Proposal of a new prognostic staging system for pulmonary metastases from colorectal cancer.

PURPOSE: The aim of this retrospective study was to establish a new prognostic staging system for pulmonary metastases from colorectal carcinoma (CRC). METHODS: The baseline characteristics and outcomes on 352 CRC patients who underwent complete pulmonary resection were collected from 19 institutions by the Japanese Society for Cancer of the Colon and Rectum (JSCCR) Study Group (group A). The clinical and pathological factors were entered into a multivariate analysis to identify independent variables that were helpful for accurately predicting the long-term prognosis after pulmonary resection. Using the selected variables in group A, we developed a new prognostic staging system (PSS). The new PSS was examined in a validation study in a series of 841 patients from 110 institutions of the JSCCR by the 78th society of the JSCCR (group B). RESULTS: We evaluated four variables selected in the multivariate analysis: the number of pulmonary metastases, the distribution, the disease-free interval and the lymph node metastases of primary cancer in group A. Using these four variables, we developed a new PSS. This PSS was found to significantly predict the prognosis in group B. CONCLUSIONS: Our new PSS was useful for the selection of patients suitable for pulmonary resection.

Lateral pelvic lymph node dissection can be omitted in lower rectal cancer in which the longest lateral pelvic and perirectal lymph node is less than 5 mm on MRI.

BACKGROUND AND OBJECTIVES: The goal of the study was to examine the use of magnetic resonance imaging (MRI) for identification of patients with lower rectal cancer who may benefit from lateral pelvic lymph node dissection (LPLD). METHODS: Diagnoses and oncological outcomes were examined in 160 cases. Patients in whom the long-axis diameter of the longest detected lymph node was < 5 mm or ≥ 5 mm were classified as LPLN(-) (n = 102) and LPLN(+) (n = 58), respectively. RESULTS: Diagnostic results gave a 21.6% positive predictive value (PPV) and a 95.0% negative predictive value (NPV) for the LPLN. These values were 59.6% and 91.5%, respectively, for the perirectal lymph node (PRLN). Multivariate analysis showed that a pathologic PRLN (pPRLN)(+) status was an independent prognostic factor for relapse-free survival (RFS) (P = 0.0424) in the LPLN(-) group. The 5-year RFS did not differ significantly between cases that did not and did undergo LPLD (90.0% vs. 83.8%) in the LPLN(-) and pPRLN(-) groups. CONCLUSIONS: The low PPV and high NPV indicate that it is difficult to identify patients who may benefit from LPLD. However, the results show that LPLD has no benefit in LPLN(-) and PRLN(-) cases and that these cases can be identified based on MRI findings.

Importance of the Postoperative Carcinoembryonic Antigen Level during Follow-Up after Curative Resection in Patients with Liver Metastatic Colorectal Carcinoma.

BACKGROUND/AIMS: To validate the conventional Japanese grading of liver metastasis for no residual tumor resection in Stage IV colorectal cancer (CRC) with liver metastasis and to identify risk factors for postoperative recurrence. METHODOLOGY: The subjects of this study were 1792 Stage IV CRC patients with liver metastasis. RESULTS: In 1792 cases, including unresectable cases, there was a significantly different prognosis by grade (P < 0.0001). In 421 R0 cases, there was no significant difference between Grade A and Grade B (P = 0.8527). In 381 cases without extra-hepatic metastasis, the prognosis was not significantly different among three grades. On multivariate analysis, carcinoembryonic antigen within 3 months from R0 operation (3M-CEA) was an independent risk factor regardless of extrahepatic metastasis. There was a significantly different prognosis (P < 0.0001) among Grade A', defined as a normal 3M-CEA level, Grade B', defined as Grade A or B and an abnormal 3M-CEA level, and Grade C', defined as Grade C and an abnormal 3M-CEA level. CONCLUSIONS: The postoperative CEA level is an important risk factor during follow-up after curative resection in patients with liver metastatic colorectal carcinoma. The combination of the 3M-CEA level and conventional grading of liver metastasis is useful for follow-up of R0 resection cases.

Sub-classification of Stage II colorectal cancer based on clinicopathological risk factors for recurrence.

PURPOSE: To make a Stage II colorectal cancer (CRC) sub-classification based on clinicopathological factors. METHODS: The subjects of this study were 422 patients with Stage II CRC, who underwent curative surgery with dissection of more than 12 lymph nodes. We used the logistic regression analysis or model and Cox's proportional hazard regression model for analysis. RESULTS: Preoperative carcinoembryonic antigen (CEA) level (p = 0.0057), macroscopic type (p = 0.0316), and depth of invasion (p = 0.0401) were extracted as independent risk factors for recurrence, whereas the preoperative CEA level (p = 0.0045) and depth of invasion (p = 0.0395) were extracted as independent predictors of 5-year disease-free survival. We defined depth of invasion (pT4) and the preoperative CEA level (abnormal) as risk factors for recurrence, and classified Grade A as a normal CEA level regardless of depth invasion, Grade B as depth of invasion to pT3 and an elevated CEA level, and Grade C as depth of invasion to pT4 and an elevated CEA level. There were significant differences in cumulative 5-year disease-free survival rates among each grade (Grade A vs. Grade B, p = 0.0474; Grade A vs. Grade C, p < 0.0001; Grade B vs. Grade C, p = 0.0134). CONCLUSION: The sub-classification of Stage II CRC, according not only to depth of invasion but also to preoperative CEA level, is important for predicting the prognosis.

Treatment strategy for preventing pouchitis as a postoperative complication of ulcerative colitis: the significance of the management of cuffitis.

PURPOSE: The aim of this study was to examine the risk factors for and to evaluate strategies for preventing pouchitis as a postoperative complication of ulcerative colitis (UC). METHODS: A total of 119 cases of UC in which restorative proctocolectomy with an ileal pouch-anal anastomosis (IPAA) was performed at our institution between 2000 and 2012 was investigated; nine patients in whom it was impossible to close the ileostomy due to an intractable anal fistula or pelvic abscess were excluded. RESULTS: The cumulative risk of developing pouchitis 5 years after IPAA with stoma closure was 31.0%. Significant relationships with pouchitis were found for the surgical indication (p = 0.0126) and surgical method (p = 0.0214). A significant correlation was found between pouchitis and cuffitis. Pouchitis was significantly more common in the cases with cuffitis than in those without (p = 0.0002). There was also a significantly different cumulative incidence observed between the cases with and without cuffitis (p < 0.0001). In addition, pouchitis had a greater tendency to recur in the cases with cuffitis than in those without (p = 0.2730). CONCLUSION: The cumulative incidence rate of pouchitis was 10.6% at 1 year, 15.1% at 2 years and 31.0% at 5 years. Controlling cuffitis is important to prevent pouchitis.

Prognostic factors in patients undergoing complete resection of pulmonary metastases of colorectal cancer: a multi-institutional cumulative follow-up study.

PURPOSE: The aim of this retrospective study was to establish the prognostic factors for overall survival after pulmonary resection for lung metastases of colorectal carcinoma (CRC). METHODS: The baseline characteristics and outcomes of 266 CRC patients undergoing complete pulmonary resection were collected from 19 institutions by the Japanese Society for Cancer of the Colon and Rectum (JSCCR) Study Group. We used the Cox proportional hazard regression to identify independent prognostic factors for OS. RESULTS: The 5-year overall survival rate of patients undergoing complete resection of isolated pulmonary metastases was 56.5 %. The independent unfavorable prognostic factors after pulmonary resection included stage T4 (p = 0.0004) and N2 (p = 0.0082) as primary cancer-related factors, and more than three metastases (p = 0.0342), bilateral distribution (p = 0.0450), metastatic disease-free interval (DFI) of less than 2 years (p = 0.0257), and a preoperative carcinoembryonic antigen (CEA) level greater than 5.0 ng/mL (p = 0.0209) as pulmonary metastases-related factors. CONCLUSIONS: This retrospective analysis suggested that the indications for pulmonary resection of CRC metastases should be decided not only by the status of lung metastases, but also by pulmonary-related factors such as the T and N stage of the primary lesion, preoperative CEA level, and the DFI.

[The feasibility of oral fluoropyrimidines as adjuvant chemotherapy after resection and local coagulation therapy of colorectal liver metastases].

OBJECTIVE: To evaluate the feasibility of oral fluoropyrimidines after resection and microwave coagulation(MCT), or radiofrequency ablation(RFA)of liver metastases from colorectal cancer. PATIENTS AND METHODS: Background factors, fluoropyrimidine administration(S-1 or UFT/LV), and adverse events were analyzed in 20 patients(17 males, 3 females; an average of 62. 4 years)with colorectal liver metastases after resection and RFA or MCT. RESULTS: The synchronous: metachronous metastases ratio was 13:7. Fifteen patients received the recommended dose and 5 received a reduced dose. S-1 was administered for 4 weeks followed by a 2-week rest for 7 patients, and for 2 weeks followed by a 1-week rest for 9 patients. UFT/LV was administered for 4 weeks followed by a 1-week rest for 4 patients. Fourteen patients(70%)had adverse events. One patient showed grade 3 leukocyte toxicity while other patients showed grade 1 or 2. Two patients discontinued chemotherapy because of grade 2 delirium and grade 2 CPK elevation; another 2 discontinued voluntarily. Eight patients with recurrence changed the rugs, while 8 of 12(67%)continued for 1 year. Median disease-free and med ian overall survival lengths were 16. 1 and 4 7. 6 months, respectively. CONCLUSION: S-1 and UFT /LV were used safely as adjuvant chemotherapies after the resection and local coagulation therapy of liver metastases.

Study of a high-risk group of stage II colon cancer.

This study was conducted for the purpose of identifying a high-risk group for recurrence of stage II colon cancer and determine those cases for which postoperative adjuvant chemotherapy for stage II colon cancer is indicated. The subjects of this study consisted of 179 stage II cases and 114 stage IIIa cases among 462 surgical colon cancer cases examined at this department from January 1, 1991 to December 31, 1996 classified as A for the degree of cure, with the exception of m cancer. A nonrecurrence group and a recurrence group of stage II and stage IIIa colon cancer cases were compared on the basis of parameters. Gender, age, and lymph ducts were extracted from multivariate analysis, while age and lymph ducts were extracted from a survival analysis using the Cox proportional hazard model. A high-risk group for recurrence of stage II colon cancer was determined to consist of young men of ly 2.3. Since the nonrecurrence survival rates and survival prognoses of ly 2.3 cases in particular were equivalent to those of stage IIIa, this is considered to be a risk factor for recurrence of stage II colon cancer, and postoperative chemotherapy is believed to be indicated.

Case of peritoneal dissemination of colon cancer in which PET/CT was useful in determining the indicated surgical procedure.

The right half of the colon was resected in a 70-year-old woman in August 2002 for ascending colon cancer. The peritoneum was also resected because of metastasis (Stage IV). Since tumor markers gradually increased, positron emission tomography (PET)/ computed tomography (CT) revealed peritoneal dissemination. Abdominal pain appeared 40 months after surgery. Barium enema findings revealed an ileal constriction approximately 25 cm from the anastomosed site toward the anus. Repeat PET/CT revealed peritoneal dissemination coinciding with ileal constriction. CT did not reveal well-defined tumor shadows. The patient was diagnosed with constriction associated with peritoneal metastasis and underwent surgery. Surgical findings revealed a roughly 2-cm peritoneal metastatic focus and ileal constriction. The site was resected and anastomosed. Postoperative progress was favorable; the patient was discharged and enjoys a favorable quality of life through outpatient adjuvant chemotherapy. PET/CT is suggested to be useful in observing the progress of peritoneal dissemination and may be of assistance in determining the course of treatment.

[Roles of positron emission tomography/computed tomography (PET/CT) in the management of colorectal cancer].

In diagnosis and treatment of colorectal cancer, PET/CT has high sensitivity and specificity in comparison to other modalities, and in the near future is expected to play important roles in these areas. However, because of the high cost, PET/CT must be used cost-effectively. In the diagnosis of colorectal cancer with PET/CT, evaluation of cancer growth is possible, but evaluation of tumor invasion is inadequate. In the diagnosis of lymph node metastases, PET/CT provides higher sensitivity of evaluation in distant lymph nodes. The reason for difficulty in proximal lymph node evaluation is due to the close proximity of the main cancer tumor. In the diagnosis of liver metastases, meta-analysis indicates the need for higher sensitivity and specificity compared to CT and MRI. In the diagnosis of pulmonary metastases, chest CT should be obtained in very early pulmonary metastases because of the tiny tumor size in the early stage. In the diagnosis of local recurrence, discrimination between postoperative change and recurrence is difficult, but PET/CT is very useful as a qualitative diagnostic tool. Recent reports have also indicated the usefulness of PET/CT in the evaluation of treatment efficacy in chemotherapy or radiotherapy.

Follow-up and recurrence of T1 colorectal cancer.

This study was performed to clarify the clinical and pathological characteristics of T1 colorectal cancer. From 1987 to 2003, a total of 223 patients with T1 colorectal cancer were treated at our institute. Disease recurrence occurred in eight (3%) of these cases. The original sites of cancer were the ascending colon (n = 1), sigmoid colon (n = 2), and rectum (n = 5). We performed three local resections per anus and five bowel resections with lymph node dissection. In cases showing recurrence after resection, lymph node metastasis was observed more frequently (four of five cases; 80%) compared with the cases showing no recurrence (11%). The average recurrence time was <36 months in seven of the eight cases (88%). Local recurrence occurred in five of the eight cases (63%). We conclude that careful follow-up is necessary in cases of T1 colorectal cancer in the first 3 years after treatment.

Diagnosis of lateral pelvic lymph node metastasis of T1 lower rectal cancer using diffusion-weighted magnetic resonance imaging: A case report with lateral pelvic lymph node dissection of lower rectal cancer.

The present study presented a 35-year-old female patient in whom fecal occult blood was detected in a medical check-up. Colonoscopy revealed a superficial elevated-type tumor with central depression in the lower rectum. The tumor was diagnosed as T1 deep invasive cancer. No swollen lymph nodes or distant metastasis were found on computed tomography or [18F]-fluorodeoxyglucose-positron emission tomography with computed tomography. However, a swollen right lateral pelvic lymph node (LPLN; short axis 4 mm) was revealed on magnetic resonance imaging (MRI). This lymph node exhibited high intensity on diffusion-weighted imaging (DWI), suggesting metastasis. Low anterior resection, regional lymph node dissection and right LPLN dissection (LPLD) were performed. Histological analysis revealed metastasis in the right LPLN, as suggested by the high DWI intensity. The indication for LPLD in the current Japanese guidelines is based on the tumor location and depth of invasion (≥T3), however, not on the status of LPLN metastasis in pre-operative evaluation. The present case was cT1, which is not included in this indication. DWI is sensitive for the diagnosis of lymph node metastasis of colorectal cancer, although inflammation-induced swelling of lymph nodes in advanced rectal cancer may cause a false-positive result, which is uncommon in T1 cases. Therefore, an LPLN with a high intensity DWI signal in T1 cases is likely to be metastasis-positive. Pre-operative DWI-MRI may be useful for identifying LPLN metastasis when planning the treatment strategy in these cases. The present study suggested reinvestigation of the indication for LPLD with inclusion of LPLN status on pre-operative imaging.

A logistic model including risk factors for lymph node metastasis can improve the accuracy of magnetic resonance imaging diagnosis of rectal cancer.

BACKGROUND: To evaluate use of magnetic resonance imaging (MRI) and a logistic model including risk factors for lymph node metastasis for improved diagnosis. MATERIALS AND METHODS: The subjects were 176 patients with rectal cancer who underwent preoperative MRI. The longest lymph node diameter was measured and a cut-off value for positive lymph node metastasis was established based on a receiver operating characteristic (ROC) curve. A logistic model was constructed based on MRI findings and risk factors for lymph node metastasis extracted from logistic-regression analysis. The diagnostic capabilities of MRI alone and those of the logistic model were compared using the area under the curve (AUC) of the ROC curve. RESULTS: The cut-off value was a diameter of 5.47 mm. Diagnosis using MRI had an accuracy of 65.9%, sensitivity 73.5%, specificity 61.3%, positive predictive value (PPV) 62.9%, and negative predictive value (NPV) 72.2% [AUC: 0.6739 (95%CI: 0.6016-0.7388)]. Age (<59) (p=0.0163), pT (T3+T4) (p=0.0001), and BMI (<23.5) (p=0.0003) were extracted as independent risk factors for lymph node metastasis. Diagnosis using MRI with the logistic model had an accuracy of 75.0%, sensitivity 72.3%, specificity 77.4%, PPV 74.1%, and NPV 75.8% [AUC: 0.7853 (95%CI: 0.7098-0.8454)], showing a significantly improved diagnostic capacity using the logistic model (p=0.0002). CONCLUSIONS: A logistic model including risk factors for lymph node metastasis can improve the accuracy of MRI diagnosis of rectal cancer.