Choong Bai Kim

Putative chromosomal deletions on 9p, 9q and 22q occur preferentially in malignant gastrointestinal stromal tumors

To characterize the type of genetic alterations in gastrointestinal stromal tumors (GISTs), we performed a comprehensive allelotype study of 14 GISTs (2 benign, 7 borderline and 5 malignant) by polymerase‐chain‐reaction and loss‐of‐heterozygosity (PCR‐LOH) analysis using 102 microsatellite markers, and compared the results with comparative‐genomic‐hybridization (CGH) analysis. Among the 38 evaluated chromosomal arms, 16 (42.1%) showed LOH in at least one patient. Most frequent LOH was observed at chromosome 14p and 14q (9/14, 64%) and this was demonstrated in all types of GISTs (50% in benign, 71% in borderline and 80% in malignant). Additional chromosomal deletions were found in several chromosomal arms. Among them, deletions on chromosomal arms of 22q (3/14, 21.4%), 9p (2/14, 14.3%) and 9q (2/14, 14.3%) were the most frequent, and were detected only in malignant GISTs both by PCR‐LOH and by CGH analysis. Additionally, 2 malignant GISTs with LOH on 9p showed homozygous deletions in the restricted area of 9p by multiplex PCR‐LOH analysis. Thus, several putative chromosomal changes were preferentially present in malignant GISTs but rare in benign and borderline GISTs. These findings suggest that accumulated chromosomal changes may contribute to the progression and/or malignant transformation of GISTs. Int. J. Cancer 85:633–638, 2000.

Endoscopic resection for undifferentiated early gastric cancer

BACKGROUND AND OBJECTIVE Endoscopic resection (ER) has become an important curative option for early gastric cancer (EGC). However, the application of ER for undifferentiated EGC remains controversial. The aim of this study was to evaluate the clinicopathologic outcomes of ER performed in undifferentiated EGC with special reference to histopathologic subtypes to examine the feasibility of ER in undifferentiated EGC. DESIGN AND SETTING Retrospective, single-center study. PATIENTS From January 2001 to April 2007, 58 lesions in 58 patients with undifferentiated EGC (17 poorly differentiated adenocarcinoma; 41 signet-ring cell carcinoma) were treated by ER at Severance Hospital, Seoul, Korea. MAIN OUTCOME MEASUREMENTS The therapeutic efficacy of ER was assessed according to en bloc resection, histologic complete resection (CR), lateral or vertical cut end-positive (including submucosal invasion), and recurrence rates in 3- to 65-month follow-up periods. RESULTS The en bloc resection and CR rates were 84.5% and 67.2%, respectively. The en bloc and CR rates in poorly differentiated were 82.4% and 58.8%, whereas those in signet-ring cell were 85.4% and 70.7%, respectively. There were no significant differences between poorly differentiated and signet-ring cell. However, all (100%) of the histologic incomplete resections in poorly differentiated were vertical cut end-positive, whereas 83.3% of these resections in signet-ring cell were lateral cut end-positive. The recurrence rate was 5.1% in CR during the follow-up period. LIMITATIONS Retrospective, short-term follow-up period. CONCLUSIONS ER may be a feasible local treatment for undifferentiated EGC if CR can be achieved. However, a different approach is necessary between poorly differentiated and signet-ring cell before ER to prevent incomplete resection.

Clinicopathological aspects and prognostic value with respect to age: an analysis of 3,362 consecutive gastric cancer patients.

Several studies have reported controversial results about clinicopathological features and prognoses in gastric cancer patients with respect to age, partly due to variable definitions of young age and inhomogeneity of the patient population. The aim of study was to analyze clinicopathological features and prognostic value of all stages of gastric cancer in a large consecutive series.

Changes in Treatment Outcomes of Gastric Cancer Surgery Over 45 Years at A Single Institution

Purpose Although many studies have demonstrated improvements in short-and long-term outcomes of gastric cancer surgery, changes in long-term survival over time are not well-established. This study was conducted to evaluate changes in host, tumor, and treatment factors in patients treated at a single institution over a period of 45-yr. Patients and Methods We retrospectively evaluated 9282 patients with gastric cancer from 1955 to 1999, and divided the 45-yr into 4 time frames based on published articles: 1955 to 1962 (n = 228), 1963 to 1972 (n = 891), 1973 to 1988 (n = 2789), and 1989 to 1999 (n = 5374). Results Remarkable changes were noted in host, tumor, treatment factors, and prognosis. Among host factors, patients of more advanced age were identified in the 4th period and mean age shifted from 49 to 55 yrs. Among tumor factors, early gastric cancers and upper body tumors increased up to 32% and from 7% to 13%, respectively. An increase in the annual number of patients (from 29 to 649), gastrectomies (from 14 to 600), rate of resection (from 50% to 90%), rate of curative resection (up to 92%), and proportion of total gastrectomy (from 8% to 29%) was noted. Operative mortality was reduced from 6.1% to 0.7%. The overall 5-yr survival rate significantly increased from 22% to 65%. Conclusion Treatment results of gastric cancer surgery have improved remarkably over the 45-year period. Increase of early stage gastric cancer with early diagnosis considerably influenced the improved survival of patients with gastric cancer.

Establishment and characterisation of patient-derived xenografts as paraclinical models for gastric cancer.

The patient-derived xenograft (PDX) model is emerging as a promising translational platform to duplicate the characteristics of tumours. However, few studies have reported detailed histological and genomic analyses for model fidelity and for factors affecting successful model establishment of gastric cancer. Here, we generated PDX tumours surgically-derived from 62 gastric cancer patients. Fifteen PDX models were successfully established (24.2%, 15/62) and passaged to maintain tumours in immune-compromised mice. Diffuse type and low tumour cell percentage were negatively correlated with success rates (p = 0.005 and p = 0.025, respectively), while reducing ex vivo and overall procedure times were positively correlated with success rates (p = 0.003 and p = 0.01, respectively). The histology and genetic characteristics of PDX tumour models were stable over subsequent passages. Lymphoma transformation occurred in five cases (33.3%, 5/15), and all were in the NOG mouse, with none in the nude mouse. Together, the present study identified Lauren classification, tumour cell percentages, and ex vivo times along with overall procedure times, as key determinants for successful PDX engraftment. Furthermore, genetic and histological characteristics were highly consistent between primary and PDX tumours, which provide realistic paraclinical models, enabling personalised development of treatment options for gastric cancer.

Staging of Adenocarcinoma of the Esophagogastric Junction: Comparison of AJCC 6th and 7th Gastric and 7th Esophageal Staging Systems

BackgroundAdenocarcinoma of esophagogastric junction (EGJ) is currently staged by the esophageal staging criteria according to the American Joint Committee on Cancer (AJCC) staging system, 7th edition. We compared the performance of 6th gastric (G6), 7th gastric (G7), and 7th esophageal (E7) staging systems.MethodsA total of 202 curatively resected adenocarcinomas of EGJ were analyzed. Patient outcomes were assessed according to G6, G7, and E7 staging. Tumor invasion to the subserosal or serosa layer was regarded as invasion to the adventitia for E7 staging. Performance was measured based on monotonicity (decreasing survival with increasing stage), distinctiveness (survival difference between different stages), and homogeneity (homogenous survival in the same stage).ResultsEach staging system was monotonous except for T1-2N0 lesions of E7. This was related to the introduction of histologic grade in E7 staging. Distinctiveness in each staging system was variable. As for the homogeneity, patients whose disease was staged as Ib (E7) exhibited different survival when reassessed by G6 and G7; again, this was related to histologic grading. Patients with IIIb (G7) and IIIc (E7) disease had different survival when reassessed by G6 staging, reflecting the poorer survival of patients with more than 15 lymph node metastases.ConclusionsStaging of EGJ cancer based on the current AJCC, 7th edition, criteria of esophageal cancer staging has several limitations. We recommend considering modifications of the following in future updates of the staging system: accurate anatomical definition of tumor depth, removal of histologic grade from staging parameters, and classification of more than 15 lymph node metastases as a highly advanced stage.

Method of reconstruction governs iron metabolism after gastrectomy for patients with gastric cancer

Objective: Anemia after gastrectomy is commonly neglected by clinicians despite being an important and frequent long-term metabolic sequela. We hypothesized that the incidence and timing of the occurrence of iron deficiency after gastrectomy is closely associated with the extent of gastrectomy and the reconstruction method, and we investigated the treatment outcomes of iron supplementation to understand iron metabolism and determine the optimal reconstruction method after gastrectomy. Patients and Methods: Using a prospective gastric cancer database, we identified 381 patients with early gastric cancer with complete hematologic parameters who underwent gastrectomy between January 2004 and May 2008. Kaplan-Meier methods, Cox regression, and logistic regression were used to evaluate the associations of the extent of gastrectomy and reconstruction method with iron metabolism. Results: The prevalence of iron deficiency 3 years after gastrectomy was 69.1%, and iron-deficiency anemia was observed in 31.0% of patients. Iron deficiency developed in 64.8% and 90.5% of patients after distal gastrectomy and total gastrectomy within 3 years after surgery (P < 0.0001), respectively. Iron deficiency was significantly more frequent in women than in men (P < 0.0001) and after gastrojejunostomy than after gastroduodenostomy (P < 0.0001). Serum ferritin levels were different according to the extent of gastrectomy and reconstruction method. The proportion of patients treated for iron-deficiency anemia was also significantly different according to the extent of gastrectomy (P = 0.020). Conclusions: Iron deficiency occurs in most patients with gastric cancer after gastrectomy, and its incidence was different according to the extent of gastrectomy and reconstruction method. To improve iron metabolism after distal gastrectomy, gastroduodenostomy would be the method of reconstruction whenever possible.

Clinicopathological features and prognostic factors of proximal gastric carcinoma in a population with high Helicobacter pylori prevalence: a single-center, large-volume study in Korea.

BackgroundThe incidence of gastric cancers has fallen in recent decades. However, a substantial reduction in Helicobacter pylori prevalence and a substantial increase in the incidence of proximal gastric cancer (PGC) have been observed in the West and Japan, but not in other East Asian countries. The purpose of this large-volume study was to analyze prevalence, clinicopathological features, and prognosis of PGC compared with other types of gastric cancer in Korea, where there is high incidence of H. pylori infection.MethodsBetween 2000 and 2005, a total of 3,193 patients were enrolled. We analyzed clinicopathological features and survival outcomes.ResultsChronological analysis showed increasing incidence of PGC over the study period. PGC patients were younger and had higher incidence of Bormann types III and IV than did distal gastric cancer (DGC) patients. Also, PGC was associated with a significantly higher proportion of poorly differentiated type, T3 and T4 stage, and positive lymph nodes compared with DGC. Peritoneal and other distant metastases were more common in PGC group than in DGC group. The 5-year survival rate was significantly lower in PGC than in DGC group, regardless of curative resection. Also, the N0 and N1 category significantly influenced the 5-year survival rate. Tumor–node–metastasis (TNM) stage, hepatic metastasis, and curative resection were significant prognostic factors in PGC patients.ConclusionsPGC has increased in incidence with the respective decline in H. pylori prevalence in Korea. Survival was worse for patients with PGC than for those with DGC, regardless of curative respectability. PGC is often diagnosed at more advanced stage than other gastric cancers, and therefore early detection is critical for successful treatment.

Intra-abdominal Esophageal Duplication Cyst in an Adult

Esophageal duplication cysts are congenital anomalies of the foregut that are rarely found in the abdomen. An accurate preoperative diagnosis is not always possible, so the definitive diagnosis can be made by histologic examination of the surgical specimen. We experienced a case of Intra-abdominal esophageal duplication cyst in a 52-year-old female, who initially presented with an esophageal submucosal tumor on upper gastrointestinal endoscopy. She did not have any gastrointestinal symptoms. Barium esophagography, chest computed tomography scan and endoscopic ultrasonography demonstrated the cystic lesion in the intra-abdominal esophagus. Transhiatal enucleation of the lesion was performed successfully via the abdominal approach with no postoperative complications. Histologic study showed that the cyst wall contained a two-layered muscle coat and the surface of the lumen was lined by pseudo-ciliated columnar epithelium. The patient has been doing well without any complaints for 3 months of follow-up period.

Clinical significance of the prognostic nutritional index for predicting short-and long-term surgical outcomes after gastrectomy a retrospective analysis of 7781 gastric cancer patients

AbstractTo evaluate the predictive and prognostic significance of the prognostic nutritional index (PNI) in a large cohort of gastric cancer patients who underwent gastrectomy.Assessing a patients immune and nutritional status, PNI has been reported as a predictive marker for surgical outcomes in various types of cancer.We retrospectively reviewed data from a prospectively maintained database of 7781 gastric cancer patients who underwent gastrectomy from January 2001 to December 2010 at a single center. From this data, we analyzed clinicopathologic characteristics, PNI, and short- and long-term surgical outcomes for each patient. We used the PNI value for the 10th percentile (46.70) of the study cohort as a cut-off for dividing patients into low and high PNI groups.Regarding short-term outcomes, multivariate analysis showed a low PNI (odds ratio [OR] = 1.505, 95% CI = 1.212–1.869, P <0.001), old age, male sex, high body mass index, medical comorbidity, total gastrectomy, and combined resection to be independent predictors of postoperative complications. Among these, only low PNI (OR = 4.279, 95% CI = 1.760–10.404, P = 0.001) and medical comorbidity were independent predictors of postoperative mortality. For long-term outcomes, low PNI was a poor prognostic factor for overall survival, but not recurrence (overall survival: hazard ratio [HR] = 1.383, 95% CI = 1.221–1.568, P < 0.001; recurrence-free survival: HR = 1.142, 95% CI = 0.985–1.325, P = 0.078).PNI can be used to predict patients at increased risk of postoperative morbidity and mortality. Although PNI was an independent prognostic factor for overall survival, the index was not associated with cancer recurrence.