Successful treatment with atezolizumab combination chemotherapy in a patient with high-grade fetal adenocarcinoma of the lung: A case report.

High-grade fetal lung adenocarcinoma (H-FLAC) is a rare tumor, with little known of its response to chemotherapy with or without an immune checkpoint inhibitor or of its molecular profile. We report the first case of a 56-year-old man with stage IV H-FLAC who was successfully treated with carboplatin plus nab-paclitaxel in combination with atezolizumab. In addition, the tumor was found to be positive for amplification of the human epidermal growth factor receptor 2 gene.

Upregulation of viral RNA polymerase activity promotes adaptation of SSPE virus to neuronal cells.

Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurodegenerative disease caused by measles virus variants (SSPE viruses) that results in eventual death. Amino acid substitution(s) in the viral fusion (F) protein are key for viral propagation in the brain in a cell-to-cell manner, a specific trait of SSPE viruses, leading to neuropathogenicity. In this study, we passaged an SSPE virus in cultured human neuronal cells and isolated an adapted virus that propagated more efficiently in neuronal cells and exhibited increased cell-to-cell fusion. Contrary to our expectation, the virus harbored mutations in the large protein, a viral RNA-dependent RNA polymerase, and in the phosphoprotein, its co-factor, rather than in the F protein. Our results imply that upregulated RNA polymerase activity, which increases F protein expression and cell-to-cell fusion, could be a viral factor that provides a growth advantage and contributes to the adaptation of SSPE viruses to neuronal cells.

The safety and efficacy of durvalumab consolidation therapy in the management of patients with stage III non-small-cell lung cancer and preexisting interstitial lung disease.

BACKGROUND: Some lung cancer patients have preexisting interstitial lung disease (ILD), which is considered a risk factor for lung cancer treatment. This study investigated the safety and efficacy of durvalumab consolidation therapy for patients with stage III non-small-cell lung cancer (NSCLC) and preexisting ILD. METHODS: Fifty consecutive patients who were judged to be tolerable to concurrent chemoradiotherapy (CCRT) for stage III NSCLC were enrolled. Differences in the incidence rate of radiation pneumonitis (RP) and progression-free survival (PFS) were assessed in patients with or without ILD of which CT showed non-usual interstitial pneumonia pattern between the durvalumab consolidation group and chemotherapy (combination of carboplatin and paclitaxel [CP]) consolidation group. RESULTS: The incidence of RP was higher in patients with preexisting ILD (40% and 20% in the durvalumab and CP groups, respectively) than in those without ILD (26% and 8% in the durvalumab and CP groups, respectively). Univariate analysis showed that durvalumab therapy tended to increase the incidence of RP; however, preexisting ILD did not significantly increase the incidence of RP. The condition of all patients who developed RP improved with the administration of oral prednisolone. Among patients without ILD, the median PFS was 17 and 16 months in the durvalumab and CP groups, respectively. Among patients with preexisting ILD, median PFS was not achieved in the durvalumab group and was 8 months in the CP group. CONCLUSIONS: Although durvalumab consolidation therapy tended to increase the incidence of RP, it might be tolerable in stage III NSCLC patients with preexisting ILD.

Efficacy of the combination of baricitinib, remdesivir, and dexamethasone in hypoxic adults with COVID-19: A retrospective study.

BACKGROUND: Remdesivir with dexamethasone and remdesivir with baricitinib are effective in coronavirus disease 2019 (COVID-19) patients. However, there has been few evidence regarding the efficacy of the combination of baricitinib, remdesivir, and dexamethasone in hypoxic COVID-19 patients. METHODS: Consecutive patients who required oxygen therapy at the time of admission and received remdesivir and dexamethasone at Kishiwada City Hospital between March 1, 2021 and May 31, 2021 were retrospectively analyzed. RESULTS: A total of 90 patients were investigated, including 30 receiving a combination of remdesivir, dexamethasone, and baricitinib (baricitinib group) and 60 receiving remdesivir and dexamethasone (control group). The use of direct oral anticoagulants, the level of C-reactive protein, and chest X-ray abnormalities were significantly higher in the baricitinib group than in the control group. Patients in the baricitinib group recovered a median of four days faster than those in the control group (median, 7 days vs. 11 days; Gray's test, p < 0.001). The recovery rate was 90.0% in the baricitinib group and 63.3% in the control group (p = 0.011). Fine and Gray regression analysis showed that adjusted rate ratio for recovery with the baricitinib combination therapy was 5.26 (95% confidential interval, 1.99-13.9; p < 0.001). The incidence of new onset of bacterial infection was 6.7% in the baricitinib group and 16.7% in the control group (p = 0.324). CONCLUSIONS: Our study suggests that the combination of baricitinib, dexamethasone, and remdesivir is effective and tolerable in hypoxic patients with COVID-19.

Successful laparoscopic lavage and drainage for intestinal perforation in a patient with COVID-19: A case report.

INTRODUCTION: Some patients with coronavirus disease 2019 (COVID-19) have acute abdomen and need surgery. However, surgery in the acute phase of COVID-19 is associated with worse postoperative outcomes and an increased risk of mortality. We report a case of a patient with COVID-19 who developed intestinal perforation that was treated acutely with antibiotics and delayed surgical intervention. PRESENTATION OF CASE: A 79-year-old man with COVID-19 was treated with remdesivir and dexamethasone, and his respiratory symptoms and hypoxia improved. However, abdominal symptoms developed, and intestinal perforation occurred. As the nasopharyngeal swab PCR test was positive for SARS-CoV-2, conservative treatment with tazobactam/piperacillin was started to avoid surgery in the acute phase of COVID-19. An intraperitoneal abscess was confirmed on follow-up computed tomography. Emergent laparoscopic lavage and drainage, and transverse colon stoma construction were performed with medical staff using full personal protective equipment. Bacterial culture from the ascites detected Escherichia coli and Bacteroides. The SARS-CoV-2 PCR test of the ascites sample was negative. No infection was observed in the medical staff. DISCUSSION: COVID-19 has been associated with a higher perioperative risk and postoperative mortality. There has also been a report of ascitic fluid testing positive for SARS-CoV-2 on PCR, suggesting the possibility of intraoperative aerosolization. Avoiding surgical treatment in the acute phase of COVID-19 may reduce deaths from perioperative complications. CONCLUSION: Our case suggests that in acute COVID-19 lung infection, careful observation and delayed surgical treatment could prevent worsening of the COVID-19 and reduce the risk of infection to the medical staff.

Successful treatment with metronidazole and paromomycin for fulminant amoebic colitis during cytotoxic chemotherapy in a patient with small-cell lung cancer.

We report the case of a 64-year-old man with advanced small-cell lung cancer who developed fulminant amoebic colitis during cytotoxic chemotherapy. During the first cycle of carboplatin/etoposide treatment, febrile neutropenia and grade 4 neutropenia developed. Because diarrhea, abdominal pain, and bloody stool were observed, abdominal computed tomography was performed, showing intussusception, and extensive colectomy and colostomy were performed. Histopathology of the colon revealed gastrointestinal necrosis and perforation due to Entamoeba histolytica infection. Amoebiasis improved after treatment with metronidazole and paromomycin. The second cycle of carboplatin/etoposide with dose reduction was completed, resulting in a partial response to small-cell lung cancer. The results of this case suggest that paromomycin is an additional option for amoebiasis during cytotoxic chemotherapy, and persistent diarrhea during cytotoxic chemotherapy should alert clinicians to consider the development of amoebiasis.

Toll-like receptor 2 mediates the immune response of the bovine oviductal ampulla to sperm binding.

We previously reported that sperm binding to cultured bovine oviduct epithelial cells induces an anti-inflammatory immune response. Now we have developed a differentiated explant model to focus on the oviductal ampulla, where fertilization occurs, and to study the effect of sperm capacitation on the immune response. We used heparin to stimulate bovine sperm capacitation. Fluorescence imaging showed that 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide-labeled sperm pretreated with (Hep(+) ) or without (Hep(-) ) heparin rapidly attached to the explant ciliated epithelium in similar numbers. However, only Hep(+) sperm upregulated explant messenger RNA (mRNA) transcription of TLR2, IL8, TGFB1, and PGES, without changes in TNFA and IL-10 expression, while Hep(-) sperm only upregulated PGES. The responses were primarily anti-inflammatory, with a greater response produced by Hep(+) sperm, which also produced a substantial increase in TLR2 protein expression in the epithelium. The addition of TLR1/2 (toll-like receptor 1/2) antagonist to the Hep(+) and (Hep(-) ) sperm-explant coincubations reduced sperm attachment to the epithelium and inhibited TLR2 protein expression and some of the Hep(+) sperm-induced mRNA transcription. Our observations suggest that the ampullar epithelium immunologically reacts more strongly to sperm that have undergone heparin stimulation of capacitation. This anti-inflammatory response could serve to protect capacitated sperm as they approach the oocyte in the ampulla.

Bronchoscopic Surgery for a Solitary Tracheal Tumor of Tracheobronchopathia Osteochondroplastica.

Tracheobronchopathia osteochondroplastica is a rare benign condition in which multiple cartilaginous or bony submucosal nodules project into the trachea or bronchi. A 71-year-old man complained of cough for 3 months. Computed tomography scanning revealed a calcified tracheal tumor near the tracheal bifurcation. Pulmonary function testing indicated airflow limitation, and bronchoscopic examination confirmed a solitary rigid tumor. Bronchoscopic resection was performed under general anesthesia, and the tumor was detached by cauterizing its stem with high-frequency coagulation. The tumor was pathologically indicative of tracheobronchopathia osteochondroplastica. After surgery, the clinical signs of cough and dyspnea resolved and pulmonary function normalized.

Bovine oviduct epithelial cells suppress the phagocytic activity of neutrophils towards sperm but not for bacteria in vitro: Immunofluorescence and electron microscopic observations.

Previously, we reported that polymorphonuclear neutrophils (PMNs) are constantly existent in the bovine oviduct fluid during the pre-ovulatory stage under physiological conditions. Moreover, incubation of PMNs with bovine oviduct epithelial cells-conditioned medium (BOEC-CM) resulted in suppression of their phagocytic activity for sperm. During pathophysiological conditions, cows may be inseminated by infected semen which exposes oviductal PMNs to allogenic sperm simultaneously with pathogens. This study aimed to visually investigate the role of oviduct epithelium in regulating the phagocytic behavior of PMNs toward sperm as a physiological stimulus, with Escherichia coli (E. coli) as a pathological stimulus. In our experiment, PMNs were incubated for 2 h in BOEC-CM. Phagocytosis was then assayed by co-incubation of these PMNs either with sperm, E. coli, or latex beads. BOEC-CM significantly suppressed the direct phagocytosis of PMNs for sperm, but did not affect their phagocytic activity for E. coli or latex beads. Additionally, an investigation with scanning electron microscopy revealed that BOEC-CM suppressed the formation of DNA-based neutrophil extracellular traps (NETs) for sperm entanglement. BOEC-CM did not alter NETs formation towards E. coli. A quantification of NETs formation using an immunofluorescence microscopy showed that the areas of NETs formation for E. coli were significantly larger than those formed for sperm. Our data clearly show that the bovine oviduct, through secretions, protects sperm from phagocytosis by PMNs and eliminates bacterial dissemination through maintaining the phagocytic activity of PMNs towards bacteria.

Evidence-based clinical practice guidelines for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic disorder involving mainly the intestinal tract, but possibly other gastrointestinal and extraintestinal organs. Although etiology is still uncertain, recent knowledge in pathogenesis has accumulated, and novel diagnostic and therapeutic modalities have become available for clinical use. Therefore, the previous guidelines were urged to be updated. In 2016, the Japanese Society of Gastroenterology revised the previous versions of evidence-based clinical practice guidelines for ulcerative colitis (UC) and Crohn's disease (CD) in Japanese. A total of 59 clinical questions for 9 categories (1. clinical features of IBD; 2. diagnosis; 3. general consideration in treatment; 4. therapeutic interventions for IBD; 5. treatment of UC; 6. treatment of CD; 7. extraintestinal complications; 8. cancer surveillance; 9. IBD in special situation) were selected, and a literature search was performed for the clinical questions with use of the MEDLINE, Cochrane, and Igaku Chuo Zasshi databases. The guidelines were developed with the basic concept of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Recommendations were made using Delphi rounds. This English version was produced and edited based on the existing updated guidelines in Japanese.

Postoperative therapy with infliximab for Crohn's disease: a 2-year prospective randomized multicenter study in Japan.

PURPOSE: The prevention of postoperative recurrence is a critical issue in surgery for Crohn's disease. Prospective randomized trials in Western countries have shown that the postoperative use of anti-tumor necrosis factor α-antibodies was effective in reducing the recurrence rate. We investigated the efficacy of infliximab (IFX) for the prevention of postoperative Crohn's disease recurrence. METHODS: We performed a prospective randomized multicenter study. Patients who underwent intestinal resection were assigned to groups treated with or without IFX. Immediately after surgery, patients in the IFX group received IFX at 5 mg/kg at 0, 2, and 6 weeks, followed by every 8 weeks for 2 years. The primary study outcome was the proportion of patients with endoscopic and/or clinical recurrence at 2 years after surgery. RESULTS: Thirty-eight eligible patients participated in this study: 19 in the IFX group and 19 in the non-IFX group. The disease recurrence rate in the IFX group was 52.6% (10/19), which was significantly lower than that in the non-IFX group (94.7% [18/19]). CONCLUSION: The postoperative use of IFX is effective in preventing Crohn's disease recurrence for 2 years.

[A Resected Case of Cancer in the Ileum of the Blind Loop after an Ileotransverse Colostomy].

We report a resected case of cancer at the ileum of the blind loop. An 81-year-old male underwent an appendectomy for acute appendicitis and an ileotransverse colostomy for postoperative obstruction when he was 14 years old. He underwent radiation therapy for prostate cancer when he was 75 years old. Six years later, enhanced computed tomography revealed a 7 cm mass in the ileum of the blind loop. Colonoscopy showed wall thickening at the ileum of the blind loop, and biopsy revealed an adenocarcinoma. We performed partial resection of the ileum. The patient was discharged 17 days after surgery. Cancer at the ileum of the blind loop after an ileotransverse colostomy has rarely been reported.

Surveillance for dysplasia in patients with ulcerative colitis: Discrepancy between guidelines and practice.

BACKGROUND AND AIM: The risk of developing colorectal cancer is higher in patients with ulcerative colitis (UC) than in the general population. Guidelines recommend surveillance colonoscopy (SCS) to reduce mortality; however, few studies have assessed physicians' adherence to guidelines. This study was aimed to clarify the current status of SCS and adherence to guidelines through the characteristics of cancer/dysplasia surveillance for UC patients in Japan. METHODS: A questionnaire was mailed to 541 physicians who attended meetings on inflammatory bowel disease. RESULTS: The respondents encountered a median of 100 UC cases. Thirty percent of the respondents had never managed a UC patient with cancer. Fifty-one percent of the respondents had never diagnosed colorectal cancer with UC. Forty-seven percent of the respondents considered extensive colitis and left-sided colitis as indications for SCS, and 38% carried out SCS regardless of the disease extent. Sixty-three percent of the respondents started SCS at 7-10 years after UC onset, whereas 20% started SCS at 3 years or less. Fifty-two percent of the respondents obtained targeted biopsies only, and chromoendoscopy was used by 49% of the respondents as a special technique for surveillance. Median number of biopsies at SCS was five per patient; it was three among patients whose biopsy was carried out by physicians who obtained targeted biopsies only and seven among those carried out by physicians who obtained step biopsies and targeted biopsies (P < 0.0001). CONCLUSION: A considerable proportion of the respondents did not follow the guidelines when selecting patients for surveillance and carrying out SCS.

A residue located at the junction of the head and stalk regions of measles virus fusion protein regulates membrane fusion by controlling conformational stability.

The fusion (F) protein of measles virus performs refolding from the thermodynamically metastable prefusion form to the highly stable postfusion form via an activated unstable intermediate stage, to induce membrane fusion. Some amino acids involved in the fusion regulation cluster in the heptad repeat B (HR-B) domain of the stalk region, among which substitution of residue 465 by various amino acids revealed that fusion activity correlates well with its side chain length from the Cα (P<0.01) and van der Waals volume (P<0.001), except for Phe, Tyr, Trp, Pro and His carrying ring structures. Directed towards the head region, longer side chains of the non-ring-type 465 residues penetrate more deeply into the head region and may disturb the hydrophobic interaction between the stalk and head regions and cause destabilization of the molecule by lowering the energy barrier for refolding, which conferred the F protein enhanced fusion activity. Contrarily, the side chain of ring-type 465 residues turned away from the head region, resulting in not only no contact with the head region but also extensive coverage of the HR-B surface, which may prevent the dissociation of the HR-B bundle for initiation of membrane fusion and suppress fusion activity. Located in the HR-B domain just at the junction between the head and stalk regions, amino acid 465 is endowed with a possible ability to either destabilize or stabilize the F protein depending on its molecular volume and the direction of the side chain, regulating fusion activity of measles virus F protein.

Parastomal hernia repair with the Sugarbaker technique using e-PTFE mesh.

PURPOSES: Although surgery is commonly used to treat parastomal hernia, it is very difficult and has shown poor results. Recently, repair with prosthetic materials has been thought to be a more promising method. METHODS: The Sugarbaker technique with e-PTFE mesh (Dualmesh®) performed via open surgery was adopted for seven patients with parastomal hernia. Two of them were recurrent cases. Three of the patients experienced incarceration of the intestine and recovered conservatively before surgery. The median age of the patients at the parastomal hernia repair was 77.6 years old (range 37.7-84.7). RESULTS: The median operative time was 211 min (range 147-256). The median hernia size was 28 cm2 (range 7.5-60 cm2). The median amount of blood loss during the operation was 158 g (range 0-370 g). Surgical site infection was not observed. The postoperative median hospital stay was 17 days (range 13-40) and the median follow-up was 2.4 years (range 1.0-3.7). During the follow-up period, we did not observe recurrence or readmission. CONCLUSIONS: The surgical results were satisfactory with minimal morbidity and no recurrences. The Sugarbaker technique for parastomal repair using e-PTFE mesh may be suitable as a standard method for treating parastomal hernia.

[Successful Anesthetic Management of a Patient with Critical Bleeding during Hepatectomy Using Recombinant Activated Factor VII and Intraoperative Blood Salvage].

A 58-year-old 79 kg male with metastatic liver cancer was scheduled for hepatectomy. Preoperative examination did not reveal any hemostatic abnormalities. Nine hours into the surgery, a vascular clip attached to the middle hepatic vein was disconnected and rapid bleeding followed. Unscheduled intraoperative cell salvage was employed. Despite surgical hemostasis as well as transfusion with fresh frozen plasma and platelets, significant oozing persisted for 10 hours, and cumulative blood loss amounted to 30,000 ml. Therefore, we administered fibrinogen products and recombinant activated factor VLL (rFVIIa, NovoSeven), a potent hemostatic initiator used in treating congenital factor VII deficient patients. After injecting 5 mg of rFVIIa, the bleeding was controlled almost immediately, and the surgery was completed within an hour. Although postoperative computed tomography detected subclinical but extensive thrombosis in the middle hepatic vein, the inferior vena cava, and the deep femoral veins, the thrombus spontaneously dissolved within seven months postoperatively. There was no evidence of metastatic disease 24 months postoperatively. Off-label use of rFVIIa and intraoperatively salvaged autologous blood transfusions are life-saving procedures for cancer patients who have massive bleeding during surgery, although we cannot completely exclude the possibility of serious postoperative thrombotic events and/or hematogenous cancer dissemination.

[Anesthetic Management of an Infant with Rapidly Developed Hyponatremia due to Bowel Perforation during Enema Reduction Using Diluted Contrast Medium].

A 7-kg 8-month-old boy was transferred to our institution after failed enema reduction of intussusception elsewhere. During the redo intervention using a 6-fold-diluted solution of Gastrografin with water as contrast medium, the bowel was perforated. Urgent surgical repair was planned and preoperative examination revealed serum sodium of 137 mEq x l(-1). On arrival in the operating room, the patient presented abdominal distension, drowsiness and tachypnea. His trachea was intubated and anesthesia was maintained with sevoflurane. Arterial blood examination immediately before the surgery (approximate by 80 minutes after the previous blood test) showed the following findings: pH 7.27, base excess -8.5 mEq x l(-1) and sodium 122 mEq x l(-1). Watery ascites estimated at 450 ml was evacuated upon a peritoneal incision. At termination of anesthesia, serum sodium recovered to 133 mEq x l(-1), resulting from replenishment of electrolytes and sodium bicarbonate administration. The patient became fully awake and his trachea was extubated in the operating room. Gastrografin has osmolarity of 1,900 mOsm x l(-1), containing sodium of 158 mEq x l(-1). Massive intraperitoneal accumulation of diluted Gastrografin is a rational explanation for the rapidly developed hyponatremia, which can lead to hyponatremic encephalopathy, especially in infants. Prompt surgical intervention is therefore essential for successful management of such cases.

[Surgical management of intestinal Crohn's disease].

Various intestinal conditions such as stricture, fistula, abscess, perforation, and hemorrhage are complications of Crohn's disease. Surgical intervention remains important, even in the era of biologic therapy. Limited surgical resection is essential to avoid short bowel syndrome after massive resection or multiple operations. Strictureplasty is effective for short, isolated stricture of the small intestine and provides good results equivalent to those of intestinal resection. Fecal diversion in the case of very complicated lesions not suitable for immediate resection can offer patients general and local improvement. Although bypass surgery is currently not performed because of the possibility of deterioration or carcinogenesis of the bypassed segment, bypass surgery is useful for avoiding stoma. Laparoscopic surgery is indicated for patients with nonperforating, localized ileocecal lesions, and for those presenting initially. The cumulative postoperative reoperation rate is about 50% to 60% at 10 years. The risk factors for early recurrence are smoking, perforating type, previous reoperation, and small intestinal disease. During postoperative follow-up and maintenance treatment, the importance of an algorithm comprising regular check-ups with ileocolonoscopy and the use of thioprines and biologics has been proposed.

Intramolecular complementation of measles virus fusion protein stability confers cell-cell fusion activity at 37 °C.

The fusion (F) protein of measles virus mediates membrane fusion. In this study, we investigated the molecular basis of the cell-cell fusion activity of the F protein. The N465H substitution in the heptad repeat B domain of the stalk region of the F protein eliminates this activity, but an additional mutation in the DIII domain of the head region - N183D, F217L, P219S, I225T or G240R - restores cell-cell fusion. Thermodynamically stabilized by the N465H substitution, the F protein required elevated temperature as high as 40 °C to promote cell-cell fusion, whereas all five DIII mutations caused destabilization of the F protein allowing the highest fusion activity at 30 °C. Stability complementation between the two domains conferred an efficient cell-cell fusion activity on the F protein at 37 °C.

Successful treatment of two consecutive cases of pulmonary pleomorphic carcinoma with platinum chemotherapy.

Pulmonary pleomorphic carcinoma (PPC) is a rare pulmonary malignant tumor that has a more aggressive clinical course and a poorer prognosis compared with non-small cell lung cancer (NSCLC) due to its resistance to chemotherapy and radiotherapy. In patients with advanced or relapsed PPC, it has been reported that the response rate to chemotherapy regimens known to be effective in patients with NSCLC is only 0-17%. The present study reports the cases of two consecutive patients with advanced PPC who exhibited marked responses to chemotherapy with carboplatin plus paclitaxel chemotherapy and long-term survival without tumor progression. This suggests that carboplatin plus paclitaxel chemotherapy is a good option for the treatment of advanced PPC.