Intensified First Cycle of Rituximab Plus Eight Cycles of Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone with Rituximab Chemotherapy for Advanced-Stage or Bulky Diffuse Large B-Cell Lymphoma: A Multicenter Phase II Consortium for Improving Survival of Lymphoma (CISL) Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This phase II, open-label, multicenter study aimed to investigate the efficacy and safety of a rituximab intensification for the 1st cycle with every 21-day of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP-21) among patients with previously untreated advanced-stage or bulky diffuse large B-cell lymphoma (DLBCL). @*Materials and Methods@#Ninety-two patients with stage III/IV or bulky DLBCL from 21 institutions were administered 8 cycles of R-CHOP-21 with an additional one dose of rituximab intensification on day 0 of the 1st cycle (RR-CHOP). The primary endpoint was a complete response (CR) rate after 3 cycles of chemotherapy. @*Results@#Among the 92 DLBCL patients assessed herein, the response rate after 3 cycles of chemotherapy was 88.0% (38.0% CR+50.0% partial response [PR]). After the completion of 8 cycles of chemotherapy, the overall response rate was observed for 68.4% (58.7% CR+9.8% PR). The 3-year progression-free survival rate was 64.0%, and the 3-year overall survival rate was 70.4%. Febrile neutropenia was one of the most frequent grade 3 adverse events (40.0%) and 5 treatment-related deaths occurred. Compared with the clinical outcomes of patients who received R-CHOP chemotherapy as a historical control, the interim CR rate was higher in male patients with RR-CHOP (20.5% vs. 48.8%, p=0.016). @*Conclusion@#Rituximab intensification on days 0 to the 1st cycle of the standard 8 cycles R-CHOP-21 for advanced DLBCL yielded favorable response rates after the 3 cycles of chemotherapy and acceptable toxicities, especially for male patients. ClinicalTrials.gov ID: NCT01054781.

Factors Affecting Nutritional Index and Length of Stay in Pancreatic Cancer in the Older Adults

Purpose@#This retrospective study aimed to clarify the relation between nutritional index and length of hospital stay in elderly patients undergoing pancreatic cancer surgery, and to identify factors affecting the length of hospital stay. @*Methods@#Total 102 patients aged over 65 years who underwent pancreaticoduodenectomy were retrospectively enrolled from January 1, 2010 to September 30, 2020. All patients were subjected to nutritional screening using Geriatric Nutritional Risk Index (GNRI) and Prognostic Nutritional Index (PNI). @*Results@#The GNRI average was 95. 66±6.95, with 67.6% of patients having a low GNRI score (malnutrition group). The average regarding PNI was 45.46±5.65, with 54.9% of patients having a low PNI (malnutrition group). The average total length of hospital stay was 23.12±10.69 days. Total length of hospital stay according to the nutritional indexes of the subjects was longer in the low GNRI (t=-2.09, p=.039) and low PNI (t=-2.29, p=.024) groups. @*Conclusion@#Poorer preoperative nutritional status increased total length of hospital stay in elderly patients with pancreatic cancer. Assessment of nutritional status of patients using GNRI and PNI is a good strategy for evaluating elderly patients at high risk of having to stay in hospital for more extended periods of time.

Intraoperative Radiotherapy for Resectable Pancreatic Cancer Using a Low-Energy X-Ray Source:Postoperative Complications and Early Outcomes

Purpose@#We evaluated the safety, feasibility, and early treatment outcomes of intraoperative radiotherapy (IORT) using a lowenergy X-ray source. @*Materials and Methods@#Patients with resectable pancreatic cancer were enrolled in this single-institution, prospective, singlearm, phase II trial. Patients underwent surgery and IORT with 10 Gy prescribed at a 5-mm depth from the tumor bed using a 50 kV X-ray source (Intrabeam, Carl Zeiss). Six cycles of adjuvant gemcitabine-based chemotherapy were administered 8–12 weeks after surgery. @*Results@#A total of 41 patients were included. Thirty-one patients (75.6%) underwent wide R0 resection, while 5 (12.2%) underwent R1 resection and 5 (12.2%) underwent narrow R0 resection (retroperitoneal margin <1 mm). Grade 3 postoperative complications were reported in only one patient (4.9%) who needed additional surgery due to ulcer perforation. At a median follow-up of 9 months, four patients showed local-only recurrence, nine had distant metastases, and two showed both local and distant recurrence. The 1-year local control rate was 76.4%. @*Conclusion@#Our preliminary report suggests that IORT is well-tolerated and feasible in patients with resectable pancreatic cancer. Further follow-up is needed to confirm the clinical benefits of IORT in terms of local control and overall survival.Trial Registration: Clinical trial registration No. (NCT03273374).

Development and External Validation of Survival Prediction Model for Pancreatic Cancer Using Two Nationwide Databases: Surveillance, Epidemiology and End Results (SEER) and Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP)

Background/Aims@#Several prediction models for evaluating the prognosis of nonmetastatic resected pancreatic ductal adenocarcinoma (PDAC) have been developed, and their performances were reported to be superior to that of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. We developed a prediction model to evaluate the prognosis of resected PDAC and externally validated it with data from a nationwide Korean database. @*Methods@#Data from the Surveillance, Epidemiology and End Results (SEER) database were utilized for model development, and data from the Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP) database were used for external validation. Potential candidate variables for model development were age, sex, histologic differentiation, tumor location, adjuvant chemotherapy, and the AJCC 8th staging system T and N stages. For external validation, the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (AUC) were evaluated. @*Results@#Between 2004 and 2016, data from 9,624 patients were utilized for model development, and data from 3,282 patients were used for external validation. In the multivariate Cox proportional hazard model, age, sex, tumor location, T and N stages, histologic differentiation, and adjuvant chemotherapy were independent prognostic factors for resected PDAC. After an exhaustive search and 10-fold cross validation, the best model was finally developed, which included all prognostic variables. The C-index, 1-year, 2-year, 3-year, and 5-year time-dependent AUCs were 0.628, 0.650, 0.665, 0.675, and 0.686, respectively. @*Conclusions@#The survival prediction model for resected PDAC could provide quantitative survival probabilities with reliable performance. External validation studies with other nationwide databases are needed to evaluate the performance of this model.

Validation of the 8th AJCC Cancer Staging System for Pancreas Neuroendocrine Tumors Using Korean Nationwide Surgery Database / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic neuroendocrine tumor (PNET) included several significant changes. We aim to evaluate this staging system compared to the 7th edition AJCC staging system and European Neuroendocrine Tumors Society (ENETS) system. MATERIALS AND METHODS: We used Korean nationwide surgery database (2000-2014). Of 972 patients who had undergone surgery for PNET, excluding patients diagnosed with ENETS/World Health Organization 2010 grade 3 (G3), only 472 patients with accurate stage were included. RESULTS: Poor discrimination in overall survival rate (OSR) was noted between AJCC 8th stage III and IV (p=0.180). The disease-free survival (DFS) curves of 8th AJCC classification were well separated between all stages. Compared with stage I, the hazard ratio of II, III, and IV was 3.808, 13.928, and 30.618, respectively (p=0.007, p < 0.001, and p < 0.001). The curves of OSR and DFS of certain prognostic group in AJCC 7th and ENETS overlapped. In ENETS staging system, no significant difference in DFS between stage IIB versus IIIA (p=0.909) and IIIA versus IIIB (p=0.291). In multivariable analysis, lymphovascular invasion (p=0.002), perineural invasion (p=0.003), and grade (p < 0.001) were identified as independent prognostic factors for DFS. CONCLUSION: This is the first large-scale validation of the AJCC 8th edition staging system for PNET. The revised 8th system provides better discrimination compared to that of the 7th edition and ENETS TNM system. This supports the clinical use of the system.

Frey's procedure for chronic pancreatitis: a 10-year single-center experience in Korea

PURPOSE: Chronic pancreatitis (CP) is progressive inflammatory disease that leads to irreversible destruction of the pancreatic parenchyma. The main indications for surgical intervention in cases involving CP are intractable pain, suspicion of malignancy, and failure of other methods. However, there is no report related to Frey's procedure in Korea; hence, we aimed to investigate and analyze our institution's experience and determine the benefits of surgical treatment for CP. METHODS: This was a retrospective study of 24 patients with CP who underwent Frey's procedure at Gangnam Severance Yonsei University between January 2007 and December 2017. Preoperative exocrine and endocrine pancreatic function, perioperative finding (blood loss, operation time), postoperative complications were evaluated. Statistical analytics were chi-square test, Fisher exact tests, and Wilcoxon signed-rank test and Mann-Whitney U-test. RESULTS: Surgery was performed due to alcohol-derived CP in 12 of 24 patients (50%) and due to pancreatic stones in 15 of 24 patients (62.5%). Two patients had postoperative complications which were managed conservatively. After surgery, 7 of 24 patients were prescribed with exocrine medication. Comparison of the preoperative and postoperative conditions showed that glycated hemoglobin had no significant differences. After surgery, only 5 patients (21%) complained of intermittent abdominal pain. CONCLUSION: In conclusion, Frey's procedure appears to be a less burdensome surgical procedure. Thus, it could be the first option for management of patients with large pancreatic stone.

Protective effect of Korean red ginseng on oxaliplatin-mediated splenomegaly in colon cancer

PURPOSE: This study investigated how adding Korean red ginseng extract (KRG) to folinic acid, fluorouracil and oxaliplatin (FOLFOX) chemotherapy affected the rate of splenomegaly in colon cancer. METHODS: This retrospective study analyzed 42 patients who were randomly assigned to receive a FOLFOX regimen with or without KRG. Spleen volume change was assessed by computed tomography scans measured before surgery (presurgery volume) and 3 weeks after cessation of the 12th cycle of FOLFOX (postchemotherapy volume). RESULTS: All patients showed increased spleen volume. No difference was observed in median presurgery and postchemotherapy volume between the KRG and control groups. However, a ratio defined as postchemotherapy volume divided by presurgery volume was significantly lower in the KRG group than the control group (median, 1.38 [range, 1.0–2.8] in KRG group vs. median, 1.89 [range, 1.1–3.0] in control group, P = 0.028). When splenomegaly was defined as a >61% increase in spleen volume, the rate of splenomegaly was significantly lower in the KRG group than the control group (28.6% vs. 61.9%, P = 0.03). KRG consumption was inversely associated with developing splenomegaly in multivariate analysis. CONCLUSION: Adding KRG during FOLFOX chemotherapy for colon cancer might protect against oxaliplatin-induced splenomegaly. The protective effect of Korean red ginseng should be investigated with further research.

Preliminary Findings on the Effectiveness of Meaning-Centered Psychotherapy in Patients with Pancreatobiliary Cancer

PURPOSE: This study investigated the effectiveness of meaning-centered psychotherapy (MCP), which is known to be a helpful psychotherapeutic intervention in distressing conditions, for patients with pancreatobiliary cancer. MATERIALS AND METHODS: We recruited 37 patients with pancreatobiliary cancer from three university general hospitals and assessed their psychological characteristics. Patients who reported clinically significant emotional distress were recommended to undergo MCP. Patients who consented to MCP were provided four sessions of the therapy. Patient psychological characteristics were assessed again 2 months after MCP. For statistical comparison, outcome variables included anxiety, depression, mental adjustment to cancer, and quality of life (QoL), as well as the degree of stress and physical symptoms. RESULTS: Sixteen patients completed the MCP and the final assessment 2 months later. In the initial assessment, the patients receiving MCP showed higher levels of anxiety and depression than those not receiving MCP, and QoL was also lower in terms of role function, emotional function, social function, and global QoL. At the 2-month follow-up, the MCP group showed a significant improvement in anxiety (p=0.007), depression (p=0.010), and anxious preoccupation (p < 0.001). In addition, QoL significantly improved in the MCP group, while there was no significant change in the non-MCP group. CONCLUSION: In this study, MCP showed potential therapeutic benefits against emotional distress in patients with pancreatobiliary cancer, improving their QoL.

The 2016 WHO versus 2008 WHO Criteria for the Diagnosis of Chronic Myelomonocytic Leukemia

The 2016 WHO diagnostic criteria for chronic myelomonocytic leukemia (CMML) require both absolute and relative monocytosis (≥1×10⁹/L and ≥10% of white blood cell counts) in peripheral blood. Moreover, myeloproliferative neoplasm (MPN) features in bone marrow and/or MPN-associated mutations tend to support MPN with monocytosis rather than CMML. We assessed the impact of the 2016 WHO criteria on CMML diagnosis, compared with the 2008 WHO criteria, through a retrospective review of the medical records of 38 CMML patients diagnosed according to the 2008 WHO classification. Application of the 2016 WHO criteria resulted in the exclusion of three (8%) patients who did not fulfill the relative monocytosis criterion and eight (21%) patients with an MPN-associated mutation. These 11 patients formed the 2016 WHO others group; the remaining 27 formed the 2016 WHO CMML group. The significant difference in the platelet count and monocyte percentage between the two groups indicated that the 2016 WHO criteria lead to a more homogenous and improved definition of CMML compared with the 2008 WHO criteria, which may have led to over-diagnosis of CMML. More widespread use of molecular tests and more sophisticated clinical and morphological evaluations are necessary to diagnose CMML accurately.

Pseudo-Chediak-Higashi granules in myeloid cells in therapy-related AML with RUNX1-RUNX1T1

No abstract available.

Laparoscopic resection of retroperitoneal benign neurilemmoma

PURPOSE: The aim of this study was to verify that laparoscopic resection for treating retroperitoneal benign neurilemmoma (NL) is expected to be favorable for complete resection of tumor with technical feasibility and safety. METHODS: We retrospectively analyzed 47 operations for retroperitoneal neurogenic tumor at Yonsei University College of Medicine, Severance Hospital and Gangnam Severance Hospital between January 2005 and September 2015. After excluding 21 patients, the remaining 26 were divided into 2 groups: those who underwent open surgery (OS) and those who underwent laparoscopic surgery (LS). We compared clinicopathological features between the 2 groups. RESULTS: There was no significant difference in operation time, estimated blood loss, transfusion, complication, recurrence, or follow-up period between 2 groups. Postoperative hospital stay was significantly shorter in the LS group versus the OS group (OS vs. LS, 7.00 ± 3.43 days vs. 4.50 ± 2.16 days; P = 0.031). CONCLUSION: We suggest that laparoscopic resection of retroperitoneal benign NL is feasible and safe by obtaining complete resection of the tumor. LS for treating retroperitoneal benign NL could be useful with appropriate laparoscopic technique and proper patient selection.

Prognostic Factors and Scoring Model for Survival in Metastatic Biliary Tract Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Metastatic biliary tract cancer (mBTC) has a dismal prognosis. In this study, an independent dataset of patients with mBTC was used to implement and validate a routine clinico-laboratory parameter-based scoring model for risk group identification. MATERIALS AND METHODS: From September 2006 to February 2015, 482 patients with mBTC were assigned randomly (ratio, 7:3) into investigational (n=340) and validation datasets (n=142). The continuous variables were dichotomized using a normal range or the best cutoff values determined using the Contal and O'Quigley statistical methods. Following a Cox’s proportional hazard model, the scoring model was derived by summing the rounded chi-square scores for the factors identified by multivariate analysis. RESULTS: The performance status (Eastern Cooperative Oncology Group 3-4), hypoalbuminemia (< 3.4 mg/dL), carcinoembryonic antigen (≥ 9 ng/mL), neutrophil-to-lymphocyte ratio (≥ 3.0), and carbohydrate antigen 19-9 (≥ 120 U/mL) were identified as independent prognosticators (Harrell’s C index, 0.682; integrated area under the curve, 0.653). Survival was clearly correlated with the risk groups (low, intermediate, and high, 14.0, 7.3, and 2.3 months, respectively; p < 0.001). The prognosis was also discriminative in the validation data set (median survival, 16.7, 7.5, and 1.9 months, respectively; p < 0.001). Chemotherapy did not offer any survival benefits for high-risk patients. CONCLUSION: These proposed prognostic criteria for mBTC can facilitate accurate patient risk stratification and treatment-related decision-making.

Serum amyloid A inhibits dendritic cell differentiation by suppressing GM-CSF receptor expression and signaling

In this study, we report that an acute phase reactant, serum amyloid A (SAA), strongly inhibits dendritic cell differentiation induced by GM-CSF plus IL-4. SAA markedly decreased the expression of MHCII and CD11c. Moreover, SAA decreased cell surface GM-CSF receptor expression. SAA also decreased the expression of PU.1 and C/EBPα, which play roles in the expression of GM-CSF receptor. This inhibitory response by SAA is partly mediated by the well-known SAA receptors, Toll-like receptor 2 and formyl peptide receptor 2. Taken together, we suggest a novel insight into the inhibitory role of SAA in dendritic cell differentiation.

Establishing a colorectal cancer liver metastasis patient-derived tumor xenograft model for the evaluation of personalized chemotherapy

PURPOSE: In order to suggest optimal anticancer drugs for patient-tailored chemotherapy, we developed a colorectal cancer (CRC)-liver metastasis patient-derived tumor xenograft (PDTX) model. METHODS: Tissue obtained from a patient with CRC-liver metastasis (F0) was transplanted in a nonobese female mouse with diabetic/severe combined immune deficiency (F1) and the tumor tissue was retransplanted into nude mice (F2). When tumor volumes reached ~500 mm³, the F2 mice were randomly divided into 4 groups (n = 4/group) of doxorubicin, cisplatin, docetaxel, and nontreated control groups. The tumor tissues were investigated using H&E staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assays, and immunohistochemistry. To determine where the mutant allele frequencies varied across the different passages, we isolated genomic DNA from the primary tumor, liver metastasis, and PDTX models (F1/F2). RESULTS: The physiological properties of the tumor were in accord with those of the patient's tumors. Anticancer drugs delayed tumor growth, inhibited proliferation, and caused apoptosis. Histological assessments revealed no observable heterogeneity among the intragenerational PDTX models. Target exon sequencing analysis without high-quality filter conditions revealed some genetic variations in the 83 cancer-related genes across the generations. However, when de novo mutations were defined as a total count of zero in F0 and ≥5 in F2, exactly prognostic impact of clone cancer profiling (EGFR, KRAS, BRAF, PIK3CA, NRAS, APC and TP53) were detected in the paired. CONCLUSION: A CRC liver metastasis PDTX model was established for the evaluation of chemotherapeutic efficacy. This model retained the physiological characters of the patient tumors and potentially provides a powerful means of assessing chemotherapeutic efficacy.

Surgical Management of Chronic pancreatitis: What Can Surgeons Do? / 대한췌담도학회지

Chronic pancreatitis (CP) is an inflammatory disease and causes chronic pain, exocrine and endocrine function failure. Pain is major indication for surgical procedure indication in CP. Advances in noninvasive treatment now allow for better therapeutic options at an early stage of CP. However, many data show that surgical procedure may produce superior results to endoscopic treatment in CP management. Considerable controversy remains with respect to the surgical management of chronic pancreatitis. There are many surgical options to control chronic pain in CP, therefore preoperative assessment is important to choose optimal surgical management. Effective surgical procedures and timing of surgery for chronic pancreatitis remain unclear. This review comprehensively assesses the evidence for these different approaches to surgical intervention in chronic pancreatitis.

Pancreatic perforation caused by the Soehendra® retrieval device in a patient with chronic pancreatitis

SUMMARY OF EVENT: An endoscopic retrograde pancreatic duct (ERPD) stent was inserted in a male patient with chronic pancreatitis via endoscopic retrograde cholangiopancreatography (ERCP) to relieve chronic epigastric pain. After the procedure, an abdominal computed tomography scan showed localized peritonitis with a dislocated ERPD stent. The patient underwent an emergency operation, which revealed that the peritonitis was caused by perforation of the pancreatic parenchyma by the ERPD stent. TEACHING POINT: A hydrophilic guide wire can puncture the pancreas during ERPD stent insertion. Therefore, it is necessary to ensure that the guide wire reaches the main pancreatic duct, especially in patients with chronic pancreatitis.

A Study on the Dietary Intake and the Nutritional Status among the Pancreatic Cancer Surgical Patients

The adequate dietary intake is important to maintain the nutritional status of the patients after pancreatic cancer surgery. This prospective study was designed to investigate the dietary intake and the nutritional status of the patients who had pancreatic cancer surgery. Thirty-one patients (15 men, 16 women) were enrolled and measured body weight, body mass index (BMI), nutritional risk index (NRI), and Malnutrition Universal Screening Tool (MUST). Actual oral intake with nutritional impact symptoms recorded on the clinical research foam at every meal and medical information were collected from electronic medical charts. The rates of malnutrition at admission were 45.1% (14/31) and 28.9% (9/31) by NRI and MUST method, respectively, but those were increased to 87% (27/31) and 86.6% (26/31) after operation on discharge. The median values of daily intake of energy, carbohydrates, fat, and protein were 588.1 kcal, 96.0 g, 11.8 g, and 27.0 g, respectively. Most patients (n = 20, 64.5%) experienced two or more symptoms such as anorexia, abdominal bloating and early satiety. There were negative correlations between C-reactive protein (CRP) levels and the intake of total energy, protein, fat, and zinc. The rates of malnutrition were increased sharply after surgery and the dietary intake also influenced the inflammatory indicators. The results suggested that need of considering special therapeutic diets for the patients who received pancreatic surgery.

Mirizzi Syndrome: A Single Center Experience

PURPOSE: Mirizzi syndrome is caused by extrinsic compression of the common hepatic duct by stones impacted in the cystic duct or the gallbladder neck. The standard treatment for Mirizzi syndrome has been open cholecystectomy. The aim of this study was to review our experience of Mirizzi syndrome and consider its surgical treatment. METHODS: Data were collected retrospectively through chart review of 9,360 patients who underwent cholecystectomy between April 1983 and August 2016. RESULTS: Mirizzi syndrome was identified in 21 of 9,360 patients (0.22%). The mean age at diagnosis was 56 years. The most common symptom was abdominal pain (85.7%). A total of 16 patients (76.2%) were diagnosed with McSherry type I and 5 patients (23.8%) with McSherry type II. Laparoscopic cholecystectomy (LC) was initiated in 13 patients and open cholecystectomy (OC) in 8 patients. Conversion from LC to OC was reported for 3 patients (conversion rate 18.8%). In 4 patients with McSherry type II, an additional procedure (T tube insertion or hepaticojejunostomy) was required. CONCLUSION: Preoperative diagnosis of Mirizzi syndrome is very important in order to plan surgical strategy. LC is possible in selected patients with Mirizzi syndrome. However, OC is suitable in patients with McSherry type II. In the near future, laparoscopic procedures may be adaptable in patients with McSherry type II.

Prognostic Scoring Index for Patients with Metastatic Pancreatic Adenocarcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study focused on implementation of a prognostic scoring index based on clinico-laboratory parameters measured routinely on admission in metastatic pancreatic cancer patients. MATERIALS AND METHODS: Records from 403 patients of metastatic disease were analyzed retrospectively. Continuous variables were dichotomized according to the normal range or the best cut-off values statistically determined by Contal and O’Quigley method, and then analyzed in association with prognosis—overall survival (OS), using Cox's proportional hazard model. Scores were calculated by summing the rounded chi-square scores for the factors that emerged in the multivariate analysis. RESULTS: Performance status, hemoglobin, leucocyte count, neutrophil-lymphocyte ratio, and carcinoembryonic antigen were independent factors for OS. When patients were divided into three risk groups according to these factors, median survival was 11.7, 6.2, and 1.3 months for the low, intermediate, and high-risk groups, respectively (p < 0.001). Palliative chemotherapy has a significant survival benefit for low and intermediate-risk patients (median OS; 12.5 months vs. 5.9 months, p < 0.001 and 8.0 months vs. 2.0 months, p < 0.001, respectively). CONCLUSION: We advocate the use of a multivariable approach with continuous variables for prognostic modeling. Our index is helpful in accurate patient risk stratification and may aid in treatment selection.

Comparison of an international scale method and a log reduction method for monitoring of early molecular response in chronic myeloid leukemia patients

No abstract available.