Clinical utility of artificial intelligence assistance in histopathologic review of lymph node metastasis for gastric adenocarcinoma.

BACKGROUND: Advances in whole-slide image capture and computer image analyses using deep learning technologies have enabled the development of computer-assisted diagnostics in pathology. Herein, we built a deep learning algorithm to detect lymph node (LN) metastasis on whole-slide images of LNs retrieved from patients with gastric adenocarcinoma and evaluated its performance in clinical settings. METHODS: We randomly selected 18 patients with gastric adenocarcinoma who underwent surgery with curative intent and were positive for LN metastasis at Chiba University Hospital. A ResNet-152-based assistance system was established to detect LN metastases and to outline regions that are highly probable for metastasis in LN images. Reference standards comprising 70 LN images from two different institutions were reviewed by six pathologists with or without algorithm assistance, and their diagnostic performances were compared between the two settings. RESULTS: No statistically significant differences were observed between these two settings regarding sensitivity, review time, or confidence levels in classifying macrometastases, isolated tumor cells, and metastasis-negative. Meanwhile, the sensitivity for detecting micrometastases significantly improved with algorithm assistance, although the review time was significantly longer than that without assistance. Analysis of the algorithm's sensitivity in detecting metastasis in the reference standard indicated an area under the curve of 0.869, whereas that for the detection of micrometastases was 0.785. CONCLUSIONS: A wide variety of histological types in gastric adenocarcinoma could account for these relatively low performances; however, this level of algorithm performance could suffice to help pathologists improve diagnostic accuracy.

Effects of Fat Repositioning for Tear Trough Deformity on Eye Movement.

ABSTRACT: Fat repositioning is a common surgical technique for treating tear trough deformity. As this technique is mainly performed for cosmetic purposes, its functional outcomes have rarely been evaluated. The purpose of this study was to evaluate the changes in eye movements that occur after fat repositioning for tear trough deformity. The authors performed fat repositioning on 18 eyelids of 9 patients and evaluated their eye movements and binocular vision before surgery and at 1, 3, and 6 months after surgery. Hess screen and Binocular single vision tests were performed during each follow-up examination and the scores were recorded. The authors observed that fat repositioning did not affect binocular vision; however, vertical and horizontal eye movements worsened at 3 months after surgery. Nevertheless, there was no significant difference between the eye movements recorded before surgery and those recorded 6 months after surgery. Regardless of this finding, it should be noted that vertical or horizontal strabismus might occur after fat repositioning for tear trough deformity.

Cerebellar tonsillar herniation in sudden death of an adolescent anorexia nervosa patient: a case report.

BACKGROUND: Anorexia nervosa not only results in severe malnutrition but also carries a high risk of sudden death. Although fatal arrhythmias are the most common cause of sudden death, it is often unclear what exactly causes them. To the best of our knowledge, there have been no reports of cerebellar tonsillar herniations in patients with anorexia nervosa. CASE PRESENTATION: A 17-year-old girl with anorexia nervosa and autism spectrum disorder was admitted to the pediatric ward for extreme weight loss. Since she refused to take oral nutrition or tube feeding, we started continuous intravenous fluids. Eight hours after admission, she suddenly went into cardiopulmonary arrest and died despite resuscitation. A postmortem autopsy revealed the unexpected findings of generalized severe cerebral edema and cerebellar tonsillar herniation. CONCLUSION: Intracranial hypertension may need to be considered when the condition of patients with anorexia nervosa suddenly worsens during refeeding periods. Postmortem autopsy and autopsy imaging are recommended to determine the exact cause of sudden death. LEVEL OF EVIDENCE: Level IV: Evidence obtained from multiple time series analysis such as case studies. (NB: Dramatic results in uncontrolled trials might also be regarded as this type of evidence).

Combination of Dermal fat Grafting and Frontalis Suspension Using Polytetrafluoroethylene Sheet for Blepharoptosis With a Deep Sulcus.

ABSTRACT: The frontalis suspension procedure is a common surgical method for patients with severe blepharoptosis. While frontalis suspension is a very effective method, the transplant material may be visualized after surgery in patients with a deep sulcus and severe blepharoptosis. To prevent this complication, we performed a combination of dermal fat grafting and frontalis suspension using a polytetrafluoroethylene sheet in 5 patients (6 eyelids). We followed-up the patients for at least 6 months postoperatively (mean: 6.8 months) and observed no transplant material visualization or occurrence of infection. The mean pre- and postoperative margin reflex distance-1 was -3.75 (-5 to -2) and 2.10 (1-3), respectively. Bulky upper eyelids were observed 6 months postoperatively in 1 patient (2 eyelids). None of the patients underwent reoperation. In conclusion, the combination of frontalis suspension using a polytetrafluoroethylene sheet and dermal fat grafting for severe blepharoptosis and a deep upper eyelid sulcus was effective in preventing visualization of the transplant material.

A New Surgical Method for Medial Ectropion Repair: Fixing the Lower Eyelid Retractor to the Back of the Tarsal Plate.

ABSTRACT: Involutional ectropion is a disease in which the eyelids are everted outwards, and because the eyelids move away from the eyeballs, the ocular surface and conjunctiva are exposed causing inflammation, pain, photophobia, foreign body sensation, epiphora, and blurred vision. It is thought to be caused by horizontal and vertical laxity. Various surgical methods have reportedly been used to correct involutional ectropion. Shortening the lower eyelid retractor (LER) is an indispensable surgical operation for medial ectropion. When the LER is shortened, it is usually fixed to the lower edge of the tarsal plate. Herein we describe a new type of surgery that has now been performed on 6 eyes in 4 patients. The procedure involves separating the conjunctiva from the tarsal plate, inserting the LER between the conjunctiva and the tarsal plate, and then fixing it to the back of the tarsal plate. In all 6 eyes, the lower eyelid now contacts the eyeball, and morphological improvements were achieved. This new surgical method is a useful way to raise the tarsal plate.

Comparison between the effects of normal saline with and without heparin for the prevention and management of arterial catheter occlusion: a triple-blinded randomized trial.

PURPOSE: We aimed to compare the effects of saline with and without heparin on the catheter-occlusion rate and coagulation-related blood test results for the management of arterial catheters among patients admitted to a short-term intensive care unit postoperatively. METHODS: This prospective, triple-blinded, randomized controlled study recruited patients aged 20-90 years scheduled to undergo radial arterial catheter insertion and postoperative intensive care unit admission between February and August 2019. Patients were randomly allocated to two groups (1:1 ratio) depending on the use of heparin: study (normal saline with heparin, 3000 units to 500 ml of normal saline) and control (normal saline without heparin) groups with arterial catheters. The allocated management method was employed immediately after intensive care unit admission. Occlusion assessment (every 12 h), arterial blood gas tests (every 6 h), and blood sample collection (every 24 h) were performed. The occlusion of arterial catheter was assessed using occlusion rate, and blood test results were assessed using a linear mixed model. RESULTS: There were 147 patients in the arterial catheter groups. There were no significant differences in occlusion rates and changes in platelet counts and activated partial thromboplastin time between the groups with arterial (p = 0.98, 0.16, and 0.32, respectively) catheters during the first 6 days after intensive care unit admission. CONCLUSION: Normal saline with and without heparin showed similar efficiency for both the prevention of occlusion and the results of coagulation.

Longitudinal monitoring of somatic genetic alterations in circulating cell-free DNA during treatment with epidermal growth factor receptor-tyrosine kinase inhibitors.

BACKGROUND: The aim of this study was to evaluate the potential of liquid biopsy for prediction of the efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment and for assessment of the changes in genetic alterations during such treatment. METHODS: Plasma samples were prospectively collected from non-small cell lung cancer patients with EGFR-activating mutations during EGFR-TKI treatment until disease progression and were analyzed for such mutations with droplet digital polymerase chain reaction and for other somatic alterations with next-generation sequencing. RESULTS: One hundred patients, including 87 who were EGFR-TKI naïve, were enrolled. Median progression-free survival was significantly shorter for EGFR-TKI-naïve patients with EGFR-activating mutations detected in plasma at baseline than for those without them (7.9 vs 19.0 months; P < .001), with the values being significantly longer for initially positive patients who became negative for these mutations at 12 or 24 weeks than for those who remained positive. An increase in the number of alleles positive for EGFR-activating mutations in plasma during treatment was associated with disease progression, with a hazard ratio of 4.72 (95% CI, 2.07-10.79; P < .001) for EGFR-TKI-naïve patients showing an increase within 36 weeks. For 55 patients with available samples, the total number of somatic alterations (other than activating mutations or T790M of EGFR) in plasma was higher at disease progression than at baseline (33 vs 19; P = 0.04). CONCLUSION: Liquid biopsy shows potential for prediction of EGFR-TKI efficacy and elucidation of clonal tumor evolution during targeted therapy.

A Randomized Phase 2 Trial of Antibiotic Prophylaxis Versus No Intervention for Muscle Biopsy in A Neurology Department.

Muscle biopsy can be used to confirm the diagnosis of neuromuscular diseases. However, it is unclear whether antibiotic prophylaxis prior to muscle biopsy is needed to prevent surgical site infection (SSI). We are conducting a phase 2, single-center, open-labeled, prospective randomized trial to clarify the need for antibiotic prophylaxis in patients at low risk for SSI undergoing muscle biopsy. Patients will be randomized to an antibiotic prophylaxis group or a control group, and the incidence of SSI will be compared between the groups. Our findings will clarify the need for antibiotic prophylaxis in this patient population.

Gingival Sulcus Incision for Zygomaticomaxillary Complex Fracture.

The usual surgical approaches for zygomaticomaxillary complex fracture are subciliary incision, transconjunctival incision, eyebrow incision, lateral canthal incision, coronal incision, preauricular incision, and superior gingivobuccal incision. In the intraoral approach, a horizontal mucoperiosteal incision is performed at the superior gingivobuccal region, and sometimes, includes the upper labial frenum. This may cause discomfort in the oral cavity because of postoperative scarring and shortening of the upper labial frenum. To avoid these complications, the authors performed a novel approach using gingival sulcus incision instead of oral mucosal incision to treat 5 zygomatic fractures. The authors evaluated the regression of the gingival interdental papillae, gingival swelling, and gingival perception at 2 weeks, 1 month, 3 months, and 6 months after the operation. The regression of the gingival papillae and gingival swelling disappeared 3 months and 1 month after the operation, respectively. No paresthesia was observed in any of the cases. The gingival sulcus approach can lead to scarless results and contribute considerably to the aesthetic appearance of the oral cavity.

[The association between alcohol consumption and Mild Cognitive Impairment: the Toon Health Study].

AIM: The effects of alcohol consumption on Mild Cognitive Impairment (MCI) among the Japanese population had not been fully examined. Therefore, the objective of this study was to examine the association between alcohol consumption and MCI among the Japanese elderly population. METHODS: In total, 421 men and 700 women aged 60-84 years participated in this cross-sectional study. Alcohol consumption was estimated according to frequency and amount of major alcoholic beverages (i.e., beer, Japanese sake, shochu, and wine) consumed by each individual using a self-administered questionnaire. MCI was assessed using the Japanese version of the Montreal Cognitive Assessment. Multivariable odds ratio (OR) and 95% confidence intervals (CIs) of MCI according to alcohol consumption were calculated using logistic models. We further analyzed the associations of the major alcoholic beverages with MCI. RESULTS: The prevalence of MCI was 50.4% among the male participants and 31.4% among the females. A positive association between alcohol consumption and MCI was observed in men, but not in women. The multivariable OR (95% CI) of MCI for ≥ 2 go (46 g ethanol) /day vs. non-drinkers was 1.78 (0.93-3.40, p for trend = 0.045) in men and for ≥ 1 go (23 g ethanol) /day was 0.96 (0.39-2.38, p for trend = 0.92) in women, respectively. We also observed an association between shochu consumption and MCI in men, whereby the multivariable OR (95% CI) of MCI for each 1 go increment was 1.57 (1.18-2.07). CONCLUSION: Our findings suggest that alcohol consumption in moderation may contribute to the prevention of MCI development in men.

The origin of p40-negative and CDX2-positive primary squamous cell carcinoma of the stomach: case report.

BACKGROUND: Primary gastric squamous cell carcinoma (SCC) is a very rare disease. The origin of this tumor remains unclear, although there are some hypotheses. A 60-year-old man consulted a previous physician complaining of upper abdominal pain. Esophagogastroduodenoscopy revealed type 2 gastric cancer, and the patient was referred to our hospital. After close examination, the patient was diagnosed as cStage IIA gastric adenocarcinoma, and distal gastrectomy was performed. Histochemical studies showed typical findings of SCC, and the tumor was surrounded by intestinal metaplasia. Immunohistochemical examination was positive for cytokeratin (CK) 5/6 and caudal-type homeobox protein 2 (CDX2) and negative for p63/p40. CONCLUSION: The results of immunostaining for CK5/6 supported that this tumor was SCC, but the question why p63/p40 were negative and CDX2 was positive still remained. Concerning about the origin of p63/p40 and CDX2, it was suggested that the tumor cells were not derived from ectopic squamous epithelium but from intestinal metaplasia. And tumor cells looked like homogeneous and squamous metaplasia was not observed. These findings supported the idea that these tumor cells arose from stem cells in the intestinal metaplasia of the stomach.

Longitudinal assessment of pain management with the pain management index in cancer outpatients receiving chemotherapy.

PURPOSE: The adequacy of pain management for individuals with cancer who receive outpatient chemotherapy is unclear. The primary objective of this study was to assess pain prevalence and intensity in such patients. The secondary objectives included assessment of pain management with the pain management index (PMI) and exploration of predictors of inadequate pain management. METHODS: Cancer patients who received outpatient chemotherapy were enrolled. Patients were required to complete questionnaires covering demographic data and including the Brief Pain Inventory and the Distress Thermometer and Impact Thermometer. The PMI score was determined twice with an interval of at least 3 weeks. RESULTS: Of the 740 patients enrolled in the study, 524 individuals (70.8%) completed all questionnaires. Totals of 282 patients (53.8%) and 264 patients (50.4%) reported pain at baseline and follow-up, respectively, with ∼14% of patients having moderate or severe pain at each assessment. Totals of 365 patients (69.7%) at baseline and 320 patients (61.1%) at follow-up reported pain or were prescribed analgesics, with the rate of inadequate pain management for these patients being 39.7 and 51.6%, respectively. Multivariable analysis for 418 patients (79.8%) who had pain or required analgesics at baseline or follow-up (or both) revealed that the most significant predictor of inadequate pain management was depressive state. CONCLUSIONS: Pain in cancer patients receiving outpatient chemotherapy is prevalent and at risk for undertreatment. Pain management should be assessed on a regular basis and is likely to be improved by screening for depression.

Rectal carcinoma and multiple gastrointestinal stromal tumors (GIST) of the small intestine in a patient with neurofibromatosis type 1: a case report.

BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomally dominant inherited disorder characterized by multiple pigmented skin spots (café-au-lait spots) and neurofibroma. NF1 is associated with a wide variety of benign or malignant tumors. We report a NF1 patient who received surgical treatment for rectal carcinoma and multifocal small intestinal gastrointestinal stromal tumors (GISTs). CASE PRESENTATION: A 70-year-old female patient with NF1 was referred to our hospital after a positive fecal occult blood test. Locally advanced rectal carcinoma was detected in the upper rectum using colonoscopy. A submucosal tumor 20 mm in diameter was detected in the duodenal bulb during the upper gastrointestinal endoscopy. The biopsy specimen from the duodenum was GIST with positive immunostaining of KIT and CD34 microscopically. Laparoscopic low anterior resection for rectal carcinoma and local excision of the duodenal GIST were performed successfully. During the operation, five white small nodules were found on the serosa of the jejunum. One nodule was excised for histological examination. The resected rectal tumor was a well-differentiated adenocarcinoma with multiple lymph nodes metastases according to the histology. The duodenal tumor was found to be low-risk GIST. Moreover, the nodule from the jejunum was very low risk GIST. An excised skin wart was neurofibroma according to the histology. CONCLUSIONS: GIST or carcinomas have been reported to occasionally occur in the digestive tract of the patients with NF1. We present a rare case of a NF1 patient with GISTs and colorectal carcinoma.

Pathological autopsy of a patient that underwent a successful ablation of an electrical storm from the left ventricular summit.

A 65-year-old man with non-ischemic cardiomyopathy, underwent an autopsy 2 months after the successful ablation of a sustained left ventricular (LV) summit ventricular tachycardia (VT). The patient died due to interstitial pneumonia from amiodarone use. The earliest activation sites of the VT were documented from both inside the anterior interventricular vein (AIV) and epicardial surface. The diameter of the AIV was 3-4 mm, and the radiofrequency (RF) lesion inside the AIV was a slight lesion due to high impedance with a high temperature. The lesion from the epicardial surface was also superficial and insufficient due to neighboring coronary arteries and the existence of epicardial fat. A successful application was performed from the LV endocardium, and diffuse myocardial fibrosis was observed in the mid-myocardium including inside the RF lesions. The actual relationship between the myocardial fibrosis and LV summit VT remains unclear, but this case showed the difficulty of achieving a successful ablation from the epicardial side, when the focus exists in the mid-myocardium around the LV summit.

Dialysis Amyloid Deposition in the Aortic Valve and Its Association with Aortic Stenosis.

BACKGROUND: The relationship between dialysis amyloid (DA) deposition in the aortic valve (AV) and aortic stenosis (AS) is unknown. METHODS: This was a cross-sectional study. AV specimens of dialysis patients (median vintage: 8.8 years) consecutively collected from cardiac surgeries (n = 56) or autopsies (n = 13) were examined by a board-certified pathologist blinded to clinical data. DAs were considered to be present if deposits were stained both by Congo red with apple-green birefringence under polarized light and by anti-ß2-microblobulin antibody. Degree of deposition was graded as follows: Amyloid (-), no deposit; Amyloid (1+), occasional small deposits; Amyloid (2+), multiple small to large deposits or a single large deposit. Calcification was defined as a calcified deposit with a diameter >1 mm in the specimen. Severe AS (sAS) was defined as a mean gradient >50 mm Hg by echocardiogram. We examined the proportion of DAs and the association between DAs and the sAS. RESULTS: DAs were present in 71% (n = 49) of specimens and primarily co-localized with calcification. Non-dialysis related amyloid was found in one specimen. After excluding this specimen, sAS was associated with 'Amyloid (1+) and Calcification >1 mm' and 'Amyloid (2+) and Calcification >1 mm' (vs. 'Amyloid (-) and Calcification ≤1 mm', odds ratios (ORs): 13.5 and 34.2, respectively). Furthermore, after adjustment for covariates, sAS was found to be associated with 'Amyloid (2+) and Calcification >1 mm' (OR: 24.3). CONCLUSIONS: DA deposition in the AV was prevalent among dialysis patients. DA deposition with accompanying calcification might contribute to the severity of AS.

Atypical hemolytic uremic syndrome diagnosed four years after ABO-incompatible kidney transplantation.

Atypical hemolytic uremic syndrome (aHUS) in allograft kidney transplantation is caused by various factors including rejection, infection, and immunosuppressive drugs. We present a case of a 32 year old woman with aHUS four years after an ABO-incompatible kidney transplantation from a living relative. The primary cause of end-stage renal disease was unknown; however, IgA nephropathy (IgAN) was suspected from her clinical course. She underwent pre-emptive kidney transplantation from her 60 year old mother. The allograft preserved good renal function [serum creatinine (sCr) level 110-130 µmol/L] until a sudden attack of abdominal pain four years after transplant, with acute renal failure (sCr level, 385.3 µmol/L), decreasing platelet count, and hemolytic anemia with schizocytes. On allograft biopsy, there was thrombotic microangiopathy in the glomeruli, with a cellular crescent formation and mesangial IgA and C3 deposition. Microvascular inflammation, such as glomerulitis, peritubular capillaritis, and arteriole endarteritis were also detected. A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) did not decrease and Shiga toxin was not detected. Donor-specific antibodies or autoantibodies, including anti-neutrophil cytoplasmic antibody and anti-glomerular basement membrane (anti-GBM) antibody, were negative. The patient was diagnosed with aHUS and received three sessions of plasmapheresis and methylprednisolone pulse therapy, followed by oral methylprednisolone (0.25-0.5 mg/kg) instead of tacrolimus. She temporarily required hemodialysis (sCr level, 658.3 µmol/L). Thereafter, her sCr level improved to 284.5 µmol/L without dialysis therapy. This case is clinically considered as aHUS after kidney transplantation, associated with various factors, including rejection, glomerulonephritis, and toxicity from drugs such as tacrolimus.

Rotating suture technique combined with lid margin split and lower eyelid retractor disinsertion for epiblepharon.

Epiblepharon is an eyelid disease affecting 46-52.5% of Asian children. The Hotz procedure was commonly used for the treatment. However, the currently preferred technique is the rotating suture technique. This study aimed to report the recurrence rate and the complications of using the rotating suture technique combined with lid margin split and lower eyelid retractor (LER) disinsertion of epiblepharon. This was a retrospective study of the procedures performed between January 2017 and December 2020. This study included 64 eyelids of 37 patients who underwent the consecutive rotating suture technique, lid margin split, and LER disinsertion simultaneously for lower eyelid epiblepharon and were followed up for at least 6 months. The mean age of the patients who underwent surgery was 9.5 (5-28) years. The mean observation period was 8.3 (6-27) months. Recurrence was observed in one eyelid (1.6%). The complications included an ectopic eyelash on one eyelid (1.6%). LER disinsertion performed in this study had two advantages. First, the imbalance between the anterior and posterior lamellae was corrected. Disinserting the LER, the tarsal plate could be repositioned cranially, effectively addressing this imbalance. Second, LER disinsertion ensured direct exposure of the lower margin of the tarsal plate, facilitating the implementation of a reliable rotating suture. In conclusion, promising results were achieved by combining the rotating suture technique with LER disinsertion and lid margin splitting.

Two tumor types in a unilateral testis in a patient with severe oligozoospermia and a history of cryptorchidism surgery: A case report.

Testicular cancer, the most common cancer among young male adults, is associated with infertility. A 38-year-old male patient was admitted to Dokkyo Medical University Saitama Medical Center, Japan, with infertility associated with severe oligozoospermia. Scrotal ultrasonography revealed two distinct tumors in the left testis: A mass with abundant blood flow on the cranial side and a mass with poor blood flow on the caudal side. Additional analysis revealed mild elevation of intact human chorionic gonadotropin (hCG) levels (tumor marker level assessment), high testosterone and low luteinizing hormone and follicle-stimulating hormone levels (hormonal level assessment) and severe oligoasthenozoospermia (semen assessment). The preoperative diagnosis was left-sided testicular cancer and severe oligoasthenozoospermia and the patient underwent left high orchiectomy and oncological testicular sperm extraction. Based on the pathological assessment, the cranial tumor was diagnosed as a seminoma with syncytiotrophoblastic cells, whereas the caudal tumor had only scar tissue with germ cell neoplasia in situ in the adjacent parenchyma. Following surgery, intact hCG and hormone levels of the patient were normalized, and the semen parameters (semen volume, sperm density, and motility) improved dramatically. To the best of our knowledge, the present case is the first report of two types of testicular tumor in a unilateral testis in a patient with a history of cryptorchidism surgery. The present case demonstrated that scrotal ultrasonography should be performed in patients with abnormal semen results to rule out testicular tumors.

Post-embolization syndrome-like symptoms due to shedding of necrotic material of hepatocellular carcinoma into the bile duct following transcatheter arterial chemoembolization: an instructive case.

Fever, abdominal pain, and liver dysfunction are almost inevitable complications of transcatheter arterial chemo embolization (TACE) for hepatocellular carcinoma, but these symptoms may also be due to bile duct obstruction caused by shedding of necrotic tumor material into the bile duct. A 68-year-old man presented with persistent fever, liver dysfunction, and abdominal pain after TACE. Computed tomography revealed stone-like hyperdensities in the bile duct. Endoscopic retrograde cholangiopancreatography revealed these structures to be necrotic material from hepatocellular carcinoma. We believe this is an instructive case of an often overlooked situation.

Sensitivity and kinase activity of epidermal growth factor receptor (EGFR) exon 19 and others to EGFR-tyrosine kinase inhibitors.

The presence of epidermal growth factor receptor (EGFR) somatic mutations in non-small-cell lung cancer patients is associated with response to treatment with EGFR-tyrosine kinase inhibitors, such as gefitinib and erlotinib. More than 100 mutations in the kinase domain of EGFR have been identified. In particular there are many variations of deletion mutations in exon 19. In this study, using yellow fluorescent protein-tagged fragments of the EGFR intracellular domain, we examined the differences in sensitivity to gefitinib, erlotinib and afatinib between several exon 19 mutants and other common EGFR mutations. We also used serum of patients undergoing treatment with EGFR-tyrosine kinase inhibitors in this system. In addition, we examined the relative kinase activity of these mutants by measuring relative fluorescent intensity after immunofluorescence staining. We found that both sensitivity to EGFR-tyrosine kinase inhibitors and relative kinase activity differed among several EGFR mutations found in the same region of the kinase domain. This study underscores the importance of reporting the clinical outcome of treatment in relation to different EGFR mutations.