[A Case of Advanced Esophagogastric Junction Adenocarcinoma with Enlarged Lymph Node Metastases of the Middle Mediastinum and Intraperitoneal That Exhibited pCR by Preoperative SOX Therapy].

A 79-year-old man was diagnosed with esophagogastric junction adenocarcinoma, cT3N3M0, cStage Ⅲ, including enlarged lymph node metastases(Bulky N)in the middle mediastinum and intraperitoneal. A total of 2 cycles of S-1 plus oxaliplatin(SOX)was administered. After neoadjuvant chemotherapy, the primary tumor and enlarged lymph nodes had greatly decreased in size. Subsequently, thoracoscopic subtotal esophagectomy and reconstruction with a gastric tube were performed. Histopathological examinations showed no residual cancer cells in the primary lesion and dissected lymph nodes (pathological complete response). Preoperative chemotherapy containing SOX could be a useful treatment strategy for patients with esophagogastric junction adenocarcinoma with enlarged lymph node metastasis.

Right axillary lymph node metastasis of carcinoma of the cecum with histologically proven cutaneous lymphatic invasion by carcinoma cells: a case report.

Axillary lymph node metastasis from colorectal carcinoma is extremely rare, and this scarcity hinders understanding of its pathogenesis and, thus, the application of appropriate management. Here, we present a case with axillary lymph node metastasis of cecal carcinoma associated with macroscopic invasion of the skin of the abdominal wall with histological evidence of such invasion, findings which support our hypothesis that the axillary lymph node metastasis developed via the lymph channels in the skin of the abdominal wall. A 76-year-old woman with cecal carcinoma (T4N1M0), complicated with an abdominal wall abscess, underwent right hemicolectomy with partial resection of the abdominal wall. Histology demonstrated multiple sites of lymphatic invasion in the skin. Two months later, an enlarged right axillary lymph node was noticed on CT, and an excisional biopsy was obtained, which later confirmed metastatic adenocarcinoma. This is the first case report of axillary lymph node metastasis of carcinoma of the cecum with histologically proven invasion via the lymphatic system in the skin. If axillary lymph node metastasis results from aberrant lymphatics due to invasion from an adjacent organ, and not the result of systemic malignant disease, it may be considered as a surgically curable pathology. Therefore, the authors advocate that patients with axillary lymph node metastasis should be evaluated with regard to the possibility of surgical curability.

Success rate of informed consent acquisition and factors influencing participation in a multicenter randomized controlled trial of laparoscopic versus open surgery for stage II/III colon cancer in Japan (JCOG0404).

INTRODUCTION: Successful completion of randomized controlled trials (RCT) is dependent on informed consent (IC) acquisition from patients. The aim of this study was to prospectively calculate the proportion of participation in a surgical RCT and to identify the reasons for failed IC acquisition. METHODS: A 30-institute RCT was conducted to evaluate oncological outcomes of open and laparoscopic surgery for stage II/III colon cancer (JCOG0404: UMIN-CTR C000000105). The success rate of obtaining IC, which was supported by a DVD that helped patients understand this trial, was evaluated in eight periods between October 2004 and March 2009. In addition, reasons for failed IC acquisition were identified from questionnaires. RESULTS: A total of 1767 patients were informed of their eligibility for the trial, and 1057 (60%) were randomly assigned to either the laparoscopic surgery (n = 529) or open surgery (n = 528) group. The success rate of IC acquisition ranged from 50% to 62% in eight periods. The most common reasons for failed IC acquisition were anxiety/unhappiness about the randomization, patients' preference for one form of surgery, and strong recommendations from referring doctors or relatives. CONCLUSIONS: With the assistance of a DVD, high success rates of IC acquisition were obtained for an RCT of laparoscopic versus open surgery for stage II/III colon cancers. To obtain such a rate, investigators should make efforts to inform patients, their relatives, and referring doctors about the medical contributions a surgical RCT can make.

Multiple primary malignancies involving primary sporadic colorectal cancer in Japan: incidence of gastric cancer with colorectal cancer patients may be higher than previously recognized.

BACKGROUND: Improvement in the prognosis of colorectal cancer (CRC) patients has led to increasing occurrences of multiple primary malignancies (MPMs) alongside CRC but little is known about their characteristics. This study was undertaken to clarify the clinical and pathological features of MPMs, especially those at extra colonic sites, in patients with CRC. METHODS: We reviewed 1,111 patients who underwent operations for primary sporadic CRC in Saitama Medical Center, Jichi Medical University between April 2007 and March 2012. Two patients with familial adenomatous polyposis, one with hereditary non-polyposis colorectal cancer, two with colitic cancer, and any patients with metastasis from CRC were excluded. We compared the clinicopathological features of CRC patients with and without MPMs. As a control, we used a database compiled of patients with gastric cancer (GC) detected by mass screening performed in the Saitama Prefecture in Japan 2010 and compared these with CRC patients with synchronous GC. RESULTS: Multiple primary malignancies at extracolonic sites were identified in 117 of 1,111 CRC patients (10.5%). The median age was 68 (range, 29 to 96) versus 71 (50 to 92) (P < 0.001). The incidence of GC (44.4% (52 of 117)) was the highest of all MPMs. All CRC patients with GC were older than 57 years. Synchronous GC was detected in 26 patients. By contrast, out of 200,007 screened people, 225 people were diagnosed as having GC in the Saitama Prefecture. The age-standardized incidence of synchronous GC in CRC patients was significantly higher (0.53%) than in the control group (0.03%) (odds ratio, 18.8; 95% confidence interval, 18.6 to 19.0; P < 0.001). CONCLUSION: Patients with CRC who were older than 50 years preferentially developed GC synchronously and metachronously. Thus, this patient group should undergo careful perioperative screening for GC.

XELIRI regimen plus continuous treatment with bevacizumab is well-tolerated and effective in metastatic colorectal cancer patients in a second-line setting involving the sequential administration of XELOX and XELIRI.

The aim of the present study was to present a retrospective review of 42 metastatic colorectal cancer (mCRC) patients treated using the XELIRI regimen as second-line chemotherapy during the period between 2010 and 2012. Patients were treated with capecitabine, 1,600 (≥65 years) or 2,000 mg/m2 (<65 years), on days 1-15, 200 mg/m2 irinotecan (CPT-11) on day 1, with or without 7.5 mg/kg bevacizumab on day 1 and every 21 days. A total of 21 patients underwent XELIRI and 21 underwent XELIRI plus bevacizumab treatment. Fifteen patients received continuous administration of bevacizumab in the first- and second-line settings [bevacizumab beyond progression (BBP)+], whereas 27 patients did not receive the treatment (BBP-). Forty patients (95.2%), including all the patients in the BBP+ group, received sequentially administered XELOX and XELIRI regimens from the first- to the second-line setting. The disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and adverse events were compared between the BBP- and BBP+ groups. The median relative dose intensity was similar (93.9% for capecitabine and 96.3% for CPT-11 in the BBP- group vs. 94.8% for capecitabine and 91.5% for CPT-11 in the BBP+ group). The DCR was 25.9% in the BBP- and 66.6% in the BBP+ groups (P=0.020). The median PFS was 3.5 months in the BBP- and 7.2 months in the BBP+ groups (P=0.028). The BBP+ group exhibited a higher median OS time compared to the BBP- group (12.5 months in the BBP- group vs. not reached in the BBP+ group; P=0.0267). The most common grade 3/4 adverse event (n≥20) was hypertension observed in the BBP+ group [three patients (20%)]: these three patients were well-controlled with a single antihypertensive drug. Treatment with sequentially administered XELOX and XELIRI regimens did not aggravate adverse events in the 40 patients. The results showed that the XELIRI regimen, involving continuous treatment with bevacizumab, was well-tolerated and effective as a second-line chemotherapy and sequentially administering XELOX and XELIRI was feasible and manageable for patients with mCRC.

Laparoscopic colectomy for obstructive colorectal carcinoma.

Laparoscopic surgery for obstructive colorectal carcinoma is a controversial issue. Defining the obstructive carcinoma as colonoscopic impassability, the patients with obstructive carcinoma were managed according to the treatment algorithm, by which the indication of open or laparoscopic surgery was determined. As a result, 31 patients with obstructive colorectal carcinoma underwent laparoscopic surgery. The location of the tumor was in the right side in 10 patients and in the left in 21 patients. Preoperatively, all cases were managed by restriction of oral intake and/or decompression. Laparoscopic surgery was completed in 26 cases and colonic obstruction was the direct cause of the conversion in only 1 case. Regarding postoperative complications, there were 3 surgical site infections and 3 instances of postoperative prolonged ileus but no mortality. Oncologically, the primary tumor was completely resected in each case and lymph node harvest (26.6) was adequate.

Oncological 3-port laparoscopic colectomy by 1 surgeon and 1 camera operator: a preliminary report.

This retrospective study analyzed the short-term outcomes of oncological reduced-port laparoscopic colectomy (RPLC) using 3 ports performed by 1 surgeon and 1 camera operator. Patients who underwent laparoscopic colectomy for colorectal carcinoma in 2010 and 2011 were divided into 2 groups: the CLC group, which included 62 patients who underwent a conventional laparoscopic colectomy and the RPLC group, which included 28 patients who underwent reduced-port laparoscopic colectomy, respectively. There were no significant differences between the groups with regard to TNM stage, estimated blood loss, complications, conversion rate, pain score, the length of postoperative stay, or the number of harvested lymph nodes. However, the prevalence of right-side colectomy was higher and the operative time was significantly shorter in the RPLC group. RPLC was technically feasible, providing that the appropriate patients were selected. Therefore, even though its surgical benefit might be subtle, we believe that RPLC definitively contributes to the reduction of equipment and manpower costs and will be considered as a standard procedure in the near future.

Acute fulminant pseudomembranous colitis which developed after ileostomy closure and required emergent total colectomy: a case report.

INTRODUCTION: Pseudomembranous colitis is known to be caused by Clostridium difficile; and, in 3% to 8% of patients, it lapses into an aggressive clinical course that is described as fulminant. We present here a case of extremely rapid and fatal fulminant pseudomembranous colitis that developed after ileostomy closure, a minor surgical procedure. To the best of our knowledge, this is the first case report of fatal fulminant pseudomembranous colitis after closure of a diversion ileostomy in an adult. CASE PRESENTATION: A 69-year-old Japanese man, who had previously undergone low anterior resection and creation of a diverting ileostomy for stage III rectal carcinoma was admitted for ileostomy closure. Preoperatively, he received oral kanamycin and metronidazole along with parenteral cefmetazole. His surgery and postoperative course were uneventful until the third postoperative day, when fever and watery diarrhea became apparent. The next day he presented with epigastric and left lower abdominal pain. Computed tomography revealed a slightly distended colon. Later that night, his blood pressure fell and intravenous infusion was started. In the early morning of the fifth postoperative day, his blood pressure could be maintained only with a vasopressor. Follow-up computed tomography demonstrated severe colonic dilation. A colonoscopy confirmed the presence of pseudomembranous colitis, and so oral vancomycin was administered immediately. However, within three hours of the administration, his condition rapidly deteriorated into shock. Although an emergent total colectomy with creation of an end ileostomy was performed, our patient died 26 hours after the surgery. The histopathological examination was consistent with pseudomembranous colitis. CONCLUSION: It is important to recognize that, although rare, there is a type of extremely aggressive pseudomembranous colitis in which the usual waiting period for medical treatment might be lethal. We consider that colonoscopy and computed tomography are helpful to decide the necessity of emergent surgical treatment without delay.

Right colectomy with simultaneous vascular reconstruction for celiac and superior mesenteric arterial occlusion.

INTRODUCTION: Identification of the primary feeding vessel and its removal with corresponding lymphatics is crucial for oncologic bowel resection for colon cancer. However, this notion would be challenged if we encountered abnormal mesenteric vascular anatomy. We report a case of colon cancer with abnormal mesenteric circulation, for whom we performed oncologic colectomy with vascular reconstruction. PRESENTATION OF CASE: A 61-year-old man presented with obstructing transverse colon cancer. A contrast-enhanced computed tomography (CT) scan showed complete occlusion at the root of the superior mesenteric artery (SMA) and the celiac artery (CA), with evidently dilated marginal artery (MA). An X-ray angiography revealed retrograde arterial blood flow originating from the inferior mesenteric artery (IMA) via the MA, the SMA, and to the CA. At laparotomy, we found remarkably dilated MA with the mid-transverse colon cancer. There were no other communicating vessels between the IMA and the SMA. Right colectomy with proper lymph node dissection was completed, following vascular anastomosis between the MA to the SMA. His postoperative course was uneventful. A postoperative CT angiography showed revascularization of the areas where the SMA and the CA supplied. DISCUSSION: In this patient, if the abberant mesenteric circulation remained unrecognized at the time of surgery, and the MA were divided without vascular reconstruction, severe ischemia and subsequent gangrene of large part of the visceral organs would have occurred. CONCLUSION: This case illustrates the fundamental importance of assessment for vascular anatomy in patients undergoing oncologic abdominal surgery which associates with division of major mesenteric arteries.

Assessment for frailty is useful for predicting morbidity in elderly patients undergoing colorectal cancer resection whose comorbidities are already optimized.

BACKGROUND: The clinical syndrome of frailty identified through the assessment of weight loss, gait speed, grip strength, physical activity, and physical exhaustion has been used to identify patients with reduced reserves. We hypothesized that frailty is useful in predicting adverse outcomes in optimized elective elderly colorectal surgery patients. METHODS: A prospective study was conducted at 2 centers (Singapore and Japan). All patients over 75 years of age undergoing colorectal resection were assessed for the presence of the syndrome of frailty. All these patients had already had their comorbidities optimized for surgery. The outcome measure was postoperative major complications (defined as Clavien-Dindo type II and above complications). RESULTS: Eighty-three patients were studied from February 2008 to April 2010. The mean age was 81.5 years (range 75-93 years). The mean comorbidity index was 3.37 (range 0-11). Twenty-six (31.3%) patients were an American Society of Anesthesiologists (ASA) score of 3 and above. Chi-square analysis revealed that the odds ratio of postoperative major complications was 4.083 (95% confidence interval, 1.433-11.638) when the patient satisfied the criteria for frailty. Albumin <35, ASA >3, comorbidity index >5, and Physiologic and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) scores were not predictive of postoperative major complications. CONCLUSIONS: Preliminary findings show that frailty is a potent adjunctive tool of predicting postoperative morbidity. Frailty can be used to identify elderly patients needing further optimization before major surgery.

Interleukin-13 damages intestinal mucosa via TWEAK and Fn14 in mice-a pathway associated with ulcerative colitis.

BACKGROUND & AIMS: TWEAK, a member of the tumor necrosis factor (TNF) superfamily, promotes intestinal epithelial cell injury and signals through the receptor Fn14 following irradiation-induced tissue damage and during development of colitis in mice. Interleukin (IL)-13, an effector of tissue damage in similar models, has been associated with the pathogenesis of ulcerative colitis (UC). We investigated interactions between TWEAK and IL-13 following mucosal damage in mice. METHODS: We compared patterns of gene expression in intestinal tissues from wild-type and TWEAK knockout mice following γ-irradiation. Intestinal explants from these mice were used to detect cell damage induced by IL-13 and TNF-α. Levels of messenger RNA for IL-13, TWEAK, and Fn14 were measured in mucosal samples from patients with UC. RESULTS: Based on gene expression analysis, TWEAK mediates γ-irradiation-induced epithelial cell cycle arrest and apoptosis. However, TWEAK alone did not induce damage or apoptosis of primary intestinal epithelial cells. On the other hand, exogenous IL-13 activated caspase-3 in naïve intestinal explants; this process required TWEAK, Fn14, and secretion of endogenous TNF-α which was mediated by ADAM17. Conversely, activation of caspase by exogenous TNF-α required IL-13, TWEAK, and Fn14. In mucosa from patients with UC, messenger RNA levels of IL-13, TWEAK, and Fn14 increased with level of disease severity. CONCLUSIONS: IL-13-induced damage of intestinal epithelial cells requires TWEAK, its receptor (Fn14), and TNF-α. IL-13, TNF-α, TWEAK, and Fn14 could perpetuate and aggravate intestinal inflammation in patients with UC.

Laparoscopic colorectal surgery in elderly patients: a case-control study of 15 years of experience.

INTRODUCTION: The aim of this study was to review the impact of age (≥75 years) on the short-term outcomes of laparoscopic colorectal surgery. METHODS: Three hundred seventy-nine patients under 70 years of age and 91 patients 75 years and older were analyzed. Quantification of comorbidities was performed using the Charlson Weighted Comorbidity Index. Outcome measures were postoperative complications and 30-day mortality. RESULTS: There was no difference in the occurrence of postoperative complications between the younger and older patients. Bivariate analysis revealed that patient age was not a risk factor of major complications (odds ratio = 1.2; 95% confidence interval, .6-2.3). Although bivariate analysis revealed that older age had a statistically significant odds ratio for 30-day mortality (odds ratio = 12.8; 95% confidence interval, 1.3-125.4), multivariate analysis revealed that it was a weighted comorbidity index score of 5 or more (P = .02) and long operative time (P = .01) that were independent predictors of 30-day mortality and not age per se. CONCLUSIONS: Age is not an independent predictor of morbidity and mortality in laparoscopic colorectal cancer surgery.

First alert for recurrence during follow-up after potentially curative resection for colorectal carcinoma: CA 19-9 should be included in surveillance programs.

BACKGROUND: The aim of this study was to evaluate the contribution of each examination included in the postoperative surveillance program, especially that of serum tumor markers. PATIENTS AND METHODS: Patients who underwent curative surgery for colorectal carcinoma (CRC) from January 2000 to December 2006 were enrolled. The postoperative surveillance program in our department includes tumor marker (carcinoembryonic antigen [CEA] and carbohydrate antigen [CA] 19-9) measurement every 3 months for 5 years, chest radiograph or chest computed tomography (CT) every 3 months for 2 years and then every 6 months until 5 years, and abdominal CT every 3 months for 2 years and then every 6 months until 5 years. The first examination that revealed abnormality in patients who developed recurrence was analyzed. RESULTS: During the study period, 105 recurrences were diagnosed. There were 45 hepatic recurrences, 23 local recurrences, 20 pulmonary recurrences, 16 lymph node recurrences, and 10 peritoneal recurrences. Computed tomography, CEA, and CA 19-9 were the first abnormal examination(s) in 77, 23, and 26 patients, respectively. Tumor markers detected the recurrence earlier than did CT in 27% of patients. CEA and CA 19-9 equally contributed to detection with respect to the number of patients, while the sites of detected recurrences differed. CONCLUSION: For early detection of occult recurrence of CRC, CT was the most reliable modality. On the other hand, tumor markers were also relevant. Given the recent advances in multimodal approaches for advanced CRC, the combination of CT, CEA, and CA 19-9, which is currently not included in guidelines, should be routinely performed.

Patient's appetite is a good indicator for postoperative feeding: a proposal for individualized postoperative feeding after surgery for colon cancer.

BACKGROUND: In modern postoperative management, early and enforced feeding has been implemented. The aim of this study is to determine the feasibility of individualized feeding according to the patient's appetite. METHODS: Patients who underwent elective surgery for colon cancer from January 2007 to December 2008 were studied. Liquid intake was allowed on the day of operation and solid normal meal (1800 Kcal) was served according to the recovery of appetite. RESULTS: Two hundred and nine patients were included. Open and laparoscopic surgeries were performed in 104 and 105 patients, respectively. Solid meal was started by the second postoperative day in 81.3% of patients. Intravenous drip infusion was completed within 1 day of the start of the solid meal in 86.6% of the patients and 182 out of 209 patients (87.1%) did not require drip infusion by the third postoperative day. There were no mortalities and readmission rate was 1.0% (2/209). CONCLUSION: The introduction of feeding according to the recovery of appetite was safe and feasible with no delay in establishing oral intake.

Diagnostic accuracy of CT colonography and optical colonoscopy evaluated using surgically resected specimens.

OBJECTIVE: The aim of this study was to clarify the diagnostic ability of CT colonography (CTC) using surgically resected specimens to avoid inaccuracy associated with optical colonoscopy (OC). SUBJECTS AND METHODS: CTC and OC were performed in 152 consecutive patients with colorectal cancer. Forty patients had simultaneous lesions other than the ones for which the surgery was intended, and these lesions were used as the gold standard. In 24 patients without stenosis, the sensitivity and positive predictive values (PPV) of CTC and OC were evaluated. In 16 patients with stenosis, the diagnostic ability of CTC for lesions located proximal to the stenosis was assessed. RESULTS: Sensitivity of CTC and OC was 81% and 66% (P = 0.16), and PPV was 90% and 100% (P = 0.13), respectively. For 22 lesions larger than 5 mm, the sensitivity of CTC and OCS was 96% and 91% (P > 0.50), and PPV was 100% and 100%, respectively. In patients with stenosis, sensitivity and PPV were 89% and 80%, respectively. These results were not significantly different from those in patients without stenosis. CONCLUSIONS: CTC is a reliable modality for the diagnosis of colorectal polyps. It is also useful to evaluate the colon proximal to severe stenosis which could not be observed by OC.

Trainee surgeons do not cause more conversions in laparoscopic colorectal surgery if they are well supervised.

INTRODUCTION: This study was designed to look at the conversion rates and morbidity associated with laparoscopic operations performed by trainee surgeons ascending the learning curve when they are well supervised by staff surgeons. METHODS: A review of 204 consecutive cases was performed. We defined experienced staff surgeons as those who have performed more than 300 laparoscopic resection cases. The trainee surgeons had less than 50 cases of experience during the study period. All operations were performed by the experienced staff surgeon or by the trainee surgeon with the staff surgeon as the first assistant and supervisor. RESULTS: A total of 204 laparoscopic resections for colorectal cancer were studied. The dissection was D3 in 73% (n = 149) of cases with a mean lymph node harvest of 19.4 nodes (range 1-56). The staff surgeons performed 90 cases and trainees performed 114 cases. Twenty-one cases (10.3%) required conversion. The overall morbidity rate was 17.6% and perioperative mortality rate was 1.5%. On bivariate analysis, trainee surgeons were not found to be significantly associated with a higher conversion risk. Multivariate analysis revealed that only the factor of T3 and above was an independent predictor of conversion (odds ratio (OR) 4.1; 95% confidence interval (CI) 1.09-15.48). Multivariate analysis of risk factors for morbidity revealed that it was not conversion (OR 2.37; 95% CI, 0.86-6.76) but rectal surgery (OR 4.09; 95% CI 2.04-9.9) that was the independent risk factor of morbidity. CONCLUSIONS: Inexperienced surgeons do not cause more conversions or postoperative morbidity in laparoscopic colorectal surgery if they are well supervised. Conversion is not independently associated with increased postoperative morbidity.

Clinical outcome in patients with small-intestinal non-Hodgkin lymphoma.

The clinical features and outcome of small intestinal lymphoma remain unclear. We retrospectively analyzed 23 patients who had non-Hodgkin lymphoma with a small intestinal lesion. With a median follow-up of 37 months, the 5-year overall survival and failure-free survival (FFS) were 64% and 60%, respectively. In a univariate analysis, a worse performance status at the start of treatment and the occurrence of abdominal symptoms or perforation during treatment were associated with poor survival. Perforation often resulted in a dismal prognosis in patients with uncontrollable lymphoma, but not in patients with lymphoma in remission. The role of surgery in small intestinal lymphoma remains equivocal. In the current study, surgery before other therapies favorably influenced FFS, and all patients who underwent complete resection of the small intestinal lesion had extremely favorable results. Further studies are warranted to establish optimal therapeutic strategies.

Colorectal carcinoma with extremely low CA19-9.

AIM: The aim of this study is to determine the significance of postoperative sequential measurements of serum CA19-9 in patients with extremely low serum level. PATIENTS AND METHODS: Serum level of CA19-9 of 1096 patients who underwent surgery was measured preoperatively and every three months after surgery for 5 years. Patients with CA19-9 level of less than 2 U/mL at the time of diagnosis were defined as Extremely Low CA19-9 (ELCA). RESULTS: One hundred and seven patients (9.8%) were ELCA. Of these, 86 underwent surgery with curative intent. Serum levels of CA19-9 in patients who did not undergo curative resection (N = 12) and who developed recurrence (N = 10) were less than 2.0 U/mL in all occasions during followup. In all patients without recurrence, serum level of CA19-9 also remained less than 2.0 U/mL. CONCLUSION: In patients with extremely low CA19-9, who consist of 9.8% of colorectal carcinoma cases, postoperative sequential measurement of serum level of CA19-9 contributed neither to assessment of curability of surgical resection nor to detection of recurrence.

Promoter hypermethylation of tumor-related genes in peritoneal lavage and the prognosis of patients with colorectal cancer.

BACKGROUND AND OBJECTIVES: The predictive value of free cancer cells in the peritoneal fluid of patients with colorectal cancer (CRC) remain to be elucidated. The aim of this study was to determine the prognostic relevance of the methylation of tumor-related genes detected in the peritoneal lavage fluid (PLF) of patients undergoing a resection for CRC. METHODS: The promoter methylation pattern of four target genes, CDH1, CDKN2A (p16), MGMT, and APC, was examined in 51 primary CRC and corresponding matched PLF DNA. The relative methylation levels of these genes in primary CRC tissue and paired PLF were assessed by quantitative methylation-specific polymerase chain reaction (QMSP). RESULTS: An aberrant methylation of at least one gene was found in 45 of 51 (88%) primary tumors. In matched PLF specimens, the frequencies of aberrant promoter methylation detected for each marker were 16% for CDH1, 2% for p16, 4% for MGMT and 24% for APC. Patients with PLF demonstrating the methylation of more than one of these four target genes demonstrated significantly shorter relapse-free survival. CONCLUSIONS: These findings suggest that disseminated tumor cells in PLF detected by QMSP may correlate with the postoperative clinical course of patients undergoing curative surgery for CRC.

Pathological predictors for lymph node metastasis in T1 colorectal cancer.

PURPOSE: To clarify pathological predictor for lymph node metastasis in T1 colorectal cancer. METHODS: One hundred and sixty-four patients who underwent surgery for single T1 colorectal cancer were reviewed. The pathological differentiations of non-well differentiation, invasion depth (> or =2 000 microm), lymphatic channel involvement, venous invasion, and tumor budding were selected as candidate predictors. Tumor budding was estimated according to the definition proposed by Ueno et al. (Gastroenterology 2004; 127:385-394). The lymph node status was set for the endpoint. Logistic regression model was applied to analyze the predictors. RESULTS: Lymph node involvement was observed in 9.8%. The positive rates were 13.4% for the pathological differentiations of non-well differentiation, 51.8% for invasion depth (> or =2 000 microm), 6.1% for lymphatic channel involvement, 8.5% for venous invasion, and 14.6% for tumor budding. The pathological differentiations of non-well differentiation (P < 0.001) and tumor budding (P = 0.002) were significantly associated with lymph node metastasis in multivariate analysis. When either two significant factors was adopted for the prediction of the lymph node metastasis, the sensitivity, specificity, positive predictive value, and negative predictive value were 94%, 82%, 36%, and 99%, respectively. CONCLUSION: The pathological differentiations of non-well differentiation and tumor budding are useful predictors for lymph node metastasis in T1 colorectal cancer.