Fusobacterium nucleatum putatively affects the alveoli by disrupting the alveolar epithelial cell tight junction, enlarging the alveolar space, and increasing paracellular permeability.

Fusobacterium nucleatum (Fn) is abundant in the human oral cavity and has been associated with periodontal disease, which in-turn has been linked to respiratory disease development. Tight junctions (TJs) line the airway and alveoli surfaces serving as a first line of defense against multiple pathogens. Fn has already been linked to respiratory diseases, however, how Fn affects the alveolar TJ was not fully elucidated. Here, we designed and analyzed a TJ network, grew Fn cells and inoculated it in vitro (16HBE and primary cells) and in vivo (mice lung), measured transepithelial electrical resistance, performed RT-PCR, checked for in vitro cell and mice lung permeability, and determined air space size through morphometric measurements. We found that Fn can potentially affect TJs proteins that are directly exposed to the alveolar surface. Additionally, Fn could possibly cause neutrophil accumulation and an increase in alveolar space. Moreover, Fn putatively may cause an increase in paracellular permeability in the alveoli.

Porphyromonas gingivalis Mfa1 fimbria putatively binds to TLR2 and induces both IL-6 and IL-8 production in human bronchial epithelial cells.

Porphyromonas gingivalis (Pg) a major periodontal pathogen involved in periodontal disease development and progression. Moreover, Pg has two fimbriae surface proteins (FimA and Mfa1) that are genetically distinct and make-up the fimbrial shaft which in-turn form crucial attachment to oral bacteria and multiple host cells. However, unlike FimA, Mfa1 attachment to non-periodontal cells has not been fully elucidated. Considering Pg-associated periodontal disease contributes to pulmonary disease development, we investigated whether Mfa1 can functionally interact with human bronchial epithelial cells and, likewise, trigger a functional response. Initially, we simulated molecular docking and performed both luciferase and neutralization assays to confirm Mfa1-related functional interaction. Subsequently, we treated BEAS-2B cells with purified Mfa1 and performed cytokine quantification through real time-PCR and ELISA to establish Mfa1-related functional response. We found that both Mfa1-TLR2 and Mfa1-TLR4 docking is possible, however, only Mfa1-TLR2 showed a functional interaction. Additionally, we observed that both IL-8 and IL-6 gene expression and protein levels were induced confirming Mfa1-related functional response. Taken together, we propose that BEAS-2B human bronchial epithelial cells are able to recognize Pg Mfa1 and induce both IL-8 and IL-6 inflammatory responses.

Expression of the SARS-CoV-2 Receptor ACE2 and Proinflammatory Cytokines Induced by the Periodontopathic Bacterium Fusobacterium nucleatum in Human Respiratory Epithelial Cells.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a global public health emergency. Periodontitis, the most prevalent disease that leads to tooth loss, is caused by infection by periodontopathic bacteria. Periodontitis is also a risk factor for pneumonia and the exacerbation of chronic obstructive pulmonary disease, presumably because of the aspiration of saliva contaminated with periodontopathic bacteria into the lower respiratory tract. Patients with these diseases have increased rates of COVID-19 aggravation and mortality. Because periodontopathic bacteria have been isolated from the bronchoalveolar lavage fluid of patients with COVID-19, periodontitis may be a risk factor for COVID-19 aggravation. However, the molecular links between periodontitis and COVID-19 have not been clarified. In this study, we found that the culture supernatant of the periodontopathic bacterium Fusobacterium nucleatum (CSF) upregulated the SARS-CoV-2 receptor angiotensin-converting enzyme 2 in A549 alveolar epithelial cells. In addition, CSF induced interleukin (IL)-6 and IL-8 production by both A549 and primary alveolar epithelial cells. CSF also strongly induced IL-6 and IL-8 expression by BEAS-2B bronchial epithelial cells and Detroit 562 pharyngeal epithelial cells. These results suggest that when patients with mild COVID-19 frequently aspirate periodontopathic bacteria, SARS-CoV-2 infection is promoted, and inflammation in the lower respiratory tract may become severe in the presence of viral pneumonia.

[A Case of Colon Metastasis from Breast Cancer with Resection by Laparoscopic Surgery].

A 50-year-old woman underwent breast-conserving surgery and axillary lymph node dissection for left breast cancer in May 2003. She received chemotherapy and radiation for lymph node, lung, and brain metastases. In October 2015, because of abdominal pain and melena, she underwent colonoscopy for suspected sigmoid colon metastasis from breast cancer. We performed laparoscopic sigmoidectomy and diagnosed sigmoid colon metastasis from breast cancer after histopathological examination. Colon metastasis from breast cancer can occur, although it is very rare.

A bilateral thoracic approach for esophageal cancer in the prone position.

Esophagectomy in the prone position has recently been introduced as a less-invasive procedure for treating esophageal cancer. We herein present a case of esophageal squamous cell carcinoma (ESCC) treated with a bilateral thoracic approach in the prone position. The patient was a 69-year-old male diagnosed with middle thoracic ESCC. Computed tomography scans and fluorine-18-fluorodeoxyglucose revealed possible metastasis to the lymph nodes on the left dorsal side of the descending thoracic aorta (DTA). After preoperative chemotherapy, we dissected the lymph node metastasis on the left dorsal DTA using the left thoracic approach, following resection of the ESCC by a right thoracic approach in the same prone position. The postoperative course was uneventful, and the patient was discharged 23 days after surgery. A bilateral thoracic approach for esophageal cancer in the prone position may be a new option for surgically treating esophageal cancer.

Laparoscopic posterior pelvic exenteration for clear cell adenocarcinoma arising in an episiotomy scar.

Malignant degeneration of endometriosis is a very rare event, especially when it develops in an episiotomy scar. A 53-year-old woman with an enlarged perineal mass presented to the hospital. She had undergone vaginal delivery with episiotomy twice. Imaging analyses showed a mass involving the levator ani muscle apart from the rectum, with lymph node metastases to the right inguinal and internal iliac regions. A biopsy specimen of the right inguinal lymph node revealed poorly differentiated adenocarcinoma. She underwent neoadjuvant chemotherapy according to the treatment strategy of anal fistula cancer. Laparoscopic posterior pelvic exenteration and pelvic lymph node dissection with anterior inguinal node dissection was performed, along with perineal reconstruction. Pathological examination revealed clear cell adenocarcinoma with lymph node metastases, derived from extrapelvic endometriosis in the episiotomy scar. She was treated with adjuvant chemotherapy according to the treatment strategy of vulvar cancer, and showed no evidence of recurrence after 15 months of surgery.

Aspiration of periodontopathic bacteria due to poor oral hygiene potentially contributes to the aggravation of COVID-19.

Coronavirus infectious disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared a pandemic in March 2020 by the World Health Organization. Periodontitis, one of the most prevalent diseases worldwide, leads to alveolar bone destruction and subsequent tooth loss, and develops due to pro-inflammatory cytokine production induced by periodontopathic bacteria. Periodontopathic bacteria are involved in respiratory diseases, including aspiration pneumonia and chronic obstructive pulmonary disease (COPD), and other systemic diseases, such as diabetes and cardiovascular disease. Patients with these diseases have an increased COVID-19 aggravation rate and mortality. Because aspiration of periodontopathic bacteria induces the expression of angiotensin-converting enzyme 2, a receptor for SARS-CoV-2, and production of inflammatory cytokines in the lower respiratory tract, poor oral hygiene can lead to COVID-19 aggravation. Conversely, oral care, including periodontal treatment, prevents the onset of pneumonia and influenza and the exacerbation of COPD. The reduced chance of receiving professional oral care owing to long-term hospitalization of patients with COVID-19 may increase the aggravation risk of infection in the lower respiratory tract. It can be hypothesized that periodontopathic bacteria are involved in the COVID-19 aggravation and therefore, the management of good oral hygiene potentially contributes to its prevention.

Barium-induced appendicitis mimicking accidental ingestion of a dental metal crown in radiological findings.

Barium appendicitis is a rare complication that has only been reported in a small number of case reports in the medical literature. A 57-year-old male presented to the emergency room with a sudden onset of sharp right lower quadrant abdominal pain. He had undergone contrast barium examination of his stomach 2 months previously as part of a periodic examination for gastric cancer. The radiological findings showed that the shape and radiopaque levels were similar to those of a dental metal crown silhouette. The patient was strongly suspected to have a localized intra-abdominal abscess due to ileocaecal perforation with a foreign body such as a dental metal crown. Emergency surgery revealed acute phlegmonous appendicitis. The resected specimen demonstrated a phlegmonous appendix which contained solid coproma. Pathological diagnosis and composition analysis confirmed the onset of appendicitis to be a result of the patient's ingestion of barium sulfate.