Sang Hoon Ji

Whole blood Epstein-Barr virus DNA load as a diagnostic and prognostic surrogate: extranodal natural killer/T-cell lymphoma.

We investigated the value of Epstein-Barr virus (EBV) DNA load in unfractionated whole blood for the diagnosis and prognosis of EBV-associated lymphoma. From July 2004 to July 2007, we compared EBV DNA loads in 101 patients with lymphoma and 105 control individuals. The median copy number of EBV was higher in patients with EBV-positive lymphoma (p<0.001). In patients with natural killer (NK)/T-cell lymphomas, the median EBV DNA load at presentation was significantly related to the stage (p = 0.011) and response (p = 0.026). The newly proposed classification model for NK/T cell lymphoma showed EBV DNA load differed significantly between patients with upper and extra-upper aerodigestive tracts (p = 0.017). In 16 patients with NK/T-cell lymphoma monitored serially, EBV DNA load correlated well with the treatment response and clinical course. Further prospective studies are required to evaluate the diagnosing and monitoring role of whole blood EBV DNA for uniformly treated patients.

Excision repair cross‐complementation group 1 (ERCC1) expression in advanced urothelial carcinoma patients receiving cisplatin‐based chemotherapy

Kim KH, Do I‐G, Kim HS, Chang MH, Kim HS, Jun HJ, Uhm J, Yi SY, Lim DH, Ji SH, Park MJ, Lee J, Park SH, Kwon GY, Lim HY. Excision repair cross‐complementation group 1 (ERCC1) expression in advanced urothelial carcinoma patients receiving cisplatin‐based chemotherapy. APMIS 2010; 118: 941–8.

Pulmonary Complications After Hematopoietic Stem Cell Transplantation

Despite advanced effective prophylaxes, pulmonary complications still occur in a high proportion of all hematopoietic stem cell recipients, accounting for considerable morbidity and mortality. The aim of our study was to describe the causes, incidences and mortality rates secondary to pulmonary complications and risk factors of such complications following hematopoietic stem cell transplantation (HSCT). We reviewed the medical records of 287 patients who underwent either autologous or allogeneic HSCT for hematologic disorders from February 1996 to October 2003 at Samsung Medical Center (134 autografts, 153 allografts). The timing of pulmonary complications was divided into pre-engraftment, early and late period. The spectrum of pulmonary complications included infectious and non-infectious conditions. 73 of the 287 patients (25.4%) developed pulmonary complications. Among these patients, 40 (54.8%) and 29 (39.7%) had infectious and non-infectious conditions, respectively. The overall mortality rate from pulmonary complications was 28.8%. Allogeneic transplant, grade II-IV acute graft-versus-host disease (GVHD) and extensive chronic GVHD were the risk factors with statistical significance for pulmonary complications after HSCT. The mortality rates from pulmonary complications following HSCT were high, especially those of viral and fungal pneumonia, diffuse alveolar hemorrhage and idiopathic pneumonia syndrome.

Can upfront systemic chemotherapy replace stereotactic radiosurgery or whole brain radiotherapy in the treatment of non-small cell lung cancer patients with asymptomatic brain metastases?

BACKGROUND The optimal treatment for non-small cell lung cancer (NSCLC) patients with asymptomatic brain metastasis is still controversial. This study aimed to analyze the outcome for various treatment modalities including chemotherapy only, upfront whole brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) in NSCLC patients with asymptomatic brain metastases. METHODS We retrospectively reviewed the medical records of patients with histopathologically proven NSCLC and synchronous asymptomatic brain metastasis between January 2003 and December 2007. RESULTS From the database, 741 NSCLC patients were identified to have been diagnosed of brain metastases during initial staging or follow-up between January 2003 and December 2007. Of 741 NSCLC patients, 135 (18%) NSCLC patients were identified to have synchronous brain metastasis without associated symptoms. Of the 129 patients included in the analysis, 78 (57.8%) patients received systemic chemotherapy only, 27 (20.0%) upfront WBRT followed by chemotherapy and 24 (17.8%) patients received upfront SRS and chemotherapy. There was no significant difference in overall survival among three groups (systemic chemotherapy alone, 13.9 versus upfront SRS followed by chemotherapy, 22.4 versus upfront WBRT followed by chemotherapy, 17.7 months, respectively; P=0.86). Subset analysis of 110 adenocarcinoma patients showed that the median OS for patients treated with upfront SRS was longer than those of upfront WRBT (29.3 months versus 17.7 months; P=0.01) or chemotherapy alone (29.3 months versus 14.6 months; P=0.04). CONCLUSION This study suggested a potential role of systemic chemotherapy alone or upfront SRS followed by chemotherapy instead of WBRT as an initial treatment of NSCLC patients with synchronous, asymptomatic brain metastases. The optimal treatment modality, however, needs to be defined in prospective trials for this subset of patients.

Esophageal Squamous Cell Carcinoma Recurring as a Solitary Renal Mass

Herein, a case of solitary, unilateral renal metastasis in a patient with curatively resected thoracic esophageal carcinoma, who achieved a pathological complete remission after neoadjuvant concurrent chemoradiotherapy, is reported. The kidney is the 4(th) or 5(th) most common visceral metastasis site of a primary esophageal carcinoma. More than 50% of renal metastases typically show bilateral involvement. Solitary, unilateral renal metastasis is extremely rare. Renal metastases from a primary esophageal carcinoma are usually latent and its diagnosis is very unusual in a live patient. The solitary renal metastasis in this case was not accompanied by metastases to other sites. The value of a nephrectomy in solitary renal metastasis of esophageal cancer is not known due to the rarity of such cases. A nephrectomy could be justified in limited situations, such as with uncertainty of histological diagnosis, severe life-threatening hematuria, which cannot be controlled by embolization, or solitary renal metastasis with a long disease-free interval.

Favorable response to doxorubicin combination chemotherapy does not yield good clinical outcome in patients with metastatic breast cancer with triple-negative phenotype.

BackgroundWe analyzed the responses to first line treatment and clinical outcomes of metastatic breast cancer patients treated with palliative doxorubicin/cyclophosphamide (AC) according to molecular cancer subtype.MethodsA retrospective analysis was performed for 110 metastatic breast cancer patients selected on the basis of palliative AC treatment and the availability of immunohistochemical data for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2/neu) status.ResultsOf the 110 patients analyzed, 71 (64.5%) were hormone receptor positive (HR+), 14 (12.7%) were HER2+, and 25 (22.7%) were triple negative (TN). There were no differences in age, stage at diagnosis, total number of cycles of palliative chemotherapy, incidence of visceral metastasis, and metastatic sites with the exception of liver among breast cancer subtypes. The overall response rates to AC were 55.9% for the HR+ subgroup, 42.9% for the HER2+ subgroup, and 56.5% for the TN subgroup. The progression-free survival (PFS) in patients with HER2+ and TN were significantly shorter than in the HR+ (median PFS, 9.1 vs 8.1 vs 11.5 months, respectively; p = 0.0002). The overall survival (OS) was 25.4 months in the TN subgroup and 27.3 months in HER2+ subgroup. The median OS for these two groups was significantly shorter than for patients in the HR+ subgroup (median, 38.5 months; 95% CI, 30.1-46.9 months; p < 0.0001).ConclusionsThe response to palliative AC chemotherapy did not differ among breast cancer subtypes. Despite chemosensitivity for palliative AC, the TN subtype has a shorter overall survival than non-TN subtypes. Innovative treatment strategies should be developed to slow the course of disease.

Metastatic lymph node in gastric cancer; Is it a real distant metastasis?

BackgroundCurrently, the TNM staging system is a widely accepted method for assessing the prognosis of the disease and planning therapeutic strategies for cancer. Of the TNM system, the extent of lymph node involvement is the most important independent prognostic factor for gastric cancer. The aim of our study is to evaluate the survival and prognosis of gastric cancer patients with LN#12 or #13 involvement only and to assess the impact of anatomic regions of primary gastric tumor on survival in this particular subset of patients.MethodsAmong data of 1,008 stage IV gastric cancer patients who received curative R0 gastrectomy, a total of 79 patients with LN#12 (n = 68) and/or #13 (n = 11) were identified. All patients performed gastrectomy with D2 or D3 lymph node dissection.ResultsIn 79 patients with LN#12/13 involvement, the estimated one-, three- and five-year survival rate was 77.2%, 41.8% and 26.6% respectively. When we compared the patients with LN#12/13 involvement to those without involvement, there was no significant difference in OS (21.0 months vs. 25.0 months, respectively; P = 0.140). However, OS was significantly longer in patients with LN#12/13 involvement only than in those with M1 lymph node involvement (14.3 months; P = 0.001). There was a significant difference in survival according to anatomic locations of the primary tumor (lower to mid-body vs. high body or whole stomach): 26.5 vs. 9.2 months (P = 0.009). In Cox proportional hazard analysis, only N stage (p = 0.002) had significance to predict poor survival.ConclusionIn this study we found that curatively resected gastric cancer patients with pathologic involvement of LN #12 and/or LN #13 had favorable survival outcome, especially those with primary tumor location of mid-body to antrum. Prospective analysis of survival in gastric cancer patients with L N#12 or #13 metastasis is warranted especially with regards to primary tumor location.

Three cases of synchronous solid tumor and multiple myeloma.

The association between a multiple myeloma and a secondary solid tumor is not well established. Some reports showed an increased risk of secondary solid neoplasms in multiple myeloma patients, but others have not. Three cases of the synchronous occurrence of multiple myelomas and solid tumors, namely, a small cell carcinoma of the lung, an adenocarcinoma of the colon and a squamous carcinoma of the pyriform sinus were experienced at our hospital. Therefore, herein is reported the clinical courses and treatment results. The stage of multiple myeloma was Durie-Salmon stage I in all of three cases; therefore, the solid tumors were treated as a primary target because the prognosis of early stage multiple myeloma is generally better than that of advanced solid tumor, while a smoldering or stage I myeloma do not need primary therapy until progression of the multiple myeloma. Two patients died of their solid tumors, but one patient is alive.

Mutational spectrum in eight Korean patients with 3‐methylcrotonyl‐CoA carboxylase deficiency

To the Editor : Isolated 3-methylcrotonyl-CoA carboxylase (MCC) deficiency is a rare metabolic disorder inherited as an autosomal recessive trait (1). Clinical presentation is extremely variable, ranging from severe neurological abnormalities and death in infancy to asymptomatic adults detected in family studies or in mothers because of positive findings on screening of their unaffected newborn babies (2, 3). By expansion of tandem mass spectrometry (MS/MS) in neonatal screening, MCC deficiency appears to be the most frequently detected organic aciduria, with an overall frequency of approximately 1 in 50,000 (2). Most infants detected by neonatal screening appear clinically normal and remain healthy (2, 4, 5). However, some children who were diagnosed on neonatal screening tests and lost to follow-up presented with profound ketoacidosis during a later intercurrent illness (6). Herein, we have described the mutational spectrum in eight Korean patients with MCC deficiency (six unrelated families). All the patients were full term with appropriate birth weight and were detected by MS/MS in neonatal screening. Their parents were non-consanguineous. None of the patients showed clinical symptoms, such as seizure, failure to thrive from birth, hypotonia, hypoglycemia, psychomotor retardation, or other neurological symptoms. On physical examination, all of them showed a normal percentage of height and weight, and vital signs were normal. Patient 1 and patient 2, who were elder brothers of patient 3, were diagnosed by family member screening just after diagnosis of patient 3. With parental informed consent, peripheral venous blood samples were collected from each of the subjects. All exons of the MCCC1 and MCCC2 genes were amplified by polymerase chain reaction on a thermal cycler (Applied Biosystems, Foster City, CA) using primer pairs designed by the authors. Numbering of nucleotide positions was done according to the complementary DNA sequences of MCCC1 and MCCC2, and the GenBank accession number was NM_020166.3 and NM_022132.4, respectively. Sequence variation was described according to the recommendations of the Human Genome Variation Society (http://www.hgvs.org/mutnomen). Of the six probands, excluding two siblings (patients 1 and 2) of patient 3, a total of 11 mutant alleles were detected. Eight different mutant alleles were identified (Table 1) and six of them were novel mutations (c.842G>A of MCCC1, c.1375C>T of MCCC2, c.1666A>G of MCCC2, c.1614A>T of MCCC2, c.826T>C of MCCC1, and c. 449_450delTG of MCCC2 ). Missense mutations constitute the absolute majority of mutations in our study. Considering that patients 1–3 were siblings, there might be no mutational hotspot in Korean patients with MCC deficiency. It is worthwhile to note that c.838G>T of MCCC2, which was described in one Japanese patient who presented with Reye-like syndrome at the age of 1 year (7), was the most common mutation type [25% (3 of 12)]. According to a study by Dantas et al. (5), c.1155A>C (p.R385S) of MCCC1 (four alleles of 28 probands, 7.1%) and c.295G>A (p.E99Q) of MCCC2 and c.1574+1G>A (p.F497_V526>GfsX4) of MCCC2 (each of three alleles of 28 probands, 5.4%) were of particular relevance. These mutations were not found in our patients; therefore, a difference exists between races. c.214C>T of MCCC2 in patient 4 has been reported in one Turkish patient with no clinical symptoms, who was detected by a neonatal screening test (5). Both known mutations c.838G>T of MCCC2 and c.214C>T of MCCC2 were not frequent mutations. Taking several studies (5, 7–10) together, exon 11 of MCCC1 and exons 6 and 11 of MCCC2 were of particular relevance. In our study, all the three mutations of MCCC1 are on exon 8,

Irinotecan and oxaliplatin combination as the first-line treatment for patients with advanced non-small cell lung cancer

BackgroundWe conducted a prospective phase II trial of IrOx in patients with advanced non-small cell lung cancer to evaluate the efficacy and toxicity.Patients and methodsPatients with histologically or cytologically proven non-small cell lung cancer (NSCLC), aged ≥18 years, Eastern Cooperative Oncology Group performance status 0–1, at stage IIIB (pleural effusion)/IV or with recurrent disease not suitable for primary surgical treatment, with no palliative chemotherapy or radiotherapy to the chest or immunotherapy or biologic therapy, the presence of measurable disease by RECIST, and who had given signed written informed consent, were eligible. Treatment consisted of irinotecan 65 mg/m2 on days 1 and 8 and oxaliplatin 130 mg/m2 on day 1, repeated every 3 weeks.ResultsA total of 18 patients were enrolled in June and August 2007, the median age was 59 years (47–73). In total, 71 cycles were administered with a median of 4 cycles per patient (range, 1–6 cycles) and 18 patients were evaluable for treatment response. An independent review of tumor responses gave an overall response rate of 27.7% (CR: 0, PR: 5/18; 95% CI, 7–48.4%) by intent-to-treat analysis. The median overall survival of all patients was 14 months and the median time-to-progression was 4.2 months (95% CI, 1.959–6.441). The most common grade 3/4 toxicities were diarrhea (7% of all cycles) and neutropenia (5.6% of all cycles). Grade 3 peripheral neuropathy occurred in one patient and one patient died due to sepsis.ConclusionThis study suggests that IrOx combination therapy has moderate activity with a tolerable toxicity profile. However, it was not warranted to evaluate further this regimen as first-line treatment for patients with advanced or metastatic NSCLC using the current dosages and schedule.