Purpose: The role of tumor-infiltrating lymphocytes (TILs) in predicting lymph node metastasis (LNM) in patients with T1 colorectal cancer (CRC) remains unclear. Furthermore, clinical utility of a machine learning–based approach has not been widely studied. Materials and Methods: Immunohistochemistry for TILs against CD3, CD8, and forkhead box P3 in both center and invasive margin of the tumor were performed using surgically resected T1 CRC slides. Three hundred and sixteen patients were enrolled and categorized into training (n=221) and validation (n=95) sets via random sampling. Using clinicopathologic variables including TILs, the least absolute shrinkage and selection operator (LASSO) regression model was applied for variable selection and predictive signature building in the training set. The predictive accuracy of our model and the Japanese criteria were compared using area under the receiver operating characteristic (AUROC), net reclassification improvement (NRI)/integrated discrimination improvement (IDI), and decision curve analysis (DCA) in the validation set. Results: LNM was detected in 29 (13.1%) and 12 (12.6%) patients in training and validation sets, respectively. Nine variables were selected and used to generate the LASSO model. Its performance was similar in training and validation sets (AUROC, 0.795 vs. 0.765; p=0.747). In the validation set, the LASSO model showed better outcomes in predicting LNM than Japanese criteria, as measured by AUROC (0.765 vs. 0.518, p=0.003) and NRI (0.447, p=0.039)/IDI (0.121, p=0.034). DCA showed positive net benefits in using our model. Conclusion Our LASSO model incorporating histopathologic parameters and TILs showed superior performance compared to conventional Japanese criteria in predicting LNM in patients with T1 CRC.

Purpose: The role of tumor-infiltrating lymphocytes (TILs) in predicting lymph node metastasis (LNM) in patients with T1 colorectal cancer (CRC) remains unclear. Furthermore, clinical utility of a machine learning–based approach has not been widely studied. Materials and Methods: Immunohistochemistry for TILs against CD3, CD8, and forkhead box P3 in both center and invasive margin of the tumor were performed using surgically resected T1 CRC slides. Three hundred and sixteen patients were enrolled and categorized into training (n=221) and validation (n=95) sets via random sampling. Using clinicopathologic variables including TILs, the least absolute shrinkage and selection operator (LASSO) regression model was applied for variable selection and predictive signature building in the training set. The predictive accuracy of our model and the Japanese criteria were compared using area under the receiver operating characteristic (AUROC), net reclassification improvement (NRI)/integrated discrimination improvement (IDI), and decision curve analysis (DCA) in the validation set. Results: LNM was detected in 29 (13.1%) and 12 (12.6%) patients in training and validation sets, respectively. Nine variables were selected and used to generate the LASSO model. Its performance was similar in training and validation sets (AUROC, 0.795 vs. 0.765; p=0.747). In the validation set, the LASSO model showed better outcomes in predicting LNM than Japanese criteria, as measured by AUROC (0.765 vs. 0.518, p=0.003) and NRI (0.447, p=0.039)/IDI (0.121, p=0.034). DCA showed positive net benefits in using our model. Conclusion Our LASSO model incorporating histopathologic parameters and TILs showed superior performance compared to conventional Japanese criteria in predicting LNM in patients with T1 CRC.

Most tumors affecting the extrahepatic bile duct are adenocarcinomas; the other histologic types occur only rarely. We herein report the extremely rare case of signet ring cell carcinoma (SRCC) originating from the extrahepatic bile duct. A 55-year-old man was hospitalized for jaundice and pruritus. Computed tomography and positron emission tomography suggested the presence of distal extrahepatic bile-duct cancer. He underwent a pylorus preserving pancreaticoduodenectomy. A histologic study confirmed a signet ring cell neoplasm of the distal common bile duct. Because the upper resection margin was invaded by the tumor, he received postoperative concurrent chemoradiotherapy and four cycles of chemotherapy. The patient has survived with no evidence of recurrence for 2 years. This is the second case of primary SRCC of the distal extrahepatic bile duct reported in the literature; further reports of cases are warranted to determine the nature of SRCC in the extrahepatic bile duct.
Bile Ducts, Extrahepatic ; Carcinoma, Signet Ring Cell ; Chemoradiotherapy ; Common Bile Duct ; Humans ; Jaundice ; Middle Aged ; Pancreaticoduodenectomy ; Positron-Emission Tomography and Computed Tomography ; Pruritus ; Pylorus ; Recurrence

PURPOSE: The purpose of this study was to investigate the reliability and the clinical applicability of the adenosine-triphosphate-based chemotherapy response assay (ATP-CRA) as a method of determining in vitro chemosensitivity in patients with gastric cancer. MATERIALS AND METHODS: A total of 243 gastric cancer tissue samples were obtained from gastrectomies performed between February 2007 and January 2010. We evaluated the effectiveness of the ATP-CRA assay in determining the chemosensitivity of gastric cancer specimens using eleven chemotherapeutic agents - etoposide, doxorubicin, epirubicin, mytomicin, 5-fluorouracil, oxaliplatin, irinotecan, docetaxel, paclitaxel, methotraxate, and cisplatin - for chemosensitivity studies using ATP-CRA. We assessed the failure rate, the cell death rate, and the chemosensitivity index. RESULTS: The failure rate of ATP-CRA was 1.6% (4/243). The mean coefficient of variation for triplicate ATP measurements was 6.5%. Etoposide showed the highest cell death rate (35.9%) while methotrexate showed the lowest (16.6%). The most active chemotherapeutic agent was etoposide, which most frequently ranked highest in the chemosensitivity test: 31.9% (51/160). Oxaliplatin was more active against early gastric cancers than advanced gastric cancers, whereas docetaxel was more active against advanced cancers. The lymph node negative group showed a significantly higher cell death rate than the lymph node positive group when treated with doxorubicin, epirubicin, and mitomycin. CONCLUSIONS: ATP-CRA is a stable and clinically applicable in vitro chemosensitivity test with a low failure rate. The clinical usefulness of ATP-CRA should be evaluated by prospective studies comparing the regimen guided by ATP-CRA with an empirical regimen.
Adenosine ; Adenosine Triphosphate ; Camptothecin ; Cell Death ; Cisplatin ; Doxorubicin ; Epirubicin ; Etoposide ; Fluorouracil ; Gastrectomy ; Humans ; Lymph Nodes ; Methotrexate ; Organoplatinum Compounds ; Paclitaxel ; Polyphosphates ; Stomach Neoplasms ; Taxoids

PURPOSE: The purpose of this study was to investigate the reliability and the clinical applicability of the adenosine-triphosphate-based chemotherapy response assay (ATP-CRA) as a method of determining in vitro chemosensitivity in patients with gastric cancer. MATERIALS AND METHODS: A total of 243 gastric cancer tissue samples were obtained from gastrectomies performed between February 2007 and January 2010. We evaluated the effectiveness of the ATP-CRA assay in determining the chemosensitivity of gastric cancer specimens using eleven chemotherapeutic agents - etoposide, doxorubicin, epirubicin, mytomicin, 5-fluorouracil, oxaliplatin, irinotecan, docetaxel, paclitaxel, methotraxate, and cisplatin - for chemosensitivity studies using ATP-CRA. We assessed the failure rate, the cell death rate, and the chemosensitivity index. RESULTS: The failure rate of ATP-CRA was 1.6% (4/243). The mean coefficient of variation for triplicate ATP measurements was 6.5%. Etoposide showed the highest cell death rate (35.9%) while methotrexate showed the lowest (16.6%). The most active chemotherapeutic agent was etoposide, which most frequently ranked highest in the chemosensitivity test: 31.9% (51/160). Oxaliplatin was more active against early gastric cancers than advanced gastric cancers, whereas docetaxel was more active against advanced cancers. The lymph node negative group showed a significantly higher cell death rate than the lymph node positive group when treated with doxorubicin, epirubicin, and mitomycin. CONCLUSIONS: ATP-CRA is a stable and clinically applicable in vitro chemosensitivity test with a low failure rate. The clinical usefulness of ATP-CRA should be evaluated by prospective studies comparing the regimen guided by ATP-CRA with an empirical regimen.
Adenosine ; Adenosine Triphosphate ; Camptothecin ; Cell Death ; Cisplatin ; Doxorubicin ; Epirubicin ; Etoposide ; Fluorouracil ; Gastrectomy ; Humans ; Lymph Nodes ; Methotrexate ; Organoplatinum Compounds ; Paclitaxel ; Polyphosphates ; Stomach Neoplasms ; Taxoids

Despite remarkable progress in understanding and treating gastrointestinal stromal tumors (GISTs) during the past two decades, the pathological characteristics of GISTs have not been made clear yet. Furthermore, concrete diagnostic criteria of malignant GISTs are still uncertain. We collected pathology reports of 1,227 GISTs from 38 hospitals in Korea between 2003 and 2004 and evaluated the efficacy of the NIH and AFIP classification schemes as well as the prognostic factors among pathologic findings. The incidence of GISTs in Korea is about 1.6 to 2.2 patients per 100,000. Extra-gastrointestinal GISTs (10.1%) are more common in Korea than in Western countries. In univariate analysis, gender, age, tumor location, size, mitosis, tumor necrosis, vascular and mucosal invasions, histologic type, CD34 and s-100 protein expression, and classifications by the NIH and AFIP criteria were found to be significantly correlated with patient's survival. However, the primary tumor location, stage and classification of the AFIP criteria were prognostically significant in predicting patient's survival in multivariate analysis. The GIST classification based on original tumor location, size, and mitosis is more efficient than the NIH criteria in predicting patient's survival, but the mechanism still needs to be clarified through future studies.

Although the required extent of lymph node dissection remains controversial, surgery is the cornerstone of the treatment of advanced gastric cancer. However, only approximately 30% of patients are diagnosed as operable, and an R0 resection will be achieved in only 40~60% of these. Since R0 resection and the treatment response of the primary cancer or resected specimen are significant prognostic factors in locally advanced gastric cancer, various preoperative treatment modalities have been attempted to induce downstaging and improve complete nodal resection. Several recent studies revealed that preoperative chemoradiation therapy can prolong patient survival by improving the R0 resection rate and treatment response. Here, we present an advanced gastric cancer patient with serosal penetration involving multiple perigastric and celiac lymph nodes who underwent radical surgery and entered complete remission after S1 and cisplatin-based concurrent chemoradiation therapy. Pathology revealed total necrosis of the tumor cells, and fibrous nodules in 2 out of 47 resected lymph nodes indicated dead cancer cells due to chemoradiation therapy. Subsequently, the patient received an additional six rounds of postoperative adjuvant chemotherapy with uracil/tegafur (UFT) and cisplatin. Follow-up imaging showed no evidence of tumor recurrence.
Chemotherapy, Adjuvant ; Cisplatin ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Lymph Nodes ; Necrosis ; Recurrence ; Stomach Neoplasms

A multiplex PCR method has been developed to classify extended spectrum beta-lactamase (ESBL) and plasmid-mediated AmpC beta-lactamase (PABL). This method consists of the use of two four-multiplex PCRs for the detection of TEM, OXA, SHV, CTX-M, CMY, and DHA type beta-lactamases. We have compared findings from the use of conventional detection methods with that of this newly developed typing method. In testing for 73 ESBL-producing and PABL-producing isolates, 100% of the isolates were correctly identified as previously characterized types and, 44 types of beta-lactamases were additionally identified from 33 isolates. This assay not only reduces the time for classification but also increases the accuracy for detection.
Bacterial Proteins ; beta-Lactamases ; Enterobacteriaceae ; Multiplex Polymerase Chain Reaction ; Oxytocin ; Polymerase Chain Reaction

A multiplex PCR method has been developed to classify extended spectrum beta-lactamase (ESBL) and plasmid-mediated AmpC beta-lactamase (PABL). This method consists of the use of two four-multiplex PCRs for the detection of TEM, OXA, SHV, CTX-M, CMY, and DHA type beta-lactamases. We have compared findings from the use of conventional detection methods with that of this newly developed typing method. In testing for 73 ESBL-producing and PABL-producing isolates, 100% of the isolates were correctly identified as previously characterized types and, 44 types of beta-lactamases were additionally identified from 33 isolates. This assay not only reduces the time for classification but also increases the accuracy for detection.
Bacterial Proteins ; beta-Lactamases ; Enterobacteriaceae ; Multiplex Polymerase Chain Reaction ; Oxytocin ; Polymerase Chain Reaction

Zygomycosis (mucormycosis) is a rare fungal infectious disease, usually found in association with an immunocompromised state. Gastrointestinal mucormycosis is extremely rare and fatal, thus it is important to detect and manage this disease at an early stage in an effort to improve survival. To date, no cases of mucormycosis superimposed on gastrointestinal Behcet's disease have been reported. Herein we report a case in which gastrointestinal mucormycosis occurred in a 17-year-old-female with Behcet's disease. The patient recovered from her disease after undergoing an ileocecectomy.
Behcet Syndrome ; Communicable Diseases ; Glycogen Storage Disease Type VI ; Humans ; Intestine, Small ; Mucormycosis