Afatinib-Induced Acute Fatal Pneumonitis in Metastatic Lung Adenocarcinoma / 가정의학회지

Afatinib is an oral tyrosine kinase inhibitor (TKI) that inhibit Endothelial Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), and HER4. The common side effects of EGFR TKI are rash, acne, diarrhea, stomatitis, pruritus, nausea, and loss of appetite. Drug induced pneumonitis is the less common adverse effects of EGFR TKI. Afatinib, 2nd generation EGFR TKI is anticipated to overcome drug resistance from 1st generation EGFR TKI according to preclinical study, and several studies are being conducted to compare clinical efficacy between 1st and 2nd EGFR TKI. Several cases of rug induced acute fatal pneumonitis were reported after use of erlotinib or gefitinib. However, a case of acute fatal pneumonitis associated with afatinib was note reported except drug induced pneumonitis in other clinical study. Here, we present a cases of acute severe pneumonitis related with afatinib in metastatic lung adenocarcinoma with literature review.

Afatinib-Induced Acute Fatal Pneumonitis in Metastatic Lung Adenocarcinoma / 가정의학회지

Afatinib is an oral tyrosine kinase inhibitor (TKI) that inhibit Endothelial Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), and HER4. The common side effects of EGFR TKI are rash, acne, diarrhea, stomatitis, pruritus, nausea, and loss of appetite. Drug induced pneumonitis is the less common adverse effects of EGFR TKI. Afatinib, 2nd generation EGFR TKI is anticipated to overcome drug resistance from 1st generation EGFR TKI according to preclinical study, and several studies are being conducted to compare clinical efficacy between 1st and 2nd EGFR TKI. Several cases of rug induced acute fatal pneumonitis were reported after use of erlotinib or gefitinib. However, a case of acute fatal pneumonitis associated with afatinib was note reported except drug induced pneumonitis in other clinical study. Here, we present a cases of acute severe pneumonitis related with afatinib in metastatic lung adenocarcinoma with literature review.

Two Cases of Intravascular Lymphoma Presenting with Pulmonary Involvement

No abstract available.

The Efficacy and Safety of Platinum/Vinorelbine as More Than Second-Line Chemotherapy for Advanced Non-small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: There is no regimen that is strongly recommended for more than second-line treatment. We investigated the efficacy and safety of platinum/vinorelbine as more than second-line treatment. MATERIALS AND METHODS: We selected patients with advanced non-small cell lung cancer (NSCLC) who received treatment with platinum/vinorelbine at Chungnam National University Hospital from August 2001 to December 2013. The primary end point was the response rate, and secondary end points were progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: Thirty-five patients were enrolled. Response rate was 22.9% (complete response, 0 patients [0%]; partial response, eight patients [22.9%]; stable disease, 10 patients [28.6%]; progressive disease, 14 patients [40.0%]). A significantly higher response rate was observed for patients who had responded to previous chemotherapy than for those who did not (34.8% [8/23] vs. 0% [0/12], p=0.020). The median PFS was 4 months (range, 1 to 21 months). Patients with adenocarcinoma and non-smokers had a significantly longer PFS than patients with non-adenocarcinoma and smokers (5 months vs. 2 months, p=0.007; 4.5 months vs. 2 months, p=0.046, respectively). The median OS was 10 months (range, 1 to 41 months). Patients with good performance status and non-smokers had a significantly longer OS than patients with poor performance status and smokers (14 months vs. 4 months, p=0.02; 18.5 months vs. 6 months, p=0.049, respectively). The main serious adverse event (grade 3 or 4) was neutropenia (15 events, 13.3%) in a total of 113 cycles. CONCLUSION: Platinum/vinorelbine was effective as more than second-line chemotherapy, and the toxicity was tolerable, in patients with advanced NSCLC.

Small Cell Lung Cancer with Mutation of Epidermal Growth Factor Receptor in Patients with Lung Adenocarcinoma Resistant to Gefitinib / 대한내과학회지

Most epidermal growth factor receptor (EGFR) gene mutations are detected in lung adenocarcinomas. In contrast, these mutations have rarely been reported in small cell lung cancer (SCLC). We herein report two cases of EGFR-mutant SCLC transformed from and combined with lung adenocarcinoma. In one case, SCLC appeared to be transformed from EGFR mutant 19-del adenocarcinoma when the patient became resistant to gefitinib. The other patient had combined EGFR-mutant 19-del SCLC and adenocarcinoma at the initial diagnosis, which was resistant to gefitinib at multiple sites. Further comparative molecular analyses of these histologically distinct tumors would provide useful information regarding the role of EGFR mutation in the pathogenesis of SCLC. In conclusion, despite the presence of the same EGFR mutation, gefitinib was not effective in treatment of SCLC. Therefore, confirmation of SCLC cell morphology may become an important means of predicting resistance to EGFR tyrosine kinase inhibitors in addition to common secondary genetic alterations.

A Case of Patient with Lung Adenocarcinoma with Double Rare EGFR Mutation of G719C and L861Q / 계명의대학술지

The vast majority of epidermal growth factor receptor (EGFR) gene mutations are detected in lung adenocarcinoma. EGFR mutations are the strongest predictor of response to EGFR tyrosine kinase inhibitor (TKI) treatment in patient with advanced non-small cell lung cancer. Of these, exon 19 deletions and exon 21 L858R point mutations account for more than 80% of mutations detected in tumor with EGFR mutations, which called classical EGFR mutations, and double mutations mainly composed of classical and uncommon EGFR mutations are reported to be present in 13% of total EGFR mutations. But there has been no report to date of patient with double mutation of TKI sensitive uncommon EGFR mutations (G719C and L861Q). We experienced a case of patient with lung adenocarcinoma with double mutation of G719C and L861Q, the first case on our literature review, and showing partial response to TKI treatment.

A Multicenter Retrospective Analysis of the Clinical Features of Pernicious Anemia in a Korean Population

To determine the approximate incidence and clinical features of pernicious anemia in a Korean population, we retrospectively analyzed clinical data for patients with pernicious anemia who were diagnosed between 1995 and 2010 at five hospitals in Chungnam province. Ninety-seven patients were enrolled, who accounted for 24% of patients with vitamin B12 deficiency anemia. The approximate annual incidence of pernicious anemia was 0.3 per 100,000. The median age was 66 (range, 32-98) yr, and the male/female ratio was 1.25. Anemia-associated discomfort was the most common symptom (79.4%), followed by gastrointestinal and neurological symptoms (78.4% and 38.1%, respectively). Pancytopenia was found in 36 patients (37.1%), and autoimmune disorders were found in 15 patients (15.5%). Antibody to intrinsic factor was detected in 62 (77.5%) of 80 patients examined, and antibody to parietal cells was detected in 35 (43.2%) of 81 patients examined. Of the 34 patients who underwent tests for Helicobacter pylori, 7 (12.5%) were positive. The anemia-associated and gastrointestinal symptoms resolved completely in all patients after intramuscular injection of cobalamin, whereas neurological symptoms remained in some. In conclusion, pernicious anemia is less frequent in Koreans than in Western populations; however, the clinical features of this disorder in Koreans do not differ from those of Western cases.

A Case of Pneumatosis Intestinalis Associated with Sunitinib Treatment for Renal Cell Carcinoma / 대한소화기학회지

Sunitinib as a multitarget tyrosine kinase inhibitor is one of the anti-tumor agents, approved by the United States Food and Drug Administration to use treat gastrointestinal stromal tumor and metastatic renal cell carcinoma. The agent is known to commonly induce adverse reactions such as fatigue, nausea, diarrhea, stomatitis, esophagitis, hypertension, skin toxicity, reduciton in cardiac output of left ventricle, and hypothyroidism. However, it has been reported to rarely induce adverse reactions such as nephrotic syndrome and irreversible reduction in renal functions, and cases of intestinal perforation or pneumatosis interstinalis as such reactions have been consistently reported. In this report, a 66-year old man showing abdominal pain had renal cell carcinoma and history of sunitinib at a dosage of 50 mg/day on a 4-weeks-on, 2-weeks-off schedule. Seven days after the third cycle he was referred to the hospital because of abdominal pain. Computed tomography showed pneumoperitoneum with linear pneumatosis intestinalis in his small bowel. The patient underwent surgical exploration that confirmed the pneumatosis intestinalis at 100 cm distal to Treitz's ligament. We report a rare case of intestinal perforation with pneumatosis intestinalis after administration of sunitinib to a patient with metastatic renal cell carcinoma.

Long-term outcome of isolated thrombocytopenia accompanied by hypocellular marrow

BACKGROUND: Hypocellularity of bone marrow (BM), not associated with significant dyshematopoiesis, is often found in patients with isolated thrombocytopenia, but its clinical implications have not been studied. We prospectively studied the clinical features and natural history of these patients. METHODS: Adults with isolated thrombocytopenia (platelet counts 50x10(9)/L in 16 patients (80%). BM cellularity ranged from 5% to 25% (median, 15%) and was 150x10(9)/L) after 12, 56 and 66 months. Three patients developed pancytopenia after 11, 70 and 90 months. Two patients were consistent with moderate aplastic anemia, and 1 was confirmed as having refractory cytopenia with multilineage dysplasia. In the remainder of the patients, platelet counts remained unchanged. CONCLUSION: Isolated thrombocytopenia accompanied by hypocellular marrow encompasses a group of heterogeneous conditions.

A Case of Multiple Solitary Plasmacytoma Recurring in Multiple Visceral Organs / 대한내과학회지

Multiple solitary plasmacytoma is a very rare disease entity, which occurs in up to 5% of patients with solitary plasmacytomas. We report an atypical case of multiple solitary plasmacytoma that recurred in multiple visceral organs without any evidence of bone marrow involvement. A 68-year-old male presented with voiding difficulty. Twenty months earlier, he had been placed on local radiotherapy for solitary plasmacytomas in the right 6th rib and right iliac bone. Recurrences were noted 14 and 12 months later in several ribs and the 5th cervical vertebra, respectively. These were well controlled with local radiotherapy and conventional systemic chemotherapy. He had multiple soft tissue masses in the stomach, pancreas, pelvic cavity, and right buttock. An endoscopic biopsy of the gastric mass confirmed the diagnosis of plasmacytoma. Local radiotherapy to the pelvic mass and systemic therapy consisting of bortezomib and dexamethasone were given, and he has been well for 8 months.

Differential effects of CXCR4 antagonists on the survival and proliferation of myeloid leukemia cells in vitro

BACKGROUND: Antagonists of CXC chemokine receptor 4 (CXCR4), including AMD3100, induce peripheral mobilization of hematopoietic stem cells and have been approved for clinical use. We explored whether the CXCR4 antagonists affected the survival and proliferation of myeloid leukemia cells in vitro. METHODS: The effects of CXCR4 antagonists AMD3100 and T140 on the survival and proliferation of myeloid leukemia cell lines (U937, HL-60, MO7e, KG1a, and K562) as well as CD34+ cells obtained from patients with AML and CML were analyzed by flow cytometry by using annexin V and a colorimetric cell proliferation assay. RESULTS: AMD3100, but not T140, stimulated the proliferation of leukemia cells in vitro in a dose-dependent manner for up to 5 days (~2-fold increase at a concentration of 10-5 M), which was not abrogated by pretreatment of the cells with pertussis toxin, but was attenuated by RNAi knockdown of CXCR7 transcripts. In contrast, AMD3100 induced a marked decrease in the cell numbers after 5-7 days. AMD3100, but not T140, induced phosphorylation of MAPK p44/p42. AMD3100 increased the number and size of leukemia cell colonies and reduced cell apoptosis during the first 5-7 days of incubation, but the phenomena were reversed during the later period of incubation. CONCLUSION: The effects of CXCR4 antagonists on the proliferation of myeloid leukemia cells are not uniform. AMD3100, but not T140, exerts dual effects, initially enhancing and subsequently inhibiting the survival and proliferation of the cells in vitro.

Arthrodesis of the Knee with a Huckstep Nail Following the Treatment Failure of an Infected Total Knee Arthroplasty

We performed knee arthrodesis with a Huckstep nail in 4 patients that had failed in controlling infection after TKA. The purpose of this study is to introduce our surgical methods and report our clinical results. We retrospectively reviewed 4 patients who underwent knee arthrodesis with a Huckstep nail after the treatment failure of infection following TKA from 2003 to 2007. Mean age was 73 years (70~79 years). All patients had type II diabetes and hypertension. From primary TKA to knee arthrodesis with a Huckstep nail, patients underwent 3.2 operations (3~4 times) on average including removal of implant, synovectomy, antibiotic cement insertion, and revisional TKA. Allo-bone grafting was performed additionally in all cases to minimize lower limb shortening. Patients were evaluated clinically, hematologically and radiologically. The mean duration of follow-up was 20.2 months (12~36 months). All patients showed bony union radiologically within one year. There was no migration or loosening of a nail and screws. Limb length discrepancy was 3 cm on average. Although 1 patient complained ambulatory pain, all patients returned to ambulation without evidence of infection recurrence. Arthrodesis of the knee with a Huckstep nail for patients who had failed in controlling infection after TKA was considered effective treatment option.

A Case of Cystadenocarcinoma of the Pancreas in a Patient with Autosomal Dominant Polycystic Kidney Disease / 대한신장학회지

Polycystic kidney disease is an autosomal dominant disease that may be associated with liver and pancretic cysts. Mitral valve prolapse and intracranial berry aneurysms are also well-known manifestations of autosomal dominant polycystic kidney disease (ADPKD). Cystadenocarcinoma of the pancreas is uncommon and accounts for only 1% of primary pancreatic malignancies. Few cases were reported to have an association of ADPKD and pancreatic malignancies. We report a 63-year-old man with ADPKD who was admitted to our hospital with anorexia and severe weight loss. After abdominal CT and histologic examination, he was diagnosed as pancreatic cystadenocarcinoma with lung, spleen, and liver metastasis. To prolong the life of the patient, we tried gemcitabine and cisplatin combination chemotherapy. But the patient died 2 months after diagnosis due to the disease progression.

The Effect of Combined Immunosuppressive Treatment with FK 506-Cyclophosphamide on Surgical Angiogenesis / 대한정형외과연구학회지

PURPOSE: To evaluate the effect of combined immunosuppressive treatment with FK 506-cyclophosphamide on surgical angiogenesis in non-vascularized bone xenografts. MATERIALS AND METHODS: Twenty-seven hamster-to-rat non-vascularized bone xenografts were performed. For surgical angiogenesis, recipient origin saphenous arteriovenous bundles were implanted into the medullary canals of graft bones. Immunosuppression with FK 506-cyclophosphamide was performed in group 1, not in group 2, control group. At postoperative 4 weeks, microangiography with microfil was conducted. Decalcified bones were cleared and the area of newly formed capillary, capillary density, were quantitatively evaluated using Scion image program. Bone specimens stained with hematoxylin-eosin were evaluated histologically also. RESULTS: There was no significant difference of capillary densities between immunosuppressed group and non-immunosuppressed control group (0.37+/-0.03/0.39+/-0.02, P=0.58). On histological examination, both groups showed neoangiogenesis into the medullary canals and endosteal bones. CONCLUSION: FK 506-cyclophosphamide immunosuppression did not suppress the angiogenesis in non-vascularized bone xenografts, FK 506-cyclophosphamide combination of immunosuppression will be useful even in the condition of surgical angiogenesis.

The Effect of Combined Immunosuppressive Treatment with FK 506-Cyclophosphamide on Surgical Angiogenesis / 대한정형외과연구학회지

PURPOSE: To evaluate the effect of combined immunosuppressive treatment with FK 506-cyclophosphamide on surgical angiogenesis in non-vascularized bone xenografts. MATERIALS AND METHODS: Twenty-seven hamster-to-rat non-vascularized bone xenografts were performed. For surgical angiogenesis, recipient origin saphenous arteriovenous bundles were implanted into the medullary canals of graft bones. Immunosuppression with FK 506-cyclophosphamide was performed in group 1, not in group 2, control group. At postoperative 4 weeks, microangiography with microfil was conducted. Decalcified bones were cleared and the area of newly formed capillary, capillary density, were quantitatively evaluated using Scion image program. Bone specimens stained with hematoxylin-eosin were evaluated histologically also. RESULTS: There was no significant difference of capillary densities between immunosuppressed group and non-immunosuppressed control group (0.37+/-0.03/0.39+/-0.02, P=0.58). On histological examination, both groups showed neoangiogenesis into the medullary canals and endosteal bones. CONCLUSION: FK 506-cyclophosphamide immunosuppression did not suppress the angiogenesis in non-vascularized bone xenografts, FK 506-cyclophosphamide combination of immunosuppression will be useful even in the condition of surgical angiogenesis.

Clinical Efficiency after Fixation with Cable in Patellar Fracture

PURPOSE: To evaluate the clinical results of cable fixation in patellar fractures followed by early ROM exercise and early weight bearing. MATERIALS AND METHODS: We analyzed 46 patients who had operation for transverse or comminuted patellar fractures with cable fixation from April 1995 to January 2003. Mean term of follow up was 15 months (range, 15~24 months). We reviewed the clinical and radiologic bony unions, ROM, time of weight bearings retrospectively. All cases were fixed with Dall-Miles' cable, and additional fixation was done with K-wires in 25 cases and with screws in 11 cases. At next day after surgery, all patients started CPM, except 3 cases who had severly comminuted fractures. Full weight bearing was started 2-3 days after surgery with LMB in full extended state. RESULTS: We gained bony union in all cases, Average ROM was 115 degree(80-130 degree) at postoperative 2nd week, all patients showed more than 130 degree at 8th week and final results showed normal ROM compared with opposite knee. During follow up, K-wires were migrated in 2 cases, but there was no difference in ROM or bony union compared with other patients. CONCLUSION: Fixations using Dall-Miles' cable for transverse or comminuted patellar fractures are considered to be enough stable for early ROM exercise and early weight bearing without major complications.

Osteochondroma of the 5th and 6th Cervical Vertebral Body: One Case Report / 대한척추외과학회지

Here, the case of an osteochondroma, which developed on the cervical spine of an 18-year old boy, is presented. Generally, an osteochondroma is very difficult to diagnose, due to their rarity and non-specific or lack of symptoms, and because they show radiolucency on plain X-ray. Due to the neurological symptoms of this patient, including radiating pain and a palpable protruding hard mass, the CT and MRI images were checked for a more accurate radiological evaluation. These images showed evidence of spinal cord compression or obliteration of the neural foramen. An en bloc excisional biopsy of the bony mass and cartilage cap, and a decompressive laminectomy were performed.

Anterior Fixation Techniques on Unstable Pelvic Ring Injury / 대한정형외과학회잡지

PURPOSE: We reviewed the clinical result of two techniques of anterior fixation method for unstable pelvic ring injuries, which are external and internal fixation. MATERIALS AND METHODS: A retrospective clinical analysis was performed on 33 cases which had been operated from September 1998 to February 2003.Mean follow-up period is 29 months (range, 12-54 months).Previous to anterior fixation percutaneous iliosacral screw fixation was applied on iliosacral joint in Type C injury. After then plate and screw fixation were done in 17 cases and external fixation in 16 cases as an anterior fixation method. The patient' functional outcome was evaluated by Postel score and comparison between two groups was performed. RESULTS: In external fixator group the complaints are long duration of application of external fixator, excessive scar formation due to pin tract infection, pain and discomfort (Postel score 9.9;range, 8-11) due to malunion. In internal fixation group all of them showed more than good result and satisfactory to the postoperative condition and clinically (Postel score 11.6;range, 10-12). CONCLUSION: An open reduction and internal fixation technique is better than external fixation for the treatment of injured anterior pelvic ring in unstable pelvis fracture.

Atypical Piriformis Syndrome: A Report of 2 Cases / 대한정형외과학회잡지

The piriformis syndome is a rare condition characterized by pain and paresthesia in the buttock, often radiating to the posterior thigh. Symptoms are made worse by hip adduction and internal rotation of the hip joint. We report two cases of piriformis syndrome caused by an atypical sciatic nerve pathway combined with hamstring hypertrophy.