially in the patients with granulomatosis with polyangiitis but rare in patients with EGPA. Central nervous system (CNS) involvement is also rare in patients with EGPA, the pathogenesis and relationship between these two rare conditions have not been elucidated. CASE PRESENTATION: A 62-year-old woman was admitted with numbness, purpura, and eosinophilia. She had a 3-year-history of bronchial asthma. Chest computed tomography showed left lower lobe collapse, and brain magnetic resonance imaging indicated occipital lobe infarction. Skin biopsy findings led to the diagnosis of EGPA. ANCA test results were negative. All symptoms improved after initiating glucocorticoids. However, atelectasis and brain infarction relapsed with increasing eosinophil counts. Atelectasis quickly disappeared with increasing glucocorticoid dose, and glucocorticoid could be reduced to a maintenance dose after the initiation of mepolizumab. CONCLUSION: Both atelectasis and brain infarction might develop not only via ANCA-associated inflammation but also via eosinophilic inflammation.