Diagnosis and treatment of drug-induced interstitial lung disease

Drug-induced interstitial lung disease (DILD) is a group of adverse drug reactions that is rare but fatally toxic. Pulmonary toxicity causes inflammation and subsequent interstitial fibrosis. As novel drugs with a variety of purposes are introduced into the medical field, the number of culprit medications that are suspected to cause lung complications is accordingly increasing. In this review, DILD will be discussed from several aspects such as causality by numerous drugs, check points for a timely diagnosis, alongside some contemporary treatment options. The exact mechanism of DILD has not been elucidated, and a useful clinical, radiological, or pathological confirmation process is still lacking. Common drugs which casue DILD include bleomycin, amiodarone, epidermal growth factor receptor-targeted agents, and immune checkpoint inhibitors. Diagnosis is based on a suspicious drug administration history, somewhat inconsistent clinical symptoms and signs, radiological hints, and histopathological assistance, together with the exclusion of other lung-injuring etiologies. Cessation of the suspected drug, meticulous corticosteroid usage, and ancillary supportive management are the mainstay therapeutic strategy for DILD. Most cases of DILD respond to these countermeasures and reductions, but in some cases the fibrotic process worsens, leading to irreversible sequelae on the affected lung.

Diagnosis and treatment of drug-induced interstitial lung disease

Drug-induced interstitial lung disease (DILD) is a group of adverse drug reactions that is rare but fatally toxic. Pulmonary toxicity causes inflammation and subsequent interstitial fibrosis. As novel drugs with a variety of purposes are introduced into the medical field, the number of culprit medications that are suspected to cause lung complications is accordingly increasing. In this review, DILD will be discussed from several aspects such as causality by numerous drugs, check points for a timely diagnosis, alongside some contemporary treatment options. The exact mechanism of DILD has not been elucidated, and a useful clinical, radiological, or pathological confirmation process is still lacking. Common drugs which casue DILD include bleomycin, amiodarone, epidermal growth factor receptor-targeted agents, and immune checkpoint inhibitors. Diagnosis is based on a suspicious drug administration history, somewhat inconsistent clinical symptoms and signs, radiological hints, and histopathological assistance, together with the exclusion of other lung-injuring etiologies. Cessation of the suspected drug, meticulous corticosteroid usage, and ancillary supportive management are the mainstay therapeutic strategy for DILD. Most cases of DILD respond to these countermeasures and reductions, but in some cases the fibrotic process worsens, leading to irreversible sequelae on the affected lung.

Diagnosis and treatment of cystic lung disease

Cystic lung disease (CLD) is a group of lung disorders characterized by the presence of multiple cysts, defined as air-filled lucencies or low-attenuating areas, bordered by a thin wall (usually < 2 mm). The recognition of CLDs has increased with the widespread use of computed tomography. This article addresses the mechanisms of cyst formation and the diagnostic approaches to CLDs. A number of assessment methods that can be used to confirm CLDs are discussed, including high-resolution computed tomography, pathologic approaches, and genetic/serologic markers, together with treatment modalities, including new therapeutic drugs currently being evaluated. The CLDs covered by this review are lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis, Birt-Hogg-Dube syndrome, lymphocytic interstitial pneumonia/follicular bronchiolitis, and amyloidosis.

Pulmonary graft-versus-host disease after autologous hematopoietic stem cell transplantation

No abstract available.

Palliation of postintubation tracheal stenosis using insulation-tipped diathermic knife 2: a case report

Objective: To report the first case of using the insulation-tipped diathermic knife 2 [IT knife-2] for the treatment of postintubation tracheal stenosis

Clinical Presentation and Intervention: A 71-year-old female patient with a history of endotracheal intubation 3 years earlier presented with throat discomfort, gross wheezing and dyspnea. Chest imaging and bronchoscopy demonstrated a strand-like tracheal stenosis in the upper trachea. The IT knife-2 was used to treat the patient and the lesion was palliated without complication

Conclusion: This case was successfully treated with the IT knife-2 and thus implies a potential usefulness of the IT knife-2 as a new modality for bronchoscopic intervention

Two Cases of Central Airway Obstruction Treated with an Insulation-Tipped Diathermic Knife-2 / 대한내과학회지

Central airway obstruction can result from various benign and malignant conditions, and often requires prompt palliation. The efficacies of a variety of bronchoscopic techniques for the treatment of central airway obstruction such as electrocautery, laser, brachytherapy, argon plasma coagulation and cryotherapy have been established. An insulation-tipped diathermic knife-2 (IT knife-2) was initially introduced for gastrointestinal endoscopic submucosal dissection and has been used globally as a safe and effective instrument. However, its use has not been reported for the treatment of endotracheal or endobronchial lesions. Here, we report the case of central airway obstruction in a 65-year-old male due to malignancy and a 52-year-old-female with post-radiation bronchial stenosis that were treated successfully with the IT-knife-2 via flexible bronchoscopy.

A Review of Current Disinfectants for Gastrointestinal Endoscopic Reprocessing

Gastrointestinal endoscopy is gaining popularity for diagnostic and therapeutic purposes. However, concerns over endoscope-related nosocomial infections are increasing, together with interest by the general public in safe and efficient endoscopy. For this reason, reprocessing the gastrointestinal endoscope is an important step for effective performance of endoscopy. Disinfectants are essential to the endoscope reprocessing procedure. Before selecting an appropriate disinfectant, their characteristics, limitations and means of use must be fully understood. Herein, we review the characteristics of several currently available disinfectants, including their uses, potency, advantages, and disadvantages. Most disinfectants can be used to reprocess gastrointestinal endoscopes if the manufacturer's guidelines are followed. The selection and use of a suitable disinfectant depends on the individual circumstances of each endoscopy suite.

Recent Advances in Idiopathic Pulmonary Fibrosis / 결핵및호흡기질환

The concept on idiopathic pulmonary fibrosis (IPF) pathogenesis has progressed from chronic inflammation to aberrant wounding healing and even more to the current paradigms of a multifactorial and heterogeneous disease process. Despite the growth of clinical trials for IPF, most of the results, including N-acetylcysteine combination, warfarin, and bosentan, were disappointing. On the other hand, there have been a number of important developments; the foremost is the licensing of pirfenidone in Europe and Asia. In this article, we briefly review the recent knowledge of pathogenesis of IPF. We also summarize the recent clinical trials regarding the management of IPF.

Organizing pneumonia associated with oxaliplatin-combined chemotherapy: a case report

To report a case of oxaliplatin-combined chemotherapy-induced interstitial lung disease. A 57-year-old man was referred complaining of dyspnea and fever after treatment with an oxaliplatin-combined chemotherapeutic agent for metastatic colorectal cancer. Fever development and spontaneous subsidence were observed during the chemotherapeutic course repeatedly until the 9th cycle. A computer-tomographic [CT] scan revealed bilateral, peripherally distributed, patchy consolidation suggestive of an interstitial lung disease. As a confirmative step, video-assisted thoracoscopic surgical biopsy was attempted; the characteristic intraluminal organizing fibrous plug in the bronchioles and alveoli was seen. Corticosteroid therapy was administered, which rapidly improved the patient's symptoms and chest CT findings. This case showed that oxaliplatin may be implicated in the etiology of interstitial lung disease, since withdrawal of the drug resulted in improvement of interstitial lung disease

Heart Rate Acceleration of a Subsidiary Pacemaker by beta-Adrenergic Stimulation

BACKGROUND AND OBJECTIVES: Recent evidence indicates that the membrane voltage and Ca2+ clocks jointly regulate sinoatrial node (SAN) automaticity. However, the mechanism of heart rhythm acceleration of the subsidiary pacemaker (SP) during beta-adrenergic stimulation is still unknown. Here we tested the hypothesis that the heart rate acceleration of the SP by beta-adrenergic stimulation involves synergistic interactions between both clock mechanisms. SUBJECTS AND METHODS: We performed optical mapping and pharmacological interventions in 15 isolated Langendorff-perfused canine right atriums (RA). The SP model was produced by ligation of the SAN artery at the mid portion of the sulcus terminalis. RESULTS: In the 6 RAs with an intact SAN, 1 micromol/L isoproterenol infusion increased the heart rate from 82+/-9 to 166+/-18 bpm (102%) with late diastolic Cai elevation (LDCAE) at the superior SAN. However, in the 6 SP models, the heart rate increased from 55+/-10 bpm to 106+/-11 bpm (92%, p=0.005) without LDCAE at the earliest activation site. The isoproterenol induced heart rate increase was reversed to 74+/-5 bpm (33% from baseline) by administering an infusion of the funny current blocker ZD 7288 (3 micromol/L, n=3), whereas, it was suppressed to 69+/-7 bpm (24% from baseline) by sarcoplasmic reticulum (SR) Ca2+ emptying with administering ryanodine (10 micromol/L) plus thapsigargin (200 nmol/L, n=3). The isoproterenol induced heart rate increase was completely abolished by combined treatment with funny current blocker and SR Ca2+ emptying (n=3). CONCLUSION: Acceleration of the Ca2+ clock in the SP plays an important role in the heart rate acceleration during beta-adrenergic stimulation, and this interacts synergistically with the voltage clock to increase the heart rate.

Usefulness of Non-invasive Markers for Predicting Significant Fibrosis in Patients with Chronic Liver Disease

The purpose of this prospective study was to verify and compare the strengths of various blood markers and fibrosis models in predicting significant liver fibrosis. One hundred fifty-eight patients with chronic liver disease who underwent liver biopsy were enrolled. The mean age was 41 yr and male patients accounted for 70.2%. The common causes of liver disease were hepatitis B (67.7%) and C (16.5%) and fatty liver (9.5%). Stages of liver fibrosis (F0-4) were assessed according to the Batts and Ludwig scoring system. Significant fibrosis was defined as > or =F2. Sixteen blood markers were measured along with liver biopsy, and estimates of hepatic fibrosis were calculated using various predictive models. Predictive accuracy was evaluated with a receiver-operating characteristics (ROC) curve. Liver biopsy revealed significant fibrosis in 106 cases (67.1%). On multivariate analysis, alpha2-macroglobulin, hyaluronic acid, and haptoglobin were found to be independently related to significant hepatic fibrosis. A new predictive model was constructed based on these variables, and its area under the ROC curve was 0.91 (95% confidence interval, 0.85-0.96). In conclusion, alpha2-macroglobulin, hyaluronic acid, and haptoglobin levels are independent predictors for significant hepatic fibrosis in chronic liver disease.

The Current Status of Natural Orifice Transluminal Endoscopic Surgery (NOTES) / 대한소화기내시경학회지

Natural orifice transluminal endoscopic surgery (NOTES) is a novel technique that utilizes the natural orifices of the human body (e.g., the mouth, anus, vagina and urethra) for surgical procedures. After insertion of an endoscope into organs such as the esophagus, stomach and urinary bladder, these hollow organs are intentionally cut to reach the peritoneal or thoracic cavity to perform various surgical procedures. NOTES is anticipated to become an important part of future medical procedures to treat diverse conditions that cannot endure ordinary surgery with the use of laparotomy or laparoscopy. To take advantage of this new technology, a number of researchers have devoted time and effort to improve both the basic and clinical aspects of NOTES in order to apply this medicinal art fully in the near future. In this review, we evaluate the status of NOTES and attempt to examine the future use of this promising technique that has also been subject to skepticism.

The Effect of Peppermint Oil on Peristalsis during Gastroscopy / 대한소화기내시경학회지

BACKGROUND/AIMS: Gastrointestinal peristalsis may hinder inspection of the gastrointestinal track or its treatment during endoscopy. Antispasmodic agents such as hyoscine-N-butylbromide are commonly administered before endoscopy for alleviating peristalsis, although it causes unwanted complications. Peppermint oil (PMO) has a spasmolytic effect on viscera and it has been used as an adjunctive remedy for some disorders. We evaluated the antispasmodic effect of PMO solution during gastroscopy, and we determined if there are any adverse effects. METHODS: 1.6% PMO solution was sprayed on the antrum of the examinees (n=40) during gastroscopy. Observation was performed 5 cm ahead of the pyloric ring to count the peristaltic waves for 3 minutes before and after spraying PMO. The intensity of peristalsis was graded from 0 (none) to 4 (severe), and the pulse rate of all the examinees was recorded every minute. RESULTS: The number of peristaltic contractions decreased after PMO spraying from 7.02+/-2.25 to 3.17+/-2.57 times/3 minutes (p<0.01). The peristaltic intensity also decreased from 3.15+/-1.18 to 1.34+/- \0.95 (p<0.01) with a difference of 1.80+/-1.29. On observing the examinees' pulse rates, using PMO did not induce tachycardia. No adverse effect during and after the investigation with PMO solution was reported. CONCLUSIONS: PMO showed a significant antispasmodic effect, and it reduced the number of peristaltic contractions and the intensity of gastric peristalsis. It also did not have any significant side effects. PMO solution may be used as an effective antispasmodic agent during gastroscopy.

Clinical Significance of Serum C-Reactive Protein in Patients with Colorectal Cancer

BACKGROUND/AIMS: C-reactive protein (CRP) is a general marker of inflammation and increased CRP level is reported in several cancers. It has been reported that CRP is an independent factor predicting survival in colorectal cancer patients, although this claim is still under debate. The aim of this study was to investigate the association between CRP and the characteristics of colorectal cancer patients. METHODS: One hundred eighty-four patients diagnosed with colorectal cancer between January 2007 and January 2009 were included. The patients with active infectious diseases, other tumors, cardiovascular disease, or inflammatory bowel disease were excluded. The CRP levels of colorectal cancer patients were compared with the control group comprised of 175 healthy adults with a normal colonoscopy. RESULTS: The median CRP in the colorectal cancer patients (3.36 mg/L) was higher than the control group (0.48 mg/L). There was a significant correlation between CRP and the stage of colorectal cancer (p<0.001). CRP was increased significantly in Dukes' stage D. CRP had a significant correlations with the CEA and CA 19-9 levels, the ESR, and the white blood cell count, and an inverse correlation with albumin. The CRP level in colon cancer patients was higher than rectal cancer patients (p=0.032). There were no significant difference in the CRP according to metastatic sites, such as the liver and peritoneum. CONCLUSIONS: Serum CRP levels were higher in patients with colorectal cancer and high CRP level is a predictor of advanced disease.

Clinical Significance of Serum C-Reactive Protein in Patients with Colorectal Cancer

BACKGROUND/AIMS: C-reactive protein (CRP) is a general marker of inflammation and increased CRP level is reported in several cancers. It has been reported that CRP is an independent factor predicting survival in colorectal cancer patients, although this claim is still under debate. The aim of this study was to investigate the association between CRP and the characteristics of colorectal cancer patients. METHODS: One hundred eighty-four patients diagnosed with colorectal cancer between January 2007 and January 2009 were included. The patients with active infectious diseases, other tumors, cardiovascular disease, or inflammatory bowel disease were excluded. The CRP levels of colorectal cancer patients were compared with the control group comprised of 175 healthy adults with a normal colonoscopy. RESULTS: The median CRP in the colorectal cancer patients (3.36 mg/L) was higher than the control group (0.48 mg/L). There was a significant correlation between CRP and the stage of colorectal cancer (p<0.001). CRP was increased significantly in Dukes' stage D. CRP had a significant correlations with the CEA and CA 19-9 levels, the ESR, and the white blood cell count, and an inverse correlation with albumin. The CRP level in colon cancer patients was higher than rectal cancer patients (p=0.032). There were no significant difference in the CRP according to metastatic sites, such as the liver and peritoneum. CONCLUSIONS: Serum CRP levels were higher in patients with colorectal cancer and high CRP level is a predictor of advanced disease.

Stretching Causes Extensive Changes of Gastric Submucosa: Is It Acceptable to Define 500 micrometer as the Safe Margin?

BACKGROUND/AIMS: Endoscopic mucosal resection can cure early gastric cancer. The risk of lymphatic metastasis is related to the depth of submucosal invasion by the mucosal malignancy, with a resection depth of 500 micrometer generally accepted as a safe cut-off. However, excessive thinning induced by stretching of the resected tissue sometimes preventing a precise diagnosis. We studied the effects of stretching on different layers and sites of gastric tissue. METHODS: Porcine stomachs were cut into 2.0x2.0 cm pieces, and pieces from body were stretched to 2.5, 3.0, and 3.5 cm. Pieces from the cardia, body, and antrum were also stretched to 3.0 cm. The thickness of each layer was measured and analyzed statistically. RESULTS: Whole gastric wall and submucosal layers showed gradual thinning, with stretching to 3.5 cm tearing the tissues and resulting in imperfect extension. The submucosa was thinner in body tissue than in cardia and antrum tissues. Stretching to 3.0 cm induced a consistent decrease in submucosal thickness (30-70%). The change in thickness varied widely between individual samples. CONCLUSIONS: A resection margin of 500 micrometer might be insufficient for the complete removal of malignancy. Moreover, the thickness of the submucosal layer differs with the gastric site and between individuals. Future studies are needed to confirm the findings in human tissue.

The efficacy of measuring liver stiffness for the assessment of liver fibrosis in patients with chronic liver diseases / 대한내과학회지

BACKGROUND/AIMS: Accurate assessment of liver fibrosis is very important for predicting the prognosis of patients with chronic liver diseases. Liver biopsy is still considered the gold-standard for assessing liver fibrosis. However, it is an invasive procedure with several limitations such as its questionable outcomes. Recent studies have suggested that liver stiffness measurement (LSM) using Fibroscan is noninvasive and useful for assessing liver fibrosis. This study was performed to evaluate the efficacy of LSM for evaluating liver fibrosis in patients with chronic liver diseases. METHODS: We prospectively enrolled 93 patients with chronic liver diseases, as confirmed by liver biopsy. The patients underwent liver biopsy and LSM. The METAVIR liver fibrosis stages of the biopsy specimens were assessed by an experienced pathologist. LSM was performed by Fibroscan. The efficacy of LSM and the optimal cutoff values for assessment of the fibrosis stage were determined by a receiver-operating characteristics (ROC) curve analysis. RESULTS: LSM was well correlated with the fibrosis stage (Kendall correlation coefficient: 0.58; p or =2), 0.874 (0.761-0.929) for the patients with severe fibrosis (F> or =3) and 0.894 (0.792-0.956) for the patients with cirrhosis (F=4). The optimal LSM cutoff values for F > or =2, F > or =3 and F=4 were 6.9, 11.75 and 14.5 kPa, respectively. CONCLUSIONS: LSM was a simple, effective method for assessing liver fibrosis in patients with chronic liver diseases. Its use for the follow up and management of these patients could be of great interest and so further investigation is required.

Accessibility of Peritoneal Organs according to the Routes of Approach in NOTES / 대한소화기학회지

BACKGROUND/AIMS: Natural orifice transluminal endoscopic surgery (NOTES) is a new era of minimally invasive surgery which has the potential to offer scarless surgery. So far, numerous reports on various routes to peritoneal organs in NOTES have been published. In case of transgastric approach, it is more inconvenient than transcolonic approach to access upper abdominal organs because of retroflexion. However, most data were subjective and there was no report examining the best access route for the exploration of peritoneal organs. The aim of this study was to evaluate the best access route according to the abdominal organs objectively. METHODS: Six female pigs weighing 30 to 35 kg were placed under general anesthesia. Incisions were made on both anterior wall of stomach body and rectosigmoid colon 15 to 20 cm above anal verge, respectively. Then, via each incision site, we evaluated the endoscopic visibility and checked the elapsed time to access abdominal organs in sequence (gallbladder (GB), spleen, bladder, uterus, and ovary). RESULTS: On comparison of the mean time to approach each organs, GB and ovary showed statistical difference in the mean time to approach between transgastric and transcolonic approaches. It took relatively shorter time to access GB via transcolonic route than transgastric route (352.3+/-80.1 sec vs. 222.2+/-82.0 sec, p=0.021). Next, we evaluated the time to access upper organs (GB and spleen) and lower organs (bladder, uterus and ovary). In case of lower organs, it showed no difference in time between transgastric and transcolonic approaches. However, to explore upper organs, transcolonic route was more favorable than transgastric route (351.8+/-80.7 sec vs. 273.3+/-110.3 sec, p=0.002). CONCLUSIONS: For exploration of lower organs, there is statistically no significant difference in time between transgastric and transcolonic approaches. But, in case of upper organs, transcolonic approach is superior to transgastric approach.

The Usefulness of a Suspected Blood Identification System (SBIS) in Capsule Endoscopy according to Various Small Bowel Bleeding Lesions / 대한소화기내시경학회지

BACKGROUND/AIMS: Substantial time and attention are required to read and interpret the recordings of capsule endoscopic images. A suspected blood identification system (SBIS) has been developed to assist in the reading of capsule images. This software automatically marks "red tags" that correlate with suspected blood or red areas. However, the sensitivity and accuracy of the system have not been well characterized. We investigated the usefulness of the SBIS in capsule endoscopy according to various small bowel bleeding lesions. METHODS: Two expert endoscopists reviewed the capsule images. Angiodysplasias, ulcers and erosion were considered as significant lesions, and active bleeding lesions were considered when bleeding or blood clots were seen in the capsule images. The red tags that were automatically marked by the use of the rapid software were compared to the significant lesions reviewed by the endoscopists. RESULTS: A total of 95 patients were enrolled in the study. The endoscopists identified 159 significant lesions and 71 lesions marked by red tags were identified by the SBIS. Among the 71 lesions, 31 lesions correctly coincided with the significant lesions. The overall sensitivity and positive predictive value of the use of the SBIS were 20% and 44%, respectively. The sensitivities of active ulcers and active bleeding lesions were 83% and 93%, respectively. CONCLUSIONS: The SBIS should be considered as a rapid screening tool to identify active bleeding lesions, and a complete review of capsule images by a physician is still needed.

Rectal Polypoid Endometriosis Mimicking Malignant Rectal Tumor / 대한소화기내시경학회지

Endometriosis is a disorder that presents as endometrial glands and stroma outside the uterine cavity and its musculature. It is a common gynecologic disease affecting approximately 15% of fertile women. However, polypoid endometriosis is rare. Our patient visited the hospital due to bowel habit changes and bloody stools. The colonoscopy revealed a large ulcerating polypoid mass in the rectum. Image studies including CT scan, MRI, and PET-CT suggested rectal cancer but the biopsy was negative for a malignancy. Finally, she was diagnosed with rectal polypoid endometriosis by a surgical rectal mass resection. We report a case of rectal polypoid endometriosis mimicking a rectal polypoid cancer.