Oral S-1 with 24-h Infusion of Irinotecan plus Bevacizumab versus FOLFIRI plus Bevacizumab as First-Line Chemotherapy for Metastatic Colorectal Cancer: An Open-Label Randomized Phase II Trial.

BACKGROUND: FOLFIRI plus bevacizumab have been widely used as first-line treatment for metastatic colorectal cancer (mCRC). Pharmacokinetics and pharmacodynamics suggested a low dose of irinotecan given as a long-term infusion is expected to enhance antitumor activity. We conducted a randomized phase II study to compare oral S-1 with a 24-h infusion of irinotecan plus bevacizumab versus FOLFIRI plus bevacizumab. METHODS: The subjects comprised 120 chemotherapy-naïve patients with mCRC. The study group received a 24-h infusion of irinotecan at a dose of 125 mg/m2 on days 1 and 15, combined with oral S-1 80 mg/m2 on days 1-14 (24h-SIRI/B). The FOLFIRI/B group received irinotecan at a dose of 150 mg/m2, 5-fluorouracil given at a dose of 400 mg/m2 as a bolus injection and at a dose of 2,400 mg/m2 as a 46-h infusion, and 200 mg/m2 leucovorin on days 1 and 15. Bevacizumab was given at a dose of 5.0 mg/kg on days 1 and 15 in both groups. Treatment was repeated every 4 weeks. The primary endpoint was 1-year progression-free survival (PFS). Secondary endpoints were PFS, response rates (RR), overall survival (OS), and adverse events (AEs). RESULTS: From December 2013 through January 2018, 120 patients were randomly assigned, 61 patients to the 24h-SIRI/B and 59 patients to the FOLFIRI/B. The median follow-up period was 22.8 months. The 1-year PFS rate was 43.14% in the 24h-SIRI/B arm and 19.15% in the FOLFIRI/B arm (HR = 0.312 [95%CI 0.13-0.78], p = 0.01). The median PFS was 10.2 months (95%CI 8.8-14.3) and 10.0 months (95%CI 7.4-11.0), and the median OS was 29.7 months (95%CI 22.9-43.9) and 28.8 months (95%CI 18.4-ND), respectively (p = 0.3758, p = 0.8234). The overall RR was 86.3 and 61.7%, respectively (p = 0.0053). AEs were similar. CONCLUSIONS: Our results show that the 24h-SIRI/B regimen is an effective and reasonably well-tolerated regimen for the first-line treatment of mCRC.

A prospective clinical study assessing the presence of exfoliated cancer cells and rectal washout including tumors in patients who receive neoadjuvant chemoradiotherapy for rectal cancer.

PURPOSE: Rectal washout is performed in rectal cancer surgery to eliminate exfoliated cancer cells. Before rectal washout, a cross-clamp should generally be placed distal to the tumor. In some patients with lower rectal cancer, however, the tumor cannot be adequately isolated. We, therefore, hypothesized that neoadjuvant chemoradiotherapy (nCRT) can decrease the number of exfoliated cancer cells even after the rectal washout including tumors. METHODS: We prospectively studied 86 patients with rectal cancer who underwent proctectomy after nCRT. A cross-clamp was applied proximal to the tumor, and the rectum was washed with 2000 mL of physiological saline solution. The initial 100 mL used to wash the rectum was collected as a pre-washout sample. After the rectum was washed with the remaining 1900 mL, the solution remaining in the rectum was collected as a post-washout sample. Cells classified as class IV or higher according to the papanicolaou classification were considered to indicate a positive diagnosis. RESULTS: The cytological diagnosis was positive in pre-washout samples in 21 patients (24%) and post-washout samples in two patients (2%). CONCLUSION: In patients with rectal cancer, nCRT may decrease the number of exfoliated cancer cells in the rectum, and rectal washout including the tumor may be oncologically acceptable.

Usefulness of Preoperative Mechanical Bowel Preparation in Patients with Colon Cancer who Undergo Elective Surgery: A Prospective Randomized Trial Using Oral Antibiotics.

BACKGROUND: To prevent surgical site infection (SSI) in colorectal surgery, the combination of mechanical bowel preparation (MBP), oral antibiotic bowel preparation (OABP), and the intravenous antibiotics have been proposed as standard treatment. We conducted an RCT comparing the incidence of SSI between MBP + OABP and OABP alone after receiving a single dose of intravenous antibiotics. METHODS: The study group comprised 254 patients who underwent elective surgery for colon cancer. Patients were randomly assigned to receive MBP + OABP and intravenous antibiotics (MBP + OABP group) or to receive OABP and intravenous antibiotics (OABP alone group). RESULTS: Overall, 125 patients in MBP + OABP group and 126 patients in OABP alone group were eligible. Incisional SSI occurred in 3 patients (2.4%) in MBP + OABP group, and 8 patients (6.3%) in the OABP-alone group. Organ/space SSI developed in 0 patients (0%) and in 4 patients (3.2%) in each group respectively. The OABP-alone group was thus not shown to be noninferior to the MBP + OABP group in the incidences of incisional SSI or organ/space SSI. Other infectious complications developed in 7 patients (5.6%) and in 6 patients (4.8%) in each group, indicating the non-inferiority of OABP alone to MBP + OABP. CONCLUSIONS: MBP combined with oral antibiotics and intravenous antibiotics remains standard in elective colon cancer surgery.

Preventive effects of a synthetic absorbable antiadhesive film (seprafilm) on small bowel obstruction in patients who underwent elective surgery for colon cancer: A randomized controlled trial.

BACKGROUND: Seprafilm did not decrease small bowel obstruction (SBO), but significantly decreased reoperation in patients with inflammatory bowel disease. However, the preventive effect in colon cancer remains unclear. METHODS: We conducted a randomized controlled trial in patients with colon cancer. The study group comprised 345 patients with colon cancer. In the seprafilm group (n = 166), two sheets of seprafilm were inserted under a midline incision. Patients who were admitted and required decompression were considered to have SBO. RESULTS: The median follow-up was 61.9 months. Patient characteristics were well balanced. There was no significant difference in the incidence of SBO between the seprafilm group (7.8%) and the control group (10.6%) (P = .46). In patients who underwent reoperation, SBO occurred in a midline incision in one patient and at other sites in four patients in the seprafilm group as compared with two patients and five patients, respectively, in the control group. Multivariate analysis showed that only a history of laparotomy was an independent risk factor for SBO. CONCLUSIONS: Seprafilm did not decrease SBO or reoperation in colon cancer. The incidence of SBO caused by adhesion to the midline incision was relatively low as compared with that caused by adhesion to other sites.

Distribution of Neuroendocrine Marker-Positive Cells in Colorectal Cancer Tissue and Normal Mucosal Tissue: Consideration of Histogenesis of Neuroendocrine Cancer.

BACKGROUND: Colorectal neuroendocrine carcinoma (NEC) is a rare disease, and mixed cases with colorectal adenocarcinoma also exist. The histogenesis of this disease remains unclear. We studied the numbers of neuroendocrine marker-positive cells in adenocarcinoma tissue and in normal -mucosal tissue to investigate the relation between adenocarcinoma and NEC and to discuss the histogenesis of NEC. METHODS: We studied a total of 354 curatively resected cases of stage II or III colon cancer and 36 cases of rectal cancer treated at the Tokai University Hospital between 2007 and 2012. Adenocarcinoma tissue and normal mucosal tissue were immunohistochemically stained with chromogranin A, synaptophysin, and CD56. Cases in which neuroendocrine marker-positive cells were found in cancer tissue were defined as positive. In normal mucosa, the numbers of positive cells per 15 high-power fields (HPF) were counted. RESULTS: Among the 390 cases, 181 cases had right sided colon cancer, 173 cases had left sided colon cancer, and 36 cases had rectal cancer. The rates of positive staining for chromogranin A, synaptophysin, and CD56 were significantly higher in the right sided colon than in the left sided colon, consistent with the preferred sites of NEC as reported previously. Cells positive for chromogranin A and synaptophysin in normal mucosa were significantly more common in the rectum and the left sided colon than in the right sided colon. No site-specific differences were found for CD56. CONCLUSIONS: Neuroendocrine marker-positive cells in colorectal cancer tissue are more common in the right sided colon, whereas neuroendocrine marker-positive cells in normal mucosa are more common in the rectum. These results suggest that NEC may arise from preceding adenocarcinomas.

Induction of CD3+ and FoxP3+ T Cells in Left-sided Colorectal Tumors After UFT/LV Chemotherapy.

BACKGROUND/AIM: Immune checkpoint inhibitors are mainly used for right-sided, microsatellite instability-high colorectal tumors. In this study, the effects of oral uracil-tegafur plus leucovorin (UFT/LV) chemotherapy on the gene expressions of four immunotherapy targets and the amounts of tumor-infiltrating lymphocytes (TILs) were investigated. PATIENTS AND METHODS: Data of 260 patients with stage II or stage III colorectal cancer were analyzed. Gene expression and amount of TILs were evaluated using real-time reverse transcription polymerase chain reaction (CRT-PCR) assay and immunohistochemical staining, respectively. RESULTS: Expression of CTLA4 and LAG3 in tumor tissues was significantly increased after UFT/LV chemotherapy, but only in left-sided tumors. The percentage of high-TIL, high-CD3 and high-FoxP3 patients in the UFT/LV group was significantly higher than that in the control group, only in left-sided tumors. CONCLUSION: The increase in TILs count, especially of CD3+ T cells and FoxP3+ regulatory T cells, after UFT/LV chemotherapy were specific to left-sided colorectal cancers.

Retrospective study of regorafenib and trifluridine/tipiracil efficacy as a third-line or later chemotherapy regimen for refractory metastatic colorectal cancer.

Regorafenib and trifluridine/tipiracil (TAS-102) are novel antitumor agents for patients with refractory metastatic colorectal cancer. However, it is unclear which patients may derive a survival benefit from these drugs in real-life clinical practice. We evaluated retrospectively the efficacy and safety of regorafenib and TAS-102 at a single institution between June 2013 and November 2015. Cox regression analysis was carried out to obtain predictive scores (the nearest integers of hazard ratio) for survival benefit. Forty-four patients treated with regorafenib or TAS-102 were included in the analysis; among them, 17 received crossover treatment. The median overall survival (OS) was 9.1 months for regorafenib and 9.3 months for TAS-102, and the corresponding values after crossover were 7.1 and 5.3 months, respectively. OS was not correlated to relative dose intensity, but was proportional to the total administered dose of each drug. Adverse events were tolerable even after crossover. We identified three variables as significant for prediction of OS with good discrimination (C-statistic=0.70): Poor Eastern Cooperative Oncology Group performance status, time since diagnosis of metastatic disease ≤18 months, and previous chemotherapy continued ≥2 months beyond progression were all predictors of poor OS. Regorafenib and TAS-102 can be recommended for patients with better performance status and slow progression of metastatic disease. Optimal survival benefit was provided by prompt administration of either drug after failure of previous chemotherapy, with flexible titration to the optimal dose for each individual patient.

Chemoradiotherapy-induced Changes in Mucinous Components in Rectal Cancer Tissue: Evaluation on High Iron Diamine-alcian Blue and Mucin 1 Staining.

BACKGROUND/AIM: The standard treatment for rectal cancer is neoadjuvant chemoradiotherapy (nCRT) followed by surgery. Mucinous carcinoma responds poorly to nCRT. In some patients, mucin lakes (MLs) are induced by nCRT. Identifying whether MLs are induced or originally present would be of great importance. PATIENTS AND METHODS: We studied 20 patients with MLs (CRT-MC group) among 205 patients who received nCRT. Among 88 patients who did not receive nCRT, we studied 9 patients with mucinous carcinoma (non-CRT-MC group) and 18 patients with MLs in differentiated adenocarcinoma (non-CRT-AC group). Tumors were stained with high iron diamine-Alcian blue (HID-AB) and MUC1 staining. RESULTS: Rate of AB>HID staining of cancer cells was significantly higher in the CRT-MC group than in non-CRT-MC group (p=0.0004). Rate of MUC1 staining in MLs was significantly higher in the CRT-MC group (p=0.0254). CONCLUSION: nCRT can induce qualitative changes in mucinous components, however, other methods are required to distinguish induced components from originally existing components.

The Number of Natural Killer Cells in the Largest Diameter Lymph Nodes Is Associated with the Number of Retrieved Lymph Nodes and Lymph Node Size, and Is an Independent Prognostic Factor in Patients with Stage II Colon Cancer.

OBJECTIVE: We previously reported that the largest diameter of retrieved lymph nodes (LNs) correlates with the number of LNs and is a prognostic factor in stage II colon cancer. We examine whether T, B, and natural killer (NK) cells in LNs are related to the number of LNs and survival. METHODS: The subjects comprised 320 patients with stage II colon cancer. An LN with the largest diameter was selected in each patient. The positive area ratios of cells that stained for CD3 and CD20, and the numbers of CD56-positive cells were measured. RESULTS: The CD3-positive area ratio was 0.39 ± 0.08 and CD20-positive area ratio was 0.42 ± 0.10. The mean number of CD56-positive cells was 19.3 ± 22.7. The area ratios of B cells and T cells and the number of NK cells were significantly related to the sizes of the largest diameter LNs. The number of NK cells significantly correlated with the number of LNs and was an independent prognostic factor. On multivariate analysis, pathological T stage (T4 or T3; HR 4.71; p < 0.001) and the number of CD56-positive cells (high or low; HR 0.22; p < 0.001) were found to be independent prognostic factors. CONCLUSIONS: The number of NK cells in the largest diameter LNs can most likely be used as a predictor of recurrence.

Rectal Neuroendocrine Tumor with Synchronous Pancreatic Metastasis: A Case Report.

INTRODUCTION: Gastrointestinal neuroendocrine tumors (GI-NETs) often show hematogenous metastasis, with the liver being the most common metastatic site; however, metastasis to the pancreas is rare. CASE PRESENTATION: We report a rare case of rectal NETs with pancreatic metastases in a 75-year-old man who presented with a chief complaint of constipation. Imaging and endoscopic findings revealed a rectal submucosal tumor, a pancreatic hypovascular mass, and multiple liver masses. The rectal lesion and pancreatic lesions were diagnosed as neuroendocrine tumors using biopsy and endoscopic ultrasound fine-needle aspiration, respectively. Synchronous rectal NET and pancreatic NET (P-NET) with liver metastasis of either of these two were preoperatively diagnosed. A two-stage surgery was performed, comprising abdominoperineal resection and distal pancreatectomy. Pre-operative imaging findings showed a solitary mass in the pancreas, although the resected specimen contained multiple lesions. Immunohistochemical staining of the resected rectal and pancreatic lesions showed that both were synaptophysin positive and chromogranin A (CgA) negative. Generally, rectal NET cells are positive for synaptophysin and negative for CgA, while the majority of P-NETs are positive for both. The final diagnosis was rectal NETs with pancreatic and liver metastases. Till date, there have been no reports on the outcomes in patients with pancreatic metastasis of GI-NETs. CONCLUSIONS: More case reports on metastatic NETs are needed to arrive at a consensus for a standardized treatment regimen.

Outcomes of Local Excision plus Chemoradiotherapy in Patients with T1 Rectal Cancer.

OBJECTIVE: The National Comprehensive Cancer Network (NCCN) guidelines recommend local excision and observation as standard treatment for selected patients with clinical T1N0M0 rectal cancer. In patients with pathological T1 (pT1) rectal cancer who received local excision, the local recurrence rate is at least 10%. We studied oncological outcomes in patients with pT1 rectal cancer who received chemoradiotherapy (CRT) after local excision. METHODS: Local excision was performed in 65 patients with clinical T1N0M0 rectal cancer (≤8 cm from the anal verge, tumor size < 30 mm, well or moderately differentiated adenocarcinoma). The patients received CRT (40 or 45 Gy in 1.8-2.0 fractions with concurrent oral UFT [tegafur/uracil] or S-1 [tegafur/gimeracil/ote-racil]) after confirmation of pT1 and negative margins. RESULTS: Patients who had pT2 cancer or who did not provide informed consent were excluded. The remaining 50 patients additionally received CRT. The CRT was completed in 48 patients (96%). The median follow-up period was 71 months. Local recurrence occurred in 1 patient (2%). Distant metastases occurred in 3 patients (6%). The 5-year disease-free survival rate was 86%, and the 5-year overall survival rate was 92%. CONCLUSIONS: Our study suggested that multidisciplinary treatment with local excision plus CRT can be used as a treatment option in selected patients with clinical T1N0M0 rectal cancer.

Mucinous components assessed by magnetic resonance imaging in primary rectal cancer tissue before and after chemoradiotherapy and tumor response.

BACKGROUND: Mucinous rectal carcinoma has been reported to have a lower survival rate and a poorer histologic response to chemoradiotherapy(CRT). Magnetic resonance imaging (MRI) can accurately evaluate the amount of mucin pools (MP) in primary cancer tissue. We compared the degree of MP on MRI before and after CRT with the histologic findings of resected specimens to investigate the predictors of response to CRT. METHODS: The study group comprised 205 patients with rectal adenocarcinoma who received preoperative CRT. MPs were measured on MRI before and after CRT and in resected specimens. The degree of MP was classified into five classes according to the MP area ratio: 0%, class I; 1 to 19%, class II; 20 to 49%, class III; and 50% or higher, class IV. RESULTS: The degree of MP on MRI was largely unchanged after CRT; however, the MP on MRI after CRT was underestimated in 26.3% of patients as compared with that in resected specimens. A pathological complete response was obtained in patients who initially had no MP or had an MP ratio of less than 20%. The tumor volume was significantly greater, and the rates of tumor shrinkage and T downstaging were significantly lower in patients who had an MP area ratio of 20% or higher before CRT than in those who had an MP area ratio of less than 20%. CONCLUSIONS: The MP area ratio measured on MRI before treatment was closely associated with the response to CRT and is a potentially useful predictor of treatment response.

Comparisons of Rigid Proctoscopy, Flexible Colonoscopy, and Digital Rectal Examination for Determining the Localization of Rectal Cancers.

BACKGROUND: Rigid proctoscopy is considered essential for rectal tumor localization, although the current gold standard for detection of colorectal cancers is colonoscopy. The European Society for Medical Oncology Guidelines indicate that rigid and flexible endoscopies afford essentially identical results, although little evidence is yet available to support this. OBJECTIVE: The purpose of this study was to determine the accuracy of colonoscopy in identifying the location of rectal cancer and to compare the results with those of rigid proctoscopy and digital rectal examination. DESIGN: This was a retrospective analysis of a prospective database. SETTINGS: The study was conducted at a single tertiary colorectal surgery referral center. PATIENTS: A total of 173 patients scheduled for curative surgery for histologically verified rectal adenocarcinoma between December 2009 and February 2015 were entered into the study, after having given informed consent. MAIN OUTCOME MEASURES: The main study measure was the mean difference and limits of agreement in assessment of the height of the distal edge of rectal cancer from the anal verge, using the Bland and Altman method. RESULTS: The mean difference between rigid proctoscopy and flexible colonoscopy was -0.2 cm (95% CI, -2.0 to 1.6 cm). The mean difference between rigid proctoscopy and digital rectal examination was 0.3 cm (95% CI, 1.9 to 2.4 cm). Intermethod variability larger than the 95% CI between rigid and flexible endoscopes was correlated to the tumor height (OR, 4.27 (95% CI, 1.84-3.10); p = 0.021). LIMITATIONS: This study was conducted in a single center. CONCLUSIONS: The limits of agreement (-2.0 and 1.6 cm) in identifying the height of rectal cancers from the anal verge are sufficiently small to support the view that flexible colonoscopy provides similar tumor locations to those measured by rigid proctoscopy, although the discrepancy occasionally exceeded 2 cm for tumors >5 cm above the anal verge. See Video Abstract at http://links.lww.com/DCR/A405.

Relations of Changes in Serum Carcinoembryonic Antigen Levels before and after Neoadjuvant Chemoradiotherapy and after Surgery to Histologic Response and Outcomes in Patients with Locally Advanced Rectal Cancer.

OBJECTIVES: The histologic response to neoadjuvant chemoradiotherapy (nCRT) has been intimately related to outcomes in locally advanced rectal cancer. Serum carcinoembryonic antigen (CEA) levels change after nCRT and after surgery as compared with before nCRT. METHODS: The subjects were 149 patients with locally advanced rectal cancer who received nCRT between 2005 and 2013. The patients were divided into 4 groups according to the serum CEA levels: group 1, 55 patients with negative serum CEA levels before nCRT; group 2, 41 patients with positive serum CEA levels before nCRT that became negative after nCRT; group 3, 37 patients with positive serum CEA levels after nCRT that became negative after surgery; and group 4, 16 patients with positive serum CEA levels after nCRT as well as after surgery. RESULTS: Pathological complete response, T downstaging, and tumor shrinkage were significantly higher in group 1 than in other groups. Disease-free survival was significantly poorer in group 4. The lack of a decrease in the serum CEA level in group 4 was most likely attributed to the persistence of micrometastases outside the resection field. CONCLUSIONS: Changes in serum CEA levels measured before nCRT, after nCRT, and after surgery can be used to reliably predict the histologic response to nCRT and outcomes.

Tattooing improves the detection of small lymph nodes and increases the number of retrieved lymph nodes in patients with rectal cancer who receive preoperative chemoradiotherapy: A randomized controlled clinical trial.

BACKGROUND: In rectal cancer who received chemoradiotherapy, the number of Lymph nodes (LNs) required remains unclear. We conducted a randomized controlled trial to determine whether preoperative tattooing increases the number of LNs and enhances the detection rate of metastatic LNs. METHODS: Eighty patients with rectal cancer who received chemoradiotherapy were randomly assigned to receive no tattooing (C group) or to receive tattooing (T group). RESULTS: The number of LNs was significantly higher in the T group (13.3 ± 7.4, mean ± SD) than in the C group (8.8 ± 5.9, p < 0.001), however, the number of positive LNs did not differ (0.5 ± 1.3 vs. 0.5 ± 1.1, p = 0.882). The long-axis diameter of LNs was significantly smaller in the T group than in the C group (3.4 ± 1.8 vs. 3.9 ± 2.3 mm, p < 0.001), however, the long-axis diameter of positive LNs did not differ. CONCLUSIONS: Tattooing increased the number of retrieved LNs by 51%, however, there was no increase in the number of positive LNs.

A Modified Classification of Prognostic Factors Based on Pathological Stage and Tumor Regression Grade in Patients with Rectal Cancer Who Receive Preoperative Chemoradiotherapy.

OBJECTIVE: The histologic response to neoadjuvant chemoradiotherapy (CRT) has been intimately related to outcomes in locally advanced rectal cancer. However, reliable prognostic factors have yet to be established. SUBJECTS AND METHODS: The study group comprised 198 patients with locally advanced rectal cancer who received CRT. A modified classification based on the combination of ypStage and tumor regression grade (TRG) was developed. ypStage II with TRG 2 was classified as ypTRGstage IIA, and ypStage II with TRG 3 or 4 was classified as ypTRGstage IIB. ypStage 0 and ypStage I were classified as ypTRGstage I, and ypStage III was classified as ypTRGstage III. RESULTS: The 5-year disease-free survival (DFS) was 83% in ypTRGstage I, 86% in ypTRGstage IIA, 57% in ypTRGstage IIB, and 60% in ypTRGstage III (p = 0.0001). The 5-year DFS in ypTRGstage IIA did not differ significantly from that in ypStage 0 (p = 0.865) or ypStage I (p = 0.585). The 5-year DFS in ypStage IIB did not differ from that in ypStage III (p = 0.912). Multivariate analysis showed that ypTRGstage was an independent risk factor for DFS. CONCLUSION: A modified classification allows patients with ypStage II locally advanced rectal cancer to be clearly divided into two groups: responders and nonresponders.

A comparison of the localization of rectal carcinomas according to the general rules of the Japanese classification of colorectal carcinoma (JCCRC) and Western guidelines.

PURPOSE: The aim of this study was to compare the localization of rectal cancers as classified according to the general rules of the Japanese classification of colorectal carcinoma (JCCRC) and also according to the European Society for Medical Oncology (ESMO) and the National Comprehensive Cancer Network (NCCN) guidelines, which are based on rigid endoscopic measurements. METHODS: The medical records of patients scheduled to receive curative surgery for histologically proven rectal adenocarcinoma during 2009-2015 were investigated (n = 230). Rigid proctoscopy was performed in patients with rectal cancer located in the upper (Ra) or lower (Rb) division using double-contrast barium enema. RESULTS: The median values of height from the anal verge were 7.5 cm (range 2-12) and 3 cm (0-9.5) on rigid proctoscopy for cancers assigned as Ra and Rb, respectively. All 159 cancers at Ra or Rb were located within 12 cm from the anal verge by rigid proctoscopy, while only 79.7% of Ra or 82.1% of Rb cancers were located in the mid (5.1-10 cm) or low (≤5 cm) rectum, respectively. CONCLUSION: Ra and Rb cancers are deemed to be rectal cancers according to NCCN guidelines, but these classifications are not interchangeable with mid- and low-rectal cancers, respectively, according to the ESMO guidelines.

Monitoring of Serum Carcinoembryonic Antigen Levels after Curative Resection of Colon Cancer: Cutoff Values Determined according to Preoperative Levels Enhance the Diagnostic Accuracy for Recurrence.

OBJECTIVES: Serum carcinoembryonic antigen (CEA) has been widely used for postoperative surveillance for colorectal cancer. However, serum CEA has a poor diagnostic accuracy for detecting recurrence. We tested the hypothesis that determining cutoff values according to the preoperative serum CEA levels would enhance the diagnostic accuracy. METHODS: Serum CEA was measured before and 1-6 months after surgery in 783 patients with curatively resected colon cancer from 2005 through 2013. The cutoff values during surveillance were determined separately according to preoperative serum CEA levels. RESULTS: In patients with negative preoperative serum CEA, the diagnostic accuracy for recurrence was 89.1% when a postoperative cutoff value was set at 5 ng/mL. However, in patients with positive preoperative serum CEA, the diagnostic accuracy was 58.4% when a postoperative cutoff value was set at 5 ng/mL, and was 75.6% when a cutoff value was set at 8 ng/mL. Among patients with positive preoperative serum CEA, the recurrence-free survival rate was significantly lower in patients with a serum CEA of ≥8 ng/mL than those with a serum CEA of <8 ng/mL (p = 0.0018). CONCLUSIONS: The diagnostic accuracy of serum CEA for recurrence is enhanced by separately setting cutoff values according to preoperative serum CEA.

Risk scores as useful predictors of perioperative complications in patients with rectal cancer who received radical surgery.

BACKGROUND: Rectal cancer is associated with a higher rate of surgical complications. The ability to predict the risk of complications before treatment would facilitate the design of personalized treatment strategies optimally suited for each patient. METHODS: We retrospectively studied 260 patients with rectal cancer who underwent radical surgery to examine the relations between complications and 5 types of risk scores. RESULTS: Complications developed in 56 patients (21.5%). Nineteen patients had infectious complications, 16 had intestinal obstruction, and 12 had other complications. Twelve patients out of 187 patients who received low anterior resection had anastomotic leakage. Estimation of Physiologic Ability and Surgical Stress Comprehensive Risk Score (E-PASS CRS) and Neutrophil-to-lymphocyte Ratio (NLR) were significantly related to all complications, infectious complications, and anastomotic leakage. Surgical Apgar Score was significantly related to infectious complications. Prognostic Nutritional Index was significantly related to all complications and intestinal obstruction. Colorectal Physiologic and Operative Severity Score for the Enumeration of Mortality and Morbidity was significantly related to all complications, and infectious complications. A multivariate analysis showed that body-mass index, E-PASS CRS, and NLR were independent risk factors for anastomotic leakage. In particular, NLR was the only score that could be evaluated before surgery. CONCLUSIONS: Five types of risk scores were useful methods for evaluating the risks of complications in patients with rectal cancer. NLR is a score that can be evaluated before surgery and predicted the risk of anastomotic leakage, suggesting that it is useful for assessing the need for a diverting colostomy.

Relation between Carcinoembryonic Antigen Levels in Colon Cancer Tissue and Serum Carcinoembryonic Antigen Levels at Initial Surgery and Recurrence.

OBJECTIVES: Carcinoembryonic antigen (CEA) is widely used for postoperative surveillance of colon cancer. Even if serum CEA is negative at initial surgery, it may turn positive at recurrence. We investigated the relation between serum CEA levels and the immunohistochemical staining status of CEA in the primary and resected metastatic tissues. METHODS: Out of 224 patients with recurrent colon cancer between 1998 and 2012, we studied 46 patients in whom serum CEA levels were measured and immunohistochemical staining for CEA was possible in the primary and metastatic tissues. RESULTS: The positive rate of serum CEA did not differ between initial surgery and recurrence, regardless of whether the cutoff value was set at 5 or 10 ng/ml (p = 0.829, p = 0.671). There was no relation between the CEA staining status and serum CEA level at initial surgery. However, the CEA staining status of metastatic tissue was significantly related to the serum CEA level at recurrence (p = 0.0046 and p = 0.0026). CONCLUSIONS: The immunohistochemical staining status of CEA in metastatic tissue is closely related to the serum CEA level. This finding suggests that serum CEA levels are influenced not only by the CEA production capacity of cancer cells but also by the ability of the surrounding tissue to release CEA into the blood.