Im-kyung Kim

A high-throughput assay of NK cell activity in whole blood and its clinical application

Natural killer (NK) cells are lymphocytes of the innate immune system and have the ability to kill tumor cells and virus-infected cells without prior sensitization. Malignant tumors and viruses have developed, however, strategies to suppress NK cells to escape from their responses. Thus, the evaluation of NK cell activity (NKA) could be invaluable to estimate the status and the outcome of cancers, viral infections, and immune-mediated diseases. Established methods that measure NKA, such as (51)Cr release assay and CD107a degranulation assay, may be used to determine NK cell function, but they are complicated and time-consuming because they require isolation of peripheral blood mononuclear cells (PBMC) or NK cells. In some cases these assays require hazardous material such as radioactive isotopes. To overcome these difficulties, we developed a simple assay that uses whole blood instead of PBMC or isolated NK cells. This novel assay is suitable for high-throughput screening and the monitoring of diseases, because it employs serum of ex vivo stimulated whole blood to detect interferon (IFN)-γ secreted from NK cells as an indicator of NKA. After the stimulation of NK cells, the determination of IFNγ concentration in serum samples by enzyme-linked immunosorbent assay (ELISA) provided a swift, uncomplicated, and high-throughput assay of NKA ex vivo. The NKA results microsatellite stable (MSS) colorectal cancer patients was showed significantly lower NKA, 263.6 ± 54.5 pg/mL compared with healthy subjects, 867.5 ± 50.2 pg/mL (p value <0.0001). Therefore, the NKA could be utilized as a supportive diagnostic marker for microsatellite stable (MSS) colorectal cancer.

Underweight body mass index as a predictive factor for surgical site infections after laparoscopic appendectomy.

Purpose Analyses of risk factors associated with surgical site infections (SSIs) after laparoscopic appendectomy (LA) have been limited. Especially, the association of an underweight body mass index (BMI) with SSIs has not been clearly defined. This study aimed to identify the impact of underweight BMI in predicting SSIs after LA. Materials and Methods The records of a total of 101 consecutive patients aged ≥16 years who underwent LA by a single surgeon between March 2011 and December 2012 were retrieved from a prospectively collected database. The rate of SSIs was compared among the underweight, normal and overweight and obese groups. Also, univariate and multivariate analyses were performed to identify the factors associated with SSIs. Results The overall rate of SSIs was 12.8%. The superficial incisional SSI rate was highest in the underweight group (44.4% in the underweight group, 11.0% in the normal group, and 0% in the overweight and obese group, p=0.006). In univariate analysis, open conversion and being underweight were determined to be risk factors for SSIs. Underweight BMI was also found to be a significant predictor for SSIs in multivariate analysis (odds ratio, 10.0; 95% confidence interval, 2.0-49.5; p=0.005). Conclusion This study demonstrated underweight BMI as being associated with SSIs after LA. Surgeons should be more cautious to prevent SSIs in patients that are underweight when performing LA.

Clinical Implications of Microsatellite Instability in T1 Colorectal Cancer

Purpose The estimation of regional lymph node metastasis (LNM) risk in T1 colorectal cancer is based on histologic examination and imaging of the primary tumor. High-frequency microsatellite instability (MSI-H) is likely to decrease the possibility of metastasis to either regional lymph nodes or distant organs in colorectal cancers. This study evaluated the clinical implications of MSI in T1 colorectal cancer with emphasis on the usefulness of MSI as a predictive factor for regional LNM. Materials and Methods A total of 133 patients who underwent radical resection for T1 colorectal cancer were included. Genomic DNA was extracted from normal and tumor tissues and amplified by polymerase chain reaction (PCR). Five microsatellite markers, BAT-25, BAT-26, D2S123, D5S346, and D17S250, were used. MSI and clinicopathological parameters were evaluated as potential predictors of LNM using univariate and multivariate analyses. Results Among 133 T1 colorectal cancer patients, MSI-H, low-frequency microsatellite instability (MSI-L), and microsatellite stable (MSS) colorectal cancers accounted for 7.5%, 6%, and 86.5%, respectively. MSI-H tumors showed a female predominance, a proximal location and more retrieved lymph nodes. Twenty-two patients (16.5%) had regional LNM. Lymphovascular invasion and depth of invasion were significantly associated with LNM. There was no LNM in 10 MSI-H patients; however, MSI status was not significantly correlated with LNM. Disease-free survival did not differ between patients with MSI-H and those with MSI-L/MSS. Conclusion MSI status could serve as a negative predictive factor in estimating LNM in T1 colorectal cancer, given that LNM was not detected in MSI-H patients. However, validation of our result in a different cohort is necessary.

Feasibility and Safety of a Fold-Over Diverting Ileostomy Reversal After Rectal Cancer Surgery: Case-Matched Comparison to the Resection Technique

Purpose Compared to the stapling technique, the fold-over technique (FO) has the benefit of avoiding the sacrifice of the bowel segment. The aim of this study was to compare short-term outcomes between the FO and a conventional resection. Methods Between June 2008 and March 2012, a total of 242 patients who underwent a diverting ileostomy reversal after rectal cancer surgery were selected. Among them, 29 patients underwent the FO. Using propensity scores to adjust for body mass index, previous abdominal surgery history, rectal cancer surgery type (open vs. minimally invasive), and reason for ileostomy (protective aim vs. leakage management), we created a well-balanced cohort by matching each patient who underwent the FO, as the study group, with two patients who underwent a stapled or a hand-sewn technique with bowel resection (RE), as the control group (FO : RE = 1 : 2). Morbidity and perioperative recovery were compared between the two groups. Results Twenty-four and forty-eight patients were allocated to the FO and the RE groups, respectively. The mean operation time was 91 ± 26 minutes in the FO group and 97 ± 34 minutes in the RE group (P = 0.494). The overall morbidity rates were not different between the two groups (12.5% in FO vs. 14.6% in RE, P = 1.000). The rate of postoperative ileus was similar between the two groups (8.3% in FO vs. 12.5% in RE, P = 0.710). Although time to resumption of soft diet was shorter in the FO group than in the RE group, the lengths of hospital stay were not different. Conclusion The FO and the conventional resection have similar short-term clinical outcomes for diverting ileostomy reversal.

Laparoscopic-Assisted Resection of Jejunojejunal Intussusception Caused by a Juvenile Polyp in an Adult

Most bowel intussusceptions in adults have a leading point. However, there have been few reports of jejunojejunal intussusception secondary to a solitary juvenile polyp in adult. We report herein the case of a 19-year-old female with a solitary juvenile polyp in the jejunum causing intussusception. Laparoscopic-assisted reduction and segmental resection of the jejunum were successfully done for the patient.

Clinical impact of fat clearing technique in nodal staging of rectal cancer after preoperative chemoradiotherapy

Purpose This study was designed to evaluate the efficacy of a fat clearing technique for accurate nodal staging of rectal cancer patients after preoperative chemoradiotherapy (CRT). Methods A total of 19 patients with rectal cancer within 10 cm from anal verge were divided into two groups: non-CRT group (n = 10) and CRT group (n = 9). For pathologic assessment, lymph node (LN) harvest was performed using conventional manual dissection followed by a fat clearing technique. Results A median of 3.0 additional LNs in non-CRT group and 3.8 LNs in CRT group were identified by the fat clearing technique. When subanalysis was performed in patients with fewer than 12 retrieved LNs, a median of 4.0 extra LNs in non-CRT group and 3.5 extra LNs in CRT group were identified after the fat clearing technique. None of additionally identified nodes were metastatic. In both groups, the median size of retrieved LNs following the fat clearing technique was smaller than that obtained by manual dissection (2.0 mm vs. 3.0 mm, P < 0.001). Conclusion The fat clearing technique allowed detection of additional LNs that were missed by the manual method, but these detected LNs were not proven to be metastatic.

Multiple Myeloma Mimics Bone Metastasis From a Rectal Adenocarcinoma

A presumptive diagnosis of bone metastasis can be easily made when a patient with a history of colorectal cancer develops bone lesions that are seen on follow-up imaging. In this case report, we describe a patient whose multiple bone lesions were wrongly attributed to a recurrence of rectal cancer rather than being identified as multiple myeloma lesions. When clinicians detect new, abnormal, bony lesions in a patient with a previous history of cancer, they should consider diseases such as multiple myeloma in their differential diagnosis.

The efficacy of cap-assisted colonoscopy performed by a single endoscopist in patients after colorectal resection.

Background: The use of a transparent cap is regarded as a simple method to obtain better outcomes compared with standard colonoscopy. In this study, we investigated whether cap-assisted colonoscopy can improve the quality of procedure-related outcomes in patients with a history of colorectal resection. Methods: This study was designed as a prospective, randomized, controlled trial conducted at a single tertiary center by a single endoscopist (Kang J.). A total 183 patients after colorectal resection due to primary colorectal cancer were enrolled and 1:1 randomized to undergo either cap-assisted colonoscopy (CAP group) or standard colonoscopy (non-CAP group). The primary endpoint was the comparison of cecal intubation time between the 2 groups. Results: The mean cecal intubation time of the CAP group (n = 89) was significantly shorter than that of the non-CAP group (n = 89) (538 seconds vs 677 seconds, P = 0.024). In the CAP group, the endoscopist performed faster intubation than average more often compared with the non-CAP group (71.9% vs 57.3%). In regard to moving average curve, the CAP group showed a gentle slope during the learning period, while the non-CAP group showed a steep decrease. Conclusion: The cap-assisted colonoscopy could reduce cecal intubation time and achieve more frequent faster intubation compared with standard colonoscopy in patients after colorectal resection.

In Vitro Adenosine Triphosphate-Based Chemotherapy Response Assay as a Predictor of Clinical Response to Fluorouracil-Based Adjuvant Chemotherapy in Stage II Colorectal Cancer

Purpose We evaluated the usefulness of the in vitro adenosine triphosphate-based chemotherapy response assay (ATP-CRA) for prediction of clinical response to fluorouracil-based adjuvant chemotherapy in stage II colorectal cancer. Materials and Methods Tumor specimens of 86 patients with pathologically confirmed stage II colorectal adenocarcinoma were tested for chemosensitivity to fluorouracil. Chemosensitivity was determined by cell death rate (CDR) of drug-exposed cells, calculated by comparing the intracellular ATP level with that of untreated controls. Results Among the 86 enrolled patients who underwent radical surgery followed by fluorouracil-based adjuvant chemotherapy, recurrence was found in 11 patients (12.7%). The CDR ≥ 20% group was associated with better disease-free survival than the CDR < 20% group (89.4% vs. 70.1%, p=0.027). Multivariate analysis showed that CDR < 20% and T4 stage were poor prognostic factors for disease-free survival after fluorouracil-based adjuvant chemotherapy. Conclusion In stage II colorectal cancer, the in vitro ATP-CRA may be useful in identifying patients likely to benefit from fluorouracil-based adjuvant chemotherapy.