A Randomized Phase III Study of Patients With Advanced Gastric Adenocarcinoma Without Progression After Six Cycles of XELOX (Capecitabine Plus Oxaliplatin) Followed by Capecitabine Maintenance or Clinical Observation

Purpose@#Oxaliplatin, a component of the capecitabine plus oxaliplatin (XELOX) regimen, has a more favorable toxicity profile than cisplatin in patients with advanced gastric cancer (GC). However, oxaliplatin can induce sensory neuropathy and cumulative, dose-related toxicities. Thus, the capecitabine maintenance regimen may achieve the maximum treatment effect while reducing the cumulative neurotoxicity of oxaliplatin. This study aimed to compare the survival of patients with advanced GC between capecitabine maintenance and observation after 1st line XELOX chemotherapy. @*Materials and Methods@#Sixty-three patients treated with six cycles of XELOX for advanced GC in six hospitals of the Catholic University of Korea were randomized 1:1 to receive capecitabine maintenance or observation. The primary endpoint was progression-free survival (PFS), analyzed using a two-sided log-rank test stratified at a 5% significance level. @*Results@#Between 2015 and 2020, 32 and 31 patients were randomized into the maintenance and observation groups, respectively. After randomization, the median number of capecitabine maintenance cycles was 6. The PFS was significantly higher in the maintenance group than the observation group (6.3 vs. 4.1 months, P=0.010). Overall survival was not significantly different between the 2 groups (18.2 vs. 16.5 months, P=0.624). Toxicities, such as hand-foot syndrome, were reported in some maintenance group patients. Maintenance treatment was a significant factor associated with PFS in multivariate analysis (hazard ratio, 0.472; 95% confidence interval, 0.250–0.890; P=0.020). @*Conclusions@#After 6 cycles of XELOX chemotherapy, capecitabine maintenance significantly prolonged PFS compared with observation, and toxicity was manageable. Maintenance treatment was a significant prognostic factor associated with PFS.

Clinical Features of Male Breast Cancer: Experiences from Seven Institutions Over 20 Years / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Breast cancer treatment has progressed significantly over the past 20 years. However, knowledge regarding male breast cancer (MBC) is sparse because of its rarity. This study is an investigation of the clinicopathologic features, treatments, and clinical outcomes of MBC. MATERIALS AND METHODS: Clinical records of 59 MBC patients diagnosed during 1995-2014 from seven institutions in Korea were reviewed retrospectively. RESULTS: Over a 20-year period, MBC patients accounted for 0.98% among total breast cancer patients, and increased every 5 years. The median age of MBC patientswas 66 years (range, 24 to 87 years). Forty-three patients (73%) complained of a palpable breast mass initially. The median symptom duration was 5 months (range, 1 to 36 months). Mastectomy was performed in 96% of the patients. The most frequent histology was infiltrating ductal carcinoma (75%). Ninety-one percent of tumors (38/43) were estrogen receptor–positive, and 28% (11/40) showed epidermal growth factor receptor 2 (HER-2) overexpression. After curative surgery, 42% of patients (19/45) received adjuvant chemotherapy; 77% (27/35) received hormone therapy. Five out of ten patients with HER-2 overexpressing tumors did not receive adjuvant anti–HER-2 therapy, while two out of four patients with HER-2 overexpressing tumors received palliative trastuzumab for recurrent and metastatic disease. Letrozole was used for one patient in the palliative setting. The median overall survival durations were 7.2 years (range, 0.6 to 17.0 years) in patients with localized disease and 2.9 years (range, 0.6 to 4.3 years) in those with recurrent or metastatic disease. CONCLUSION: Anti–HER-2 and hormonal therapy, except tamoxifen, have been underutilized in Korean MBC patients compared to female breast cancer patients. With the development of precision medicine, active treatment with targeted agents should be applied. Further investigation of the unique pathobiology of MBC is clinically warranted.

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.

Stomach and Colon Metastasis from Breast Cancer / 이화의대지

Gastric metastasis from breast cancer is rare and only six cases have been reported in Korea. Colon metastasis is more rare than gastric metastasis. We report a 63-year-old woman with gastric and colon metastases of invasive lobular carcinoma of breast. She was diagnosed as right breast cancer, received right modified radical mastectomy 10 years ago and has been treated with chemotherapy and hormone therapy. Investigating for melena and a small caliber of stool, we found gastric and colon metastases. The diagnosis of metastatic breast cancer was made through gross pathologic and immunohistochemistry staining. We report a case with gastric and colon metastases from breast cancer and a review of the associated six case reports in Korea.

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.

Modified FOLFIRI as Second-Line Chemotherapy after Failure of Modified FOLFOX-4 in Advanced Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to evaluate efficacy and toxicity of irinotecan, leucovorin and 5-fluorouracil (FOLFIRI) as second-line treatment after failure of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX) for advanced gastric cancer. MATERIALS AND METHODS: Patients who received modified FOLFOX-4 as first-line treatment and then received sequential modified FOLFIRI for disease progression were included in this study. The modified FOLFIRI regimen consisted of irinotecan 150 mg/m2 in a 90-minute intravenous infusion on day 1, leucovorin (LV) 20 mg/m2 and 5-fluorouracil (5-FU) 400 mg/m2 as a bolus followed by 600 mg/m2 as a 22-hour infusion on days 1 and 2 with the same dose of 5-FU/LV of modified FOLFOX-4 every 2 weeks. RESULTS: A total of 32 patients received 126 courses of FOLFIRI chemotherapy. No complete response was achieved. Three patients (9.4%; 95% confidence interval [CI], 0 to 20.1%) achieved partial response, whereas 11 (34.4%; 95% CI, 17.0 to 51.8%) patients showed stable disease. Disease control rate (complete response, partial responses and stable diseases) was 43.8% (95% CI, 25.6 to 61.9%) and median follow up duration was 11.3 months (range, 2.23 to 37.9 months). Median time to progression was 2 months (95% CI, 1.49 to 2.51 months), and median overall survival from the start of FOLFIRI was 5.84 months (95% CI, 4.34 to 7.34 months). Toxicities were tolerable. CONCLUSION: Modified FOLFIRI as second-line chemotherapy after failure of the modified FOLFOX-4 in advanced gastric cancer was tolerable but showed a lower response rate. Further study about retrying 5-FU/LV with irinotecan after failure of the 5-FU/LV combined regimen is necessary in advanced gastric cancer.

Modified FOLFIRI as Second-Line Chemotherapy after Failure of Modified FOLFOX-4 in Advanced Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to evaluate efficacy and toxicity of irinotecan, leucovorin and 5-fluorouracil (FOLFIRI) as second-line treatment after failure of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX) for advanced gastric cancer. MATERIALS AND METHODS: Patients who received modified FOLFOX-4 as first-line treatment and then received sequential modified FOLFIRI for disease progression were included in this study. The modified FOLFIRI regimen consisted of irinotecan 150 mg/m2 in a 90-minute intravenous infusion on day 1, leucovorin (LV) 20 mg/m2 and 5-fluorouracil (5-FU) 400 mg/m2 as a bolus followed by 600 mg/m2 as a 22-hour infusion on days 1 and 2 with the same dose of 5-FU/LV of modified FOLFOX-4 every 2 weeks. RESULTS: A total of 32 patients received 126 courses of FOLFIRI chemotherapy. No complete response was achieved. Three patients (9.4%; 95% confidence interval [CI], 0 to 20.1%) achieved partial response, whereas 11 (34.4%; 95% CI, 17.0 to 51.8%) patients showed stable disease. Disease control rate (complete response, partial responses and stable diseases) was 43.8% (95% CI, 25.6 to 61.9%) and median follow up duration was 11.3 months (range, 2.23 to 37.9 months). Median time to progression was 2 months (95% CI, 1.49 to 2.51 months), and median overall survival from the start of FOLFIRI was 5.84 months (95% CI, 4.34 to 7.34 months). Toxicities were tolerable. CONCLUSION: Modified FOLFIRI as second-line chemotherapy after failure of the modified FOLFOX-4 in advanced gastric cancer was tolerable but showed a lower response rate. Further study about retrying 5-FU/LV with irinotecan after failure of the 5-FU/LV combined regimen is necessary in advanced gastric cancer.

Neurolymphomatosis in a patient with T-cell non-Hodgkin's lymphoma / 대한내과학회지

Neurolymphomatosis, defined as a selective infiltration of lymphoma cells into cranial nerves, peripheral nerves and nerve roots, is a rarely recognized manifestation of lymphoma. Its characteristic symptoms are often overlooked or mistaken for other conditions, such as a peripheral polyneuropathy, due to chemotherapeutic agents or clinical findings of metastatic lesions in the central nervous system. Recently, neurolymphomatosis has been increasingly recognized using magnetic resonance imaging and positron emission tomography-computed tomography. We present a case of neurolymphomatosis manifesting as peripheral mononeuropathy in a patient with T-cell non-Hodgkin's lymphoma.

A Case of Chronic Lymphocytic Leukemia Coexisting with Basal Cell Carcinoma and Lung Cancer / 대한혈액학회지

Chronic lymphocytic leukemia (CLL) can be characterized by the accumulation of small mature lymphocytes in the peripheral blood, bone marrow and other lymphoid tissues. It is well known that the risk of secondary malignancy is high in patients with CLL. A secondary malignancy in a patient with CLL may influence the prognosis as well as the treatment of CLL. As CLL is a rare disease in Korea, there have been only a few reported Korean cases of CLL with secondary malignancy. We experienced the case of a 73-year-old man who suffered from CLL with basal cell carcinoma of the skin and non-small cell lung cancer. At first, he presented with excessive lymphocytosis (>100,000/mm3), anemia, thrombocytopenia and splenomegaly, and he was diagnosed with CLL according to the bone marrow biopsy. Simultaneously he had basal cell carcinoma on his face. Seven months later, he began to feel chest discomfort and his chest X-ray showed a mass like lesion on the left upper lung. It was proven to be non-small cell lung cancer by bronchoscopic biopsy.

Secondary Adrenal Insufficiency Associated with Megestrol Acetate in a Patient with Lung Cancer / 결핵및호흡기질환

Loss of appetite is an important factor in the quality of life for advanced cancer patients. Megestrol acetate is used to stimulate appetite, but it can cause suppression of the pituitary adrenal axis due to the affinity of the glucocorticoid receptor. Adrenal insufficiency is a life threatening disorder if left, untreated, but the initial clinical symptoms of the patients are vague. Awareness of the glucocorticoid-like activity of megestrol acetate and its side effects are important for the diagnosis of adrenal insufficiency. We present a case of secondary adrenal insufficiency associated with megestrol acetate in a patient with lung cancer.

Effect of Octreotide on Patients with Malignant Bowel Obstruction / 한국호스피스완화의료학회지

PURPOSE: Malignant bowel obstruction causes gastrointestinal symptoms and leads to diminished quality of life in patients with advanced cancer. Several studies have shown the efficacy of octreotide for the relief of malignant bowel obstruction-related symptoms. The aim of this study is to assess the efficacy and safety of octreotide in patients with malignant bowel obstruction. METHODS: We retrospectively reviewed medical records of twenty nine patients who had suffered from malignant bowel obstruction without clinical improvement of conservative care and subsequently, received octreotide treatment. Initial dosage of octreotide was 0.1 mg/day, and dose was escalated depending on the clinical effect. For each patient, we assessed visual analogue scale (VAS) of pain, number of vomiting episode, and amount of nasogastric tube drainage. RESULTS: Median dosage of octreotide was 0.2 mg/day (range 0.1~0.6), and median duration from initial medication to death was 20 days (range 2~103). VAS before and after octreotide treatment were 5.6+/-1.24, and 2.7+/-0.96, respectively. The numbers of vomiting episode before and after octreotide treatment were 3.6/day+/-2.5, and 0.4/day+/-0.8, respectively. The mean amounts of nasogastric tube drainage before and after octreotide treatment were 975+/-1,083 cc/day and 115+/-196 cc/day, respectively. Statistically significant reduction in VAS, the number of vomiting episode and the amount of nasogastric tube drainage were observed after octreotide treatment (P<0.05). CONCLUSION: Administration of octreotide in patients with malignant bowel obstruction, which is uncontrolled by other medication, was effective and safe. In such clinical situations, physicians should consider to add of octreotide for symptomatic control.

The Analysis of Predictive Factors for the Identification of Patients Who Could Benefit from Respiratory-Gated Radiotherapy in Non-Small Cell Lung Cancer / 대한방사선종양학회지

PURPOSE: 4DCT scans performed for radiotherapy were retrospectively analyzed to assess the possible benefits of respiratory gating in non-small cell lung cancer (NSCLC) and established the predictive factors for identifying patients who could benefit from this approach. MATERIALS AND METHODS: Three treatment planning was performed for 15 patients with stage I~III NSCLC using different planning target volumes (PTVs) as follows: 1) PTVroutine, derived from the addition of conventional uniform margins to gross tumor volume (GTV) of a single bin, 2) PTVall phases (patient-specific PTV), derived from the composite GTV of all 6 bins of the 4DCT, and 3) PTVgating, derived from the composite GTV of 3 consecutive bins at end-exhalation. RESULTS: The reductions in PTV were 43.2% and 9.5%, respectively, for the PTVall phases vs. PTVroutine and PTVgating vs. PTVall phases. Compared to PTVroutine, the use of PTVall phases and PTVgating reduced the mean lung dose (MLD) by 18.1% and 21.6%, and V20 by 18.2% and 22.0%, respectively. Significant correlations were seen between certain predictive factors selected from the tumor mobility and volume analysis, such as the 3D mobility vector, the reduction in 3D mobility and PTV with gating, and the ratio of GTV overlap between 2 extreme bins and additional reductions in both MLD and V20 with gating. CONCLUSION: The additional benefits with gating compared to the use of patient-specific PTV were modest; however, there were distinct correlations and differences according to the predictive factors. Therefore, these predictive factors might be useful for identifying patients who could benefit from respiratory-gated radiotherapy.

A Case of Post-transplant Lymphoproliferative Disorder Manifested as Native Kidney Mass / 대한신장학회지

Post-transplant lymphoproliferative disorder (PTLD) following solid organ transplantation is an important form of post-transplant malignancy. PTLD is typically associated with Epstein-Barr virus (EBV) and occurs in the setting of immunosuppression resulting in a deficiency of EBV-specific cytotoxic T lymphocytes. PTLD encompasses heterogeneous lymphoproliferative diseases, from polyclonal proliferation resembling infectious mononucleosis to aggressive monomorphic proliferation such as diffuse large B-cell lymphoma. Clinically, PTLD is usually manifested as lymph nodal mass or extranodal mass of solid organs such as liver, transplanted kidney, tonsil, bone marrow or spleen. The authors experienced very rare case of PTLD manifested as a single mass in a native kidney. According to a review of the literature, this is a rare case of PTLD which developed in a native kidney after kidney transplantation. Initially under the impression of renal cell carcinoma, unilateral nephrectomy of the native kidney had performed, and after confirmed as PTLD by histologic diagnosis the patient had treated with reduction of immunosuppressants and chemotheraphy for PTLD, and eventually has got in complete remission.

Autologous Stem Cell Transplantation using a Modified TAM Conditioning Regimen for Clinically Aggressive Non-Hodgkin's Lymphoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: High-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) have been used for the treatment of clinically aggressive non-Hodgkin's lymphoma (NHL). However, the superiority of specific conditioning regimens has not yet been established. The present study evaluated the efficacy and toxicity of a conditioning regimen involving fractionated total body irradiation (TBI), and the use of Ara-C and melphalan (TAM) for clinically aggressive NHL. MATERIALS AND METHODS: Between March 2002 and December 2004, 31 patients with aggressive NHL received fractionated TBI with a dose of 12 Gy over 3 days, and were administered 9 g/m2 Ara-C and 100 mg/m2 melphalan followed by autologous peripheral blood stem Cell Transplantation at the Catholic Hematopoietic Stem cell transplantation Center Korea. Patients that responded to first line chemotherapy and achieved complete remission (CR), or were in a first sensitive relapse were defined as having less advanced disease, while the other patients were defined as having more advanced disease. RESULTS: Objective responses were obtained in 24 of 31 patients (77.4%), comprising complete remission in 19 patients (61.3%) and partial remission in 5 (16.1%) patients. The median follow-up time was 28 months (range 1~62 months). At 3 years, the overall survival and event-free survival (EFS) rates were 62.3% and 47.3%, respectively. Patients with less advanced disease and more advanced disease showed 3-year EFS rates of 73.3% and 22.5 %, respectively (p=0.006). Early (within the first 100 days) treatment-related mortality occurred in 3 (9.7%) patients. Of the 31 total patients, 15 (48.4%) developed grade 3 mucositis, 22 (70.9%) developed neutropenic fever, and two (6.5%) developed interstitial pneumonia syndrome >grade 3. CONCLUSION: The modified TAM conditioning regimen and ASCT appear to be a feasible treatment regimen for clinically aggressive NHL, particularly for patients with less advanced disease.

A Case of Typhoid Fever Complicated with Massive Fatal Hemoptysis

We experienced a 25 year-old male patient with typhoid fever complicated with massive hemoptysis. Pulmonary complication in typhoid fever is very rare and to our knowledge, there has been no report of hemoptysis as a main cause of death with this disease. We herein report a rare case of typhoid fever.

A Case of Typhoid Fever Complicated with Massive Fatal Hemoptysis

We experienced a 25 year-old male patient with typhoid fever complicated with massive hemoptysis. Pulmonary complication in typhoid fever is very rare and to our knowledge, there has been no report of hemoptysis as a main cause of death with this disease. We herein report a rare case of typhoid fever.

Two Cases of Successful Use of Urokinase in Continuous Ambulatory Peritoneal Dialysis Patients with Relapsing Peritonitis / 대한신장학회잡지

Peritonitis is a frequent and serious complication in continuous ambulatory peritoneal dialysis (CAPD) patients. Recently, due to educational promotion in general hygiene and development of laboratory technique for bacterial cultures and sensitivity test, proper use of antibiotics, the incidence of CAPD peritonitis has gradually decreased. However, CAPD peritonitis is still one of the most common causes of peritoneal dialysis failure and of removal peritoneal catheter. It has been suggested that the formation of biofilm on the inner surface of peritoneal catheter leads to relapsing peritonitis and removal of the peritoneal catheter in CAPD patients. The biofilm is a kind of protecting coat which consists of fibrin inhibiting the penetration of antibiotics. It surrounds and covers the bacteria, making them to survive from the attack of antibiotics. Therefore thrombolytic therapy, urokinase modifies the structure of biofilm, and helps the antibiotics penetrating the fibrin coat, eventually amplify the bacteriocidal effect. We experienced two cases of successful treatment with urokinase and antibiotics in CAPD peritonitis patients. The combination of thrombolytic agents and antibiotics might be one of the strategies for the treatment of CAPD patients who experienced it frequently.

Gastrosplenic Fistula Complicated in a Patient with Non- Hodgkin's Lymphoma / Journal of the Korean Cancer Association, 대한암학회지

Reported cases of gastrosplenic fistulas are extremely rare in the literature. Malignancy is the primary cause in 50% of patients, followed by perforated peptic ulcer (40%). Fistulas can cause spleen rupture and potential bleeding that threaten the life of the patient. Lymphoma is the most common cause of malignancy complicated with gastrosplenic fistula. Most gastrosplenic fistulae caused by lymphoma eventually close following chemotherapy, although splenectomy should be performed to avoid further complications. We experienced a case of non-Hodgkin's lymphoma complicated with gastrosplenic fistula in a 21 year-old man. He was admitted to our hospital because of LUQ mass. On the abdominal CT, a splenic mass with central necrosis and gas was discovered. The biopsy specimen of the stomach and spleen displayed diffuse, large B cell type non-Hodgkin's lymphoma. After one cycle of CHOP chemotherapy, the LUQ mass was markedly regressed although the gastrosplenic fistula was still present on the follow-up CT. The fistula was treated by splenectomy and a partial resection of gastric fundus. Follow-up chemotherapy was continued after surgery.