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1 Background Although the efficacy of lung cancer treatment has improved, it is dependent on a reliable diagnosis via bronchoscopy. Transbronchial biopsy using ultrathin bronchoscopy can help detect small peripheral pulmonary lesions (PPLs), with a high diagnostic yield. However, the diagnosis rate using forceps biopsy when the radial endobronchial ultrasonography (rEBUS) probe is adjacent to a lesion tends to be low. Transbronchial needle aspiration (TBNA) may improve the diagnostic yield from adjacent lesions. Recently, PeriView FLEX, a new TBNA needle that can be inserted into ultrathin bronchoscopes, has become available. We examined whether TBNA with PeriView FLEX and forceps biopsy improved adjacent lesion diagnosis when using ultrathin bronchoscopes. Methods We retrospectively examined 51 consecutive patients who underwent TBNA and forceps biopsy using ultrathin bronchoscopes under rEBUS for small PPLs at the Hakodate Goryoukaku Hospital between November 2019 and August 2020. The histological diagnosis rate using TBNA and forceps biopsy, TBNA alone, or forceps biopsy alone was compared between cases where the rEBUS probe was “Within” and “Adjacent To” the lesions. Results The diagnosis rate using TBNA and forceps biopsy was 86.3% (95.7% vs. 78.6%; p = 0.08) for all lesions (Within cases vs. Adjacent To cases). The corresponding rate using TBNA alone was 68.6% (69.6% vs. 67.9%; p = 0.57), and that using forceps biopsy alone was 72.5% (91.3% vs. 57.1%; p = 0.0067). Conclusions Forceps biopsy with TBNA during ultrathin bronchoscopy for small PPLs improved the diagnostic yield when lesions were adjacent to the rEBUS probe.

A 66‐year‐old man with squamous cell carcinoma had been receiving chemoradiation therapy after stereotactic radiotherapy for brain metastases. Atezolizumab was initiated as second‐line therapy, after which the patient became progression‐ and recurrence‐free. Four days after his second dose of tozinameran (BNT162b2, Pfizer‐BioNTech), the patient developed persistent hemoptysis. The patient had no thrombocytopenia or coagulation abnormalities. Bronchoscopy revealed active bleeding from the left lingual tracheal branch. The patient was intubated and admitted to the intensive care unit because of increased bleeding. Subsequently, left bronchial artery embolization was performed using a Serescue. Hemostasis was achieved after the procedure, and the patient was discharged 7 days after the onset of hemoptysis. Vaccination against coronavirus disease has been reported to be associated with thrombosis and cerebral hemorrhage, and the hemoptysis in this case was suspected to be induced by vaccination. In summary, the benefits of vaccination exceeded the risks of adverse events in a patient with cancer. However, in conditions such as after chemoradiation, especially in patients with radiation pneumonitis wherein the vasculature is vulnerable, patients should be carefully monitored for hemorrhagic events after vaccination., Patients in conditions such as after chemoradiation, especially in patients with radiation pneumonitis wherein the vasculature is vulnerable, should be carefully monitored for hemorrhagic events after vaccination.

Pseudocirrhosis is a radiological diagnosis of cirrhosis without histological evidence and occurs as a complication of liver metastases from solid tumors. A 50‐year‐old man without any previous history of liver disease was diagnosed with adenocarcinoma of the left upper lung lobe and liver metastasis. After chemotherapy, the liver metastases shrank; however, over time, the liver shrank and showed cirrhosis‐like morphological changes. His performance status deteriorated due to ascites and leg edema, and chemotherapy was terminated. Physicians treating lung adenocarcinoma with liver metastases should be aware that pseudocirrhosis is a rare but important complication that can worsen performance status (PS) and hinder treatment continuation., Liver metastasis from adenocarcinoma of the lung with abundant stromal growths showed cirrhosis‐like morphological changes in the course of treatment, ascites and marked leg edema. Pseudocirrhosis due to liver metastasis from lung adenocarcinoma is a rare but important complication that can worsen performance status and hinder treatment continuation.

BACKGROUND Amebic colitis is an infection caused by Entamoeba histolytica and most commonly observed in regions with poor sanitation. It is also seen as a sexually transmitted disease in developed countries. While amebic colitis usually has a chronic course with repeated exacerbations and remissions, it may also manifest as a fulminant form that rapidly progresses and leads to severe, life-threatening complications, such as intestinal perforation, peritonitis, and sepsis, that have a high mortality rate. CASE SUMMARY A 68-year-old man was admitted to our hospital with chest pain and acute dyspnea. He was diagnosed with acute coronary syndrome, acute heart failure, and bacterial pneumonia. His respiratory condition worsened despite receiving intensive care and intravenous antibiotics. On the fifth day of hospitalization, he was diagnosed with acute respiratory distress syndrome and was started on steroid therapy. He subsequently developed bloody stools and was diagnosed with cytomegalovirus (CMV) enterocolitis based on biopsy results and a peripheral blood CMV pp65 antigenemia test result. Although we started antiviral therapy with ganciclovir, which was successful in reducing his antigen titers, he continued to have bloody diarrhea. Three weeks after initiation of ganciclovir therapy and six weeks after his admission, the patient died from intestinal perforation. We only posthumously diagnosed him with amebic colitis and CMV enterocolitis based on autopsy findings of transmural necrosis of the entire colon with massive ameba infiltration. CONCLUSION We urge clinicians to consider Entamoeba histolytica infection if severe colitis progresses after steroid therapy. Preemptive treatment is recommended then.

Background In advanced lung cancer, precision medicine requires repeated biopsies via bronchoscopy at therapy change. Since bronchoscopies are often stressful for patients, sedation using both fentanyl and midazolam is recommended in Europe and America. In Japan, bronchoscopies are generally orally performed under midazolam and oropharyngeal anesthesia. Nasal intubation creates a physiological route to the trachea, causing less irritation to the pharynx than intubation via the oral cavity; however, the necessity of oropharyngeal anesthesia remains unclear. We aimed to compare the safety, patient discomfort, and diagnostic rates for oropharyngeal anesthesia and sedation with pethidine and midazolam (Group A) and sedation with midazolam and fentanyl without oropharyngeal anesthesia (Group B) for ultrathin bronchoscopy of peripheral pulmonary lesions (PPLs) via nasal intubation. Methods We retrospectively reviewed 74 consecutive potential lung cancer patients who underwent ultrathin bronchoscopies at the Hakodate Goryoukaku Hospital between July 2019 and June 2020. We reviewed the following: diagnostic rates; cumulative doses of lidocaine, midazolam, and fentanyl; hemodynamic changes; procedural complications in both groups. Pharyngeal anesthesia in group A was administered by spraying 2% (w/v) lidocaine into the pharynx. The chi-squared test was used for statistical analyses. Results There were no significant changes in hemodynamic parameters and complications. The mean level of discomfort for bronchoscopic examinations was significantly lower in Group B (2.39 vs. 1.64; P = 0.014), with no significant inter-group difference in the diagnostic yields for PPLs (63.0% vs. 71.4%; P = 0.46). Conclusions Our findings indicate the advantages of sedation with fentanyl and midazolam without oropharyngeal anesthesia for ultrathin bronchoscopy through nasal intubation.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are the standard treatment for patients with non‐small cell lung cancer (NSCLC) harboring EGFR mutations. Uncommon mutations, excluding exon 19 deletions and exon 21 L858R, comprise 7%–23% of EGFR mutation‐positive NSCLC. The treatment of uncommon EGFR mutation‐positive NSCLCs is controversial. Here, we present the case of an 81‐year‐old man who was diagnosed with lung adenocarcinoma cStage IVA harboring the uncommon EGFR L861Q mutation. The patient received oral afatinib treatment (40 mg/day). One month after the initiation of afatinib treatment, Common Terminology Criteria for Adverse Events version 4.0 grade 2 stomatitis was observed. It improved upon afatinib withdrawal. After 10 days of withdrawal, afatinib treatment was resumed at a reduced dose of 20 mg/day. Subsequently, the patient continued treatment with afatinib. A partial response to afatinib treatment was maintained for 49 months until primary tumor regrowth. Afatinib treatment was continued after disease progression, but the patient died of bacterial pneumonia 59 months after initiation of afatinib treatment. Several studies have previously reported a large number of compound mutations with uncommon mutations, and that compound mutation‐induced cells are most susceptible to afatinib. This suggests the efficacy of afatinib in clinical practice and that afatinib may be safely administered to elderly patients with appropriate dose reductions., A large number of compound mutations have been observed in patients with uncommon EGFR mutation‐positive NSCLC. Compound mutation‐induced cells are most susceptible to afatinib, suggesting the efficacy of afatinib in clinical practice. Afatinib may be administered to elderly patients with appropriate dose adjustments

A clinical trial of immune checkpoint inhibitors for advanced non‐small cell lung cancer reported an overall survival plateau with a long tail to the survival curve, suggesting that immune checkpoint inhibitors prolong survival. However, little evidence supports the efficacy of immune checkpoint inhibitors as neoadjuvant chemotherapy. We performed salvage surgery on a patient who was treated with an anti‐programmed cell death protein‐1 (PD‐1) antibody and whose tumor size had not changed over time. A 69‐year‐old Japanese female with advanced lung adenocarcinoma was initially administered pembrolizumab therapy; however, owing to the development of various immune‐related adverse events (irAEs), the patient was switched to chemotherapy following steroid therapy. The tumor continued to shrink and calcification within the tumor increased. We performed salvage surgery following which the tumor cells disappeared and necrosis and calcification were detected in the tumor. We concluded that if calcification develops within the tumor and tumor shrinkage is maintained after treatment with anti‐PD‐1 drugs, the calcification may be dystrophic owing to drug‐induced tumor necrosis, and salvage surgery might be beneficial in removing the tumor. Key points Significant findings of the study If calcification develops within the tumor and tumor shrinkage is maintained after treatment with anti‐PD‐1 drugs, the calcification may be dystrophic owing to tumor necrosis caused by drug effects, and salvage surgery might be beneficial in removing the tumor. What this study adds This study showed the efficacy of immune checkpoint inhibitors as neoadjuvant chemotherapy to be followed by salvage surgery for unresectable advanced lung adenocarcinoma., If calcification develops within the tumor and tumor shrinkage is maintained after treatment with anti‐PD‐1 drugs, the calcification may be dystrophic owing to tumor necrosis caused by drug effects, and salvage surgery might be beneficial in removing the tumor.

Immune checkpoint inhibitors (ICIs) have been used for various carcinomas. However, immune‐related adverse events have been observed. There have been few reports of treatment with biologics for severe bronchial asthma induced by ICI; therefore, their efficacy is unknown. We report two cases of severe bronchial asthma requiring systemic steroid administration while using anti‐programmed death‐ligand 1 (PD‐L1) antibody for advanced non‐small‐cell lung cancer. The anti‐interleukin‐5 antibody, mepolizumab, was introduced, resulting in the discontinuation of systemic prednisolone and good asthma control. These reports suggest that treatment with biologics may be effective in severe cases of poorly controlled bronchial asthma during ICI therapy., We report two cases of severe bronchial asthma requiring systemic steroid administration while using anti‐programmed death‐ligand 1 (PD‐L1) antibody for advanced non‐small cell lung cancer. In each case, mepolizumab was introduced, resulting in discontinuation of systemic prednisolone and good control of asthma.

Immune checkpoint inhibitors (ICIs) have prolonged the survival of patients with various carcinomas, including non-small cell lung cancer (NSCLC), and have caused a paradigm shift in cancer treatment. Although programmed death-ligand 1 (PD-L1) expression in tumor cells is a predictive marker of therapeutic efficacy, additional predictive markers are required. This study aimed to explore the role of immunological and nutritional parameters in the prediction of treatment response.Patients diagnosed with NSCLC and treated with pembrolizumab were examined retrospectively. Body weight was measured 4-6 weeks before the start of the first treatment, immediately before treatment, and 4-6 weeks after the start of the first treatment. Progression-free survival (PFS) was defined as the time from the start of pembrolizumab treatment to the last follow-up date or until disease progression. Statistical analyses were performed to confirm the association between various factors and association between these factors and PFS.Thirty-eight patients with advanced NSCLC were included. We observed a significant association of weight loss and PD-L1 expression with PFS in the multivariate analysis. A significant correlation was found between the advanced lung cancer inflammation index and neutrophil-to-lymphocyte ratio. A weight loss of 5% after the start of treatment was significantly associated with worse PFS.Weight loss is an important negative prognostic factor in patients with NSCLC receiving immunotherapy. Weight maintenance may be important for good ICI treatment efficacy, and future interventions in cancer cachexia are expected to further enhance the treatment efficacy of ICIs.

Osimertinib is a potent and irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that selectively acts on both EGFR‐sensitive and EGFR T790M‐resistant mutations. Patients with pre‐treatment EGFR T790M mutations (de novo EGFR T790M) respond poorly to existing EGFR‐TKIs, whereas osimertinib has positive effects. However, the safety data for first‐line osimertinib treatment in patients aged >75 years are insufficient. We treated two elderly patients with de novo EGFR T790M mutations with osimertinib as the first‐line therapy. We found that the first‐line treatment with osimertinib was safe and resulted in a long‐term response in elderly patients with de novo EGFR T790M‐mutated lung adenocarcinoma., There are no safety data on the first‐line osimertinib treatment in patients aged 75 years or older, defined as the elderly in Japan, and very few reports exist on the efficacy of first‐line therapy for de novo epidermal growth factor receptor (EGFR) T790M‐positive lung cancer in elderly patients. We report a safe and long‐term response to the first‐line treatment with osimertinib in de novo EGFR T790M‐positive patients older than 75 years.

Key message Clinicians should be aware that interstitial shadows with extreme hypertension should be considered as indicators for diffuse alveolar haemorrhage due to pheochromocytoma crisis., Alveolar haemorrhage due to pheochromocytoma should be considered as a diagnosis for interstitial shadows with extreme hypertension.

Endoscopic ultrasound with bronchoscope‐guided fine‐needle aspiration (EUS‐B‐FNA), a minimally invasive procedure, may be useful for the diagnosis of pseudomesotheliomatous (PMC) carcinoma because a sufficient amount of tissue can be obtained for diagnosis. This is the first report of PMC diagnosed using EUS‐B‐FNA. Our findings suggest that EUS‐B‐FNA may reduce the risk of dissemination for PMC.

Background For the precise management of advanced lung cancers, bronchoscopy with a high diagnostic yield and abundant tumor specimens are required. In recent years, new devices and techniques have been rapidly developed, including the endobronchial ultrasound (EBUS) using a guide sheath, virtual bronchoscopic navigation (VBN), and ultra-thin bronchoscope (UTB), for the diagnosis of peripheral pulmonary lesions (PPLs). These techniques increase the diagnostic yield for PPL, thus requiring fewer biopsy specimens. VBN is generally not available at the city hospitals in Japan. In this study, using fluoroscopy without VBN, we studied whether the histologic diagnostic yield of radial EBUS for PPLs would be higher using a UTB (without guide sheath) or conventional bronchoscope (CB) (with guide sheath). Methods We retrospectively reviewed consecutive patients with suspected lung cancer who underwent bronchoscopy at the Hakodate Goryoukaku Hospital from April 2017 to March 2019. We analyzed 168 patients—102 using UTB and 66 using CB. Results The diagnostic yields for PPL were significantly higher in the UTB group than in the CB group (74.5% vs. 59.1%; P = 0.04). The median examination time was significantly longer in the UTB group than in the CB group (24 vs. 20 min; P = 0.01). There were no statistically significant differences in the complication rate between the UTB and CB groups (3.9% vs. 3.0%; P = 0.69). Conclusions UTB had a significantly higher tissue diagnostic yield than CB, without the use of VBN.

背景. 今回我々は, 肺原発MALTリンパ腫の1例を経験したので報告する. 症例. 62歳の男性, 胸部X線にて異常陰影を指摘され受診した. 胸部X線および胸部CTで左S10に結節影を認め, 気管支鏡検査では確定診断がつかず超音波ガイド下経皮肺生検組織よりMALTリンパ腫が疑われた. 左下葉切除術を施行し, 術後検体のパラフィン切片よりPCR法にて免疫グロブリン重鎖の遺伝子再構成を認め, MALTリンパ腫と診断した. 結論. MALTリンパ腫の診断は術後検体のパラフィン切片を用いても可能と考えられた.

症例は44歳男性.喫煙歴15本/日×24年間.平成5年5月から肺気腫にて外来で経過観察中であったが, 以後3年間来院せず平成8年9月胸部CTにて異常陰影を認めた.右S6c末梢のブラの内腔に初診時には認められなかった径16mm大のきわめて鮮明な腫瘤陰影がポリープ状に突出しているのを認めた.ブラに合併した肺癌あるいはfungus ballが疑われたが, 開胸肺生検にて腺癌との診断が得られ, 引き続き右下葉切除術とリンパ節郭清を施行した.組織学的には腺癌でT1N0M0, stage IAであった.腫瘍は肺実質からブラ側ヘダンベル様に増殖して, その大部分はブラ側にポリープ状を呈していた.気腫性嚢胞の患者に肺癌が高頻度に合併するとされ, しばしば報告はみられるが, ブラ壁内腔側ヘポリープ状に発育する症例は少ない.本邦における肺嚢胞隣接肺癌症例100例について本症例を含めて検討した.

We present a rare case of aortic malignant hemangioendothelioma with a mural growth pattern in which the endothelial nature was confirmed by immunohistochemical demonstration of Factor VIII-related antigen. Aortic sarcomas and malignant hemangioendotheliomas in the literature are reviewed.

A 10-Sb-4 type organoantimony ate complex was prepared from hexafluorocumyl alcohol and SbCl3 as an air and water stable compound. Its X-ray structural analysis revealed a distorted pseudo-trigonal bipyamidal structure. The compound reacted with both alkyl halides and organolithium reagents to yield neutral 10-Sb-5 compounds.

A female patient with idiopathic interstitial pneumonia (IIP) was admitted again 40 months after the diagnosis due to progression of clinical findings and increased activity of serum lactic dehydrogenase (LDH). Analysis of LDH isoenzyme disclosed a broad band between LDH4 and LDH5. Gel filtration and immunoelectrophoresis showed that immunoglobulin (Ig) G (κ type) bound the LDH. With prednisolone and azathioprine, her symptoms and radiological findings improved concomitant with a decrease in the serum LDH activity. The LDH-IgGκ complex disappeared in the circulation 14 months after initiation of the therapy. We report circulating LDH-Ig complex in a patient with IIP, which may be related to the disease progression of IIP. (Internal Medicine 35: 413-415, 1996)

We report a rare case of squamous cell carcinoma located in the middle mediastinum as a solitary mass. Histologically, lymphatic tissues remained together with nests of squamous cell carcinoma which were occupying the greater part of the mass. Examinations of the whole body failed to detect a primary site of the squamous cell carcinoma. It is considered that the carcinoma cells reflect metastasis from a primary-unknown carcinoma (most likely TO lung squamous cell carcinoma) or that they originated from benign epithelial inclusions in a mediastinal lymph node.

Introduction: Pancreaticoduodenectomy (PD) consists of multiple complex surgical procedures, including skeletonization of the hepatic artery for lymph node dissection. Variations in the hepatic artery can be observed in 25-45% of cases, so it is important for surgeons to have knowledge of the hepatic blood supply to avoid injury that may result in biliary fistula or hepatic ischemia after surgery. Case Report: We encountered a 67-year-old male patient with a variant common hepatic artery which originated from the normal celiac trunk and passed behind the portal vein. This patient successfully underwent a subtotal-stomach-preserving PD for middle bile duct cancer. The frequency of this variant common hepatic artery is approximately 0.1%; according to two large-scale retrospective studies on the variations of the hepatic blood supply. Unlike the different branches or number variations, it is difficult to identify the course variations with conventional visceral angiography or three-dimensional computed tomography arteriography (CTA) (3D-CT angiography image in arterial phase). The variant course of the common hepatic artery in this patient was preoperatively identified by fused images from 3D-CTA and venography. Conclusion: Fusing images from 3D-CTA and venography should be recommended as part of the routine preoperative examination for depicting anatomical variations, such as in the variant course of the common hepatic artery in the patients planning to undergo PD.

Pentacoordinate organoantimony monohalides [o-O(CF3)2C6H4]2SbX (X = F, Cl, Br, I) were found to topologically permutate intramolecularly as monomers with energy barriers in the order of F < Cl < Br < I in toluene and Br < Cl < I < F in THF.