High-output stoma is a risk factor for stoma outlet obstruction in defunctioning loop ileostomies after rectal cancer surgery.

PURPOSE: Defunctioning loop ileostomy has been reported to reduce symptomatic anastomotic leakage after rectal cancer surgery; however, stoma outlet obstruction (SOO) is a serious postileostomy complication. We, therefore, explored novel risk factors for SOO in defunctioning loop ileostomy after rectal cancer surgery. METHODS: This is a retrospective study that included 92 patients who underwent defunctioning loop ileostomy with rectal cancer surgery at our institution. Among them, 77 and 15 ileostomies were created at the right lower abdominal and umbilical sites, respectively. We defined the output volumeMAX as the maximum output volume the day before the onset of SOO or-for those without SOO-that was observed during hospitalization. Univariate and multivariate analyses were performed to evaluate risk factors for SOO. RESULTS: SOO was observed in 24 cases, and the median onset was 6 days postoperatively. The stoma output volume in the SOO group was consistently higher than that in the non-SOO group. In the multivariate analysis, the rectus abdominis thickness (p < 0.01) and output volumeMAX (p < 0.01) were independent risk factors for SOO. CONCLUSION: A high-output stoma may predict SOO in patients with defunctioning loop ileostomy for rectal cancer. Considering that SOO occurs even at umbilical sites with no rectus abdominis, a high-output stoma may trigger SOO primarily.

Increased risk of incisional hernia after stoma closure in patients with colorectal cancer.

PURPOSE: Stoma construction and closure are common surgical strategies in patients with colorectal cancer. The present study evaluated the influence of multiple incisional sites resulting from stoma closure on incisional hernia after colorectal cancer surgery. METHODS: The study included 1681 patients who underwent colorectal cancer surgery. Multiple incisional sites were defined as the coexistence of incisions at the midline and stoma closure sites. We retrospectively investigated the relationship between the presence of multiple incisional sites and incisional hernia development in patients with colorectal cancer. RESULTS: Among the 1681 patients, 420 (25%) underwent stoma construction, with a stoma closure-to-construction ratio of 33% (139/420), and 155 (9.2%) developed incisional hernias after colorectal cancer surgery. In the multivariate analysis, female sex (p < 0.001), body mass index (p < 0.001), multiple incisional sites (p = 0.001), wound infection (p = 0.003), and postoperative chemotherapy (p = 0.030) were independent predictors of incisional hernia. In the multiple incisional sites group, the age (p < 0.001), surgical approach (laparoscopic) (p = 0.013), wound infection rate (p = 0.046), small bowel obstruction rate (p < 0.001), and anastomotic leakage rate (p = 0.008) were higher in those in the single incisional site group. CONCLUSIONS: Multiple incisional sites resulting from stoma closure are associated with the development of incisional hernia following colorectal cancer surgery.

Correction to: Signification of Systemic Immune-Inflammation Index for prediction of prognosis after resecting in patients with colorectal cancer.

The authors regrets that there is a typo error on Tables 1, 2 and 3 of their published paper.

Signification of Systemic Immune-Inflammation Index for prediction of prognosis after resecting in patients with colorectal cancer.

PURPOSE: Systemic inflammatory response has been reported to be associated with prognosis in cancer patients. The aim of this study is to investigate the association between Systemic Immune-Inflammation Index (SII), a novel inflammation-based prognostic score and long-term outcomes among patients with colorectal cancer (CRC) after resection. METHODS: We retrospectively investigated 733 patients who underwent resection for CRC between January 2010 and December 2014 at the Jikei University Hospital and explored the relationship between SII, calculated by multiplying the peripheral platelet count by neutrophil count and divided by lymphocyte count, and overall survival. In survival analyses, we conducted Cox proportional hazards models, adjusting potential confounders including TNM stage, serum CEA, serum CA 19-9, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and platelet count. RESULTS: In multivariate analysis, age ≥ 65 years (p = 0.003), tumor location (p = 0.043), advanced TNM stage (p < 0.001), serum CA 19-9 > 37 mU/ml (p < 0.001), and SII (P for trend = 0.017) were independent and significant predictors of poor patient survival. Compared to patients with low SII, those with high and intermediate SII patients had poorer survival (Hazard ratio 2.48; 95% CI 1.31-4.69, Hazard ratio 1.65; 95% CI 0.83-3.27, respectively). CONCLUSION: The Systemic Immune-Inflammation Index might be an independent and significant indicator of poor long-term outcomes in patients with CRC after resection.

Clinical factors affecting the distal margin in rectal cancer surgery.

PURPOSE: In rectal cancer surgery, an insufficient distal margin (DM) is associated with a high risk of local recurrence, whereas an excessive DM will cause low anterior resection syndrome, impairing quality of life. This study aimed to identify the factors that affect the distance between the colorectal resection site and the tumor to optimize achieving the correct DM. METHODS: The subjects of this study were 219 patients who underwent resection for primary rectal cancer in our department between January 2006 and July 2014. According to Japanese guidelines, DM (rDM) was based on the tumor location, but the pathological DM (pDM) was measured from surgical specimens. The patients were divided into two groups: the pDM-less-than-rDM group (pDM < rDM) and the pDM-greater-or-equal-to-rDM group (pDM ≥ DM). The factors associated with the DM in the two groups were compared. RESULTS: In the pDM < rDM group, the tumor distance from the anal verge was shorter (p = 0.001) and significantly more patients underwent laparotomy (p = 0.047). CONCLUSION: The DM tended to be shorter than that planned by the surgeon in patients with lower rectal cancers and those treated by laparotomy,; therefore, when performing rectal resection, care must be taken to ensure that the pDM is not shorter than the rDM.

Standardization of surgical procedures to reduce risk of anastomotic leakage, reoperation, and surgical site infection in colorectal cancer surgery: a retrospective cohort study of 1189 patients.

PURPOSE: Anastomotic leakage (AL) and surgical site infection (SSI) are prevalent complications of colorectal surgery. To lower this risk, we standardized our surgical procedures in 2012, with a preferential use of laparoscopic approach (LS) for both colon and rectal surgery, combined with triangulating anastomosis (TA) for colon surgery and defunctioning ileostomy (DI) for low anterior resection. Our aim was to evaluate the outcomes of our standardized procedures. METHODS: The incidence rate of AL (primary outcome) and of reoperation and SSI (secondary outcome) was compared before (early period, n = 648) and after (late period, n = 541) standardization, through a retrospective analysis. RESULTS: The incidence rate of AL (6.6 versus 1.8%; P = 0.001), reoperation (3.5 versus 0.7%; P = 0.0012), and SSI (7.7 versus 4.6%; P = 0.029) was lower in late than in the early period. For colon cancer, TA and LS reduced the risk of AL (2.1 versus 0.3%, P = 0.020, for TA, and 3.2 versus 0.4%, P = 0.0027, for LS) and reoperation (2.9 versus 0.3%, P = 0.003, for TA, and 2.5 versus 0.2%, P = 0.0040, for LS). For rectal cancer, the incidence of all adverse outcomes (AL, reoperation, and SSI) was lower in cases treated by LS. However, the incidence of AL was lower in the late than in early period (P = 0.002) and with LS (P = 0.002). On multivariate analysis, late period and LS were independent factors of a lower risk of adverse outcomes. CONCLUSIONS: Our surgical standardization seems to be effective in lowering the risks of AL, reoperation, and SSI after colorectal cancer surgery.

Prognostic usefulness of the C-reactive protein-albumin-lymphocyte (CALLY) index as a novel biomarker in patients undergoing colorectal cancer surgery.

BACKGROUND: The C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index is a novel immuno-nutritional biomarker based on the levels of CRP, serum albumin, and lymphocyte count. This study examined the prognostic value of the CALLY index in patients with colorectal cancer undergoing curative surgery. METHODS: Between 2010 and 2017, 578 patients with stage II-III colorectal cancer who underwent curative resection were enrolled. The CALLY index was defined as (albumin × lymphocyte)/(CRP × 104). We investigated the association of the CALLY index with disease-free survival (DFS) and overall survival (OS). RESULTS: The cutoff value of the CALLY index was determined to be 2. Of the 578 patients, 175 (30%) had a preoperative CALLY index <2. In multivariate analysis, the pre-operative carcinoembryonic antigen (CEA) level (p = 0.003), cell differentiation (p = 0.045), venous invasion (p = 0.036), Tumor-Node-Metastasis stage (p < 0.001), and CALLY index score <2 (p = 0.006) were independent predictors of DFS. Meanwhile, preoperative carbohydrate antigen (CA)19-9 levels (p = 0.019), lymphatic invasion (p = 0.018), preoperative platelet (p = 0.037), and CALLY index score <2 (p = 0.007) were independent predictors of OS. CONCLUSION: The CALLY index may be an independent prognostic biomarker for long-term outcomes in patients with colorectal cancer.

Novel Colon Preparation Method Combining Bowel Cleanser Reduction and Unique Walking.

BACKGROUND AND PURPOSE: Poor bowel preparation increases the difficulty of colonoscopy and affects lesion detection. In this study, we investigated the usefulness of a new bowel preparation method using polyethylene glycol electrolyte formulation containing ascorbic acid (PEG plus ascorbic acid: PEG-Asc, MOVIPREP) to improve bowel cleansing and shorten preparation time. METHODS: This was a single-center, retrospective study. In the new method, patients were instructed to take a laxative the day before the examination and PEG1L on the day of the examination. In addition, we instructed the patients to walk, which we designed. The primary endpoints were the degree of bowel cleansing (assessed by the Boston bowel preparation scale, BBPS) and time to the cecum. RESULTS: The conventional group reached the cecum in 606.5±225.8 seconds (mean±SD), whereas the introduced group reached the cecum in 500±217.1 seconds, a significantly shorter time ( P <0.05). In the BBPS, the score in the introduced group was significantly higher ( P <0.01): 6.8±2.14 points in the conventional group and 8.6±0.74 points in the introduction group. CONCLUSION: Pretreatment combining the 1L weight loss method and walking improves bowel cleansing and shortens the time to reach the cecum.

Clinical Significance of Controlling Nutritional Status (CONUT) Score in Patients With Colorectal Liver Metastases After Hepatectomy.

BACKGROUND/AIM: The prognostic outcome of the controlling nutritional status (CONUT) score in patients with colorectal liver metastases (CRLM) who underwent hepatectomy has not been investigated. The aim of this study was to investigate the prognostic value of preoperative CONUT score and other systemic inflammation-related biomarkers in patients who underwent hepatectomy for CRLM. PATIENTS AND METHODS: The subjects included 145 patients with CRLM who underwent hepatectomy and retrospectively investigated the association of preoperative CONUT score with disease-free survival (DFS), surgical failure-free survival (SFS), and overall survival (OS) using univariate and multivariate analyses. RESULTS: In this study, the cut-off of the CONUT score was 4. In the univariate analysis, the high CONUT score was associated with worse SFS and OS (p=0.01, 0.01). The multivariate analysis showed significant and independent predictors of OS were lymph node metastases (p=0.03) and a high CONUT score (p=0.04). In patients with a high CONUT score, postoperative complications due to infections were significantly more than in those with a low CONUT score (27% vs. 9%, p=0.04). CONCLUSION: The CONUT score can be useful for predicting not only short-term but also long-term outcomes in patients with CRLM after hepatectomy.

Absence of CD71 transferrin receptor characterizes human gastric adenosquamous carcinoma stem cells.

BACKGROUND: Although the importance of cancer stem cells (CSCs) in overcoming resistance to therapy and metastasis has recently been reported, the role of CSCs in gastric cancer remains to be elucidated. METHODS: MKN-1 cells were used to study markers of CSCs in gastric adenosquamous carcinoma, as these cells are suitable for determining multidifferentiation ability. Changes in expression of CD44, CD49f, CD133, and CD71 following 5-fluorouracil (5-FU) treatment were assessed. RESULTS: After 5-FU treatment, only the CD71- fraction was significantly increased. Investigation of CD71 indicated that the CD71- cell fraction was present in the G1/G0 cell cycle phase and showed high resistance to the anticancer agent 5-FU. Limiting dilution and serial transplantation assays revealed the CD71- cell fraction to have higher tumorigenicity than the CD71+ cell fraction. The CD71- cell fraction showed multipotency to adenocarcinoma and squamous cell carcinoma. A three-dimensional (3D) invasion assay and immunohistochemical analysis showed CD71- cells to be highly invasive and to exist in the invasive fronts of cancer foci. CONCLUSION: The present study suggests that use of CD71- as a marker for adenosquamous carcinoma may provide a useful model for studying CSCs.

Increased CD13 expression reduces reactive oxygen species, promoting survival of liver cancer stem cells via an epithelial-mesenchymal transition-like phenomenon.

BACKGROUND: Recently, it has been reported that a small population of cancer stem cells (CSCs) play a role in resistance to chemotherapy and radiation therapy. We reported that CD13(+) liver CSCs survive in hypoxic lesions after chemotherapy, presumably through increased expression of CD13/Aminopeptidase N, which is a scavenger enzyme in the reactive oxygen species (ROS) metabolic pathway. On the other hand, the concept of epithelial-mesenchymal transition (EMT) was indicated by a recent study showing an increased plasticity linked to the cellular "stemness" of CSCs. METHODS: To study the relationship between CSCs and EMT, we examined biological characteristics of liver cancer cell lines with EMT by exposing transforming growth factor-ß (TGF-ß). RESULTS: We showed that a TGF-ß-induced EMT-like phenomenon is associated with increased CD13 expression in liver cancer cells. This phenomenon prevents further increases in the ROS level as well as the induction of apoptosis, promoting the survival of CD13(+) CSCs, whereas inhibition of CD13 stimulates apoptosis. Immunohistochemical analysis also indicated that after chemotherapy, CD13 was coexpressed with N-cadherin in surviving cancer cells within fibrous capsules. We have demonstrated that CD13 expression plays a role in supporting the survival of CSCs and that there is an EMT-associated reduction in ROS elevation. CONCLUSIONS: This novel and consistent linkage between functional CSC markers and the EMT phenomenon suggests a bona fide candidate for targeted therapy for EMT-mediated invasion and metastasis of liver cancer.

Short-term Postoperative Outcomes of Colorectal Cancer Patients With Chronic Renal Failure on Dialysis.

BACKGROUND/AIM: Surgery for dialysis patients requires special attention because of their physical characteristics. This study aimed to investigate the short-term postoperative outcomes of colorectal cancer patients with chronic renal failure (CRF) on dialysis and aimed to investigate safer treatment options for these patients. PATIENTS AND METHODS: A total of 1,504 colorectal cancer patients who underwent primary resection between January 2008 and December 2018 were included. A retrospective analysis of clinical data, preoperative tumor markers (carcinoembryonic antigen and carbohydrate antigen 19-9), and the Clavien-Dindo (CD) classification was performed. Patients were stratified into Groups A and B based on their need for dialysis or not, respectively. RESULTS: There were 20 and 1,484 patients in Groups A and B, respectively. No differences were observed regarding age, body mass index, and preoperative tumor markers. The rate of laparoscopic surgery was significantly lower in Group A than in Group B. There was one mortality in Group A due to pulmonary disease. Group A had a significantly higher rate of complications. CONCLUSION: CRF patients on dialysis who underwent colorectal cancer surgery tended to be ruled out of laparoscopic surgery, and their rates of postoperative complications were higher.

Evaluation of the Outcome of Local Surgery for Stomal Prolapse.

We reviewed the results of local surgical treatment of stoma prolapse, a long-term complication of stoma construction. Fifteen patients treated for stomal prolapse between 2009 and 2020 at the authors' and affiliated hospitals were included in this study. The treatment comprised local laparotomic stomal reconstruction (LLSR) in nine patients and stapling repair (SR) in six. We compared and evaluated the clinical and surgical information and postoperative complications. Operation time was significantly shorter in the SR group than in the LLSR group: 20 and 53 min, respectively (p = 0.036). The duration of postoperative hospitalization was shorter in the SR group than in the LLSR group: 5.5 and 8 days, respectively; the difference was not significant (p = 0.088). No short-term complications were found in either group. Regarding long-term, postoperative complications, parastomal hernias developed after 2.5 years in one patient in the LLSR group and after 6 months in one patient in the SR group; both patients had histories of parastomal hernia surgery and had relatively high body mass indices. Local surgery for stomal prolapse was minimally invasive and performed safely. In patients with a history of surgery for parastomal hernia, attention must be paid to the potential of parastomal hernia developing as a postoperative complication.

Umbilical Defunctioning Ileostomy for Rectal Cancer Results in Reduced Risk for Incisional Hernia.

BACKGROUND/AIM: Umbilical defunctioning ileostomy (UDI) spares one incision, which may reduce the overall incidence of incisional hernia. Our aim was to evaluate the occurrence and risk factors of incisional hernias between UDI and conventional defunctioning ileostomy (CDI) after ileostomy closure. PATIENTS AND METHODS: Incidence of incisional hernia after ileostomy closure was compared between UDI (n=51) and CDI (n=86) groups. Risk factors for incisional hernia were also considered through a retrospective analysis. RESULTS: The overall incidence of incisional hernia was 5.9% in the UDI group, which was significantly lower than the 22.1% (7.0% at the midline incision and 15.1% at the stoma site) in the CDI group (p=0.012). Multivariate analysis showed higher BMI (p=0.035) and CDI (p=0.031) as risk factors for developing incisional hernias overall. CONCLUSION: UDI results in fewer incisional hernias than CDI and seems to be superior to CDI from the standpoint of overall incidence of incisional hernias.

Identification of the Risk Factors for Recurrence of Stage III Colorectal Cancer.

BACKGROUND/AIM: This study aimed to identify risk factors for recurrence of patients with stage III colorectal cancer by assessing clinicopathological features. PATIENTS AND METHODS: The study included 231 patients with stage III colorectal cancer who underwent curative resection between 2006 and 2012 at the Department of Surgery of the Jikei University Hospital, Tokyo, Japan. Clinicopathological data of the patients were retrospectively evaluated. RESULTS: The recurrence rate was 27.7% (64/231) in the study group. The univariate analysis for recurrence identified five risk factors: site of primary tumor (rectal cancer), surgical procedure (open surgery), preoperative serum CEA level (>5 ng/ml), preoperative serum CA19-9 level (>37 U/ml), and number of metastatic lymph nodes (over three metastases). The multivariate analysis for recurrence identified three risk factors: rectal cancer, preoperative serum CEA level >5.0 ng/ml 95%, and more than three metastatic lymph nodes. CONCLUSION: The risk factors for stage III colorectal cancer recurrence seem to be rectal cancer, preoperative serum CEA level >5.0 ng/ml, and more than three metastatic lymph nodes.

CD133+CD44+ population efficiently enriches colon cancer initiating cells.

BACKGROUND: Previous reports have demonstrated that CD133(+) cells or CD44(+) cells might be cancer initiating cells (CIC) of colon cancer. However, the association between the two cell types is unclear. In this study, we evaluated the tumorigenicity of each population of human colon cancer divided by CD133 and CD44 using non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. METHODS: Using the colon cancer cell lines HT29 and Caco2 we evaluated the change of expression status of CD133 or CD44 by a treatment with sodium butyrate (NaBT) that can induce cellular differentiation. Next, we prepared ten clinical samples of colon cancer and analyzed the expression and tumorigenicity of CD133 and CD44. RESULTS: With NaBT treatment, CD44 expression was greatly downregulated in both HT29 and Caco2 (HT29: nontreatment versus treatment; 77.8% versus 0.6%, Caco2: 14.0% versus 0.4%, respectively), more than CD133 expression (HT29: nontreatment versus treatment; 90.1% versus 67.7%, Caco2: 98.9% versus 76.3%, respectively). In clinical samples, the percentages of CD133(+) cells and CD44(+) cells varied from 0.3% to 82.0% (mean 35.5%), and from 11.5% to 58.4% (mean 30.0%), respectively. Subcutaneous injection of CD133(+) or CD44(+) cells made a tumor in all mice (3/3 and 4/4, respectively). The combined analysis of CD133 and CD44 revealed that only the CD133(+)CD44(+) population had the ability to produce a tumor (3/3). CONCLUSION: The findings demonstrate that, at present, the CD133(+)CD44(+ ) population may be the best to identify tumor initiating cells of human colon cancer.

Defunctioning Ileostomy Is a Key Risk Factor for Small Bowel Obstruction After Colorectal Cancer Resection.

BACKGROUND/AIM: Early postoperative small bowel obstruction (EPSBO) prolongs hospital stays after surgery. This study aimed to evaluate the risk factors for EPSBO associated with colorectal cancer resection. PATIENTS AND METHODS: We retrospectively compared the clinical variables of patients with EPSBO (n=37) and those without (n=812) after primary tumor resection for colorectal cancer at our hospital between January 2010 and December 2015. RESULTS: In multivariate analysis, significant differences between the two groups was found in male sex, open surgery, and defunctioning ileostomy (DI) placement (p=0.024, p<0.0001, and p=0.023, respectively), but not for colostomy placement. Of 16 patients with DI who developed EPSBO, 13 (81.3%) cases resulted from obstruction of the stomal outlet. CONCLUSION: Male sex, open surgery, and DI placement are risk factors for EPSBO after colorectal cancer resection. For patients with placement of DI, obstruction of the stomal outlet should be carefully considered.

Comparison of Postoperative Outcomes Between Laparoscopic and Open Surgery for Colorectal Cancer.

BACKGROUND/AIM: To determine the superiority of the laparoscopic vs. open technique for colorectal cancer surgery. PATIENTS AND METHODS: We performed a retrospective analysis of consecutive patients who underwent curative surgery by laparoscopic colectomy (LC) or open colectomy (OC) for colon cancer. The patients were classified into two groups: as LC group and OC group. We retrospectively assessed clinical characteristics, intraoperative and postoperative outcomes and long-term outcomes between the two groups by univariate analysis. RESULTS: The LC group had significantly less intraoperative blood loss, complications, and shorter post-operative hospital stay than the OC group. The overall survival of Stage II in the LC group is significantly longer than the OC group. DFS of Stage III in the LC group was significantly longer than the OC group. CONCLUSION: LC showed more favorable results in both short-term and long-term outcomes than OC.

Enhanced Recovery After Surgery Programs for Laparoscopic Colorectal Resection May Not Need Thoracic Epidural Analgesia.

BACKGROUND/AIM: The aim of this study was to evaluate the necessity of thoracic epidural analgesia (TEA) as enhanced recovery after surgery (ERAS) programs for laparoscopic colorectal surgery (LC). PATIENTS AND METHODS: We retrospectively compared between perioperative outcomes of patients who underwent LC with TEA (n=31) and with multimodal analgesia (MMA) (n=31). Furthermore, we also evaluated the patients' satisfaction by a questionnaire survey to the nurses. RESULTS: The only numeric rating scale (NRS) score on post-operative day (POD) 1 of the MMA group was significantly higher than that in the TEA group (p=0.002). In multivariate analysis, the factors that demonstrated significant correlation with hospital stay did not include analgesia. The 74% of the nurses felt equal or higher analgesic effect in the MMA group and interestingly, 84% of them answered that they would choose MMA if they were to undergo LC. CONCLUSION: TEA may not be necessary for ERAS in LC.