Efficacy of Limited Dose Modifications for Palbociclib-Related Grade 3 Neutropenia in Hormone Receptor–Positive Metastatic Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Frequent neutropenia hinders uninterrupted palbociclib treatment in patients with hormone receptor (HR)–positive breast cancer. We compared the efficacy outcomes in multicenter cohorts of patients with metastatic breast cancer (mBC) receiving palbociclib following conventional dose modification or limited modified schemes for afebrile grade 3 neutropenia. @*Materials and Methods@#Patients with HR-positive, human epidermal growth factor receptor 2–negative mBC (n=434) receiving palbociclib with letrozole as first-line therapy were analyzed and classified based on neutropenia grade and afebrile grade 3 neutropenia management as follows: group 1 (maintained palbociclib dose, limited scheme), group 2 (dose delay or reduction, conventional scheme), group 3 (no afebrile grade 3 neutropenia event), and group 4 (grade 4 neutropenia event). The primary and secondary endpoints were progression-free survival (PFS) between groups 1 and 2 and PFS, overall survival, and safety profiles among all groups. @*Results@#During follow-up (median 23.7 months), group 1 (2-year PFS, 67.9%) showed significantly longer PFS than did group 2 (2-year PFS, 55.3%; p=0.036), maintained across all subgroups, and upon adjustment of the factors. Febrile neutropenia occurred in one and two patients of group 1 and group 2, respectively, without mortality. @*Conclusion@#Limited dose modification for palbociclib-related grade 3 neutropenia may lead to longer PFS, without increasing toxicity, than the conventional dose scheme.

Clinical Significance of Computerized Videokeratoscopic Indices for Dry Eye

PURPOSE: We evaluated the usefulness of the Tomey TMS-4N™ computerized videokeratoscopy (Tomey, Nagoya, Japan) for dry eye by analyzing the correlation between the regularity indices of TMS-4N™ and conventional dry eye parameters or dry eye severity. METHODS: In this retrospective study, the medical records of 193 dry eye patients (386 eyes) were analyzed. The regularity indices of TMS-4N™ such as the surface asymmetry index (SAI), surface regularity index (SRI), potential visual acuity (PVA), and irregular astigmatism index (IAI) were compared with conventional dry eye parameters (corrected visual acuity [CVA], ocular surface disease index [OSDI] score, tear film break-up time [TBUT], corneal staining score [CFS], and Schirmer's I test). We also analyzed correlations between the regularity indices of TMS-4N™ and dry eye severity according to the Korean Corneal Disease Study Group. RESULTS: The regularity indices of TMS-4N™ such as SAI, SRI, PVA, and IAI increased according to the severity of dry eye. The regularity indices correlated significantly and positively with the CVA and CFS, but were significantly and negatively correlated with the TBUT. The OSDI score did not correlate with the regularity indices. CONCLUSIONS: The regularity indices of TMS-4N™ provide an objective method for follow-up as well as a means to measure the severity of dry eye disease.

Immunohistochemistry Biomarkers Predict Survival in Stage II/III Gastric Cancer Patients: From a Prospective Clinical Trial / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Identification of biomarkers to predict recurrence risk is essential to improve adjuvant treatment strategies in stage II/III gastric cancer patients. This study evaluated biomarkers for predicting survival after surgical resection. MATERIALS AND METHODS: This post-hoc analysis evaluated patients from the CLASSIC trial who underwent D2 gastrectomywith orwithout adjuvant chemotherapy (capecitabine plus oxaliplatin) at the Yonsei Cancer Center. Tumor expressions of thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1), and programmed death-ligand 1 (PD-L1) were evaluated by immunohistochemical (IHC) staining to determine their predictive values. RESULTS: Among 139 patients, IHC analysis revealed high tumor expression of TS (n=22, 15.8%), ERCC1 (n=23, 16.5%), and PD-L1 (n=42, 30.2%) in the subset of patients. Among all patients, high TS expression tended to predict poor disease-free survival (DFS; hazard ratio [HR], 1.80; p=0.053), whereas PD-L1 positivity was associated with favorable DFS (HR, 0.33; p=0.001) and overall survival (OS; HR, 0.38; p=0.009) in multivariate Cox analysis. In the subgroup analysis, poor DFS was independently predicted by high TS expression (HR, 2.51; p=0.022) in the adjuvant chemotherapy subgroup (n=66). High PD-L1 expression was associated with favorable DFS (HR, 0.25; p=0.011) and OS (HR, 0.22; p=0.015) only in the surgery-alone subgroup (n=73). The prognostic impact of high ERCC1 expression was not significant in the multivariate Cox analysis. CONCLUSION: This study shows that high TS expression is a predictive factor for worse outcomes on capecitabine plus oxaliplatin adjuvant chemotherapy, whereas PD-L1 expression is a favorable prognostic factor in locally advanced gastric cancer patients.

Comparison between Modified Bilateral Lateral Rectus Recession and Augmented Unilateral Recession-resection for Convergence Insufficiency Exotropia

PURPOSE: To compare the surgical outcomes between modified bilateral lateral rectus muscle (BLR) recession and augmented unilateral recession-resection (R&R) for the convergence insufficiency intermittent exotropia (IXT). METHODS: 37 patients with convergence insufficiency IXT were divided into two groups: 13 patients (underwent BLR recession) and 24 patients (underwent unilateral R&R). Success was defined as within 10 prism diopters (PD) at distance and near, and within 10 PD of the difference between them at postoperative 12 months. RESULTS: After the patch test, the preoperative distance deviation angle in the BLR group was 29.9 ± 8.4 PD, and the near deviation angle was 42.3 ± 9.7 PD; the difference between them was 12.5 ± 3.2 PD. In the R&R group, the preoperative distance deviation angle was 26.7 ± 5.8 PD, and the near deviation angle was 41.5 ± 7.4 PD; the difference between them was 14.8 ± 4.3 PD (p = 0.235, p = 0.987, and p = 0.123). At the 12-month follow-up in the BLR group, the distance angle was 3.8 ± 5.1 PD, and the near deviation angle was 4.9 ± 6.1 PD; the difference between them was 2.9 ± 5.9 PD. In the R&R group, the postoperative distance deviation angle was 4.7 ± 6.1 PD, and the near deviation angle was 7.9 ± 6.6 PD; the difference between them was 3.65 ± 5.1 PD (p = 0.708, p = 0.162, and p = 0.632, respectively). The surgical success rate did not differ significantly between groups at 12 months postoperatively (76.9%: BLR group and 70.8%: R&R group; p = 0.690). CONCLUSIONS: Modified BLR recession showed a similar surgical success rate to augmented unilateral R&R, and was effective in reducing both distance and near exodeviation, and in decreasing the difference between distance and near deviation in convergence insufficiency IXT.

The Thickness of Each Retinal Layer and Visual Acuity after Vitrectomy in Idiopathic Epiretinal Membrane

PURPOSE: In this study, we evaluated the thickness of each retinal layer using spectral-domain optical coherence tomography (OCT) and investigated the correlation between the thickness of each retinal layer and postoperative visual acuity in eyes with idiopathic epiretinal membrane (ERM). METHODS: This retrospective study included 46 eyes from 46 patients with idiopathic ERM who underwent pars plana vitrectomy. Each retinal layer thickness was measured by spectral-domain OCT before operation and at 1, 3, and 6 months after operation. The thickness of each retinal layer was evaluated in the control group before the operation. We performed an analysis of the changes in thickness of each retinal layer at 6 months after operation and then investigated the correlation between the retinal layer thickness and visual improvement. RESULTS: Preoperatively, the thickness of the retinal nerve fiber layer (RNFL) in the ERM group showed more increased compared with that in the control group, and the thickness of photoreceptors and retinal pigment epithelium were decreased compared to those in the control group. At 6 months after the operation, thickness changes were reduced at the RNFL, ganglion cell layer (GCL), inner plexiform layer (IPL), GCL-IPL complex, and outer plexiform layer, while the photoreceptor layer increased compared with the values preoperatively. Differences in the preoperative thickness of GCL between the two groups had a significant correlation with postoperative visual acuity (r = 0.477, p = 0.008). CONCLUSIONS: Differences in preoperative thickness of the GCL between the two groups had a significant correlation with postoperative visual acuity. The greater was the thickness of the GCL, the worse was the visual outcome.

Effect of Enhancers on in vitro and in vivo Skin Permeation and Deposition of S-Methyl-(L)-Methionine

S-methyl-(L)-methionine (SMM), also known as vitamin U, is commercially available as skin care cosmetic products for its wound healing and photoprotective effects. However, the low skin permeation expected of SMM due to its hydrophilic nature with a log P value of −3.3, has not been thoroughly addressed. The purpose of this study thus was to evaluate the effect of skin permeation enhancers on the skin permeation/deposition of SMM. Among the enhancers tested for the in vitro skin permeation and deposition of SMM, oleic acid showed the most significant enhancing effect. Moreover, the combination of oleic acid and ethanol further enhanced in vitro permeation and deposition of SMM through hairless mouse skin. Furthermore, the combination of oleic acid and ethanol significantly increased the in vivo deposition of SMM in the epidermis/dermis for 12 hr, which was high enough to exert a therapeutic effect. Therefore, based on the in vitro and in vivo studies, the combination of oleic acid and ethanol was shown to be effective in improving the topical skin delivery of SMM, which may be applied in the cosmetic production process for SMM.

A Case of Retinal Hemorrhage Following a Dexamethasone Intravitreal Implant

PURPOSE: To report a case of retinal hemorrhage after a dexamethasone (Ozurdex®, Allergan, Irvine, CA, USA) intravitreal implant injection in macular edema (ME) secondary to central retinal vein occlusion (CRVO). CASE SUMMARY: A 60-year-old woman visited our hospital for ME secondary to CRVO in the right eye. Intravitreal bevacizumab injection and vitrectomy was conducted three times, but ME did not improve. Then, dexamethasone intravitreal implant was injected without any problems. Right after the dexamethasone intravitreal implant injection, retinal hemorrhage (2 disc diopter size) was observed in the infero-temporal area on fundus examination. Retinal hemorrhage completely disappeared 1 month after injection without other treatment. CONCLUSIONS: A case of dexamethasone intravitreal implant associated with retinal hemorrhage has not been previously reported in Korea. Althrough retinal hemorrhage was observed, it resolved spontaneously without treatment.

A Favorable Treatment Response of Erlotinib in Lung Adenocarcinoma with Concomitant Activating EGFR Mutation and ROS1 Rearrangement / 이화의대지

The rearrangement of c-ros oncogene 1 (ROS1) has been recently identified as an important molecular target in non small cell lung cancer (NSCLC). ROS1 rearrangement and epidermal growth factor receptor (EGFR) mutation were mutually exclusive each other in previous studies, and the clinical implication of co-existence of the two genetic alterations has not been determined. We report a case of 46-year-old female never-smoker NSCLC patient whose tumor harbored ROS1 rearrangement and EGFR mutation concomitantly. She had undergone curative surgery for stage IIIA NSCLC, and the recurrence in left pleura and brain occurred at 2 years after the surgery. She received several lines of chemotherapy including docetaxel plus carboplatin, erlotinib, pemetrexed, and gemcitabine. Erlotinib therapy showed a favorable treatment response with progression-free survival of 9.5 months and partial response of tumor on radiologic evaluations. This case represents a successful erlotinib treatment in a NSCLC patient with concurrent ROS1 rearrangement and EGFR mutation.

Cytomegalovirus Colitis with Colon Perforation and Lower Gastrointestinal Bleeding in a Immunocompetent Patient / 이화의대지

Cytomegalovirus (CMV) infection in immunocompromised patients is associated with significant morbidity, mortality, and adverse clinical outcome. However, CMV infection in immunocompetent patients has been considered to have subclinical and self-limited course, and does not require treatment. We reports a case of CMV colitis, presented with colon perforation and lower gastrointestinal bleeding in a immunocompetent 31-year-old young male. After conservative treatment, colonoscopy revealed multiple ulcers in transverse colon. CMV colitis was confirmed by microscopic findings and immunohistochemistry. After successful treatment with ganciclovir, the patient improved without invasive procedure.

Ifosfamide-induced Fanconi syndrome with diabetes insipidus

Ifosfamide-induced Fanconi syndrome is a rare complication that typically occurs in young patients due to a cumulative dose of ifosfamide > 40-60 g/m2, a reduction in kidney mass, or concurrent cisplatin treatment. It is usually characterized by severe and fatal progression accompanied by type II proximal renal tubular dysfunction, as evidenced by glycosuria, proteinuria, electrolyte loss, and metabolic acidosis. Diabetes insipidus is also a rare complication of ifosfamide-induced renal disease. We herein describe a case involving a 61-year-old man who developed ifosfamide-induced Fanconi syndrome accompanied by diabetes insipidus only a few days after the first round of chemotherapy. He had no known risk factors. In addition, we briefly review the mechanisms and possible therapeutic options for this condition based on other cases in the literature. Patients who receive ifosfamide must be closely monitored for renal impairment to avoid this rare but fatal complication.

Successful Sirolimus Treatment of Multiple Visceral Kaposi's Sarcoma in a Renal Allograft Patient / 대한이식학회지

The use of immunosuppressant's increases the risk of developing malignancies in renal allograft patients. One of the most important malignancies, Kaposi's sarcoma, can cause mortality and graft failure among renal allograft patients. We report the case of a 39-year-old male diagnosed with multiple visceral Kaposi's sarcoma 6 months after a second cadaveric renal allograft. The patient's renal function was markedly deteriorated at admission and required hemodialysis initially. Radiologic studies revealed Kaposi's sarcoma in multiple lymph nodes, liver, lung, and peritoneum. The excisional biopsy of an inguinal lymph node confirmed this diagnosis. After diagnosis, tacrolimus treatment was gradually decreased, and sirolimus treatment initiated. The patient did not receive any chemotherapy or radiotherapy. The Kaposi's sarcoma lesions decreased dramatically (both in size and number) 1 month after sirolimus treatment, and kidney graft function improved. This case thus shows successful sirolimus treatment of visceral Kaposi's sarcoma in a renal allograft patient.

Quantitative Assessment Technology of Small Animal Myocardial Infarction PET Image Using Gaussian Mixture Model / 의학물리

Nuclear medicine images (SPECT, PET) were widely used tool for assessment of myocardial viability and perfusion. However it had difficult to define accurate myocardial infarct region. The purpose of this study was to investigate methodological approach for automatic measurement of rat myocardial infarct size using polar map with adaptive threshold. Rat myocardial infarction model was induced by ligation of the left circumflex artery. PET images were obtained after intravenous injection of 37 MBq 18F-FDG. After 60 min uptake, each animal was scanned for 20 min with ECG gating. PET data were reconstructed using ordered subset expectation maximization (OSEM) 2D. To automatically make the myocardial contour and generate polar map, we used QGS software (Cedars-Sinai Medical Center). The reference infarct size was defined by infarction area percentage of the total left myocardium using TTC staining. We used three threshold methods (predefined threshold, Otsu and Multi Gaussian mixture model; MGMM). Predefined threshold method was commonly used in other studies. We applied threshold value form 10% to 90% in step of 10%. Otsu algorithm calculated threshold with the maximum between class variance. MGMM method estimated the distribution of image intensity using multiple Gaussian mixture models (MGMM2, em leader MGMM5) and calculated adaptive threshold. The infarct size in polar map was calculated as the percentage of lower threshold area in polar map from the total polar map area. The measured infarct size using different threshold methods was evaluated by comparison with reference infarct size. The mean difference between with polar map defect size by predefined thresholds (20%, 30%, and 40%) and reference infarct size were 7.04+/-3.44%, 3.87+/-2.09% and 2.15+/-2.07%, respectively. Otsu verse reference infarct size was 3.56+/-4.16%. MGMM methods verse reference infarct size was 2.29+/-1.94%. The predefined threshold (30%) showed the smallest mean difference with reference infarct size. However, MGMM was more accurate than predefined threshold in under 10% reference infarct size case (MGMM: 0.006%, predefined threshold: 0.59%). In this study, we was to evaluate myocardial infarct size in polar map using multiple Gaussian mixture model. MGMM method was provide adaptive threshold in each subject and will be a useful for automatic measurement of infarct size.

Ill-defined Granulomas Demonstrated in Ulcers of the Terminal Ileum and Transverse Colon in a Patient with Typhoid Fever / 대한소화기내시경학회지

Typhoid fever, the most serious human salmonellosis, is a systemic infectious disease caused by Salmonella enterica serovar Typhi and is characterized by prolonged fever, bacteremia, and multiplication of the organism within mononuclear phagocytic cells of the liver, spleen, lymph nodes, and Peyer's patches. The characteristic lesion of typhoid fever is an ulceration of the small intestinal lymphoid tissue, particularly the Peyer's patches. The usual histological findings of typhoid ulcer are necrosis and histiocytic proliferation that phagocytizes erythrocytes and degenerated lymphocytes. A granuloma is an unusual histopathological presentation of a typhoid lesion. Even if granulomas have been reported in the bone marrow, liver, and spleen in cases of typhoid fever, granulomas in primary ulcers of the ileum and transverse colon have been reported very rarely. We experienced a case of typhoid fever in which ill-defined granulomas were seen in ulcers of the terminal ileum and transverse colon.

Efficacy of 48-week clevudine therapy for chronic hepatitis B / 대한간학회지

BACKGROUND/AIMS: Clevudine is a nucleoside analogue that exhibits potent and sustained antiviral effects as a 24-week therapy for chronic hepatitis B (CHB). This study evaluated the efficacy and viral resistance of a 48-week course of clevudine treatment for CHB. METHODS: Data on patients with CHB and detectable serum hepatitis B virus (HBV) DNA who were treated with clevudine for 48 weeks or longer were collected retrospectively for this study. Patients who had taken lamivudine within the 3 years prior to this study were excluded. Serum HBV DNA was measured by polymerase chain reaction hybridization (lower detection limit=316 copies/mL). Serum HBV DNA and biochemical data were analyzed at weeks 24 and 48. Developments of viral breakthrough and resistance to the antiviral drug were also monitored. RESULTS: Data from 74 patients (mean age 44 years; M:F=54:20; HBeAg-positive, 47; HBeAg-negative, 27) were included in this study. Ten patients had experienced previous lamivudine treatment. Median HBV DNA at baseline was 6.49 log10 copies/mL. Median serum HBV DNA reductions from baseline at week 48 were -4.34 log10 copies/mL (HBeAg-positive, -4.84 log10 copies/mL; HBeAg-negative, -3.74 log10 copies/mL). At week 48, serum HBV DNA was not detected in 83.8% of the patients (HBeAg-positive, 76.6%; HBeAg-negative, 96.3%). Normalization of serum alanine aminotransferase levels was achieved in 84.7% of the patients. Viral breakthrough and antiviral resistance developed in two patients at week 48. The development of antiviral resistance was associated with the presence of previous lamivudine treatment and cirrhosis. CONCLUSION: A 48-week course of clevudine therapy was highly effective in patients with CHB. The risk of development of resistance to clevudine was increased in patients with previous exposure to lamivudine and cirrhosis.

A Case of an Esophageal Stricture Due to Transesophageal Echocardiography / 대한소화기내시경학회지

Transesophageal echocardiography (TEE) is widely used to assess cardiac function and anatomical relationships. Although monitoring of the heart by the use of TEE is perceived to be safe and noninvasive, there are significant complications associated with the use of a probe in the esophagus. Oropharyngeal trauma, esophageal perforation, difficulty or pain with swallowing, and gastric mucosal injury are adverse events that can occur from TEE probe insertion. However, no reports have shown that placement of a TEE probe in the esophagus can be a cause of an esophageal stricture. We report a case of a 74-year-old woman with an esophageal stricture after intraoperative TEE. Bougie dilatation is generally considered as an effective treatment for a benign esophageal stricture. The benign stricture in the esophagus was treated safely using Savary-Gilliard bougie dilatation.

A Case of Vivax Malaria with Seizure and Shock / 감염과화학요법

Vivax malaria reemerged in the Republic of Korea in 1993. Vivax malaria is generally a benign disease with few severe complications. Even in the worldwide literature, there is only a small number of case reports on severe complications in vivax malaria. We report a unique case of P. vivax infection complicated by seizure and shock. A 58 year-old male showed generalized tonic-clonic seizure and shock after P. vivax infection. The species of malarial parasite was identified using peripheral blood film examination and polymerase chain reaction (PCR). He successfully recovered after treatment with hydroxychloroquine.

A Case of Vivax Malaria with Seizure and Shock / 감염과화학요법

Vivax malaria reemerged in the Republic of Korea in 1993. Vivax malaria is generally a benign disease with few severe complications. Even in the worldwide literature, there is only a small number of case reports on severe complications in vivax malaria. We report a unique case of P. vivax infection complicated by seizure and shock. A 58 year-old male showed generalized tonic-clonic seizure and shock after P. vivax infection. The species of malarial parasite was identified using peripheral blood film examination and polymerase chain reaction (PCR). He successfully recovered after treatment with hydroxychloroquine.

A Case of Abciximab Induced Acute Profound Thrombocytopenia Resulting in Compartment Syndrome of the Forearm from Massive Bleeding at the Brachial Artery Access Site

Abciximab is one of the glycoprotein IIb/IIIa receptor inhibitors, and it is known to be effective for preventing and treating the thrombotic complications of percutaneous coronary intervention (PCI). On the other hand, there is an increasing risk of hemorrhagic complications when using abciximab, especially in the case of abciximab-induced thrombocytopenia. Acute profound thrombocytopenia is a rare, but life threatening adverse reaction to abciximab, and it can even occur within a few hours of the first exposure. We report here on a case of 56 year-old woman who experienced massive bleeding of her brachial artery access site. This was caused by abciximab-induced acute profound thrombocytopenia after performing PCI concomitant with using abciximab.

Renal Dysfunction after Spontaneous Bacterial Peritonitis in Cirrhosis: Incidence and Risk Factors / 대한소화기학회지

BACKGROUNDS: Deterioration of renal function in patients with cirrhosis and spontaneous bacterial peritonitis (SBP) is the most sensitive predictor of in-hospital mortality. It has been shown that high dose intravenous albumin in addition to antibiotics reduces the incidence of renal impairment and improve hospital survival in these patients. Besides, it is important to know which patients would benefit from albumin infusion. Therefore, we conducted a retrospective study to elucidate the incidence and risk factors of renal dysfunction in cirrhotic patients with SBP. METHODS: All medical records of 76 consecutive episodes of SBP in 60 patients were analyzed. Renal dysfunction after SBP was defined as elevation of BUN >30 mg/dL or serum creatinine >1.5 mg/dL in patients without preexisting renal insufficiency, or elevation of more than 50% of the baseline level in patients with renal dysfunction at the diagnosis of infection. RESULTS: Of the 76 episodes, renal dysfunction was present in 31 (40.8%). Age, concurrent use of diuretics, large volume paracentesis (LVP) with volume expander, initial BUN and creatinine level were significant risk factors on univariate analysis. Of these, age and LVP were independent risk factors on logistic regression model. CONCLUSIONS: Renal dysfunction occurs in 40.8% of hospitalized patients after SBP. Considering poor prognosis of patients with renal dysfunction in SBP, close monitoring of renal function is needed and high dose intravenous albumin with antibiotics should be used especially in the elderly and those with LVP.