Clinical practice guidelines for molecular tumor marker, 2nd edition review part 2.

In recent years, rapid advancement in gene/protein analysis technology has resulted in target molecule identification that may be useful in cancer treatment. Therefore, "Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition" was published in Japan in September 2021. These guidelines were established to align the clinical usefulness of external diagnostic products with the evaluation criteria of the Pharmaceuticals and Medical Devices Agency. The guidelines were scoped for each tumor, and a clinical questionnaire was developed based on a serious clinical problem. This guideline was based on a careful review of the evidence obtained through a literature search, and recommendations were identified following the recommended grades of the Medical Information Network Distribution Services (Minds). Therefore, this guideline can be a tool for cancer treatment in clinical practice. We have already reported the review portion of "Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition" as Part 1. Here, we present the English version of each part of the Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition.

Macroscopic and multiple metastases in sentinel lymph node biopsy are respectively associated with poor prognosis in early oral cancer.

BACKGROUND: A multicenter, randomized controlled phase III trial was conducted on sentinel lymph node biopsy (SLNB) and elective neck dissection for T1 (depth of invasion ≥ 4 mm)-T2N0M0 oral cavity squamous cell carcinoma. This study identified factors associated with poor prognosis in patients who underwent SLNB based on a subgroup analysis of this trial. METHODS: We analyzed 418 sentinel lymph nodes (SLNs) from 132 patients who underwent SLNB. The metastatic SLNs were classified into three categories based on size-isolated tumor cells: < 0.2 mm, micrometastasis: ≥ 0.2 mm and < 2 mm, and macrometastasis: ≥ 2 mm. Three groups were formed based on the number of metastatic SLNs: no metastasis, 1 metastatic node, and ≥ 2 metastatic nodes. The size and number of metastatic SLNs on survival were evaluated using Cox proportional hazard models. RESULTS: Patients with macrometastasis and ≥ 2 metastatic SLNs had worse overall survival (OS) and disease-free survival (DFS) after adjustment for potential confounders (HR for OS: macrometastasis, 4.85; 95% CI 1.34-17.60; ≥ 2 metastatic SLN, 3.63; 95% CI 1.02-12.89; HR for DFS: macrometastasis, 2.94; 95% CI 1.16-7.44; ≥ 2 metastatic SLN, 2.97; 95% CI 1.18-7.51). CONCLUSIONS: In patients who underwent SLNB, a poorer prognosis was associated with macrometastasis or having ≥ 2 metastatic SLNs.

First description of Lachnoanaerobaculum orale as a possible cause of human bacteremia.

Lachnoanaerobaculum spp. is an obligate anaerobic, gram-positive, spore-forming, rod-shaped bacillus. Here, we report the first known case of bacteremia due to L. orale, which was detected in a patient with acute lymphoblastic leukemia. A 69-year-old man developed neutropenic fever with severe stomatitis during chemotherapy for leukemia. The bacteria strain isolated from blood culture was successfully identified as L. orale via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Susceptibility testing revealed that the strains showed low minimum inhibitory concentrations (MICs) of beta-lactams, clindamycin, and metronidazole, but higher MICs of fluoroquinolones. The present case study indicates that Lachnoanaerobaculum can be a cause of human infection, including bloodstream infection.

A case of infective endocarditis caused by "Neisseria skkuensis".

"Neisseria skkuensis" is a gram-negative coccus that is endemic in the human oral cavity, with only few reports of infection in humans. Herein, we report a case of a male patient in his sixties presenting with infective endocarditis (IE) caused by "N. skkuensis". To our knowledge, this is the second case of IE confirmed using 16S rRNA gene to have been caused by "N. skkuensis". The accurate diagnosis of rare or difficult-to-identify pathogens is a major challenge for clinical microbiological laboratories. Although Neisseria spp. are common in the oral cavity and are often seen in routine tests, identification of their biochemical properties and mass spectrometric analysis are difficult. In this case report, we describe the accurate identification of "N. skkuensis" by 16S rRNA gene sequencing analysis compared to other identification methods. Further cases of "N. skkuensis" are needed to fully evaluate the clinical approach of this detection method.

Giant Anisotropic Magnetoresistance due to Purely Orbital Rearrangement in the Quadrupolar Heavy Fermion Superconductor PrV_{2}Al_{20}.

We report the discovery of giant and anisotropic magnetoresistance due to the orbital rearrangement in a non magnetic correlated metal. In particular, we measured the magnetoresistance under fields up to 31.4 T in the cubic Pr-based heavy fermion superconductor PrV_{2}Al_{20} with a non magnetic Γ_{3} doublet ground state, exhibiting antiferroquadrupole ordering below 0.7 K. For the [100] direction, we find that the high-field phase appears between 12 and 25 T, accompanied by a large jump at 12 T in the magnetoresistance (ΔMR∼100%) and in the anisotropic magnetoresistivity ratio by ∼20%. These observations indicate that the strong hybridization between the conduction electrons and anisotropic quadrupole moments leads to the Fermi surface reconstruction upon crossing the field-induced antiferroquadrupole (orbital) rearrangement.

Selective activator protein-1 inhibitor T-5224 prevents lymph node metastasis in an oral cancer model.

Activator protein-1 (AP-1) is a transcriptional factor that regulates the expression of various genes associated with tumor invasion and migration. The purpose of our study was to assess the therapeutic effects of a novel selective AP-1 inhibitor, T-5224, in preventing lymph node metastasis in head and neck squamous cell carcinoma (HNSCC) in an orthotopic mouse model. We assessed the effect of T-5224 on HNSCC cell invasion, migration, proliferation, and MMP activity by carrying out an in vitro study using an invasion assay, scratch assay, WST-8 assay, and gelatin zymography. We also observed morphological changes in HNSCC cells by time-lapse microscopy. Furthermore, cervical lymph node metastasis was assessed using an orthotopic tumor model of human oral squamous cell carcinoma cells (HSC-3-M3) injected in the tongue of a BALB/c nude mouse. T-5224 (150 mg/kg) or vehicle was given orally every day for 4 weeks. Animals were killed and assessed for lymph node metastasis by H&E staining of resected lymph nodes. T-5224 significantly inhibited the invasion, migration, and MMP activity of HNSCC cells in a dose-dependent manner; there was no significant influence on cell proliferation. The antimetastatic effect of T-5224 was also confirmed in our animal study. The rate of cervical lymph node metastasis in the model was 40.0% in the T-5224-treated group (n = 30) versus 74.1% in the vehicle-treated group (n = 27; P < 0.05). In conclusion, T-5224 inhibited the invasion and migration of HNSCC cells in vitro, and prevented lymph node metastasis in head and neck cancer in an animal model.

A case of pediatric patient with acute enteritis due to CTX-M-1 5 extended-spectrum ß-lactamase-producing Salmonella Blockley.

This clinical case report concerns a pediatric patient with acute enteritis caused by multi-drug resistant Salmonella enterica serovar Blockley (Salmonella Blockley). A 3-year-old boy presented to our emergency room with a 5-day history of fever, abdominal pain, and bloody diarrhea. Stool culture tested positive for a Salmonella species, while the blood culture was negative. The patient was successfully treated with an oral antibiotic regimen of fosfomycin. The stool isolate was found to be resistant to multiple drugs, including cefpodoxime, cefotaxime, ceftazidime, and aztreonam, and was confirmed to be a CTX-M-15 extended-spectrum ß-lactamase (ESBL)-producing strain of Salmonella Blockley. This is the first report of a pediatric patient in Japan with acute enteritis caused by a CTX-M-15 ESBL- producing strain of Salmonella Blockley.

A traditional Japanese medicine--Hangeshashinto (TJ-14)--alleviates chemoradiation-induced mucositis and improves rates of treatment completion.

PURPOSE: Oral mucositis induced by radiation or chemoradiation can cause devastating quality of life issues for patients undergoing treatment for head and neck cancer. In this study, we investigated the efficacy of a traditional Japanese medicine-Hangeshashinto (TJ-14)-for (chemo)radiation-induced oral mucositis. METHODS: Eighty patients who underwent whole neck radiation of >60 Gy with or without chemotherapy (high-dose cisplatin or low-dose docetaxel) were enrolled in this retrospective study; 40 had received TJ-14 during treatment, and 40 had not (controls). Factors related to alleviation of oral mucositis were identified by multivariate logistic regression analysis. Rates of completion of (chemo)radiation treatments were compared between the patients who received TJ-14 and the control group according to the treatment regimen. The comparison of the nutrition status between groups was also performed. RESULTS: Multivariate analysis indicated that the use of TJ-14 (p = 0.019), gender (p = 0.024), and primary tumor location (p = 0.028) were significant factors associated with the severity of oral mucositis. TJ-14 was associated with a significantly improved rate of completion of chemoradiation with cisplatin (p = 0.002). In the investigation of nutritional status, only serum albumin was significantly maintained better in the TJ-14 group than the control group in terms of mean change before and after (chemo)radiation (p = 0.024). CONCLUSIONS: The present study indicates that TJ-14 is effective for ameliorating oral mucositis induced by (chemo)radiation in patients with head and neck cancers. TJ-14 was associated with improved completion rates of chemoradiation treatments with cisplatin. A randomized controlled trial is necessary to confirm the efficacy of TJ-14 for chemoradiation-induced mucositis in head and neck cancer patients.

Differences in clinical features and outcomes between group A and group G Streptococcus -induced cellulitis.

BACKGROUND: Streptococci are the main causative agents of cellulitis, and group G Streptococcus (GGS) shares many important virulent factors with group A Streptococcus (GAS). The difference in the clinical features of GAS- and GGS-induced cellulitis, however, has not been thoroughly characterized. OBJECTIVE: Our aim was to recognize the differences in the clinical manifestations and outcomes of lower limb cellulitis caused by GAS and GGS. METHODS: We retrospectively analyzed a total of 29 patients diagnosed with GAS- or GGS-induced lower limb cellulitis during the period from January 2008 to September 2013. RESULTS: While the clinical manifestations of GAS-induced cellulitis were likely to be uniform, those of GGS-induced cellulitis were variable, depending on the predisposing factors. GGS-induced cellulitis occurred more frequently in older person who had chronic underlying illness. CONCLUSION: We identified clinical predisposing factors that can predict the clinical course and outcomes of GGS-induced cellulitis.

Physical activity in patients with idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: Physical activity is an important parameter in patients with chronic obstructive pulmonary disease, but has not been studied in detail in patients with interstitial lung disease. This study aimed to evaluate physical activity in patients with idiopathic pulmonary fibrosis (IPF). METHODS: Physical activity was monitored in 31 stable IPF patients using an accelerometer for 1 month. The following factors reflecting physical activity were measured: the number of steps, walking distance, the time spent at magnitude of movement (MM) 1-6, physical activity-related energy expenditure (PAEE) and total energy expenditure. We also measured the following clinical parameters: the modified Medical Research Council (MRC) scale, Krebs von den Lungen-6 (KL-6), pulmonary function parameters, 6-min walk test (6MWT) results and high-resolution computed tomography (HRCT) findings of the chest. We determined the relationship between these parameters and physical activity. RESULTS: We recorded 24 days of physical activity data. The time spent at MM < 1 was more than 10 h per day, whereas that at MM > 1 was approximately 1 h per day. The modified MRC scale, serum KL-6 levels, 6MWT distance, and the extent of honeycomb and reticular abnormality on HRCT were associated with several facets of physical activity. In particular, lower KL-6 levels were correlated with higher physical activity based on the number of steps, walking distance, the time spent at MM 1-4 and PAEE. CONCLUSIONS: The modified MRC scale, 6MWT distance, extent of fibrosis on HRCT and serum KL-6 levels are strongly associated with physical activity.

Minimally invasive surgery for pyriform sinus fistula by transoral videolaryngoscopic surgery.

Pyriform sinus fistula is a rare branchial anomaly that manifests as recurrent cervical infection resulting from contamination of the fistula internal orifice in the pyriform sinus. Although open neck surgery to resect the fistula has been recommended as a definitive treatment, identifying the fistula within the scar is difficult and occasionally results in recurrence. Here, we describe a novel transoral surgical technique for pyriform sinus fistula using transoral videolaryngoscopic surgery (TOVS) as a definitive treatment to resect and close the fistula without skin incision. Needle cautery enables fine excision and delicate dissection of the fistula tract. TOVS is a safe, easy, and reliable treatment and is a suitable first line treatment.

Breakthrough invasive Candida glabrata in patients on micafungin: a novel FKS gene conversion correlated with sequential elevation of MIC.

Candida glabrata strains sequentially isolated from blood developed resistance to micafungin (MICs from <0.015 to 4 µg/ml). A novel mutation identified in micafungin-resistant strains at bp 262 of FKS2 (containing a deletion of F659 [F659del]) was inserted into the homologous region in FKS1.

Influence of intermolecular interactions on solid state luminescence of imidazopyridines: theoretical interpretations using FMO-TDDFT and ONIOM approaches.

6-Cyano-2-(2'-hydroxyphenyl)imidazo[1,2-a]-pyridine (6CN-HPIP) shows polymorph-dependent luminescence with the three different crystal forms exhibiting the packing-controlled tuning of bright colors, orange, yellow, and red. The distinctive emission in aggregated states was treated with finite cluster models and analyzed by means of quantum chemistry calculations. The influence of structural displacements and intermolecular interactions in the crystalline state on solid state luminescence was examined in detail using the Fragment Molecular Orbital (FMO) scheme, suitable for studies of aggregated molecular systems. The FMO pair interaction analysis of the S1-S0 emission maxima indicated that the intermolecular side-to-side interactions cause hypsochromic shifts; facial interactions induce bathochromic shifts; and crystal packing effects in total induce hypsochromic shifts. The FMO predictions of the emission maxima offered qualitatively satisfactory agreements with the experiments. However, the small cluster models including up to 17 molecules did not reach quantitative convergence, i.e., the emission colour order among them was not well reproduced.

Spectroscopic tracking of Schiff base compounds' hydrogen bonding reorganization associated with solid-to-solid phase transition.

A series of 2,6-dihydroxynaphthalene-1-methylidene alkylamines whose alkyl chain lengths ranged from 9 to 12 was spectroscopically examined. Transmission ultraviolet-visible absorption microspectroscopy revealed that the spectra of solid thin-films of the crystalline samples showed two distinct profiles depending on polymorphs as well as on alkyl chain length. We concluded that these spectral changes occurred not because of conventional intramolecular proton transfer but because of the molecules' interactions with an external proton source, that is, the intermolecular proton transfer. The spectral changes were accompanied by changes in the intermolecular hydrogen bonding network. When a crystal of a sample compound was heated, its spectrum changed dramatically before the crystal underwent a solid-to-solid phase transition to another polymorph. We concluded that these spectral changes indicated strengthening of intermolecular hydrogen bonding or intermolecular proton transfer, which would have triggered a drastic change in the hydrogen bonding network structure.

A psoas abscess caused by Propionibacterium propionicum.

Pelvic actinomycosis-like disease due to Propionibacterium propionicum has been very rare and only a few cases have been reported in the literature. We herein report a probable first case of a psoas abscess caused by P. propionicum. Since P. propionicum is indistinguishable from Actinomyces israelii by morphological features or routine biochemical tests, 16S rRNA gene sequencing was useful to discriminate these two species in this case.

Targeted gene transfer into head and neck squamous cell carcinoma by nanosecond pulsed laser-induced stress waves.

The search for new strategies to improve patient outcome and organ preservation is of great clinical interest in head and neck squamous cell carcinoma (HNSCC) treatment, and gene therapy is expected to play a promising role. In this study, we demonstrated the value of laser-induced stress waves (LISWs) as a novel method for nonviral gene transfer for gene therapy in HNSCC. The in vitro and in vivo transfection efficiency as well as in vitro cytotoxicity for HNSCC was investigated. Green fluorescent protein (GFP) expression and cell viability were analyzed in vitro after administration of a GFP-expressing plasmid or cationically modified GFP-expressing plasmid with LISW application. Luciferase expression in xenograft tumors was also quantitatively analyzed in vivo. The GFP gene was successfully transfected into HNSCC cells in vitro by LISW application. The cationically modified plasmid demonstrated enhanced transfection efficiency. LISWs are not associated with adverse effects after application to cells in vitro. The reporter genes were also successfully transfected into HNSCC tumors in vivo by LISW application. This technique is site specific, safe, and easily applicable for practical purposes. LISW gene therapy with therapeutic factors that inhibit tumor growth therefore has the potential as a future treatment for HNSCC.

Transoral videolaryngoscopic surgery for oropharyngeal, hypopharyngeal, and supraglottic cancer.

In this retrospective cohort study, we evaluated the oncological and functional outcomes of transoral videolaryngoscopic surgery (TOVS). Using distending laryngoscope and videolaryngoscope, wide operative field and working space could be obtained and tumor could be resected in en bloc. Sixty patients with T1, T2, and selected T3 laryngeal or pharyngeal squamous cell carcinomas (Stage I: n = 17, Stage II: n = 16, Stage III: n = 7, Stage IV: n = 20 cases) were enrolled and followed up for at least 24 months or until the patient's death. Fifty-three patients underwent initial treatment, and seven patients had recurrent cancer after chemoradiation. In principle, node-positive patients underwent a simultaneous neck dissection. Patients with multiple nodal metastases or a positive surgical margin received postoperative radiotherapy. For initial treatment, the 5-year overall survival and disease-specific survival rates were 77 and 95 %, respectively. For supraglottic and hypopharyngeal cancers, the 5-year laryngeal preservation rates were 89 and 96 %, respectively. For salvage surgery, the overall survival, disease-specific survival, and laryngeal preservation rates were 75, 75, and 80 %, respectively. The median times before patients could resume eating and swallowing a soft diet were 6 and 9 days, respectively. The patients' Functional Outcome Swallowing Scale stages were 0-2 in 93.3 % of the cases and 3 or 4 in 6.7 % of the cases. A percutaneous endoscopic gastrostomy was indicated for 1 (1.7 %) patient. Four (6.7 %) patients received transient tracheostomy. TOVS is a satisfactory and minimally invasive treatment option for laryngeal and pharyngeal cancers.

Composite hyoid bone graft interposition for the treatment of laryngotracheal stenosis.

INTRODUCTION: Chronic laryngotracheal stenosis (LTS) remains a challenging problem for otolaryngologists. A composite hyoid bone interposition graft has the potential to be an ideal graft because the head and neck surgeon can obtain the graft in the same operative field with good vascular supply from the muscle pedicle. METHODS: A composite hyoid interposition graft was used to provide structural support for the reconstructed lumen of the larynx or trachea in 2 cases of LTS. RESULTS: Two patients underwent successful decannulation with acceptable laryngeal function over a long-term observation period. CONCLUSION: This technique allows vascularized stable graft survival with minimal donor site morbidity. Furthermore, it can be performed for thyroid, cricoid, and tracheal stenosis without fear of damage to the recurrent laryngeal nerves.

Transoral videolaryngoscopic surgery with a navigation system for excision of a metastatic retropharyngeal lymph node.

OBJECTIVES: To report the utilization of a new transoral surgery system, i.e. transoral videolaryngoscopic surgery (TOVS) with a navigation system, for the removal of a metastatic retropharyngeal lymph node (RPLN). CASE REPORT: An 86-year-old woman with tongue cancer (cT2N0M0) underwent partial glossectomy and left selective neck dissection. Three months postoperatively, a left metastatic RPLN was identified on follow-up magnetic resonance imaging. The metastatic RPLN was successfully excised by TOVS with a navigation system. After postoperative irradiation, she had no recurrence more than 1 year after the surgery. DISCUSSION: The retropharyngeal space (RPS) is a difficult area to access surgically. A transcervical approach is conventionally used to access the RPS; however, in the present case, scar tissue after neck dissection may have been problematic. Visualization of the RPS by high-definition endoscopy and a navigation system were effective in facilitating the safe performance of the surgery. CONCLUSIONS: A transoral approach may be a viable choice for surgery of a metastatic RPLN. Surgical indications for a transoral approach to the RPS include that (1) the location of the RPLN is below the level of the hard palate and the pterygoid hamulus and (2) there is only a single lesion, without adhesion to the surrounding tissue.