Endoscopic obstruction in rectal cancers: survival and recurrence patterns following curative surgery.

BACKGROUND: It is controversial whether preoperative obstruction in rectal cancers can affect prognosis or influence recurrence patterns. We investigated the association between endoscopic obstruction with survival and recurrence patterns in patients with locally advanced rectal cancers. MATERIALS AND METHODS: An observational study and multivariate analysis were conducted to identify determinants of survival and to compare recurrence patterns between patients with obstructive or nonobstructive tumors after curative resection. Endoscopic obstruction was defined as a luminal obstruction of the rectum severe enough to prevent the colonoscope from passing beyond the tumor. RESULTS: Cancer was obstructive in 91 patients (16.8%) and nonobstructive in 452 (83.2%). Median follow-up was 50 (range, 3-161) months. Local recurrence occurred in 17 patients (14 nonobstructed [5.4%] and 3obstructed [5.5%]; P=1.0) and systemic recurrence in 83 (62 nonobstructed [23.8%] and 21 obstructed [38.2%]; P=.042]). Endoscopic obstruction was a significant prognostic factor in stage III rectal cancers (P=.001) but not in stage II tumors. The multivariate analysis showed that endoscopic obstruction was an independent prognostic factor for overall survival, but not for disease-free survival, in patients with stage III rectal cancers. Endoscopic obstruction was associated with multiple-site systemic recurrence that was unsalvageable (salvageable surgery, 24 nonobstructed [40%] and 2 obstructed [10%]; P=.014). CONCLUSIONS: Endoscopic obstruction in patients with stage III rectal cancer predicted worse overall survival and was associated with multiple-site systemic recurrence.

Tumor volume reduction assessed by planning computed tomography in patients with rectal cancer during preoperative chemoradiation: impact of residual tumor volume on the prediction of pathologic tumor regression.

AIMS AND BACKGROUND: To determine whether the residual tumor volume measured using the Eclipse treatment planning system correlates with pathologic tumor regression grade after preoperative chemoradiotherpy for rectal cancer. MATERIALS AND METHODS: The study included 30 patients with rectal cancer who had undergone preoperative chemoradiotherpy followed by surgery from June 2008 to April 2011 at the Korea University Guro Hospital. The tumor volume was measured using the Eclipse treatment planning system in the initial simulation computed tomography and boost planning computed tomography. The correlation between the residual tumor volume in boost planning computed tomography and the pathologic tumor regression grade was analyzed. Tumor regression grade defined in the American Joint Committee on Cancer 7th edition was used. RESULTS: The mean and median residual tumor volume was 57.34% ± 20.37% and 52.35% (range, 18.42%-95.79%), respectively. After surgery, pathologic complete response (tumor regression grade 0) occurred in 4 patients (13.33%), moderate response (tumor regression grade 1) in 18 patients (60%), minimal response (tumor regression grade 2) in 4 patients (13.33%), and poor response (tumor regression grade 3) in 4 patients (13.33%). When residual tumor volume was categorized into two groups (<50% and ≥50%), complete or moderate regression (tumor regression grade 0 or 1) was significantly greater for patients with a residual tumor volume <50% ( P <0.05). The mean residual tumor volume of tumor regression grade 0 or 1 was 49.07% ± 18.39% and that of tumor regression grade 2 or 3 was 76.31% ± 16.94% (P <0.05). CONCLUSIONS: Residual tumor volume measured using routine boost planning computed tomography during preoperative chemoradiotherpy correlated significantly with pathologic tumor regression grade after surgery.

Reduced CDX2 expression predicts poor overall survival in patients with colorectal cancer.

The homeodomain transcription factor CDX2 directs development and maintenance of normal intestinal epithelium. However, the role of CDX2 in colorectal carcinogenesis is poorly understood. Hence, we investigated the CDX2 expression in patients with colorectal cancer and its relationship to tumor cell proliferation and differentiation and evaluated the role of this molecule as a biologic marker for the prediction of poor patient survival. We retrospectively reviewed 207 patients with colorectal cancer, with an available paraffin block, who underwent surgical resection between January 2002 and December 2004 at Korea University Guro Hospital. CDX2 expression was compared between tumor tissue and the adjacent normal mucosa using immunohistochemistry and Western blot analysis. Immunohistochemical staining for CDX2, Ki-67, and CK20 was performed in each tumor tissue. Immunohistochemistry revealed that CDX2 protein is overexpressed by colorectal cancer compared with adjacent normal mucosa (P < 0.001). In the Western blot analysis, tumor tissue showed a trend toward overexpression of CDX2 protein compared with normal mucosa (P = 0.09). CDX2 expression showed a significant direct correlation with the expression of Ki-67 and CK20 in tumor tissue (P = 0.028 and P = 0.042, respectively). Survival analysis showed that reduced CDX2 expression was statistically and significantly related to poor overall survival. Reduced CDX2 expression is associated with poor overall survival in patients with colorectal cancer and may be clinically useful as a marker for poor prognosis.

Expression of GLI1 correlates with expression of lymphangiogenesis proteins, vascular endothelial growth factor C and vascular endothelial growth factor receptor 3, in colorectal cancer.

Aberrant activation of the hedgehog (Hh) signaling pathway is associated with tumorigenesis in various tissues. In colorectal cancer (CRC), evidence for Hh activation is inconsistent, and the relationship between the Hh signaling pathway and lymphangiogenesis has not been studied. The aim of this study was to determine the relationship between Hh signaling and lymphangiogenesis and the association of this relationship with lymph node metastasis in CRC. We investigated 189 patients who underwent curative surgical resection for CRC between 2002 and 2004 at Korea University Guro Hospital. Paraffin-embedded specimens of colorectal adenocarcinoma and adjacent normal mucosa were evaluated. Immunohistochemical staining for Sonic hedgehog (Shh), Gli1, vascular endothelial growth factor C (VEGFC), and VEGF receptor 3 (VEGFR3) was performed for each specimen. Tumor specimen showed significantly strong staining of Shh, Gli1, VEGFC, and VEGFR3 compared with a normal specimen. Shh expression was not associated with Gli1 expression. Gli1 expression correlated positively with VEGFC and VEGFR3 expression (P < 0.05 in both) but not with lymph node metastasis. Activation of the Hh signaling pathway associated with Gli1 promotes expression of lymphangiogenesis proteins, VEGFC and VEGFR3, in CRC. Further studies are necessary to determine the association of this relationship with lymph node metastasis in CRC.

Pneumatosis intestinalis and laparoscopic exploration: beware of gas explosion.

Colonic gas explosion, although rare, is sometimes a fatal iatrogenic complication in endoscopic procedures or laparotomic surgery, but it has not been reported during port incision of laparoscopy. We report a case of gas detonation in a patient with pneumatosis intestinalis and pneumoperitoneum, on opening the peritoneum with a diathermy for umbilical trocar insertion. Based on our experience, in cases of pneumoperitoneum, surgeons need to avoid using a diathermy in opening the peritoneum.

Periappendiceal abscess mimicking appendiceal cancer.

Appendiceal cancer was strongly suspected in this case because of its unique colonoscopic, radiologic, and intraoperative presentation. Hence, laparoscopic enbloc right hemicolectomy and peritonectomy were performed. The diagnosis of periappendiceal abscess was confirmed later after the operation. Appendiceal disease is hard to differentiate because of the wide spectrum of differential diagnosis. So, when there is a strong suspicion of appendiceal cancer, laparoscopic right colectomy, which is minimally invasive and potentially curative can be the treatment of choice.

The efficacy of oral tegafur-uracil as maintenance therapy following intravenous 5-fluorouracil chemotherapy in stage III colon cancer.

BACKGROUND/AIMS: The aim of this study was to evaluate the impact on disease-free survival (DFS) of adding oral tegafur-uracil (UFT) to intravenous 5-fluorouracil (5-FU) as surgical adjuvant chemotherapy for stage II and III colon cancer. METHODOLOGY: The authors retrospectively analyzed 148 patients treated from 2000 through 2005 with pathologically confirmed stage II or III colon cancer. Forty seven patients were treated with 6 cycles of 5-FU+leucovorin (5-FU group) and the other 101 patients were treated with same above regimen followed by an additional 12 cycles of UFT+leucovorin (LV) for 28 days with a 7-day rest period (5-FU+UFT group). RESULTS: The median follow-up time was 64.9 months (range 15.3-95.2 months) and mean age was 58.8±10.8. The clinical characteristics of the 5-FU+UFT and 5-FU groups were similar. Furthermore, for all study subjects and stage II patients, 3-year DFS rates were not significantly different between two groups. However, for stage III patients, 3-year DFS rates were 80.0% and 60.7% in the 5-FU+UFT and 5-FU groups, respectively (HR=0.32; p=0.01; 95% CI=0.13-0.76). CONCLUSIONS: The addition of UFT to 5-FU was found that significantly improve DFS in patients with stage III colon cancer. The authors cautiously suggest UFT as a maintenance therapy following 5-FU chemotherapy could be another option in stage III colon cancer patients.

Prognostic impact of fascin-1 expression is more significant in advanced colorectal cancer.

BACKGROUND: Fascin-1 is not expressed in normal colorectal epithelium, but is up-regulated in colorectal cancer. However, its exact biological mechanism remains unknown. The purpose of this study was to investigate the relationship of fascin-1 expression with the clinicopathologic parameters and its prognostic impact in advanced colorectal cancer. MATERIALS AND METHODS: The immunohistochemical stainings for fascin-1, ß-catenin, and Ki-67 labeling index were performed with 126 stage III colorectal cancer specimens. RESULTS: Fascin-1 was found to be expressed in 74 (58.7%) of the 126 colorectal cancer specimens. Five-year survival rate was significantly low, whereas the distant recurrence rate was significantly high in patients with fascin-positive stage III colorectal cancer. There was no significant correlation between fascin-1 expression and clinicopathologic factors such as tumor size, nodal metastasis, pathologic stage, ß-catenin expression, and Ki-67 labeling index. However, fascin-1 expression was an independent prognostic factor in multivariate analysis. Patients with N1 showed no significant difference in 5-y DFS and OS according to the fascin-1 expression (79.0% versus 60.5%, P = 0.113; 86.5% versus 78.8%, P = 0.566). Patients with N2 showed marginal difference in 5-y DFS and significant difference in 5-y OS according to the fascin-1 expression (59.4% versus 32.4%, P = 0.088; 81.2% versus 39.5%, P = 0.002). CONCLUSIONS: This study suggests that fascin-1 expression in colorectal cancer may be clinically useful in predicting distant metastasis and poor survival, and we demonstrated that fascin-1 expression and N stage are significant independent prognostic factors for survival of colorectal cancer patients.

Comparison between laparoscopy and noninvasive tests for the diagnosis of tuberculous peritonitis.

BACKGROUND: Despite recent progress, the fast and accurate diagnosis of tuberculous peritonitis (TBP) continues to be a challenge, mainly because of the lack of specific clinical features and the difficulty in isolating the M. tuberculosis. The present study aimed to investigate the role of laparoscopy in the diagnosis of TBP, compared to noninvasive tests. METHODS: We retrospectively studied 60 patients who had diagnostic laparoscopy for suspected TBP between January 2002 and June 2010. RESULTS: Forty-one patients were diagnosed with TBP. In terms of accuracy and predictive value, the visual diagnosis via laparoscope was the most diagnostic test. In the noninvasive tests, both the ascitic adenosine deaminase (ADA) level over 30 U/l, and the ascitic lactate dehydrogenase (LDH) level over 90 U/l had relatively high positive, as well as negative, predictive values. The overall morbidity and mortality rates for laparoscopy were 5 and 5%, respectively. CONCLUSIONS: Laparoscopy is a rapid and accurate diagnostic test for TBP. However, complications may occur. In older patients with associated conditions, a combination of various noninvasive tests and empirical treatments is needed prior to laparoscopy.

Rectal diverticular perforation complicating diagnostic colonoscopy: a case report and review of the literature.

Abstract The presence of retroperitoneal, mediastinal, and subcutaneous emphysema due to rectal diverticular perforation during diagnostic colonoscopy has not been reported. Further, the management of colonoscopic perforation remains a controversial issue. In this case report, the authors discuss the importance of recognizing this rare complication after colonoscopy and its response to conservative treatment.

Lymph node ratio as determined by the 7th edition of the American Joint Committee on Cancer staging system predicts survival in stage III colon cancer.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the prognostic usefulness of the lymph node ratio (LNR) in stage III colon cancer using the 7th edition of the American Joint Committee on Cancer (AJCC) staging system. METHOD: We analyzed data from 130 consecutive patients with stage III colon cancer. Kaplan-Meier and Cox proportional hazard model analyses were used to evaluate prognostic effects. RESULTS: Quartile analysis indicated that an LNR of 0.1638 was the best cut-off value with regard to predicting disease-free survival (DFS). Six patients had stage IIIA disease, 102 patients had stage IIIB disease, and 22 patients had stage IIIC disease. For patients with stage IIIB disease, the 3-year DFS for an LNR of <0.1638 (N = 87) and an LNR of ≥0.1638 (N = 15) was 79.0% and 50.0%, respectively (P = 0.015). For patients with stage IIIC disease, the 3-year DFS for an LNR of <0.1638 (N = 6) and an LNR of ≥0.1638 (N = 16) was 100% and 28.6%, respectively (P = 0.03). CONCLUSIONS: The authors found that 7th AJCC stage IIIB and stage IIIC patients are heterogeneous groups with respect to DFS, when stratified by LNR, and suggest that an LNR-based algorithm be devised for incorporation into the 7th AJCC staging system.

The role of laparoscopic approach for anastomotic leakage after minimally invasive surgery for colorectal cancer.

OBJECTIVES: The objectives of this study were to evaluate the feasibility and safety of a re-laparoscopic approach to manage anastomotic leakage after minimally invasive colorectal resection and to compare its clinical outcomes with those obtained using an open approach. METHODS: We retrospectively reviewed clinical data from 1714 patients who underwent colorectal cancer resection from September 2006 to August 2009 at the Korea University Medical Center. Clinical data from a total of 57 surgery patients who developed anastomotic leakage were analyzed. RESULTS: Twenty-six leakage cases were managed laparoscopically, whereas the remaining 31 leakage cases were managed using an open approach. There were no significant differences in age, sex, or other clinical features between patients in the two groups. The total operation time was shorter in the laparoscopic group (107.3 ± 68.1 minutes) than in the open group (126.5 ± 50.1 minutes), but this difference was not statistically significant (P = .230). Six cases in each group required additional procedures such as reoperation or percutaneous intervention (P = .126). There was one case of postoperative mortality in the open group. Median (quartiles 25%-75%) number of days required to resume a soft diet tended to be shorter in the laparoscopic group than the open group (5 [3-7] versus 6 [5-10] days; P = .057). Patients in both groups showed similar postoperative complications including intraabdominal abscess; however, the incidence of wound infection was significantly lower in the laparoscopic group than the open group (3.8% versus 25.8%; P = .031). CONCLUSIONS: Compared with conventional open treatment of anastomotic leakage, the laparoscopic approach resulted in fewer wound complications and tendency of early recovery of bowel movement without an increase in adverse outcomes. Using a laparoscopic approach, all the advantages of minimally invasive surgery can be realized in patients who develop anastomotic leakage after minimally invasive surgery.

Significance of Follow-up in Detection of Pulmonary Metastasis of Colorectal Cancer.

PURPOSE: This study was performed to evaluate the effectiveness of conventional chest radiography, carcinoembrionic antigen (CEA) level and abdominal computed tomography (CT) or chest CT for early detection of pulmonary metastasis after a curative resection of colorectal cancer. METHODS: We retrospectively reviewed 84 cases of pulmonary metastasis from a group of colorectal cancer patients who had a curative surgical resection from 2000 to 2006 at the Korea University Medical Center. RESULTS: Stage I tumors were detected in 4 patients, stage II tumors in 18, stage III tumors in 43 and stage IV tumors in 19. The detection rates for pulmonary metastasis were 28.5% by conventional chest radiography, 40.5% by increased CEA level and 28.5% by abdominal CT or chest CT. Among them, fourteen patients underwent a radical pneumonectomy. After detection of pulmonary metastasis, the survival outcome for the patients who underwent a resection of the lung was superior to the survival outcome of the patients who did not undergo a resection of the lung (43.7 months vs. 17.4 months, P = 0.001). For patients who underwent resections of the lung, pulmonary metastasis was detected by conventional chest radiography in 2 (14%) patients, by elevated CEA level in 6 (42%) patients, and by abdominal CT or chest CT in 6 (42%) patients. CONCLUSION: Conventional chest radiography is no more useful in detecting early pulmonary metastasis after a curative colorectal surgery than a routine chest CT. Thus, we propose the use of routine chest CT for screening for lung metastasis.

Expression of protein S100A4 is a predictor of recurrence in colorectal cancer.

AIM: To investigate the prognostic significance of S100A4 expression in colorectal cancer and its correlation with expression of E-cadherin and p53. METHODS: A cohort of archival formalin-fixed paraffin-embedded specimens was selected from 127 patients with colorectal cancer who underwent surgical resection between April 2000 and March 2004 at the Department of Surgery, Korea University Guro Hospital. The expression of protein S100A4 was evaluated according to the proportion of positively stained cancer cells. In each case, three core biopsies with a diameter of 2 mm were punched out and positioned in a recipient paraffin array block. Four-microm sections of these tissue array blocks were used for immunohistochemical analysis of protein S100A4, E-cadherin, and p53. Clinicopathological data were based on the original histopathologic reports and clinical records of patients. RESULTS: In normal colorectal mucosa, protein S100A4 immunoreactivity was clearly absent in both cytoplasm and nucleus. However, positive immunoreactivity of protein S100A4 was detected in 45 (35.4%) of the tumor cases. There was no significant association between positive immunoreactivity of protein S100A4 and clinicopathological parameters such as tumor differentiation or TNM stage, and also no correlation between the reactivity and E-cadherin or p53 expression. However, positive immunoreactivity of protein S100A4 was found to be associated with tumor recurrence (P = 0.004), and was also associated with significantly worse overall survival in the Kaplan-Meyer survival analysis (P = 0.044). After adjustment for tumor differentiation, tumor depth and nodal status, however, it failed to achieve statistical significance (P = 0.067). CONCLUSION: The expression of protein S100A4 is associated with tumor recurrence and poor overall survival in patients with colorectal cancer.

Relationship between meat and cereal consumption and colorectal cancer in Korea and Japan.

BACKGROUND AND AIM: The incidence of colorectal cancer in Asian countries is increasing. The change to a more westernized diet is known to be related to these increases, and there are reports on the relationship between meat consumption and colorectal cancer in Japan. The aim of this study was to investigate the relationship between dietary change and colorectal cancer in Korea and Japan. METHODS: The data of meat and cereal consumption in Japan (1950-2002) and Korea (1970-2003), and the data of colorectal cancer incidence in Japan (1975-1998) and Korea (1992-2002) were investigated with a 20-year difference between the two countries. RESULT: We found that the changes in meat and cereal consumption, as well as the increases in the incidence of colon and rectal cancer, were similar between those two countries with a 20-year difference. CONCLUSION: These similarities between Korea and Japan could be helpful for predicting future colorectal cancer incidences for Korea and other Asian countries.

The prognostic significance of E-cadherin and liver intestine-cadherin expression in colorectal cancer.

PURPOSE: The significance of liver intestine-cadherin as a potential marker has been growing in the field of oncology, because of its unique features compared with classic cadherins. We investigated the coexpression patterns of E-cadherin and liver intestine-cadherin in colorectal cancer, and determined whether differences in expression patterns were associated with clinicopathologic parameters and also which relationship between these two adhesion molecules existed in colorectal cancer. METHODS: Expression pattern of E-cadherin and liver intestine-cadherin was investigated immunohistochemically in 207 colorectal cancers along with clinicopathologic parameters. RESULTS: Reduced expression of liver intestine-cadherin was detected in 51 percent (n = 105) of tumors. Such expression was found to be associated with tumoral dedifferentiation (P = 0.015) and in a multivariate analysis was associated with a significant worse overall survival after adjustment for tumor stage, differentiation, and E-cadherin status (hazard ratio, 1.951; 95 percent confidence interval, 1.06-3.592; P = 0.032). Fifteen percent (n = 32) of tumors showed reduced expression of E-cadherin and had relationship with tumoral dedifferentiation (P < 0.001), lymph node metastasis (P = 0.004), and advanced stage (P = 0.029). Reduced expression of E-cadherin was associated with short overall survival (P = 0.028); however, in a multivariate analysis, it was not statistically significant. CONCLUSIONS: Reduced expression of liver intestine-cadherin had a significant correlation with tumoral dedifferentiation and short overall survival in this series. In addition, early and frequent loss of liver intestine-cadherin expression might be a more sensitive indicator than E-cadherin to predict more aggressive tumoral behavior.

Role of regular follow-up after curative surgery for colorectal cancer.

BACKGROUND/AIMS: This investigation aimed to estimate the value of regular follow-up programs after curative resection for colorectal cancer. METHODOLOGY: We compared the recurrence rate, rate of curative re-resection, and survival rate between groups who had either regular or irregular follow-up. The medical records of 397 consecutive patients, who underwent a curative resection for colorectal cancer between January 1994 and December 1997, were analyzed retrospectively. RESULTS: The recurrence rate was 19.4% and 20.8% in the regular and irregular follow-up groups (P > 0.05), respectively. There was a significant difference in the asymptomatic recurrence rate (62.9 vs. 18.7%; P = 0.021), but curative re-resection was possible in 18 (29.0%) of those patients with cancer recurrence in the regular follow-up group, and in 2 (12.5%) in the irregular follow-up group, which was not significantly different (P > 0.05). 5-year survival rate between the groups was not significantly different (78.1 vs. 61.2%; P > 0.05). CONCLUSIONS: A regular follow-up program after a curative resection for colorectal cancer, although facilitating detection of recurrence before symptoms developed, was unlikely to succeed in increasing the rate of a curative intent re-resection and survival remarkably.

L1 expression as a marker for poor prognosis, tumor progression, and short survival in patients with colorectal cancer.

BACKGROUND: L1, a new target gene for Wnt/beta-catenin-TCF signaling, has been identified in the invasive front of colorectal cancer cells in vitro study. The L1 molecule is localized on the cell surface in tumor tissues, accompanied with loss of beta-catenin and E-cadherin. However, such association between L1 expression and prognosis of colorectal cancer has not yet been investigated in clinical study. We investigated the expression of L1, E-cadherin, and beta-catenin in tumor cells to determine correlations between the clinicopathologic characteristics and the expression of these molecules and to evaluate the efficacy of the use of these molecules as prognostic markers for patient survival. METHODS: We investigated 138 patients who received diagnoses of colorectal cancer and who underwent surgery between January 1995 and December 2000 at the Korea University Hospital. Tissues were obtained from paraffin-embedded blocks of the tumors and studied by tissue microarray analysis. Immunohistochemical staining for L1, beta-catenin, and E-cadherin was performed for each specimen. RESULTS: L1 expression was found to be correlated with advanced cancer stage (P = .001), distant metastasis (P < .001), and tumor recurrence (P = .006). Survival analysis showed that reduced expression of beta-catenin and E-cadherin, and expression of L1 were statistically significantly related to poor survival. Multivariate analysis revealed that L1 expression was an independent prognostic factor for patient survival. CONCLUSIONS: L1 expression is associated with tumor progression and poor survival in patients with colorectal cancer and may be clinically useful as a marker for poor prognosis.

Mesenteric Castleman's disease.

We report here a rare case of mesenteric Castleman's disease presenting as a mesenteric mass. A 13-year-old female child was admitted to our hospital complaining of intermittent vague abdominal pain. She had hypochromic anemia, thrombocytosis and an elevated erythrocyte sedimentation rate (ESR). Ultrasonography and computed tomography indicated an intra- abdominal mass might represent a lymphoma or gastrointestinal stromal tumor or leiomyoma, but the definitive preoperative diagnosis couldn't be confirmed. The surgical resection of the mass revealed the mesenteric hyaline vascular-type Castleman's disease.