Exploratory investigation of virtual lesions in gastrointestinal endoscopy using a novel phase-shift method for three-dimensional shape measurement.

Accurate measurement of the size of lesions or distances between any two points during endoscopic examination of the gastrointestinal tract is difficult owing to the fisheye lens used in endoscopy. To overcome this issue, we developed a phase-shift method to measure three-dimensional (3D) data on a curved surface, which we present herein. Our system allows the creation of 3D shapes on a curved surface by the phase-shift method using a stripe pattern projected from a small projecting device to an object. For evaluation, 88 measurement points were inserted in porcine stomach tissue, attached to a half-pipe jig, with an inner radius of 21 mm. The accuracy and precision of the measurement data for our shape measurement system were compared with the data obtained using an Olympus STM6 measurement microscope. The accuracy of the path length of a simulated protruded lesion was evaluated using a plaster model of the curved stomach and graph paper. The difference in height measures between the measurement microscope and measurement system data was 0.24 mm for the 88 measurement points on the curved surface of the porcine stomach. The error in the path length measurement for a lesion on an underlying curved surface was <1% for a 10-mm lesion. The software was developed for the automated calculation of the major and minor diameters of each lesion. The accuracy of our measurement system could improve the accuracy of determining the size of lesions, whether protruded or depressed, regardless of the curvature of the underlying surface.

The Effects of Boron Neutron Capture Therapy on the Lungs in Recurrent Breast Cancer Treatment.

Boron neutron capture therapy (BNCT) has predominantly been performed for brain tumors or head and neck cancers. Although BNCT is known to be applicable to breast cancer, it has only been performed in a few cases involving thoracic region irradiation with reactor-based BNCT systems. Thus, there are very few reports on the effects of BNCT on the thoracic region and no reports of BNCT for breast cancer with accelerator-based BNCT systems. This paper introduces the world's first clinical study employing an accelerator-based BNCT system targeting recurrent breast cancer after radiation therapy. We aim to assess the efficacy and safety of BNCT, focusing on the dose response in the thoracic region, especially concerning the potential for radiation pneumonitis. Preliminary findings from the first three cases indicate no evidence of radiation pneumonitis within three months post treatment. This study not only establishes a foundation for novel breast cancer treatment options but also contributes significantly to the field of BNCT in the thoracic region.

Feasibility Study of Transarterial Chemotherapy Followed by Chemoembolization for Recurrent Breast Cancer.

PURPOSE: To assess the treatment response to transarterial chemotherapy followed by chemoembolization for locally recurrent breast cancer. MATERIALS AND METHODS: Thirty-nine women with locally recurrent breast cancer after standard therapy underwent selective intra-arterial chemotherapy followed by embolization using drug-eluting microspheres for locally recurrent tumors and axillary lymph node metastases. Tumor response and toxicity were assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and Common Terminology Criteria for Adverse Events (CTCAE), and survival was evaluated by the Kaplan‒Meier method. RESULTS: The local responses of breast tumors at 3 and 6 months were as follows: complete response, 5.1% and 7.2%; partial response, 35.9% and 67.8%; stable disease, 59.0% and 21.4%; and progressive disease, 0.0% and 3.6%, respectively. All adverse events were mild and did not require treatment. The median overall survival (OS) was 46.5 months, and the OS rates for 1 and 2 years were 81.4% and 69.2%, respectively. The size of recurrent tumors and axillary lymph node metastases did not impact prognosis, but both liver and bone metastases adversely affected survival. CONCLUSION: Transarterial chemotherapy followed by chemoembolization may provide a favorable tumor response in patients with locally recurrent breast cancer in whom conventional therapy has failed.

Successful control of a large intrahepatic cholangiocarcinoma treated by transarterial chemo-embolization; a single case report.

Intrahepatic cholangiocarcinoma is hardly diagnosed in early stages as the symptoms are non-specific. Due to an advanced stages at the time of first diagnosis, the therapeutic options for patients with unresectable cholangiocarcinoma are mostly limited to systemic chemotherapy or radiotherapy, but good local control or preferable prognostic effects are hardly obtained. The transarterial chemoembolization had not been a standard of care because of hepatic functional damages caused by lipiodol and gelatin sponge. A newly developed spherical embolic material causes limited hepatic damages might be an option for these patients. It makes it possible to repeat the procedure in a short period. Eventually, better prognosis can be expected using a spherical embolic material. We report a case of a 15 cm locally advanced intrahepatic cholangiocarcinoma treated by chemoembolization using a drug-eluting spherical embolic material and achieved good local tumor control without liver damage. The patient survived longer than 4 years without additional or concomitant treatments.

Transarterial Treatment of Lung Cancer.

PURPOSE: The treatment efficacy of the transarterial approach to lung cancer is evaluated. MATERIALS AND METHODS: A total of 98 patients with advanced lung cancer or recurrent lung cancer after the standard therapies were enrolled retrospectively. The bronchial arteries and mediastinal branches from the subclavian artery were selected by a microcatheter. Immediately after the selective arterial infusion of anti-neoplastic agents, embolization with a spherical embolic material was carried out. Local tumor effects and overall survival were evaluated. RESULT: The mean reduction rate was 17.9%, with 24.2% for partial remission and with 2.1% for progression disease. The rate of stable disease was 72.6%. The response rate was 25.3%, and the disease control rate was 97.9%. The median survival time (MST) was 11.4 months, the 1-year survival rate was 45.2%, and the 2-year survival rate was 35.6%. Although it is insignificant, the MST for 51 adenocarcinomas was higher than that of 29 squamous cell carcinomas (18.6 months and 9.4 months, respectively). The local extension of tumors related to a better prognosis, though it was not significant. Lymph node metastases and distant metastases were poor prognostic factors. No major complications nor treatment-related mortalities were found in this study. CONCLUSION: The transarterial treatment for lung cancer should be considered as a treatment option when the other treatments were not indicated both in initial cases and in recurrent cases.

Combined Use of Reducing Agents and Biodegradable Chelating Agent for Iron Rust Removal.

Since many of the current chemicals used to remove iron rust are hazardous to the environment and human health, the combined use of a reducing agent and a biodegradable chelating agent has been suggested as an environmental friendly and highly safe alternative. In the present work, the compatibility of the newly devised cleaning test with a model iron rust stain was confirmed by X-ray diffraction and scanning electron microscopy. Additionally, the cleaning efficiency of the method was evaluated by X-ray fluorescence. The cleaning mechanism and the synergistic effect of the reducing agent and the chelating agent was investigated using the phenanthroline absorption measurement method, and the results revealed that the reduced iron ions were dissolved by the chelating agent. The cleaning test proved that tetrasodium 3-hydroxy-2,2'-iminodisuccinate (HIDS) is a promising biodegradable chelating agent as an alternative to ethylenediaminetetraacetic acid (EDTA) for removing iron rust. It was also confirmed that the type of reducing agent used determines the pH at which detergency is enhanced. The detergency of the combination of the reducing agent and the biodegradable chelating agent was equal to or higher than the detergency of the acid agent, and thus, it was concluded that the proposed method has a great potential for commercial use.

[Transarterial Chemoembolization for Unresectable Gastric Cancer in the Esophago-Gastric Junction-A Case Report].

A case of extensive esophageal stenosis and bleeding caused by advanced gastric cancer in esophago-gastric junction treated by the transarterial chemoembolization(TACE)was reported. After standard systemic chemotherapy and radiotherapy, TACE was introduced to control these symptoms. A microcatheter was successfully advanced to the left gastric artery and esophageal artery arising from the thoracic aorta. The blood supply to the lesion was confirmed by CT scan during contrast injection through the microcatheter. The drugs were 5-FU 250 mg/body, cisplatin 20 mg/body, docetaxel 20 mg/body and bevacizumab 100 mg/body. Embolic material was HepaSphereTM(50-100µm). The patient survived one and half years without dysphagia and bleeding. TACE for extensive esophageal stenosis caused by advanced gastric cancer can be a treatment option to control tumor growth and bleeding.

A large fraction of trisomy 12, 17p-, and 11q- CLL cases carry unidentified microdeletions of miR-15a/16-1.

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and is characterized by chromosomal aberrations including 13q, 11q, and 17p deletions and a trisomy of chromosome 12 (T12). 13q deletions are often associated with 11q and 17p deletions in aggressive cases. Conversely, T12 CLLs show a variable prognosis, and association with 13q deletions is uncommon. The miR-15a/16-1 cluster is the functional target of 13q deletions, leading to BCL2 overexpression. Chromosomal aberrations in CLL are associated with prognosis, and their identification is carried out by fluorescence in situ hybridization (FISH). Since standard FISH only detects large deletions, we investigated the presence of undetected microdeletions targeting miR-15a/16-1 in CLL cases. We found that ∼34% of CLL samples show an unreported loss of the miR-15a/16-1 locus regardless of their cytogenetic profile. Interestingly, 15 out of 39 (∼39%) of all CLLs with T12, carry microdeletions of miR-15a/16-1, indicating that, in patients with T12, miR-15a/16-1 are mostly inactivated by microdeletions. In addition, ∼40% of CLL cases bearing T12, 17p-, and 11q- showed unidentified microdeletions of miR-15a/16-1, suggesting that miR-15a/16-1 loss cooperates with such chromosomal alterations in CLL. These data may have clinical relevance for the successful stratification of patients for treatment.

[Microsphere TACE with Arterial Infusion of Bevacizumab for Portal Vein Tumor Thrombus by Hepatocellular Carcinoma].

The successful treatment of 2 cases of portal vein tumor thrombus caused by hepatocellular carcinoma was reported. It is difficult to manage portal vein tumor thrombi by conventional transarterial chemoembolization(c-TACE)using lipiodol and a gelatin sponge. On the other hand, drug-eluting-microsphere TACE(DEM-TACE)can preserve hepatic function by maintaining the capillary circulation of sinusoids and the peribiliary arterial plexus. Even in cases of portal vein tumor thrombus, DEM-TACE could be safely performed without hepatic infarction. Bevacizumab, anti-VGEF monoclonal antibody, was injected into hepatic arteries with anti-neoplastic agents, followed by the epirubicin-loaded superabsorbent polymer microsphere( HepaSphere). The tumor thrombi in 2 cases were successfully eliminated after treatment for more than 2 years without deterioration of the hepatic function.

Genomic Characterization of ESBL- and Carbapenemase-Positive Enterobacteriaceae Co-harboring mcr-9 in Japan.

Worldwide spread of Enterobacteriaceae resistant to colistin, a polypeptide antibacterial drug for last-resort treatment of carbapenemase-producing Enterobacteriaceae (CPE) infections, is concerning. This study aimed to elucidate colistin MICs and molecular characteristics of mcr-1 to mcr-9 of ESBL-producing Escherichia coli (ESBL-Ec) and CPE in Japan and clarify the genomic structure of strains harboring mcr genes (especially mcr-9). This study included 168 ESBL-Ec and 126 CPE strains isolated at Japanese medical facilities. Colistin susceptibility testing and multiplex PCR targeting mcr-1 to mcr-9 were performed for all strains with S1-nuclease pulsed-field gel electrophoresis, Southern blot hybridization, and whole-genome sequencing (WGS) with hybrid assembly performed for mcr gene-carrying strains. Two CPE strains showed a MIC ≥ 4 µg/ml in colistin susceptibility testing, with no known resistance mechanism detected. However, PCR conducted on all target strains detected three mcr-9-carrying strains showing colistin susceptibility. The bla CTX-M-62 -positive E. coli THUN648 strain simultaneously carried bla CTX-M-62 and mcr-9 on a 275-kbp plasmid. Besides, bla IMP-6 + bla CTX-M-2 -positive Klebsiella pneumoniae THUN262 and bla GES-24 -positive Enterobacter kobei THUN627 had mcr-9 encoded on the chromosome. Only THUN627 encoded qseB/C, which is suggested to be a regulatory gene for mcr-9, downstream of mcr-9. However, this strain showed no increased expression of these genes in mRNA quantitative analysis under colistin exposure. Colistin MICs of ESBL-Ec and CPE in Japan were all below 2 µg/ml, which is below the epidemiological cutoff (ECOFF) value (https://eucast.org/) or clinical breakpoint (CB) (CLSI M100-S30) reported for colistin, indicating neither "microbiological" nor "clinical" resistance. Several colistin-susceptible Enterobacteriaceae carrying silent mcr-9 encoded on plasmids and chromosomes have already spread worldwide along with other antimicrobial resistance genes. However, the mechanism of colistin resistance by mcr-9 remains unclear.

Transarterial management of advance lung cancer.

Previous reports on transarterial treatment for lung cancer were reviewed. The bronchial arterial infusion therapy has a long history since 1964. Better local control with less doses of anti-neoplastic agents was warranted by trying transarterial administration to lung and mediastinal tumors. It is reported that both primary and metastatic tumors are fed by bronchial or other systemic arteries. The bronchial arterial embolization for hemoptysis has been introduced for clinical practice since 1973. Hemoptysis by not only benign but also malignant diseases has been well controlled by embolization. In recent decades, the technical elements for transarterial treatments have markedly improved. They make it possible to carry out precise procedures of selective catheter insertion to the tumor relating arteries. Current concepts of transarterial treatment, technical aspects and treatment outcomes are summarized. Tentative result from chemo-embolization for advanced lung cancer using recent catheter techniques was also described. It provides favorable local control and survival merits. It is considered that a population of lung cancer patients can benefit from transarterial management using small doses of anti-neoplastic agents, with less complications and less medical costs.

Boron neutron capture therapy using cyclotron-based epithermal neutron source and borofalan (10B) for recurrent or locally advanced head and neck cancer (JHN002): An open-label phase II trial.

BACKGROUND AND PURPOSE: Boron neutron capture therapy (BNCT) can be performed without reactors due to development of cyclotron-based epithermal neutron source (C-BENS), which is optimized for treatment for deeper-seated tumors. The purpose of this study was to evaluate efficacy and safety of cyclotron-based BNCT with borofalan (10B) for recurrent or locally advanced head and neck cancer. MATERIALS AND METHODS: In this open-label, phase II JHN002 trial of BNCT using C-BENS with borofalan (10B), patients with recurrent squamous cell carcinoma (R-SCC) or with recurrent/locally advanced non-squamous cell carcinoma (R/LA-nSCC) of the head and neck were intravenously administered 400 mg/kg borofalan (10B), followed by neutron irradiation. The tumor dose was determined passively as the mucosal maximum dose of 12 Gy-Eq. The primary endpoint was the objective response rate (ORR). Post-trial observational JHN002 Look Up study was planned for evaluating locoregional progression-free survival (LRPFS). RESULTS: Eight R-SCC and 13 R/LA-nSCC patients were enrolled. All R-SCC patients had prior radiotherapy with a median dose of 65.5 Gy (range, 59.4-76.0 Gy). The ORR for all patients was 71%, and complete response/partial response were 50%/25% in R-SCC and 8%/62% in R/LA-nSCC. The 2-year overall survival for R-SCC and R/LA-nSCC were 58% and 100%, respectively. The median LRPFS was 11.5 months for R-SCC. Frequently observed adverse events included alopecia (95%), hyperamylasemia (86%), and nausea (81%). CONCLUSION: These data suggest that BNCT using C-BENS with borofalan (10B) is a promising treatment option for patients with R-SCC or R/LA-nSCC of the head and neck.

Proton beam therapy combined with retrograde intra-arterial infusion chemotherapy for an extremely rapid growing recurrent ameloblastic carcinoma: A case report.

Ameloblastic carcinoma (AC) is a very rare malignant odontogenic tumor. Although surgical resection is generally performed, treatment approaches have not been established for recurrent cases. Chemotherapy and radiotherapy are positioned as adjunctive therapies, and few studies investigated definitive non-operative therapy. We present the case of a 71-year-old male with recurrent secondary-type AC arising from the right maxilla, who was treated with proton beam therapy (PBT; 71.4 Gy relative biological effectiveness in 32 fractions) combined with continuous intra-arterial infusion of cisplatin (40 mg/m2) and docetaxel (8 mg/m2). The patient experienced acute grade 3 mucositis, dermatitis and neutropenia, which were resolved within 3 months of treatment. Late adverse events were grade 1 skin atrophy, and grade 2 right optic nerve disorder and retinopathy. After ~8 years of treatment, the patient died from another cause but did not experience any relapse or metastasis during the follow-up period of 94 months. To the best of our knowledge, this is the first report of recurrent AC treated with PBT and intra-arterial infusion chemotherapy without any severe late adverse events. This combination therapy approach may be considered as an effective therapeutic option for inoperable AC.

[Transcatheter Arterial Chemoembolization with HepaSphereTM for Diffuse Liver Metastases from Prostatic Cancer without Elevation of the Serum Prostate-Specific Antigen Level-A Case Report].

Although postoperative recurrence or prostate cancer metastasis is usually accompanied by high prostate-specific antigen (PSA)levels, it may occur even if PSA level is within the normal range. Neuroendocrine differentiation(NED), which is one of such cases, causes rapid disease progression. A man in his 70s underwent total prostatectomy for prostate cancer with high PSA levels. Twenty-two months later, liver, lung, and bone metastases appeared even though the PSA levels were normal. The levels of both neuron-specific enolase and pro-gastrin-releasing peptide were elevated and the patient was clinically diagnosed with NED. Although systemic chemotherapy was administered, the outcome was progressive disease. Transcatheter arterial chemoembolization(TACE)was opted because liver metastases were one of the prognostic factors. Four types of chemotherapy drugs(cisplatin 20 mg, docetaxel 20 mg, 5-FU 250 mg, and bevacizumab 100 mg)were infused through the right and left hepatic arteries, followed by embolization with HepaSphereTM. The liver tumors were remarkably reduced in size and the levels of tumor markers were reduced in 5 sessions. This treatment would avoid the lethal liver trouble; however, the patient died 7 months after the first session of TACE.

[Transcatheter Arterial Chemoembolization with HepaSphereTM for Gastric Cancer with Mediastinal Lymph Node Metastases Causing Esophageal Compression and Dysphagia-A Case Report].

A 50s man was diagnosed with esophagogastric junction cancer. Simultaneously, PET-CT demonstrated mediastinal lymph node metastases. Two months later, 4 courses of systemic chemotherapy(SOX)were provided as preoperative therapy. However, the outcome was PD; therefore, radical gastrectomy could not be performed. Two more months later, esophageal dysphagia developed. Mediastinal lymph nodes that compressed the esophagus and the primary lesion of the cardia were considered to be the causes of dysphagia, and transcatheter arterial chemoembolization targeting those 2 lesions was performed. Cisplatin 20 mg, docetaxel 20 mg, and 5-FU 250mg were the drugs administered. These drugs were injected from the right bronchial artery, left gastric artery, and left phrenic artery, followed by mild embolization with HepaSphereTM. The mediastinal lymph nodes shrunk significantly, and dysphagia improved with 2 sessions. The primary lesion was found to have reduced in size with 6 sessions. Currently, no regrowth of the mediastinal lymph nodes has been observed 16 months(9 sessions) after the first session, and control of the primary lesion has been obtained.

Combined loss of function of two different loci of miR-15/16 drives the pathogenesis of acute myeloid leukemia.

Double knockout of the two miR-15/16 loci in mouse resulted in the development of acute myeloid leukemia (AML). This result suggested that, at least, a fraction of human AMLs could be due to a similar mechanism. We analyzed the role of the two miR-15/16 clusters in 93 myelodysplastic syndrome (MDS) patients divided in three subgroups: patients with MDS, patients with MDS before transforming into AML (MDS-T), and patients with AML evolving from MDS (MDS-AML). Then, we tested 139 AML cases and 14 different AML cell lines by assessing microRNA (miRNA) expression, target protein expression, genetic loss, and silencing. MDS-T and MDS-AML patients show a reduction of the expression of miR-15a/-15b/-16 compared to MDS patients. Each miRNA can significantly predict MDS and MDS-T groups. Then, 79% of primary AMLs show a reduced expression of miR-15a and/or miR-15b. The expression of miR-15a/-15b/-16 significantly stratified AML patients in two prognostic classes. Furthermore, 40% of AML cell lines showed a combined loss of the expression of miR-15a/-15b and overexpression of their direct/indirect targets. As potential mechanisms involved in the silencing of the two miR-15/16 loci, we identified a genetic loss of miR-15a and miR-15b and silencing of these two loci by methylation. We identified a potential driver oncogenic role in the loss of expression of both miR-15/16 clusters in the progression of MDS into AML and in AML pathogenesis. The stratification of AML patients, based on miR-15/16 expression, can lead to targeted and combination therapies for the treatment of this incurable disease.

Proton Beam Therapy for Locally Recurrent Parotid Gland Cancer.

The aim of this study was to evaluate the efficacy and safety of proton beam therapy for patients with locally recurrent parotid cancer. Between 2009 and 2012, ten patients with locally recurrent parotid gland cancer were treated with proton beam therapy (70.2 Gy equivalents in 32 fractions) with or without intra-arterial infusion chemotherapy of cisplatin (50 mg/body/week, for a total of 5-8 weeks). The median follow-up was 24 months (range 10-49 months). The 1-year overall survival and local control rates were 80 %, and the 3-year overall survival and local control rates were 60 %. None of the patients experienced grade 3-5 toxicities in the treatment or the follow-up periods. These findings suggest that proton beam therapy could be applied effectively and safely for patients with locally recurrent parotid gland cancer.

Proton Beam Therapy Combined with Intra-Arterial Infusion Chemotherapy for Stage IV Adenoid Cystic Carcinoma of the Base of the Tongue.

Adenoid cystic carcinoma (ACC) is a very rare epithelial tumor of the salivary glands. Surgical resection is considered to be a standard therapy. However, the optimal treatment strategy for managing advanced cases has not yet been established. This study evaluated the efficacy and toxicity of proton beam therapy (PBT) combined with selective intra-arterial infusion chemotherapy (IAIC) using weekly cisplatin for locally advanced ACC of the base of the tongue. Between March 2009 and February 2018, 15 patients were treated. The median follow-up duration was 56 (range: 15-116) months. The 5-year local control and overall survival rates were 89% and 76%, respectively. With regard to late toxicities, grade 2 osteoradionecrosis was found in one patient and grade 5 pharyngeal necrosis was observed in one patient. Considering most cases were significantly advanced and inoperable, this therapy was effective in controlling the primary tumor, preserving function and maintaining the quality of life. Although improvements are needed to reduce adverse events, PBT in combination with IAIC can be a treatment option for locally advanced ACC of the base of the tongue.

Proton beam therapy is a safe and feasible treatment for patients with second primary lung cancer after lung resection.

BACKGROUND: The purpose of the present study was to retrospectively evaluate the safety and efficacy of proton beam therapy (PBT) in patients with second primary lung cancer after lung resection. METHODS: Patients who were diagnosed with second primary lung cancer after lung resection and underwent PBT between January 2009 and February 2015 were retrospectively recruited. Toxicities were evaluated using Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Nineteen patients were eligible for inclusion in this study. All of the patients completed the treatment. The median age was 75 (range: 63-82) years, and the median follow-up time of living patients was 60 months. The median dose of PBT was 76.8 Gy relative biological effectiveness (range: 66.0-80.0 Gy). The three-year overall survival rate was 63.2% and the three-year local control rate was 84.2%. No grade 4 or 5 toxicities were observed after PBT. CONCLUSIONS: Our results suggest that PBT is a safe and feasible treatment for second primary lung cancer compared to surgery or X-ray radiotherapy. PBT may become a treatment choice for patients with second primary lung cancer after lung resection.