Complete thoracoscopic lobectomy versus hybrid video-assisted thoracoscopic lobectomy for non-small cell lung cancer.

OBJECTIVE: Video-assisted thoracoscopic surgery (VATS) is the standard approach to lobectomy for early-stage non-small cell lung cancer (NSCLC). However, there are many different types. One of its approaches is complete thoracoscopic surgery (CTS), which may be less invasive because of low chest wall stress. This study compared the treatment outcomes of CTS and hybrid VATS lobectomy for NSCLC. METHODS: In total, 442 eligible patients with clinical N0 NSCLC underwent lobectomy between 2007 and 2016. Patients were classified into a group of patients who underwent CTS and a group of those who underwent hybrid VATS. Propensity score matching was performed between the two groups. RESULTS: There were 175 patients after matching. The median follow-up period in the CTS and hybrid VATS groups was 60 and 63 months, respectively. The CTS group showed less blood loss (CTS, 50 mL vs. 100 mL, p = 0.005), fewer complications (CTS, 25.7% vs. 36.6%, p = 0.037), and shorter postoperative hospital stays (CTS, 8 days vs. 12 days, p < 0.001). There was no significant difference in the postoperative 30-day mortality rates. Between the patients who underwent CTS and hybrid VATS groups, the 5-year overall survival rates were 85.4% and 86.0% (p = 0.701), the relapse-free survival rates were 76.5% and 74.9% (p = 0.435), and the lung cancer-specific survival rates were 91.5% and 91.7% (p = 0.90), respectively. CONCLUSIONS: CTS is less invasive and has superior short-term outcomes as an approach to lobectomy for early-stage NSCLC.

Treatment outcomes of lobectomy with and without mediastinal lymph node dissection in older patients with clinical N0 non-small cell lung cancer.

BACKGROUND: To reduce surgical stress, we omit mediastinal lymph node dissection (MLND) in patients with non-small cell lung cancer aged ≥80 years without N1 metastasis, as confirmed via surgery. This study examined the effect of MLND omission on prognosis. METHODS: Altogether, 212 eligible patients with clinical N0 non-small cell lung cancer underwent video-assisted thoracoscopic lobectomy between 2007 and 2017. Patients were classified into two groups as follows: patients aged 75-79 years who underwent MLND group, and patients aged ≥80 years in whom MLND was omitted (non-MLND group). Propensity score matching was performed between the two groups. RESULTS: There were 86 patients after matching. The non-MLND group showed shorter operative time (237.5 min vs. 207.5 min, p = 0.018). No differences in postoperative complications were noted between the two groups. Between the MLND group and non-MLND group, the 5-year overall survival rates were 84.0% and 84.7% (p = 0.989), relapse-free survival rates were 69.8% and 74.7% (p = 0.855), and cancer-specific survival rates were 91.4% and 91.6% (p = 0.700), respectively. These results did not differ significantly. CONCLUSION: This study demonstrated that MLND does not affect the prognosis of patients with non-small cell lung cancer aged ≥80 years. Lobectomy without MLND is one of the surgical treatment options in older patients with clinical N0 non-small cell lung cancer. Naturally, the clinical stage of patients must be carefully evaluated before surgery.

Cytological characteristics of histological types of lung cancer by cytomorphometric and flow cytometric analyses using liquid-based cytology materials.

BACKGROUND: Distinguishing the histological types of lung cancer is essential for determining treatment strategies in clinical practice. In this study, cytomorphological characteristics and proliferative activities were compared among histological types of lung cancer by cytomorphometric and flow cytometric analyses using liquid-based cytology (LBC) samples. METHODS: Scraped LBC samples from 73 surgically resected specimens were collected between August 2018 and November 2019. Papanicolaou-stained and paired Ki-67-stained slides were used for cytomorphometric analyses. Another sample for each case was analyzed using a flow cytometric system (LC-1000). The cell proliferation index (CPIx) was calculated to evaluate proliferative activity. RESULTS: In total, 73 cases, including cases of adenocarcinoma (n = 53), squamous cell carcinoma (n = 14), small cell carcinoma (n = 1), large cell neuroendocrine carcinoma (NEC; n = 3), and pleomorphic carcinoma (n = 2) were evaluated. Small cell carcinoma and large cell NEC were categorized into a single group, NEC. The adenocarcinoma group tended to have a larger nuclear area and longer perimeter than other histological types. The NEC group had a considerably higher Ki-67 labeling index and significantly higher CPIx than other histological types (p = .030). A significant positive correlation was observed between the Ki-67 labeling index and CPIx for all cases (r = 0.362, p = .002). CONCLUSION: The Ki-67 labeling index and flow cytometric analyses focus on proliferative activity for the distinction of histological types of lung cancer, thereby guiding clinical decision-making.

Older age is not a negative factor for video-assisted thoracoscopic lobectomy for pathological stage I non-small cell lung cancer: a single-center, retrospective, propensity score-matching study.

PURPOSE: Video-assisted thoracoscopic surgery (VATS) has changed the surgical approach to non-small cell lung cancer (NSCLC) dramatically. The current study compares the outcomes of older and younger patients who underwent VATS lobectomy for NSCLC. METHODS: In total, 424 eligible patients with pathological stage I NSCLC underwent VATS lobectomy between 2007 and 2017. Patients were classified into two groups (< 75 and ≥ 75 years old), after which propensity score-matching was performed. RESULTS: After matching, 143 patients were identified. No significant difference in postoperative complication rates was observed; however, the ≥ 75-year-old group had a longer postoperative hospital stay (p = 0.001). The 5-year overall survival, relapse-free survival, and lung cancer-specific survival rates of the < 75- and ≥ 75-year-old groups were 87.1% vs. 85.6% (p = 0.537), 82.1% vs. 79.0% (p = 0.531), and 93.5% vs. 92.7% (p = 0.832), respectively. CONCLUSION: Despite the longer postoperative recovery following VATS lobectomy, the short- and long-term outcomes of older patients did not differ from those of younger patients. Thus, for early-stage NSCLC, older age alone was not a negative factor for lobectomy performed via minimally invasive surgery. Naturally, the systemic condition of this population must be evaluated carefully before surgery.

Protective roles of cytoplasmic p21Cip1 /Waf1 in senolysis and ferroptosis of lung cancer cells.

OBJECTIVE: Therapy-induced senescent cancer cells increase the expression of the cyclin-dependent kinase inhibitors p16Ink4a and p21Cip1/Waf1 . Given that p21 regulates not only the cell cycle but also cell death, we investigated the roles of p21 in cell death using a p16-negative A549 human lung adenocarcinoma cell line. METHODS: Senescence was induced by doxorubicin (DXR) or pemetrexed (PEM). The protein expression of p21 was examined by immunoblot. Cell death, reactive oxygen species (ROS) and lipid peroxidation were determined by flow cytometry. ABT-263 and ABT-737 were used as senolytic drugs. In vivo growth of A549 cells with different levels of p21 and their sensitivity to PEM were examined in xenograft models. RESULTS: DXR-induced senescent A549 cells increased the expression of cytoplasmic p21, and the sensitivity to ABT-263 was augmented in p21-knockout A549 (A549-KOp21) cells. A similar senolytic effect was observed when PEM was combined with ABT-737. PEM alone induced a higher level of non-apoptotic cell death, ferroptosis, in A549-KOp21 cells than in A549 cells. Although there was no difference in the level of lipid peroxidation, ROS levels were higher in PEM-treated A549-KOp21 cells than in PEM-treated A549 cells. A loss of p21 increased the sensitivity of A549 cells to PEM both in vitro and in vivo. A clinical database analysis showed that CDKN1Ahigh lung adenocarcinoma patients had a poorer prognosis compared to CDKN1Alow patients. CONCLUSION: Cytoplasmic p21, which was increased in therapy-induced senescent lung cancer cells, plays protective roles in senolysis and ferroptosis.

The Transoral Endoscope-Assisted Approach for Removal of a Dental Implant Displaced into the Maxillary Sinus: A Case Report and Review of the Literature.

Purpose: A dental implant displaced into the maxillary sinus can be removed transorally or transnasally. There is no report investigating any potential positional limitations by the transoral endoscope-assisted approach. The implant's location within the maxillary sinus was reviewed to clarify indications for this approach. Case report: A 36-year-old man was referred to us for removal of a dental implant displaced into the right maxillary sinus. The implant changed position preoperatively, but the transoral endoscope-assisted approach proved successful. Methods: A literature search through October 2020 was performed in PubMed for cases of implant removal from the maxillary sinus via transoral endoscope-assisted and transnasal endoscopic approaches. Results: Sixty-two prior cases were identified, 20 cases by the transoral endoscope-assisted approach and 43 cases by one or two transnasal endoscopic approaches, including one duplicate case. There were no cases in which the implant was not identified by the transoral endoscope-assisted approach, but two cases in which the implant had moved to an unfavorable location and was not identified by only the initial transnasal endoscopic approach. Conclusion: Clinicians can preferentially choose the transoral endoscope-assisted approach, considering the possibility of unfavorable repositioning of the displaced implant within the maxillary sinus.

Cytomorphometric and flow cytometric analyses using liquid-based cytology materials in subtypes of lung adenocarcinoma.

BACKGROUND: The histological classifications of invasive lung adenocarcinoma subtypes are considered to predict patient prognosis after surgical treatment. The objectives of this study were to evaluate cytomorphological characteristics and proliferative activities among the histological predominant patterns by performing cytomorphometric and flow cytometric analyses using liquid-based cytology materials. METHODS: Cytological samples fixed by liquid-based cytology preservatives from 53 surgically-resected lung adenocarcinoma specimens were obtained between August 2018 and November 2019. The Papanicolaou-stained and paired Ki-67-stained slides were analyzed for calculating nuclear morphology (nuclear area, nuclear perimeter and nuclear circularity) and Ki-67 labeling index using software. The cell proliferation index (CPIx) was calculated and cellular information including cell cycle stage of tumor cells was obtained by flow cytometry. RESULTS: The 53 cases included papillary (n = 29), acinar (n = 8), lepidic (n = 5), and solid (n = 4) subtypes, and invasive mucinous adenocarcinoma (n = 7) were also included. In the lepidic pattern, nuclear area (79.6 ± 28.8 µm2 ) and perimeter (34.1 ± 6.1 µm) were relatively larger and longer than those of the other predominant patterns. The Ki-67 labeling index of the solid pattern (27.9 ± 12.5%) was highest compared with those of other predominant patterns. There were statistically significant differences in the lepidic versus solid patterns and the papillary versus solid patterns (p = .013 and p = .039, respectively). The calculated mean CPIx of the lepidic and the acinar patterns were approximately two-fold higher than those of the other predominant patterns. CONCLUSION: By revealing the differences of cytomorphological characteristics, these methodologies might be used for diagnosing cytopathological materials using digital cytopathology.

Optimal Preservations of Cytological Materials Using Liquid-Based Cytology Fixatives for Next-Generation Sequencing Analysis.

INTRODUCTION: Molecular targeted therapies have been established for various diseases, including cancers, and there is an increasing need for molecular testing on cytology specimens. The aim of this study was to determine the optimal preservation methods of liquid-based cytology (LBC) materials for molecular testing. METHODS: Cytological samples from 35 surgical resected non-small cell lung carcinoma specimens were obtained between June 2016 and June 2021. The samples were fixed in CytoRich™ red Preservative and stored at 4°C. One week later, three tubes were prepared from each specimen sample and divided into the following groups: the SurePath™ group (continued storage at 4°C), Frozen (Fr) group (stored at -80°C after centrifugation), and LBC-Cell Block (LBC-CB) group (generation of paraffin-embedded CB and storage at 4°C). Samples from 5 patients were used for the time course analysis, and we performed evaluations on these samples at 1, 3, 6, 12, 24, and 36 months. The concentrations and purities of extracted DNA and RNA were measured. The double-stranded DNA (dsDNA) and RNA concentrations were also measured by a fluorometer. The DNA and RNA integrities were quantified by the DNA and RNA integrity number. RESULTS: Evaluation of samples was performed at baseline and the six timepoints. In the LBC-CB group, DNA and dsDNA concentrations were higher rather than those in the other groups. The RNA concentration of the LBC-CB group was relatively high compared with those of the other groups at the 36-month timepoint. The Fr group maintained higher DNA quality compared with the other groups over 3 years. The LBC-CB group maintained a higher RNA quality than the other groups until 24 months. CONCLUSION: LBC-CB preparation is an effective method to maintain DNA/RNA quality and quantity in long-duration preservation for eventual molecular testing. Therefore, LBC-CB may have applications on preanalytical stage for molecular genomic testing such as next-generation sequencing.

A Rare Case of Acute Fibrinous and Organizing Pneumonia Associated with Systemic Lupus Erythematosus and Autoimmune-associated Hemophagocytic Syndrome: The Involvement of CD163-positive Macrophages.

Acute fibrinous and organizing pneumonia (AFOP) is rare in patients with systemic lupus erythematosus (SLE). We herein report a case of AFOP with SLE and hemophagocytic syndrome. Early-phase high-resolution computed tomography showed a fine granular lung pattern. A pathological examination revealed AFOP. An immunohistological examination revealed numerous CD163+ and fewer CD68+ macrophages present in the lung tissue and in alveolar spaces as well, including fibrin balls, the interstitium, and bronchial walls. Pneumonia and thrombocytopenia worsened during high-dose steroid therapy, plasma exchange, and intravenous immunoglobulin administration. The addition of intravenous cyclophosphamide successfully ameliorated the symptoms and radiographic lesions. Therefore, this therapy may be useful for treating severe AFOP.

MuRF1 deficiency prevents age-related fat weight gain, possibly through accumulation of PDK4 in skeletal muscle mitochondria in older mice.

Recent studies show that muscle mass and metabolic function are interlinked. Muscle RING finger 1 (MuRF1) is a critical muscle-specific ubiquitin ligase associated with muscle atrophy. Yet, the molecular target of MuRF1 in atrophy and aging remains unclear. We examined the role of MuRF1 in aging, using MuRF1-deficient (MuRF1-/- ) mice in vivo, and MuRF1-overexpressing cell in vitro. MuRF1 deficiency partially prevents age-induced skeletal muscle loss in mice. Interestingly, body weight and fat mass of more than 7-month-old MuRF1-/- mice were lower than in MuRF1+/+ mice. Serum and muscle metabolic parameters and results of indirect calorimetry suggest significantly higher energy expenditure and enhanced lipid metabolism in 3-month-old MuRF1-/- mice than in MuRF1+/+ mice, resulting in suppressed adipose tissue gain during aging. Pyruvate dehydrogenase kinase 4 (PDK4) is crucial for a switch from glucose to lipid metabolism, and the interaction between MuRF1 and PDK4 was examined. PDK4 protein levels were elevated in mitochondria from the skeletal muscle in MuRF1-/- mice. In vitro, MuRF1 interacted with PDK4 but did not induce degradation through ubiquitination. Instead, SUMO posttranscriptional modification (SUMOylation) of PDK4 was detected in MuRF1-overexpressing cells, in contrast to cells without the RING domain of MuRF1. MuRF1 deficiency enhances lipid metabolism possibly by upregulating PDK4 localization into mitochondrial through prevention of SUMOylation. Inhibition of MuRF1-mediated PDK4 SUMOylation is a potential therapeutic target for age-related dysfunction of lipid metabolism and muscle atrophy.

[Experience of Complete Video-assisted Thoracoscopic Pneumonectomy].

Thoracotomy has been preferred to video-assisted thoracoscopic surgery( VATS) for performing pulmonary pneumonectomy, and there have been no reports of complete video-assisted thoracoscopic surgery (cVATS) for such a case. We present three cases of cVATS pneumonectomy. The operation method was based on four ports, and ports were added in difficult cases. In these cases, the blood loss and length of surgery were similar to results of VATS reported previously. We experienced bleeding complications in one case but were able to manage appropriately. There were no serious postoperative complications in our cases. In addition, it was considered acceptable in terms of safety because there were no deaths within 30 days after operation in all cases. The cVATS pneumonectomy for lung cancer is one of the useful treatment option because of safety and many benefits although the long-term results are unknown at present.

Crystal structure of inhibitor-bound human MSPL that can activate high pathogenic avian influenza.

Infection of certain influenza viruses is triggered when its HA is cleaved by host cell proteases such as proprotein convertases and type II transmembrane serine proteases (TTSP). HA with a monobasic motif is cleaved by trypsin-like proteases, including TMPRSS2 and HAT, whereas the multibasic motif found in high pathogenicity avian influenza HA is cleaved by furin, PC5/6, or MSPL. MSPL belongs to the TMPRSS family and preferentially cleaves [R/K]-K-K-R↓ sequences. Here, we solved the crystal structure of the extracellular region of human MSPL in complex with an irreversible substrate-analog inhibitor. The structure revealed three domains clustered around the C-terminal α-helix of the SPD. The inhibitor structure and its putative model show that the P1-Arg inserts into the S1 pocket, whereas the P2-Lys and P4-Arg interacts with the Asp/Glu-rich 99-loop that is unique to MSPL. Based on the structure of MSPL, we also constructed a homology model of TMPRSS2, which is essential for the activation of the SARS-CoV-2 spike protein and infection. The model may provide the structural insight for the drug development for COVID-19.

Follicular tissue fragments in fine-needle aspiration cytology of lymph nodes: A useful clue in differential diagnosis of follicular lymphoma and reactive follicular hyperplasia.

BACKGROUND: In Fine-needle aspiration cytology (FNAC) of lymph nodes, tissue fragments derived from follicular structures may be observed in specimens. We defined such tissue fragments as follicular tissue fragments (FTF), and investigated differences in cytological findings for FTFs of each histological type. METHOD: A total of 41 cases with FNAC of lymph nodes were examined. In these cases, the histopathological diagnoses were reactive lymphoid hyperplasia (RLH) (n = 17), follicular lymphoma (FL) (n = 13), diffuse large B-cell lymphoma (DLBCL) (n = 18), and Burkitt lymphoma (n = 1). Specimens were analyzed for the presence of FTFs, and for tingible-body macrophages (TBMs) and monomorphism of lymphocytes in FTFs. FTFs with a maximum diameter of >500 µm were defined as large-FTFs. RESULTS: FTFs were identified in RLH (14/17, 82.4%), FL (13/13, 100%), and DLBCL (3/18, 16.7%). In the RLH subtypes, FTFs were present only in follicular hyperplasia (FH) (14/15, 93.3%) and not in paracortical hyperplasia (0/2). The number of cases with large FTFs among those with FTFs were as follows: RLH (10/14, 71.4%), FL (11/13, 84.6%), and DLBCL (0/3). Similarly, those with TBMs in FTFs were as follows: RLH (13/14, 92.9%), FL (0/13) and DLBCL (2/3, 66.7%). Monomorphism was observed in RLH (1/14, 7.1%) and FL (11/13, 84.6%), but not in DLBCL (0/3). CONCLUSIONS: Distinction between FL and FH is possible by identifying large-FTFs. In FL, TBMs are absent in FTFs and lymphocytes often show monomorphism. Therefore, recognizing FTFs and observing details inside the FTFs are useful for identification and differential diagnosis of FL and FH in FNAC of lymph nodes.

CT-guided color marking of impalpable pulmonary nodules prior to video-assisted thoracoscopic surgery.

OBJECTIVES: To investigate the utility and complications of computed tomography (CT)-guided color marking of impalpable pulmonary nodules for video-assisted thoracoscopic surgical resection. METHODS: This retrospective single institutional study has obtained Institutional Review Board approval. A total of 174 patients with 207 undiagnosed peripheral lesions of the lung were enrolled who had undergone preoperative computed tomography-guided color marking using colored collagen followed by video-assisted thoracoscopic surgery (VATS) from December 2015 to September 2018. RESULTS: All nodules (mean 14.0 mm, range 3.0-30.0 mm) were successfully marked by computed tomography-guided color marking, and 96.0% cases (167/174) were localized by means of intraoperative fluoroscopy as clear spots. Minor pneumothorax with a median volume of 3.8 mL (range 0.2-119.0 mL) occurred in 12 patients (6.9%) who were completely asymptomatic and were not in serious condition. No patient required a chest tube. No major bleeding complication occurred, and no air emboli were seen. No intra- or post-operative mortality of VATS was observed. CONCLUSIONS: Preoperative CT-guided color marking of impalpable pulmonary nodules is a safe and effective procedure that allows for successful surgical resection.

Distribution of injectate administered through a catheter inserted by three different approaches to ultrasound-guided thoracic paravertebral block: a prospective observational study.

BACKGROUND: Despite the popularity of continuous thoracic paravertebral block (TPVB), there is a paucity of information on catheter tip position and distribution of injectate through the catheter. We observed, in real time, the spread of dye, the catheter tip position and sensory block levels produced with three different (intercostal (IC), transverse process sagittal (TS) and paralaminar (PL)) approaches to ultrasound-guided TPVB in patients undergoing video-assisted thoracoscopic surgery. METHODS: After the induction of general anesthesia, ultrasound-guided TPVB was conducted with a patient in the lateral decubitus position. During surgery, 10 mL of dye was injected through a catheter to observe the catheter tip and the dye distribution under thoracoscopy. Dermatomal sensory block levels were measured postoperatively. RESULTS: Ten patients for each of three different approaches completed the study. There were a variety of dye spreading patterns. The median (range) number of segmental levels stained with dye was 1.5 (1-4), 3 (1-4) and 3 (1-5) with the IC, TS and PL approaches, respectively. We observed that a catheter tip was present at the same segmental paravertebral space as intended in 50%-90% of patients using these approaches. The median (range) number of dermatomes with sensory blockade at 6 hours after block was 2.5 (1-4), 3 (2-8) and 3 (1-8) with the IC, TS and PL approaches, respectively. CONCLUSIONS: Although a bolus injection through a catheter for ultrasound-guided TPVB produced multiple levels of spread and sensory blockade in more than half the patients, considerable differences existed in the spread regardless of approach.

Comparative postoperative outcomes of GGN-dominant vs single lesion lung adenocarcinomas.

BACKGROUND: Multiple synchronous ground glass nodules (GGNs) are known to be malignant, however, they tend to progress slowly. Multiple synchronous lesions in the same patient which show different characteristics must be treated individually. METHODS: This was a retrospective review of 34 lung adenocarcinoma patients with multiple synchronous GGNs in an Asian population. One hundred twenty-seven single lung adenocarcinoma patients were included for comparison purposes. The follow-up period was 5 years for all patients. RESULTS: The 5-year overall survival (OS) patients with multiple lesions did not differ from that of the patients with single lesions to a statistically significant extent (Single: 81.8% vs. Multiple: 88.2%, P = 0.3602). Dominant tumors (DTs) with a ground glass component and consolidation were divided into three categories based on the consolidation-to-tumor ratio on radiological imaging. No significant differences were observed among the three DT categories. Twenty-four patients had unresected GGNs, while a progression of the unresected GGN occurred in 10 of these cases. The OS and disease-free survival (DFS) curves of patients with and without GGN progression did not differ to a statistically significant extent (OS: 80% vs. 92.9%, P = 0.3870; DFS: 80% vs. 100%, P = 0.0977). CONCLUSIONS: The outcomes were best predicted by the stage of the DT. After surgery patients require a careful follow-up because unresected GGNs may show progression. At the same time, the increase in residual lesions and the appearance of new GGNs were not related to OS. The management of such patients should be determined according to the DT with the worst prognosis.

Methotrexate-Associated Lymphoproliferative Disorder Developed Ectopically in the Maxillary Gingiva and Bilateral Lungs.

A 58-year-old Japanese woman complained of a painful right maxillary premolar gingiva and ulcer. The patient had RA and had been treated with several immunosuppressive drugs such as methotrexate. Head and neck CT indicated no obvious bone destruction with maxillary. However, chest CT indicated the presence of nodular mass of the bilateral lungs. FDG-PET/CT indicated the presence of increased uptake in both lesions. On immunohistochemistry, atypical large-sized lymphocytes were positive for CD20 and EBER-ISH and negative for CD3, CD5, and CD10; the Ki-67 labeling index was high, the histopathological diagnosis was EBV-positive DLBCL, and the clinical diagnosis was MTX-LPD. The patient's treatment with MTX was then discontinued; we removed the alveolar bone which necrosed after 5 weeks. The lesion and the nodular mass at the bilateral lungs had completely disappeared after 7 weeks.

Surgical resection for advanced bisphosphonate-related osteonecrosis of the jaw associated with fibrous dysplasia: a case report.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is an adverse drug reaction represented by destruction and/or death of bone. Fibrous dysplasia (FD) is a rare bony disorder characterised by abnormal fibro-osseous tissue that has lowered resistance to infection. Effective treatments for BRONJ that follows FD are unclear. Here, we report that advanced BRONJ associated with FD was successfully treated by surgical resection. A 69-year-old woman, whose left maxillary bone showed a ground glass appearance on computed tomography (CT) images, was taking alendronate. At 1 year after teeth within the abnormal bone were extracted, exposed bone was observed in the extraction sites and CT images revealed separated sequestrums. Under the clinical diagnosis of Stage 2 BRONJ with FD, we performed not only sequestrectomy but also a partial resection of the FD. Thereafter, the healing was uneventful without recurrence. In conclusion, our case suggests that surgical resection is useful for advanced BRONJ associated with FD.

Ammonium tetrathiomolybdate enhances the antitumor effect of cisplatin via the suppression of ATPase copper transporting beta in head and neck squamous cell carcinoma.

Platinum­based antitumor agents have been widely used to treat head and neck squamous cell carcinoma (HNSCC) and numerous other malignancies. Cisplatin is the most frequently used platinum­based antitumor agent, however drug resistance and numerous undesirable side effects limit its clinical efficacy for cancer patients. Cancer cells discharge cisplatin into the extracellular space via copper transporters such as ATPase copper transporting beta (ATP7B) in order to escape from cisplatin­induced cell death. In the present study, it was demonstrated for the first time that the copper chelator ammonium tetrathiomolybdate (TM) has several promising effects on cisplatin and HNSCC. First, TM suppressed the ATP7B expression in HNSCC cell lines in vitro, thereby enhancing the accumulation and apoptotic effect of cisplatin in the cancer cells. Next, it was revealed that TM enhanced the antitumor effect of cisplatin in HNSCC cell tumor progression in a mouse model of bone invasion, which is important since HNSCC cells frequently invade to facial bone. Finally, it was demonstrated that TM was able to overcome the cisplatin resistance of a human cancer cell line, A431, via ATP7B depression in vitro.

Genotyping and cytomorphological subtyping of lung adenocarcinoma based on liquid-based cytology.

BACKGROUND: Liquid-based cytology (LBC) samples allow immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and molecular testing of nucleic acids to be performed in the remaining fixed cells. The current study aimed to examine the relationship between gene mutational status and cytomorphological features in primary lung adenocarcinoma (ADC) using LBC materials. METHODS: Forty consecutive patients with primary lung ADC underwent surgical resection in our hospital. Cytological material was obtained by scraping the cut-surface of the lesion, and samples were fixed and stored as LBC materials using CytoRich Red. Epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, anaplastic lymphoma kinase (ALK), and c-ros oncogene 1 (ROS1) gene rearrangements were detected, and cytomorphological studies were performed. RESULTS: Twenty cases (50%) were positive for EGFR mutation and four (10%) were positive for KRAS mutation. ALK gene rearrangement was identified in one case (2.5%) by IHC and FISH, and ROS1 gene rearrangement was identified in one case (2.5%) by IHC and real-time polymerase chain reaction. The KRAS-positive group included higher proportions of cases with an inflammatory background (100%), predominantly papillary architecture (75%), and papillary-type ADC pattern (75%) compared with the EGFR-positive group and the other group, which included ALK and ROS1 gene rearrangements. CONCLUSIONS: LBC material is suitable for use in molecular testing. Differences in major gene aberrations detected by this method might predict specific cytomorphological features.