Evaluation of bacterial contamination and medium-term oncological outcomes of intracorporeal anastomosis for colon cancer: A propensity score matching analysis.

BACKGROUND: Although intracorporeal anastomosis (IA) for colon cancer requires longer operative time than extracorporeal anastomosis (EA), its short-term postoperative results, such as early recovery of bowel movement, have been reported to be equal or better. As IA requires opening the intestinal tract in the abdominal cavity under pneumoperitoneum, there are concerns about intraperitoneal bacterial infection and recurrence of peritoneal dissemination due to the spread of bacteria and tumor cells. However, intraperitoneal bacterial contamination and medium-term oncological outcomes have not been clarified. AIM: To clarify the effects of bacterial and tumor cell contamination of the intra-abdominal cavity in IA. METHODS: Of 127 patients who underwent laparoscopic colon resection for colon cancer from April 2015 to December 2020, 75 underwent EA (EA group), and 52 underwent IA (IA group). After propensity score matching, the primary endpoint was 3-year disease-free survival rates, and secondary endpoints were 3-year overall survival rates, type of recurrence, surgical site infection (SSI) incidence, number of days on antibiotics, and postoperative biological responses. RESULTS: Three-year disease-free survival rates did not significantly differ between the IA and EA groups (87.2% and 82.7%, respectively, P = 0.4473). The 3-year overall survival rates also did not significantly differ between the IA and EA groups (94.7% and 94.7%, respectively; P = 0.9891). There was no difference in the type of recurrence between the two groups. In addition, there were no significant differences in SSI incidence or the number of days on antibiotics; however, postoperative biological responses, such as the white blood cell count (10200 vs 8650/mm3, P = 0.0068), C-reactive protein (6.8 vs 4.5 mg/dL, P = 0.0011), and body temperature (37.7 vs 37.5 °C, P = 0.0079), were significantly higher in the IA group. CONCLUSION: IA is an anastomotic technique that should be widely performed because its risk of intraperitoneal bacterial contamination and medium-term oncological outcomes are comparable to those of EA.

Prediction model of the risk for lateral local recurrence in locally advanced rectal cancer without enlarged lateral lymph nodes: Lessons from a Japanese multicenter pooled analysis of 812 patients.

Aim: Although the oncological impact of lateral lymph node dissection on enlarged lateral lymph nodes has been gradually accepted over the last decade, that on lateral lymph nodes without swelling remains doubtful. This study aimed to develop a prediction model for the future risk of lateral local recurrence and to clarify the value of adding lateral lymph node dissection in locally advanced rectal cancer without enlarged lateral lymph nodes. Methods: This retrospective, multi-institutional study recruited 812 patients with cStage II/III low rectal cancer without enlarged lateral lymph nodes <7 mm. Total lateral local recurrence was a hypothetical value of future risk of lateral local recurrence when lateral lymph node dissection was never performed. Results: Overall, total lateral local recurrences were observed in 67 patients (8.3%). In the multivariate analyses, the strongest risk factor for total local recurrences was no preoperative chemoradiotherapy (odds ratio [OR][95%Cl]: 33.2 [4.56-241.7], P < 0.001), followed by tumor distance ≤40 mm (OR [95%Cl]: 2.71 [1.51-4.86], P < 0.001) and lateral lymph node 5-7 mm (OR[95%Cl]: 2.38 [1.26-4.48], P = 0.007). In patients with lateral lymph nodes of 5-7 mm, the total lateral recurrence rate was 4.8% after preoperative chemoradiotherapy. Lateral lymph node dissection could reduce from a total lateral local recurrence of 21.6% to an actual lateral local recurrence of 8.0% in patients without preoperative treatment. Conclusion: We introduce a novel prediction model of future risk of lateral local recurrences, which has the potential to enable us to indicate lateral lymph node dissection selectively according to the patients' risks.

Clinical T2N0 Rectal Cancer Treated with Neoadjuvant Chemoradiotherapy plus Local Excision.

INTRODUCTION: Total mesorectal excision is the standard treatment for clinical T2 (cT2) rectal cancer; however, this procedure can result in postoperative dysfunction, decreased quality of life, and stoma creation in some patients. We investigated neoadjuvant chemoradiotherapy (nCRT) plus local excision (LE) as an alternative treatment strategy for patients with cT2N0 rectal cancer. METHOD: Fifty-six patients with cT2N0M0 rectal cancer who exhibited the following characteristics (an anal verge of ≤8 cm, tumor size of <30 mm, well- or moderately differentiated adenocarcinoma on biopsy) underwent LE following nCRT. Chemoradiotherapy was administered at 40 or 45 Gy in 20-25 fractions with concurrent oral UFT (tegafur/uracil; 400 mg/m2) or S-1 (tegafur/gimeracil/oteracil; 80 mg/m2). RESULTS: Fifty-five patients (98%) completed nCRT as planned. Histologically, the excision margin was negative in all patients, and four patients with ypT3 disease underwent total mesorectal excision. Recurrence was observed in 15 patients (27%), local recurrence in 7 (13%), and distant recurrence in 10 (18%). The salvage surgery was possible for the local recurrence group. The 5-year disease-free and overall survival rates were 68.4% and 84.9%, respectively. Multivariate analysis showed that only the tumor regression grade (TRG) was an independent risk factor for recurrence (p = 0.025). Although 7 (26%) out of 27 patients with a TRG of 3 or 4 developed local recurrence and 6 (22%) had distant metastasis, 25 patients with a TRG of 1 or 2 did not exhibit local recurrence, and only 1 (4%) experienced distant metastasis. CONCLUSION: nCRT plus LE may be an alternative treatment for patients with cT2N0 rectal cancer who achieved a TRG of 1 or 2. However, additional treatment was required in patients who achieved a TRG of 3 or 4.

Predictors and histological effects of preoperative chemoradiotherapy for rectal cancer and control of lateral lymph node metastasis.

INTRODUCTION: Standard treatment strategy for low rectal cancer in Japan is different from Western countries. Total mesorectum excision (TME) + lateral lymph node dissection (LLND) is mainly carried out in Japan, whereas neoadjuvant chemoradiotherapy (nCRT) + TME is selected in Western countries. There is no clear definition of preoperative diagnosis of lateral lymph node metastasis. If we can predict lateral lymph node swelling that can be managed by nCRT from lateral lymph node swelling that require surgical resection, clinical benefit is significant. In the current study we assessed characteristics of the lateral lymph node recurrence (LLNR) and LLND that can be managed by nCRT. PATIENTS AND METHODS: Patients with low rectal cancer (n = 168) underwent nCRT between 2009 and 2016. We evaluated CEA, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and lateral lymph node short axis pre and post nCRT, respectively, and also evaluated tumor shrinkage rate, tumor regression grade (TRG). We evaluated the relationship between each and LLNR. RESULTS: LLND was not carried out all patients. Factors associated with LLNR were PLR and lymph node short axis pre and post nCRT. (p = 0.0269, 0.0278, p < 0.0001, p < 0.0001, respectively). Positive recurrence cut-off values of lateral lymph node short-axis calculated were 11.6 mm pre nCRT and 5.5 mm post nCRT. CONCLUSION: Results suggest that PLR before and after CRT was associated with control of LLNR, and LLND should be performed on lateral lymph nodes with short-axis of 5 mm and 11 mm pre and post nCRT.

Internal hernia caused by bridge formation between the medial and lateral segments of the liver: a case report.

BACKGROUND: Despite numerous reports on ischemic bowel obstruction caused by internal hernia, no case presentation has been reported of an internal hernia caused by a bridge formed between the medial and lateral zones of the liver. Herein, we report the first case of ischemic bowel obstruction caused by a hepatic bridge. CASE PRESENTATION: A 24-year-old man complaining of abdominal pain was referred to our hospital and admitted. Computed tomography showed formation of a closed loop of small bowel with a hernia orifice near the hilar region, and poor contrast of the prolapsed small bowel. We suspected ischemic bowel obstruction caused by an internal hernia with a fissure of the greater omentum as the hernia orifice, and performed emergency surgery. Laparoscopic observation revealed that the medial and lateral segments of the liver formed a bridge on the dorsal side at the liver portal, and that the small intestine was ischemic in the gap created between the bridge and the medial and lateral liver segments. A Meckel's diverticulum was also invaginated in the gap. The bridge was dissected out and the hernia orifice was opened to release the bowel obstruction. The small bowel was preserved and the Meckel's diverticulum was resected. The patient's postoperative course was uneventful. CONCLUSIONS: We experienced a case of ischemic bowel obstruction caused by hepatic bridge formation, which was successfully treated by laparoscopic surgery.

Classification of rectal cancer according to recurrence types - comparison of Japanese guidelines and Western guidelines.

BACKGROUND: Rectal cancer is characterized by more local recurrence (LR) and lung metastasis than colon cancer. However, the diagnosis of rectal cancer is not standardized as there is no global consensus on its definition and classification. The classification of rectal cancer differs between Japanese and Western guidelines. AIM: To clarify the characteristics of rectal cancer by comparing the tumor location and characteristics of rectal cancer with those of colon cancer according to each set of guidelines. METHODS: A total of 958 patients with Stage II and III colorectal cancer were included in the analysis: 607 with colon cancer and 351 with rectal cancer. Localization of rectal cancers was assessed by enema examination and rigid endoscopy. According to Japan guidelines, rectal cancer is classified as Rb (below the peritoneal inversion), Ra (between the inferior margin of second sacral vertebrae and Rb) or RS (between Ra and sacral promontory). RESULTS: There were no significant differences between RS rectal cancer and colon cancer in the rates of liver and lung metastasis or LR. Lung metastasis and LR were significantly more common among Rb rectal cancer (in Japan) than in colon cancer (P = 0.0043 and P = 0.0002, respectively). Lung metastases and LR occurred at significantly higher rates in rectal cancer measuring ≤ 12 cm and ≤ 10 cm than in colon cancers (P = 0.0117, P = 0.0467, P = 0.0036, P = 0.0010). Finally, the rates of liver metastasis, lung metastasis, and LR in rectal cancers measuring 11 cm to 15 cm were 6.9%, 2.8%, and 5.7%, respectively. These were equivalent to the rates in colon cancer. CONCLUSION: High rectal cancer may be treated with the same treatment strategies as colon cancer. There was no difference in the classification of colorectal cancer between Japan and Western countries.

Tumor-Infiltrating Lymphocytes in Biopsy Specimens Obtained 7 Days after Starting Chemoradiotherapy for Rectal Cancer Are Predictors of the Response to Chemoradiotherapy.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision surgery is a standard treatment for locally advanced rectal cancer (LARC). Tumor-infiltrating lymphocytes (TILs) have been reported to be associated with tumor response; however, this remains to be established. We previously reported that histological changes on biopsy specimens obtained 7 days after starting nCRT are strong predictors of response to nCRT. METHODS: The subjects were 208 patients with LARC who received nCRT. TILs on hematoxylin-eosin staining together with immunohistochemical staining of lymphocyte surface markers including CD3, CD4, CD8, and FoxP3 were performed both on the biopsy specimens before and 7 days after starting nCRT. RESULTS: The proportions of patients with high densities of CD3+, CD4+, CD8+, and FoxP3+ cells 7 days after starting CRT were significantly lower than the respective values before starting nCRT (p < 0.0001, p < 0.0001, p = 0.0023, and p = 0.0046). In biopsy specimens obtained before treatment, high-density CD4+ cells and FOXP3+ cells were significantly associated with tumor shrinkage rate. High-density FOXP3+ cells were significantly associated with marked tumor regression. In biopsy specimens obtained 7 days after starting treatment, high-density CD4+ cells were significantly associated with marked tumor regression, tumor regression grade 1, and tumor shrinkage rate. High-density FoxP3+ cells were significantly associated with marked tumor regression and tumor shrinkage rate. CONCLUSIONS: In patients who received nCRT for LARC, the evaluations of immunohistochemical staining for CD4+ and FOXP3+ TILs were more intimately related to histological response to CRT and tumor shrinkage rates in biopsy specimens obtained 7 days after starting treatment than in biopsy specimens obtained before CRT.

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.

Tissue-Infiltrating Lymphocytes as a Predictive Factor for Recurrence in Patients with Curatively Resected Colon Cancer: A Propensity Score Matching Analysis.

BACKGROUND: In patients with colorectal cancer, the rate of recurrence increases as the histologic stage progresses. However, the prediction of recurrence in individual patients is difficult. Many studies have reported on the relation between outcomes and tissue-infiltrating lymphocytes (TILs). The aim of our study was to clarify the relation between TILs and oncologic outcomes in patients with colon cancer using propensity score matching analysis. METHODS: The study group comprised 513 patients with colon cancer who received curative resection. By using propensity score matching for sex, age, tumor location, T stage, N stage, histologic type, and adjuvant therapy as conventional prognostic factors, 61 patients with recurrence and 61 patients with no recurrence were selected. Hematoxylin-eosin staining and immunohistochemical staining using CD3, CD8, CD4, and FoxP3 were performed for lymphocytes in the primary tissue. The results were evaluated separately in the whole tumor, the central part, and the invasive margin. RESULTS: The median follow-up period was 53 months. Among the 513 patients, 70 had recurrence and 443 had no recurrence. In the comparison of outcomes between the 61 patients with recurrence and the 61 patients with no recurrence, univariate analysis showed that the disease-free survival rate was significantly higher among the patients with positive TILs in the whole tumor and in the invasive margin (p = 0.016 and p = 0.012, respectively) and with CD8+ cells in the central part (p = 0.039) than among those with negative results. A multivariate analysis showed that TILs in the invasive margin (hazard ratio 1.81; 95% confidence interval, 1.03-3.05; p = 0.037) and CD8+ cell density in the central part (hazard ratio 1.76; 95% confidence interval, 1.07-2.93; p = 0.023) were prognostic factors that were independent from conventional prognostic factors. CONCLUSIONS: In patients with curatively resected colon cancer, TILs in the invasive margin and CD8+ cell density in the central part may be prognostic factors suggesting host antitumor immune response.

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.

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.

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.

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.

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.

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.

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.