Cancer Stem Cells Persist Despite Cellular Damage, Emergence of the Refractory Cell Population.

PURPOSE: Cancer stem cells (CSCs) are responsible for chemotherapy resistance and have unique properties that protect them from chemotherapy. Investigating CSCs may help to identify the population that is more resistant to treatments, leading to recurrence. We evaluated persisting CSCs, emerging after chemotherapy that cause tumor recurrence. METHODS: Using human colorectal cancer organoids prepared from surgical specimens, we looked at changes in CSCs, the emergence and changes in the original population, which single-cell analysis identified. RESULTS: With regards to changes in cancer stem cell markers, CD44 showed low levels after 5-fluorouracil administration. Once the CD44-ve population was sorted and cultured, the CD44+ve population gradually emerged, and the CD44-ve population decreased. Compared with the CD44-ve population of an organoid parent, the CD44-ve population proliferated after chemotherapeutic agent stimulation. The CD44-ve population was derived from the CD44+ve population before chemotherapeutic agents. In addition, when the CD44 variants were evaluated, the CD44v9 population remained. In single-cell analysis, we found that POU5F1 was highly expressed in the CD44low population. Velocity analysis showed that the CD44-ve population was induced after chemotherapy and expressed POU5F1. POU5F1-EGFP-Casp9 transfected organoids resulted in the appearance of a CD44-ve population after administration of a chemotherapeutic reagent. Both in vivo and in vitro, the dimerizer administration inhibited tumor growth significantly. CONCLUSIONS: POU5F1 is involved in chemotherapy resistance in relation to stemness. For the treatment against refractory tumors, such as the recurrence after chemotherapy, the treatment should target the emerging specific population such as CD44 (or CD44v9) and proliferative cancer cells.

Ischemia prediction score (IsPS) in patients with strangulated small bowel obstruction: a retrospective cohort study.

BACKGROUNDS: Intestinal ischemia of strangulated small bowel obstruction (SSBO) requires prompt identification and early intervention. This study aimed to evaluate the risk factors and develop a prediction model of intestinal ischemia requiring bowel resection in SSBO. METHODS: This was a single-center, retrospective cohort study of consecutive patients underwent emergency surgery for SSBO from April 2007 to December 2021. Univariate analysis was performed to identify the risk factors for bowel resection in these patients. Two clinical scores (with contrasted computed tomography [CT] and without contrasted CT) were developed to predict intestinal ischemia. The scores were validated in an independent cohort. RESULTS: A total of 127 patients were included, 100 in the development cohort (DC) and 27 in the validation cohort (VC). Univariate analysis showed that high white blood cell count (WBC), low base excess (BE), ascites and reduced bowel enhancement were significantly associated with bowel resection. The ischemia prediction score (IsPS) comprised 1 point each for WBC ≥ 10,000/L, BE ≤ -1.0 mmol/L, ascites, and 2 points for reduced bowel enhancement. The simple IsPS (s-IsPS, without contrasted CT) of 2 or more had a sensitivity of 69.4%, specificity of 65.4%. The modified IsPS (m-IsPS, with contrasted CT) of 3 or more had a sensitivity of 86.7%, specificity of 76.0%. AUC of s-IsPS was 0.716 in DC and 0.812 in VC, and AUC of m-IsPS was 0.838 and 0.814. CONCLUSION: IsPS predicted possibility of ischemic intestinal resection with high accuracy and can help in the early identification of intestinal ischemia in SSBO.

[A Case of Long-Term Survival with Tumor Resection and DOX plus DTIC Therapy for Desmoid Tumor after FAP Surgery].

The patient is a 22-year-old, female. She had a family history of familial adenomatous polyposis(FAP)and a prophylactic total colorectal resection was performed for FAP at age of 18. She presented with fever and abdominal distention and palpated a mass with tenderness in the right lower abdomen. Contrast-enhanced CT scan of the abdomen showed a heterogeneous contrast effect around the tumor margins. With the diagnosis of intra-abdominal desmoid tumor, a partial duodenal resection, small bowel mass resection, and right fallopian tube resection were performed along with the tumor, and an artificial anus was created with the jejunum. Contrast-enhanced CT scan of the abdomen 16 months after resection of desmoid tumor showed a 6.5 cm long desmoid tumor recurrence in the mesentery. She received 5 courses of doxorubicin (DOX)plus dacarbazine(DTIC)therapy followed by continued NSAIDs. Seven years after the operation, she has been able to maintain the shrinkage of the recurrent tumor and is still on medication. Long-term surveillance is necessary because of the possibility of the appearance of other associated lesions in the future.

PLXND1/SEMA3E Promotes Epithelial-Mesenchymal Transition Partly via the PI3K/AKT-Signaling Pathway and Induces Heterogenity in Colorectal Cancer.

Colorectal cancer (CRC) is a major cause of cancer-related deaths. Metastasis is enhanced through epithelial-mesenchymal transition (EMT), a process primarily induced by the transforming growth factor beta (TGF-ß)-mediated canonical Smad pathway. This study focused on plexin D1 (PLXND1), a chemoreceptor for the ligand SEMA3E to mechanosensory, showing that PLXND1 induces EMT via activation of the PI3K/AKT pathway in CRC cells. The findings showed that PLXND1-knockdown decreases cell migration and invasion significantly, and that the binding of p61-SEMA3E to the PLXND1 enhances the invasiveness and migration through EMT. Furin inhibitor suppresses EMT, decreasing cell migration and invasion. Furin cleaves full-length SEMA3E and converts it to p61-SEMA3E, suggesting that furin inhibitors block PLXND1 and p61-SEMA3E binding. Furin is a potential therapeutic target for the purpose of suppressing EMT by inhibiting the binding of p61-SEMA3E to PLXND1. In vivo experiments have shown that PLXND1-knockdown suppresses EMT. Mesenchymal cells labeled with ZEB1 showed heterogeneity depending on PLXND1 expression status. The high-expression group of PLXND1 in 182 CRC samples was significantly associated with poor overall survival compared with the low-expression group (P = 0.0352, median follow-up period of 60.7 months) using quantitative real-time polymerase chain reaction analysis. Further research is needed to determine whether cell fractions with a different expression of PLXND1 have different functions.

Development and evaluation of a Japanese prediction model for low anterior resection syndrome after rectal cancer surgery.

BACKGROUND: Low anterior resection syndrome (LARS) is the most common complication after rectal cancer resection. We aimed to identify LARS' predictive factors and construct and evaluate a predictive model for LARS. METHODS: This retrospective study included patients with rectal cancer more than 1 year after laparoscopic or robotic-assisted surgery. We administered a questionnaire to evaluate the degree of LARS. In addition, we examined clinical characteristics with univariate and multivariate analysis to identify predictive factors for major LARS. Finally, we divided the obtained data into a learning set and a validation set. We constructed a predictive model for major LARS using the learning set and assessed the predictive accuracy of the validation set. RESULTS: We reviewed 160 patients with rectal cancer and divided them into a learning set (n = 115) and a validation set (n = 45). Univariate and multivariate analyses in the learning set showed that male (odds ratio [OR]: 2.88, 95% confidence interval [95%CI] 1.11-8.09, p = 0.03), age < 75 years (OR: 5.87, 95%CI 1.14-47.25, p = 0.03) and tumors located < 8.5 cm from the AV (OR: 7.20, 95%CI 2.86-19.49, p < 0.01) were significantly related to major LARS. A prediction model based on the patients in the learning set was well-calibrated. CONCLUSIONS: We found that sex, age, and tumor location were independent predictors of major LARS in Japanese patients that underwent rectal cancer surgery. Our predictive model for major LARS could aid medical staff in educating and treating patients with rectal cancer before and after surgery.

Fecal Stream Diversion Changes Intestinal Environment, Modulates Mucosal Barrier, and Attenuates Inflammatory Cells in Crohn's Disease.

BACKGROUND: The intestinal environment plays important roles in mucosal barrier homeostasis and intestinal inflammation, as clarified in studies using experimental animals but not in humans. AIMS: We investigated whether environmental changes in the fecal stream cause phenotypic changes in the human mucosal barrier. METHODS: We obtained human ileal samples after fecal stream diversions in patients with rectal cancer or Crohn's disease. We investigated the bacterial load and diversity in the human defunctioned ileum, defined as the anal side of the ileum relative to the ileostomy. We also examined the epithelium and lamina propria cell phenotypes in the defunctioned ileum. RESULTS: After fecal stream diversion, bacterial loads decreased significantly in the defunctioned ileum. Based on the Chao1, Shannon, and observed species indices, the diversity of mucosa-associated microbiota was lower in the defunctioned ileum than in the functional ileum. Moreover, the healthy defunctioned ileum showed reductions in villous height, goblet cell numbers, and Ki-67+ cell numbers. Additionally, interferon-γ+, interleukin-17+, and immunoglobulin A+ cell abundance in the lamina propria decreased. After the intestinal environment was restored with an ileostomy closure, the impaired ileal homeostasis recovered. The defunctioned ileum samples from patients with Crohn's disease also showed reductions in interferon-γ+ and interleukin-17+ cell numbers. CONCLUSIONS: Fecal stream diversion reduced the abundance and diversity of intestinal bacteria. It also altered the intestinal mucosal barrier, similar to the alterations observed in germ-free animals. In patients with Crohn's disease, Th1 and Th17 cell numbers were attenuated, which suggests that the host-microbiome interaction is important in disease pathogenesis.

The prediction of postoperative anorectal dysfunction after low anterior resection for lower rectal cancer by measuring the volume of defecation-related muscles.

PURPOSE: Approximately 90% of patients are thought to develop bowel dysfunction after low anterior resection (LAR). Although some prognostic factors have been reported, the volumes of defecation-related muscles have not been examined. This retrospective study investigated the association between the preoperative volume of defecation-related muscles and major LARS. METHODS: Forty-six patients who underwent LAR for rectal cancer between 2013 and 2020 in our institution were analyzed. They had no local residual tumor or local recurrence at the time of the study and no problems with their defecation function pre-operatively. Defecation-related muscle volume measurements were made before surgery, and the patients answered a low anterior resection syndrome (LARS) score questionnaire after surgery. The muscle volume was adjusted by the patient's height squared. RESULTS: Twenty-seven patients (58.7%) developed major LARS. In the univariate analysis, sex, lateral lymph node dissection, and diverting ileostomy as well as muscle volume of the external anal sphincter, pubococcygeal + iliococcygeus muscle, and puborectal muscle were associated with major LARS. In a multivariate analysis, pubococcygeal + iliococcygeus muscle (< 5.96 ml/m2) was the only factor (p = 0.02). CONCLUSIONS: Measuring the volume of the defecation-related muscles may aid in predicting major LARS.

Postoperative pain management after concomitant sacrectomy for locally recurrent rectal cancer.

PURPOSE: To assess pain management in patients post-sacrectomy, focusing on opioid use, and to identify the factors associated with postoperative pain. METHODS: Patients who underwent resection of locally recurrent rectal cancer (LRRC) with concomitant sacrectomy at one of two hospitals between 2007 and 2020 were reviewed retrospectively. We examined the use of opioids preoperatively and postoperatively. Patients were classified into high and low sacrectomy groups based on the sacral bone resection level passing through the S3 vertebra. RESULTS: Sixty-four patients were enrolled. Opioid use was significantly higher in the high sacrectomy group than in the low sacrectomy group at all times assessed: on postoperative days 7, 14, 30, 90, 180, and 365. Opioid use 3 months after locally recurrent rectal cancer surgery was significantly higher in patients with local re-recurrence of the tumor than in those without re-recurrence (p < 0.05), and the median morphine-equivalent opioid use 3 months postoperatively was significantly higher in the high sacrectomy group (30 vs. 0 mg/day; p < 0.05). CONCLUSIONS: Opioid use after concomitant sacrectomy for LRRC was higher in the high sacrectomy group. Prolonged postoperative pain or increasing pain was associated with local recurrence.

[A Case of Malignant Rectal B Cell Lymphoma That Was Difficult to Differentiate from Rectal Neuroendocrine Tumor].

A 74-year-old woman with a chief complaint of hematochezia was admitted to our hospital. Colonoscopy revealed a 2 cm submucosal tumor with an erosion in the Rb of the rectum. Biopsy showed various inflammatory cell clusters, but no malignant findings. Thoracoabdominal CT and abdominal MRI showed no abnormal findings other than that of rectal wall thickening. Somatostatin receptor scintigraphy performed on suspected rectal NET showed no abnormal accumulation. A total of 3 biopsies were performed, but a definitive diagnosis was not confirmed, and transanal rectal mucosal resection was performed for diagnostic purposes. Immunohistochemistry showed CD20(+)and bcl-2(+), and the lesion was diagnosed as malignant rectal B cell lymphoma. For 1 year postoperatively, the patient showed no recurrence. For this case, biopsy often failed to confirm a definitive diagnosis on rectal submucosal tumors. If the tumor is >1 cm in diameter in a rectal NET, a rectal resection with lymph node dissection is required, and anal function may be impaired. Local tumor excision for diagnosis and treatment may be worthwhile in rectal submucosal tumors if pre-resection diagnosis with biopsy is difficult.

[A Case of Nivolumab Responding to Multiple Lymph Node Metastases during Multidisciplinary Treatment for Esophageal Cancer].

In nivolumab therapy for unresectable advanced esophageal cancer, there are a few cases that show a complete response, and long-term survival can be expected in such cases. Here, we report a case in which nivolumab had a complete response to multiple lymph node metastases during multidisciplinary treatment for esophageal cancer and survived for a relatively long period despite being elderly. Examination of complete response cases provides us with significant insights in considering the unexplained biomarkers of immune checkpoint inhibitors and treatment discontinuation during complete response.

Specific activation of glycolytic enzyme enolase 2 in BRAF V600E-mutated colorectal cancer.

The BRAF V600E mutation occurs in approximately 10% of patients with metastatic colorectal cancer (CRC) and constitutes a distinct subtype of the disease with extremely poor prognosis. To address this refractory disease, we investigated the unique metabolic gene profile of BRAF V600E-mutated tumors via in silico analysis using a large-scale clinical database. We found that BRAF V600E-mutated tumors exhibited a specific metabolic gene expression signature, including some genes that are associated with poor prognosis in CRC. We discovered that BRAF V600E-mutated tumors expressed high levels of glycolytic enzyme enolase 2 (ENO2), which is mainly expressed in neuronal tissues under physiological conditions. In vitro experiments using CRC cells demonstrated that BRAF V600E-mutated cells exhibited enhanced dependency on ENO2 compared to BRAF wild-type cancer cells and that knockdown of ENO2 led to the inhibition of proliferation and migration of BRAF V600E-mutated cancer cells. Moreover, inhibition of ENO2 resulted in enhanced sensitivity to vemurafenib, a selective inhibitor of BRAF V600E. We identified AP-1 transcription factor subunit (FOSL1) as being involved in the transcription of ENO2 in CRC cells. In addition, both MAPK and PI3K/Akt signaling were suppressed upon inhibition of ENO2, implying an additional oncogenic role of ENO2. These results suggest the crucial role of ENO2 in the progression of BRAF V600E-mutated CRC and indicate the therapeutic implications of targeting this gene.

SIRT3-Mediated SOD2 and PGC-1α Contribute to Chemoresistance in Colorectal Cancer Cells.

BACKGROUND: Anticancer drugs generate excessive reactive oxygen species (ROS), which can cause cell death. Cancer cells can resist this oxidative stress, but the mechanism of resistance and associations with chemoresistance are unclear. Here, we focused on Sirtuin 3 (SIRT3), a deacetylating mitochondrial enzyme, in oxidative stress resistance in colorectal cancer (CRC). METHODS: To evaluate SIRT3-related changes in mitochondrial function, ROS (mtROS) induction, and apoptosis, we used the human CRC cell lines HT29 and HCT116 transfected with short-hairpin RNA targeting SIRT3 and small interfering RNAs targeting superoxide dismutase 2 mitochondrial (SOD2) and peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1α). In 142 clinical specimens from patients with CRC, we also assessed the association of SIRT3 protein levels (high/low) and prognosis. RESULTS: SIRT3 expression correlated with mtROS generation and apoptosis induction in cells treated with anticancer agents. Suppressing SIRT3 increased mtROS levels and cell sensitivity to anticancer agents. SIRT3 knockdown decreased SOD2 expression and activity, and suppressing SOD2 also improved sensitivity to anticancer drugs. In addition, SIRT3 was recruited with PGC-1α under oxidative stress, and suppressing SIRT3 decreased PGC-1α expression and mitochondrial function. PGC-1α knockdown decreased mitochondrial activity and increased apoptosis in cells treated with anticancer drugs. In resected CRC specimens, high vs low SIRT3 protein levels were associated with significantly reduced cancer-specific survival. CONCLUSIONS: SIRT3 expression affected CRC cell chemoresistance through SOD2 and PGC-1α regulation and was an independent prognostic factor in CRC. SIRT3 may be a novel target for CRC therapies and a predictive marker of sensitivity to chemotherapy.

Impact of the preoperative prognostic nutritional index as a predictor for postoperative complications after resection of locally recurrent rectal cancer.

BACKGROUND: Local recurrence is common after curative resections for rectal cancer. Surgical intervention is among the best treatment choices. However, achieving a negative resection margin often requires extensive pelvic organ resections; thus, the postoperative complication rate is quite high. Recent studies have reported that the inflammatory index could predict postoperative complications. This study aimed to validate the correlation between clinical factors, including inflammatory markers, and severe complications after surgery for local recurrent rectal cancer. METHODS: This retrospective study included 99 patients that underwent radical resections for local recurrences of rectal cancer. Postoperative complications were graded according to the Clavien-Dindo classification. Grades ≥3 were defined as severe complications. Risk factors for severe complications were identified with univariate and multivariate logistic regression models and assessed with receiver-operating characteristic curves. RESULTS: Severe postoperative complications occurred in 38 patients (38.4%). Analyses of correlations between inflammatory markers and severe postoperative complications revealed that the strongest correlation was found between the prognostic nutrition index and severe postoperative complications. The receiver-operating characteristic analysis showed that the optimal prognostic nutrition index cut-off value was 42.2 (sensitivity: 0.790, specificity: 0.508). In univariate and multivariate analyses, a prognostic nutrition index ≤44.2 (Odds ratio: 3.007, 95%CI:1.171-8.255, p = 0.02) and a blood loss ≥2850 mL (Odds ratio: 2.545, 95%CI: 1.044-6.367, p = 0.04) were associated with a significantly higher incidence of severe postoperative complications. CONCLUSIONS: We found that a low preoperative prognostic nutrition index and excessive intraoperative blood loss were risk factors for severe complications after surgery for local recurrent rectal cancer.

Exploratory analysis of lateral pelvic sentinel lymph node status for optimal management of laparoscopic lateral lymph node dissection in advanced lower rectal cancer without suspected lateral lymph node metastasis.

BACKGROUND: Total mesorectal excision (TME) and lateral lymph node dissection (LLND) without radiotherapy (RT) are standard treatment for lower cT3/4 rectal cancers in Eastern countries. In comparative studies, both TME + LLND and RT + TME yield good local control. Although Japanese guidelines recommend LLND for locally advanced rectal cancers below the peritoneal reflection, LLND dissection of clinically negative lateral pelvic lymph nodes (LPLN) is controversial, and laparoscopic TME + LLND is technically challenging and time-consuming. New optical instruments for laparoscopy allow easy perioperative sentinel lymph node (SLN) identification using ICG. The SLN concept may facilitate accurate diagnosis of LPLN involvement, and thus reduce LLND in laparoscopic rectal cancer surgery. Here we investigated lateral pelvic SLN navigation surgery for SLN detection during laparoscopic rectal cancer surgery. METHODS: This study included 21 patients with clinical StageII/III lower rectal cancer without LPLN enlargement, who underwent curative laparoscopic surgery. All patients underwent TME, followed by lateral SLN identification and biopsy using ICG, and then laparoscopic LLND. ICG fluorescence imaging was conducted using the laparoscopic near-infrared camera system. RESULTS: Lateral SLNs were successfully identified in 16 (76.2%) of the 21 patients. Among the 15 patients without SLN tumor metastasis, the dissected lateral non-SLNs were all negative. CONCLUSIONS: A lack of metastasis in the lateral pelvic SLN seems to reflect a lack of metastases to all lateral LNs. Our present results suggest that this laparoscopic ICG-guided SLN strategy may be a low-risk and time-saving method to prevent laparoscopic LLND in cases with negative lateral pelvic lymph nodes.

Efficacy of positron emission tomography in diagnosis of lateral lymph node metastases in patients with rectal Cancer: a retrospective study.

BACKGROUND: The presence of lateral pelvic lymph node (LLN) metastasis is an essential prognostic factor in rectal cancer patients. Thus, preoperative diagnosis of LLN metastasis is clinically important to determine the therapeutic strategy. The aim of this study was to evaluate the efficacy of preoperative positron emission tomography/computed tomography (PET/CT) in the diagnosis of LLN metastasis. METHODS: Eighty-four patients with rectal cancer who underwent LLN dissection at Osaka University were included in this study. The maximum standardized uptake value (SUVmax) of the primary tumor and LLN were preoperatively calculated using PET/CT. Simultaneously, the short axis of the lymph node was measured using multi-detector row computed tomography (MDCT). The presence of metastases was evaluated by postoperative pathological examination. RESULTS: Of the 84 patients, LLN metastases developed in the left, right, and both LLN regions in 6, 7, and 2 patients, respectively. The diagnosis of the metastases was predicted with a sensitivity of 82%, specificity of 93%, positive predictive value of 58%, negative predictive value of 98%, false positive value of 7%, and false negative value of 18% when the cutoff value of the LLN SUVmax was set at 1.5. The cutoff value of the short axis set at 7 mm on MDCT was most useful in diagnosing LLN metastases, but SUVmax was even more useful in terms of specificity. CONCLUSIONS: The cutoff value of 1.5 for lymph node SUVmax in PET is a reasonable measure to predict the risk of preoperative LLN metastases in rectal cancer patients.

Dipeptidyl Peptidase 9 Increases Chemoresistance and is an Indicator of Poor Prognosis in Colorectal Cancer.

BACKGROUND: In recent years, systemic chemotherapy has significantly improved the prognosis of metastatic colorectal cancer (CRC); however, different patients have different responses to chemotherapeutics. METHODS: Dipeptidyl peptidase 9 (DPP9) is an enzyme in the dipeptidyl peptidase IV family that has been reported to increase drug sensitivity in acute myeloid leukemia. In this study, we examined the relationship between DPP9 expression and the prognosis of patients with CRC, as well as the role of DPP9 in anticancer drug resistance. Moreover, the effects of the DPP9 inhibitors talabostat and vildagliptin in CRC cell lines and primary cultured cells were assessed. RESULTS: High expression of DPP9 was associated with worse prognosis in 196 patients with CRC. Cell viability was markedly inhibited in CRC cell lines transfected with DPP9 small interfering RNA or small hairpin RNA. Talabostat suppressed proliferation in CRC cell lines and primary cultured cells, and increased their sensitivity to chemotherapy. Vildagliptin, a DPP family inhibitor currently administered for diabetes, also increased the sensitivity of CRC cells to anticancer drugs. CONCLUSION: DPP9 was a poor prognostic factor for CRC and could be a new therapeutic target, while vildagliptin could be used as a repositioned drug for CRC treatment.

Implantation of human adipose-derived stromal cells for the functional recovery of a murine heat-damaged muscle model.

In cases of lower rectum-located tumor or severe disease, surgical resection is currently the effective management; however, it also carries increased risks of function loss. The interdisciplinary field of regenerative medicine offers strategies that can potentially restore severely diseased and injured tissues and organs. Adipose-derived stromal cells (ASCs) are an abundant and accessible source of adult stem cells and hold great promise as therapeutic agents for tissue regeneration. In this work, we transplanted cells isolated from human stromal tissues, including a 6%-7% ASC population, into heat-damaged femoral muscles of non-obese diabetic immunodeficient mice. The movement of the limbs was observed to determine the functional recovery 3 months after transplantation. Among the mice that did not receive cell transplantation, 20% were able to walk with the injured limb touching the ground, while all of the mice in the ASC-treatment group were able to walk. Furthermore, all ASC-treated mice were able to stand on both back paws, in contrast to the control group mice. The human stromal cell population containing ASCs was able to differentiate and engraft the injured muscle tissues successfully. Our results indicate that stromal material/ASC-based therapies are a promising strategy for the regeneration of tissues and function restoration after severe injury due to surgery.

Development of a novel prediction model for recurrent stage II colon cancer.

PURPOSE: Adjuvant chemotherapy is recommended for patients with high-risk stage II colon cancer. High-risk stage II is defined by clinicopathological factors in some guidelines. However, there is no unified definition. The aim of this study was to examine the risk factors and develop a novel model to predict the recurrence of stage II colon cancer. METHODS: Three hundred fifty patients who underwent curative resection for stage II colon cancer at Osaka International Cancer Institute and Yao Municipal Hospital from 2004 to 2012 were included. Clinicopathological factors were assessed in a subgroup of 298 patients (Learning Set), and the relapse-free survival (RFS) rate was evaluated as the main outcome. A statistical analysis was performed using a proportional hazards model to determine the factors associated with RFS and a nomogram was developed to predict recurrence. A second subgroup of 52 independent patients who underwent curative resection in 2012 (Validation Set) was used to validate the nomogram. RESULTS: The median RFS time was 4.96 years, and recurrence was observed in 35 patients. A univariate analysis revealed that a high serum CEA level, preoperative occlusion, tumor location (left-side colon), lymphatic invasion, and vascular invasion were significantly correlated with RFS. These variables were used to develop the nomogram. The C-index was 0.701 in the learning set and 0.585 in the validation set. Using nomogram points, the patients were classified into low-risk, middle-risk, and high-risk categories. CONCLUSION: A recurrence prediction model was developed that integrated multiple risk factors in stage II colon cancer patients. High-risk patients were identified by the nomogram.

The inflammation-nutrition score supports the prognostic prediction of the TNM stage for colorectal cancer patients after curative resection.

PURPOSE: Inflammation and the nutritional and immunologic status are known to be associated with the prognosis of malignant tumors. We aimed to examine inflammation-nutrition scores and predict the prognosis of colorectal cancer (CRC) patients by integrating nutritional and immunologic factors and tumor stage. METHODS: This study investigated 511 patients with CRC from 2007 to 2013: 380 in a training set (TS) and 131 in a validation set (VS). The Osaka Prognostic Score (OPS) used comprised 1 point each for C-reactive protein > 1.0 mg/dL, albumin (< 3.5 g/dL), and lymphocyte count < 1600. Patients were classified according to the total points. The modified Glasgow Prognostic Score and the Prognostic Nutritional Index were also examined. A nomogram for predicting the disease-free survival (DFS) and overall survival (OS) was constructed based on the OPS and TNM stage. RESULTS: In the TS, a high OPS and high TNM stage were significant predictors of the DFS and OS. The C-indexes of the OPS for the DFS and OS were higher than those of other reported scoring systems. The C-index of the nomogram for the DFS was 0.762 in the TS and 0.675 in the VS. The C-index of the nomogram for the OS was 0.805 in the TS and 0.743 in the VS. CONCLUSION: Integrating the TNM stage and OPS accurately predicted the prognosis of patients with CRC.

Predicting lateral pelvic lymph node metastasis based on magnetic resonance imaging before and after neoadjuvant chemotherapy for patients with locally advanced lower rectal cancer.

PURPOSE: We examined the association between pathological lateral pelvic lymph node (LPLN) metastasis and the LPLN diameter in patients with locally advanced rectal cancer (LARC) who received a neoadjuvant chemotherapy (NAC) regimen based on oxaliplatin as induction chemotherapy. We aimed to determine whether or not the LPLN size predicts LPLN metastasis in NAC cases. METHODS: We retrospectively examined data from 3 institutes for 60 patients with LARC who received mesorectal excision and LPLN dissection after NAC. We evaluated the LPLN size on magnetic resonance imaging (MRI) scans acquired before and after NAC. We performed multivariate analyses to analyze the relationship between the LPLN size and clinicopathological factors. RESULTS: For patients with visible LPLNs, the median short-axis diameter (SA) was significantly reduced from 5.1 mm (range 2.0-17.4) before NAC to 3.7 mm (range 2.1-19.0) after NAC (p = 0.0479). SA diameters were significantly larger in pathological LPLNs than in healthy LPLNs, both before (p = 0.0002) and after NAC (p < 0.0001). A SA cut-off value of 7 mm before NAC was able to independently predict lymph node metastasis (p = 0.0178). CONCLUSIONS: We showed that MRI-based evaluations of LPLN size were able to predict metastasis in patients who underwent NAC for LARC. This finding might be useful when considering selective LPLN dissection in NAC cases.