Sang Woo Lim

High-frequency minisatellite instability of the mitochondrial genome in colorectal cancer tissue associated with clinicopathological values.

Most studies of mitochondrial DNA (mtDNA) mutations in colorectal cancer have used case‐control and case‐database comparisons without searching their clinical relevance. This study was to investigate colorectal cancer tissue‐specific mtDNA mutations from 54 matched colorectal cancer and adjacent normal tissues and then to evaluate their clinical values. This study focused on analyzing control region including mtDNA minisatellites and coding regions. Cancer tissue‐specific mtDNA mutations were found in over half of the patients (59%). The patterns of mtDNA mutations were substitution only (13%), mtDNA minisatellite instability (mtMSI) (20%) and both mutations combined (26%). mtMSI in colorectal cancer was mainly occurred in the 303 polyC (35%) and 16184 poly C (19%) minisatellite. mtDNA copy number and hydrogen peroxide level were significantly increased in colorectal cancer tissue. The amount of mtDNA large deletions was significantly decreased in colorectal cancer tissue compared with those from matched normal mucosa (p = 0.03). The activity of the mitochondrial respiratory chain enzyme complexes I, II and III in colorectal cancer tissues was impaired. mtDNA haplogroup B4 might be closely associated with colorectal cancer risk. The patient group harboring cancer tissue‐specific mtDNA mutations showed larger tumor sizes (p = 0.005) and more advanced TNM stages (p = 0.002). Thus, mtDNA mutations in colorectal cancer might be implicated in risk factors that induce poor outcomes and tumorigenesis.

Clinical Significance of Tumor Regression Grade in Rectal Cancer with Preoperative Chemoradiotherapy

Purpose Neoadjuvant chemoradiotherapy applied to the locally advanced rectal cancer reduces local recurrence and improves survival. We assessed tumor regression grade (TRG) and its influence on survival in rectal cancer patients treated with chemoradiotherapy followed by surgical resection. Methods We studied 108 patients that were seen at our hospital between August 2004 and December 2008. Patients received preoperative chemoradiotherapy consisting of 5-fluorouracil and leucovorin by continous infusion during the first and fifth week, delivered with concurrent pelvic radiation of 50.4 Gy, followed by radical surgery at 6-8 weeks. The TRG was determined by the amount of fibrosis in the tumor embedding area and was divided into 5 grades based on the relative amount of fibrosis. We analyzed all preoperative clinicopathologic factors, postoperative pathologic stages, TRG and prognosis, retrospectively. Results Downstaging of rectal cancer through neoadjuvant chemoradiotherapy occurred in 64 (59%) patients. The numbers of total regressions (TRG4), good regressions (TRG3), moderate regressions (TRG2), minor regressions (TRG1), and no regression (TRG0) were 19 (18%), 65 (60%), 17 (16%), 6 (5%), and 1 (1%) respectively. The TRG was inversely correlated with perineural invasion and lymphovascular invasion (P = 0.008, P = 0.032). The local recurrence rate declined as the tumor regression grade increased (P = 0.032). The 19 patients with TRG4 had a better three-year disease free survival than the 89 patients with TRG0-3 (P = 0.034). The 16 patients with pathologic complete remission (pCR) had a better three-year disease free survival than the 92 patients with non-pCR (P = 0.025). Conclusion Higher TRG after preoperative chemoradiotherapy for rectal cancer closely correlates with better survival and low local recurrence. The TRG is considered to be a significant prognostic factor.

Laparoscopic low anterior resection for hematogenous rectal metastasis from gastric adenocarcinoma: A Case Report

BackgroundGastric cancer is one of the most common malignancies in the world and is the second most common cause of cancer-related death in Korea. Colorectal metastases from gastric adenocarcinoma are known to be very rare. We report an unusual case of rectal metastasis of gastric adenocarcinoma.Case presentationWe report a case of a 43-year-old female patient with gastric cancer who first presented with epigastric pain. The endoscopic and radiologic findings were suggestive of Borrmann type III advanced gastric cancer with linitis plastica. Radical total gastrectomy with D2 lymph node dissection was performed. The pathology report was AJCC TNM Stage II gastric adenocarcinoma (T3N0M0). On follow up at 34 months after surgery, the patient complained of difficulty in defecation. On colonoscopy, a hard, indurated extraluminal mass was detected 7 cm proximal to the anal verge. The biopsy demonstrated chronic nonspecific colitis. Abdominal CT, rectal MRI and PET-CT revealed rectal metastasis from gastric cancer. Laparoscopic ultralow anterior resection with diverting ileostomy was performed. The pathology report was metastatic adenocarcinoma, and this diagnosis was identical to the gastric pathology reported in the previous pathology report. The patient was discharged after the 11th postoperative day with no adverse events.ConclusionRectal metastasis from gastric cancer is known to be very rare. However, metastatic gastric adenocarcinoma should be considered as a differential diagnosis for patients presenting with a colorectal mass and a past history of gastric cancer.

Schwannoma of ascending colon treated by laparoscopic right hemicolectomy

Schwannomas of the colon are rare and are difficult to diagnose preoperatively, since they often defy endoscopic and radiographic detection. Immunohistochemical stains are useful postoperatively to confirm this tumor, but more reliable diagnostic techniques (such as colonoscopic biopsy with immunohistochemistry) have emerged to enhance preoperative diagnostic accuracy. Here we report an instance of schwannoma arising in the ascending colon, where immunohistochemical staining of a preoperative biopsy facilitated diagnosis. After laparoscopic resection, histologic examination was confirmatory.

Effects of Postoperative Adjuvant Radiotherapy on Recurrence and Survival in Stage III Rectal Cancer

BackgroundThe aim of this study is to evaluate whether the addition of radiotherapy to chemotherapy would enhance the benefits obtained with chemotherapy alone, in stage III rectal cancer in the era of preoperative chemoradiotherapy and total mesorectal excision (TME).MethodsFrom January 1999 to January 2008, 300 stage III rectal cancer patients who underwent TME were prospectively identified; a total of 46 patients who received preoperative chemoradiotherapy or did not receive adjuvant therapy were excluded. Patients who received postoperative chemotherapy alone (n=190) and those who received postoperative chemoradiotherapy (n=64) were compared.ResultsThe median follow-up period was 52 (range, 4–129) months. Patients receiving radiotherapy were younger and had a higher percentage of advanced pT category or perineural invasion than patients who did not. The estimated 5-year local recurrence-free survival rate was radiotherapy 92% with radiotherapy and 86% without. The disease-free survival rate was 55% with radiotherapy compared to 57% without and the overall survival rates were similar (63% vs. 68%, all P>0.05). In patients with a positive circumferential resection margin or insufficient distal resection margin, the local recurrence-free, disease-free, and overall survival rates were unaffected by radiotherapy.ConclusionsThe addition of postoperative radiotherapy to chemotherapy did not reduce the recurrence or mortality in node-positive rectal cancer when compared with chemotherapy alone. Moreover, this approach may not compensate for a positive circumferential resection margin or insufficient distal resection margin following rectal cancer surgery.

Over-expression of Her-2 in colorectal cancer tissue, but not in serum, constitutes an independent worse prognostic factor

BackgroundCurrently, conflicting information exists regarding Her-2 over-expression and its clinicopathological implications in colorectal cancer (CRC). This study was undertaken to determine Her-2 over-expression in both serum and tumor tissue of CRC patients, and to assess its clinicopathological and targeted therapeutic implications.MethodsNinety five CRC patients and sixty healthy controls were prospectively enrolled. Her-2 expression status in serum and CRC tissue were examined by chemiluminescent immunoassay and immunohistochemical staining, respectively. The results were confirmed using fluorescent in situ hybridization. Clinicopathological parameters were analyzed according to Her-2 expression status.ResultsSerum Her-2 levels were found to be increased in CRC patients as compared to those of healthy controls. However, serum Her-2 levels were not found to be significantly associated with prognostic parameters. Her-2 expression analysis of CRC tissues revealed Her-2 over-expression in 23 patients (25%), i.e., 13 patients (14%) showed moderate over-expression and 10 patients (11%) showed strong over-expression. The overall survival of patients negative for Her-2 expression was significantly better than that of patients positive for Her-2 expression (P = 0.018). The disease-free survival of patients with Her-2 over-expression was significantly shorter than that of patients with no Her-2 expression (P = 0.021).ConclusionsHer-2 over-expression in CRC tissue, but not in serum, acts as a significant independent worse prognostic factor. Assessment of Her-2 expression status may be valuable for the targeted therapeutic management of CRC.

Clinical Significance of Serial Serum Carcinoembryonic Antigen Values for Treating Rectal Cancer with Preoperative Chemoradiotherapy

Purpose Preoperative chemoradiotherapy is now widely accepted to treat rectal cancer; however, the prognosis for rectal cancer patients during and after chemoradiotherapy must be determined. The aim of this study was to evaluate the serial serum carcinoembryonic antigen (s-CEA) samples in patients with rectal cancer who underwent radical surgery after concurrent chemoradiotherapy (CRT). Methods This study evaluated 236 patients with rectal cancer who received preoperative CRT followed by curative surgery between June 2005 and June 2010. We measured the patients s-CEA levels pre-CRT, post-CRT and post-surgery. Patients were classified into four groups according to their s-CEA concentrations (group 1, high, high, high; group 2, high, high, normal; group 3, high, normal, normal; group 4, normal, normal, normal). We analyzed the clinicopathologic factors and the outcomes among these groups. Results Of the 236 patients, 12 were in group 1, 31 were in group 2, 67 were in group 3, and 126 were in group 4. The 3-year disease-free survival rate in group 1 was poorer than those in group 3 (P = 0.007) and group 4 (P < 0.001). In a univariate analysis, type of surgery, clinical N stage, pathologic T or N stage, lymphovascular invasion, perineural invasion, and CEA group were prognostic factors. A multivariate analysis revealed that type of surgery, pathologic T stage, and lymphovascular invasion were independent prognostic factors; however, no statistical significance was associated with the CEA group. Conclusion High pre-CRT, post-CRT, and post-surgery s-CEA levels in patients with rectal cancer were associated with high rates of systemic recurrence and poor survival. Therefore, patients with sustained high s-CEA levels during CRT require careful monitoring after surgery.