[A Case of Clostridium difficile Enteritis with Ileostomy for Rectal Cancer Surgery].

A 74-year-old male presenting with bloody stools was diagnosed with advanced rectal cancer. He underwent robot- assisted low anterior resection and temporary ileostomy. Cefmetazole(CMZ)was administered during surgery and on postoperative day(POD)1. His postoperative course was generally good. On POD8, he developed abdominal fullness, vomiting, renal dysfunction, and hyperkalemia. Plain CT revealed small bowel ileus and outlet obstruction with ileostomy was suspected. A nasogastric tube was placed in the stomach, and a balloon catheter was inserted from the ileostomy to the oral side of the ileum. The patient went into shock on the same day and was transferred to a high-care unit. Contrast-enhanced CT indicated pneumatosis intestinalis of the small bowel and portal venous gas. However, the wall of the small bowel was enhanced, so the patient was observed carefully without attempting an operation. The patient's condition improved with systemic management. On POD10, a stool culture from the ileostomy tested positive for CD toxin. Clostridium difficile enteritis(CDE)was diagnosed. The condition improved with systemic control. On POD52, paralytic ileus recurred, and his stool tested positive for the CD toxin again. The ileus improved with conservative treatment. On POD70, the patient was transferred to the hospital for rehabilitation. We report a case of CDE with ileostomy for rectal cancer surgery.

12-Chemokine signature, a predictor of tumor recurrence in colorectal cancer.

Tertiary lymphoid structures (TLSs) provide an immunological antineoplastic effect. Recent evidences link a unique 12-chemokine (CCL2, -3, -4, -5, -8, -18, -19, -21, CXCL9, -10, -11, -13) signature status from tumor tissue and the TLS expression. However, the potential significance of 12-chemokine signature status for clinical use is unknown. We aimed to evaluate the association of 12-chemokine signature status with patient outcomes in colorectal cancer (CRC). We used integrated data of resected 975 CRC cases within three independent cohorts from France, Japan and the United States (GSE39582, KUMAMOTO from Kumamoto university hospital and TCGA). The association of 12-chemokine signature status with clinicopathological features, patient outcome, TLS expression status and key tumor molecular features was analyzed. Patients with low 12-chemokine signature status had a significant shorter relapse-free survival in discovery cohort (HR: 1.61, 95% CI: 1.11-2.39, p = 0.0123), which was confirmed in validation cohort (HR: 3.31, 95% CI: 1.33-10.08, p = 0.0087). High 12-chemokine signature status had significant associations with right-sided tumor, high tumor-localized TLS expression, BRAF mutant, CIMP-high status and MSI-high status. Furthermore, RNA-seq based analysis showed that high 12-chemokine signature status was strongly associated with inflammation-related, immune cells-related and apoptosis pathways (using gene set enrichment analysis), and more tumor-infiltrating immune cells, such as cytotoxic T lymphocytes and myeloid dendritic cells (using MCP-counter analysis). We investigated a promising effect of 12-chemokine signature status in CRC patients who underwent resection. Our data may be helpful in developing novel immunological treatment strategies for CRC.

[A Case of Small Bowel Perforation Due to Lung Cancer Metastasis].

A 79-year-old man was diagnosed with Stage ⅢB(T4N2M0)adenocarcinoma of the lung, administered. He suddenly developed abdominal pain with muscle guarding and rebound tenderness. An abdominal computed tomography scan revealed a thickened small bowel wall and mesenteric mass, as well as massive ascites and free air. He underwent an emergency laparotomy following a diagnosis of pan-peritonitis due to intestinalperforation. A partialresection of the smallintestine and abdominal drainage were performed. The resected specimen included an ulcerative lesion on the mucosal surface. The pathological diagnosis was a metastasis of lung cancer. The patient died in hospice 29 days postoperatively. In the present case, however, surgery improved the patient's quality of life. Although lung cancer metastasis to the small bowel is associated with a poor prognosis, palliative surgery is indicated in otherwise fatal circumstances.

[A Clinical Study of Seven Cases of LECS for Gastric Submucosal Tumors].

Laparoscopy and endoscopy cooperative surgery(LECS)is a surgical technique to resect a tumor with minimal invasion, using both a laparoscope and endoscope. Twenty-eight surgeries for gastric submucosal tumors(SMT)were performed between 2009 and 2019. Seven of those cases were performed using LECS. Two male and 5 female patients underwent LECS; their mean age was 53 years. The tumors were located at the anterior wall of the fornix in 1 case, anterior wall of the subcardia in 2 cases, anterior wall of the upper gastric body in 3 cases, and anterior wall of the lower gastric body in 1 case. Two cases were intraductal growing types, and 5 cases were intramural growing types. No postoperative complications have occurred. The mean size of the tumors was 21.1 mm. In pathological findings, 5 cases were gastrointestinal stromal tumor (GIST); 1 case was high risk, 2 cases were low risk, and 1 case was very low risk as classified using the modified-Fletcher's classification. Imatinib was administered to the high risk case, and there have been no recurrences in any cases.

[Radical Surgery Following Chemotherapy in a Patient with Mesenteric Recurrence Associated with Hematoma upon ESD for Rectal Cancer Three Years Six months Later].

A63 -year-old man complaining of anal pain visited our hospital. Three years 6 months previously, the patient underwent endoscopic submucosal dissection(ESD)for early-stage rectal cancer. Based on the pathological findings, adenocarcinoma with invasion to the submucosal layer(2,000 mm)and lymphovascular invasion were diagnosed. Abdominal computed tomography( CT)revealed a solid tumor 50mm in diameter and hematoma measuring approximately 90mm in length adjoining the tumor in the mesorectum. We performed exploratory laparoscopy. Ahematoma was confirmed in the mesentery from the sigmoid colon and rectum. After the surgery, endoscopic ultrasound-guided fine needle aspiration(EUS-FNA)revealed well-differentiated adenocarcinoma. We diagnosed a hematoma associated with mesenteric recurrence following ESD for rectal cancer. The patient received chemotherapy first because of the large size of the recurrent cancer. Four courses of mFOLFOX6(5-FU: bolus 400mg/m / / / 2,2,400mg/m2,oxaliplatin 85 mg/m2) and panitumumab(6 mg/kg)were administered. Based on the CT findings following chemotherapy, the hematoma had disappeared, and the size of the recurrent cancer in the mesorectum reduced to 28 mm. The patient underwent laparoscopic lower anterior resection with D3 lymph node dissection and ileostomy. The postoperative course was uneventful. Currently, the patient has no recurrence.

Colorectal Cancer Stem Cells Acquire Chemoresistance Through the Upregulation of F-Box/WD Repeat-Containing Protein 7 and the Consequent Degradation of c-Myc.

The cancer stem cell (CSC) paradigm suggests that tumors are organized hierarchically. Chugai previously established an LGR5+ human colorectal cancer (CRC) stem-cell-enriched cell line (colorectal CSCs) that expresses well-accepted colorectal CSC markers and that can dynamically switch between proliferative and drug-resistant noncycling states. We performed this study to elucidate the molecular mechanisms responsible for evading cell death in colorectal CSCs mediated by anticancer agents. During the cell cycle arrest caused by anticancer agents, we found that c-Myc expression was substantially decreased in colorectal CSCs. The c-Myc expression alterations were mediated by upregulation of F-box/WD repeat-containing protein 7 (FBXW7), as evidenced through FBXW7-small interfering RNA knockdown experiments that resulted in enhanced cell sensitivity to anticancer agents. Upregulation of FBXW7 following drug treatment was not evident in commercially available cancer cell lines. Colorectal CSCs were induced to differentiation by Matrigel and fetal bovine serum. Differentiated CSCs treated with anticancer agents did not show upregulation of FBXW7 and were more sensitive to irinotecan (CPT-11), highlighting the potential CSC-specific nature of our data. The FBXW7 over-expression was further validated in resected liver metastatic sites in CRC patients after chemotherapy. In conclusion, our study revealed that a CSC-specific FBXW7-regulatory mechanism is strongly associated with resistance to chemotherapeutic agents. Inhibition of FBXW7-upregulation in CSCs following chemotherapy may enhance the response to anticancer agents and represents an attractive strategy for the elimination of colorectal CSCs. Stem Cells 2017;35:2027-2036.

Controlling Nutritional Status (CONUT) score is a prognostic marker for gastric cancer patients after curative resection.

BACKGROUND: Controlling Nutritional Status (CONUT), as calculated from serum albumin, total cholesterol concentration, and total lymphocyte count, was previously shown to be useful for nutritional assessment. The current study investigated the potential use of CONUT as a prognostic marker in gastric cancer patients after curative resection. METHODS: Preoperative CONUT was retrospectively calculated in 416 gastric cancer patients who underwent curative resection at Kumamoto University Hospital from 2005 to 2014. The patients were divided into two groups: CONUT-high (≥4) and CONUT-low (≤3), according to time-dependent receiver operating characteristic (ROC) analysis. The associations of CONUT with clinicopathological factors and survival were evaluated. RESULTS: CONUT-high patients were significantly older (p < 0.001) and had a lower body mass index (p = 0.019), deeper invasion (p < 0.001), higher serum carcinoembryonic antigen (p = 0.037), and higher serum carbohydrate antigen 19-9 (p = 0.007) compared with CONUT-low patients. CONUT-high patients had significantly poorer overall survival (OS) compared with CONUT-low patients according to univariate and multivariate analyses (hazard ratio: 5.09, 95% confidence interval 3.12-8.30, p < 0.001). In time-dependent ROC analysis, CONUT had a higher area under the ROC curve (AUC) for the prediction of 5-year OS than the neutrophil lymphocyte ratio, the Modified Glasgow Prognostic Score, or pStage. When the time-dependent AUC curve was used to predict OS, CONUT tended to maintain its predictive accuracy for long-term survival at a significantly higher level for an extended period after surgery when compared with the other markers tested. CONCLUSIONS: CONUT is useful for not only estimating nutritional status but also for predicting long-term OS in gastric cancer patients after curative resection.

Risk factors for pulmonary morbidities after minimally invasive esophagectomy for esophageal cancer.

BACKGROUND: Pulmonary morbidities after esophagectomy are still common and are a major cause of surgery-related mortality. The relationship between minimally invasive esophagectomy (MIE) and pulmonary morbidities is not clear. The current study aimed to examine the incidence of pulmonary morbidities after MIE and to clarify the associated risk factors. METHODS: Between May 2011 and December 2016, 184 patients underwent MIE for esophageal cancer. Clinical data were prospectively collected and analyzed. Patient- and surgery-related factors, relating to pulmonary complications, were compared between the complicated and uncomplicated cases. RESULTS: The incidence of any pulmonary morbidity following MIE was 17.9%. Univariate analysis showed that past heavy smoking [Brinkman index (BI) ≥ 1000], presence of neoadjuvant therapy, advanced clinical stage (stage III, IV), and intraoperative bleeding ≥ 600 g were candidates for being postoperative pulmonary morbidity risk factors. Multivariate analysis suggested that BI ≥ 1000 and advanced clinical stage were independent risk factors for causing pulmonary morbidities. CONCLUSIONS: Past heavy smoking and advanced stage are independent risk factors for pulmonary morbidities after MIE. When performing MIE for such cases, various preoperative precautions and careful postoperative monitoring are necessary.

Additional lymph node dissection for primary colorectal cancer invading another colon region.

PURPOSE: Surgery remains the curative treatment of choice for colorectal cancer (CRC). However, to our knowledge, no report has addressed the usefulness of additional regional lymph node dissection for primary CRC that has invaded another colon region. METHODS: We reviewed the clinicopathological characteristics and outcomes of eight patients who underwent surgery between March, 2005 and August, 2014, for CRC that invaded another region of the colon. RESULTS: Five patients underwent additional regional lymph node dissection in the area of the invaded colon and one patient had lymph node metastasis in the region. Two of three patients who did not undergo additional regional lymph node dissection were found to have regional lymph node recurrences in the area during the follow-up period. Although there was no statistical correlation between extra-regional lymph node metastasis and clinicopathological or operative factors, the patients with extra-regional lymph node metastasis or recurrence had primary regional lymph node metastasis. CONCLUSION: For curative intent, surgeons may need to perform additional regional lymph node dissection for primary CRC invading another colon region.

[A Case of Mesenteric Malignant Lymphoma Treated Using Single-Port Surgery and an Umbilical ZigZag Incision].

A 73 -year-old man was found to have a mesenteric tumor on abdominal ultrasonography and computed tomography (CT). Single-port laparoscopic surgery using an umbilical ZigZag incision was performed. Operative findings revealed that the tumor involved the mesentery. The tumor and a section of small intestines were resected. Pathological examination diagnosed follicular lymphoma. Single-port laparoscopic surgery using an umbilical ZigZag incision is superior for manipulation of forceps and evisceration. This operative method may be useful for resection or biopsy of mesenteric tumors.

CONUT: a novel independent predictive score for colorectal cancer patients undergoing potentially curative resection.

BACKGROUND: Controlling nutritional status (CONUT) score, calculated from serum albumin and total cholesterol concentrations and total lymphocyte count, is reportedly valuable for nutritional assessment. This study investigated whether CONUT score was predictive of outcomes in colorectal cancer (CRC) patients undergoing surgical resection. METHODS: Preoperative CONUT scores were retrospectively evaluated in 417 CRC patients who underwent potentially curative resection at Kumamoto University Hospital from March 2005 to August 2014. Patients were divided into four groups based on preoperative CONUT scores: normal, light, moderate, and severe. The associations of CONUT score with clinicopathological factors, patient survival, and postoperative complications were examined. RESULTS: CONUT score correlated significantly with age (P < 0.001), body mass index (P = 0.005), carcinoembryonic antigen (P = 0.002), and carbohydrate antigen 19-9 (P = 0.005) concentrations. Overall survival (OS) rate was significantly lower in patients with moderate/severe than light or normal CONUT scores. CONUT score was independently prognostic of OS [moderate/severe vs. normal, hazard ratio = 5.92, 95 % confidence interval (CI) 2.30-14.92; P < 0.001)]. Patients with moderate/severe CONUT scores were at greater risk for complications, especially for severe complications. Multivariate analysis showed that CONUT score was independently predictive of severe complications (moderate/severe vs. normal, odds ratio = 4.51, 95 % CI 1.89-10.74; P < 0.001). CONCLUSIONS: CONUT score may predict survival and postoperative severe complications in CRC patients undergoing potentially curative resection. Management of CRC patients may need consideration of host nutritional status.

The Presence of Serum p53 Antibody Predicts the Pathological Tumor Response to Neoadjuvant Chemotherapy with Docetaxel, Cisplatin and Fluorouracil (DCF) in Esophageal Squamous Cell Carcinoma.

BACKGROUND: Docetaxel, cisplatin and fluorouracil (DCF) is a candidate neoadjuvant chemotherapy (NAC) regimen for esophageal squamous cell carcinoma (ESCC). Although the efficacy and safety of DCF have been reported, the markers that predict the patient's response are still unknown. The aim of this study was to identify the predictive markers for a response to NAC with DCF in patients with ESCC. METHODS: A total of 79 patients who received preoperative DCF followed by esophagectomy between August 2008 and December 2014 were enrolled in this study. All of the patients completed 2 preoperative courses of DCF. The clinical and pathological responses to DCF were investigated, and the associations between the pathological response, the clinicopathological factors and the prognosis were retrospectively analyzed. RESULTS: Among the 79 patients, the pathological response to DCF (evaluated according to the Japanese Classification of Esophageal Cancer) was grade 3 (complete pathological response) in 7 patients (8.9 %), grade 2 in 13 patients (16.5 %), grade 1b in 8 patients (10.1 %) and grade 1a in 51 patients (64.6 %). A good pathological response (grade 2-3) was significantly associated with both favorable disease-free survival (P = 0.0051) and favorable cancer-specific survival (P = 0.0366). A multivariate analysis revealed that a good clinical response (HR 13.743, 95 % CI 2.455-76.917) and the presence of serum p53 antibody before treatment (HR 3.987, 95 % CI 1.103-14.416) were independent predictors of good pathological response. CONCLUSIONS: The presence of serum p53 antibody can be used as a novel, noninvasive predictor of the pathological tumor response to NAC with DCF in ESCC patients.

Preoperative controlling nutritional status (CONUT) is useful to estimate the prognosis after esophagectomy for esophageal cancer.

PURPOSE: The aim of this study is to confirm the predictive value of controlling nutritional status (CONUT), as a postoperative prognostic marker for esophageal cancer patients undergoing esophagectomy. METHODS: We retrospectively analyzed 373 patients who underwent three-incision esophagectomy with 2- or 3-field lymphadenectomy for esophageal cancer between April 2005 and March 2016. The patients were divided into three groups based on the degree of preoperative malnutrition as assessed by CONUT: normal, light malnutrition, and moderate or severe malnutrition. RESULTS: The patients with moderate or severe malnutrition experienced a significantly higher frequency of reoperation (normal or light malnutrition, 6.3%; moderate or severe malnutrition, 18.2%; P = 0.033) and a higher tendency for respiratory morbidities (normal or light malnutrition, 14.0%; moderate or severe malnutrition, 27.3%; P = 0.088). Cox regression analysis identified a significantly poor prognosis, in both overall survival (hazard ratio (HR), 3.56; 95% confidence interval (CI), 1.714-7.390; P < 0.001) and cancer-specific survival (HR, 3.41; 95% CI, 1.790-6.516; P = 0.046). CONCLUSIONS: CONUT is convenient and useful for preoperatively assessing malnutrition and prognosis of esophageal cancer patients who underwent surgery.

Comparison of systemic inflammatory and nutritional scores in colorectal cancer patients who underwent potentially curative resection.

BACKGROUND: Various systemic inflammatory and nutritional scores have been reported to predict postoperative outcomes. This study aimed to investigate the best systemic inflammatory and nutritional scores in colorectal cancer (CRC) patients who underwent potentially curative resection. METHOD: We evaluated 468 consecutive CRC patients in this study. Comparisons of systemic inflammatory and nutritional scores, including the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), prognostic index (PI), prognostic nutritional index (PNI), and modified Glasgow prognostic score (mGPS), were performed using univariate/multivariate analyses for patient survival. RESULTS: The PNI and mGPS, but not the NLR, PLR, and PI, were significantly associated with overall and relapse-free survival. The mGPS, but not the PNI, was strongly correlated with TNM stage (P < 0.001). Cox multivariate analysis showed that both the PNI and mGPS were exclusive independent prognostic factors for both overall and relapse-free survival (P < 0.001). Furthermore, the PNI status predicted patient survival more clearly than the mGPS in combination with TNM stage. CONCLUSIONS: This study suggests that the PNI and mGPS are useful predictive scores in CRC patients who undergo potentially curative resection, especially the PNI in combination with TNM stage. Routine evaluation of the host status using the scores may be useful in CRC treatment.

Elevated preoperative neutrophil-to-lymphocytes ratio predicts poor prognosis after esophagectomy in T1 esophageal cancer.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has been reported to predict the prognosis of various malignant tumors, including esophageal cancer. However, no previous reports have supported the use of the preoperative NLR as an independent prognostic marker focused on superficial (T1) esophageal cancer. The aim of this study was to elucidate the prognostic impact of the preoperative NLR in T1 esophageal cancer. METHODS: This retrospective study recruited 245 consecutive patients with T1 esophageal cancer who underwent subtotal esophagectomy between 2005 and 2016. The relationship between the preoperative NLR and clinicopathological characteristics was analyzed. RESULTS: The preoperative NLR was significantly higher in male patients (p = 0.029), patients with T1b esophageal cancer (p = 0.0274), and patients with venous vessel invasion (p = 0.0082). In the Kaplan-Meier analysis, the elevated preoperative NLR was significantly associated with a poorer disease-free survival (p < 0.0001) and overall survival (p = 0.0004). In the multivariate Cox model, the elevated preoperative NLR was an independent prognostic marker for both disease-free survival (p = 0.0013) and overall survival (p = 0.0027). CONCLUSION: An elevated preoperative NLR predicts poor prognosis in T1 esophageal cancer, suggesting the utility of the NLR as an easily measurable and generally available independent prognostic marker.

Estimation of Physiologic Ability and Surgical Stress (E-PASS) versus modified E-PASS for prediction of postoperative complications in elderly patients who undergo gastrectomy for gastric cancer.

BACKGROUND: Improvements in operative technique and perioperative management have resulted in increasing numbers of elderly patients undergoing gastrectomy for gastric cancer (GC). We evaluated the accuracy of Estimation of Physiologic Ability and Surgical Stress (E-PASS) and modified (m)E-PASS scores in predicting postoperative complications in elderly patients with GC. METHODS: We retrospectively analyzed short-term outcomes in 413 patients who underwent gastrectomy for GC between 2005 and 2014. They were divided into two groups: Group N comprised 341 non-elderly patients <80 years of age and Group E comprised 72 elderly patients ≥80 years of age. We calculated the E-PASS and mE-PASS scores and evaluated the correlation between the comprehensive risk score (CRS) and occurrence of postoperative complications. RESULTS: Morbidity rates were 25.5 % in Group N and 31.9 % in Group E. In Group N, the CRS values of both the E-PASS (P < 0.0001) and mE-PASS (P < 0.0001) scores were significantly higher in patients with complications than in those without complications. In Group E, although the E-PASS CRS was significantly higher in patients with complications than in patients without complications (P = 0.01), the mE-PASS CRS fixed (CRSf) score was not significantly correlated with the occurrence of postoperative complications (P = 0.08). CONCLUSION: Both E-PASS and mE-PASS can be used to predict the occurrence of postoperative complications in GC patients undergoing gastrectomy. However, the E-PASS CRS is more accurate for elderly patients because variations in intraoperative parameters such as operation time, blood loss, and extent of skin incision have a strong influence on the occurrence of postoperative complications.

A prospective study of XELIRI plus bevacizumab as a first-line therapy in Japanese patients with unresectable or recurrent colorectal cancer (KSCC1101).

BACKGROUND: This study was designed to evaluate the efficacy and toxicity of XELIRI plus bevacizumab for the treatment of Japanese patients with unresectable or recurrent colorectal cancer (CRC). METHODS: This was a multicenter, single-arm, open-label prospective study. The major inclusion criteria were previously untreated unresectable or recurrent CRC, presence of measurable lesions, ≥20 years of age, Eastern Cooperative Oncology Group performance status 0 or 1, and adequate organ function. Patients received bevacizumab (7.5 mg/kg on day 1) and XELIRI (irinotecan 200 mg/m2 on day 1 plus capecitabine 800 mg/m2 b.i.d. on days 1-14) every 3 weeks. The primary endpoint was the objective tumor response rate. RESULTS: A total of 36 patients were enrolled in this study from July 2011 to September 2012. One patient did not fulfill the eligibility criteria and one patient withdrew their consent before the start of the treatment protocol. The confirmed objective response rate was 58.8% (95% CI 35.1-70.2%). The median progression-free survival was 9.6 months (95% CI 5.1-11.1 months) and the median overall survival was 23.1 months (95% CI 11.3-36.7 months). The grade ≥3 adverse events that were frequently encountered in this study were neutropenia (31.4%), leukopenia (22.9%), diarrhea (22.9%), anemia (20.0%), anorexia (20.0%) and febrile neutropenia (17.2%). The frequency of grade 3/4 adverse events, such as neutropenia and leukopenia, was much higher in patients with a UGT1A1 polymorphism. CONCLUSIONS: A first-line therapy comprising XELIRI plus bevacizumab yielded a promising response rate. However, careful attention should be given to adverse clinical events in Japanese patients receiving treatment with unresectable or recurrent CRC.

The utility of tumor marker combination, including serum P53 antibody, in colorectal cancer treatment.

PURPOSES: Serum P53 antibody (S-P53Ab) is reportedly an effective screening tool for cancer. The aim of this study is to investigate the clinical significance of tumor markers combination in colorectal cancer (CRC) patients. METHODS: Carcinoembryonic antigen (CEA), carbohydrate 19 - 9 (CA19-9), and S-P53Ab levels were measured before tumor resection. Of the CRC patients with primary tumor resection at Kumamoto University Hospital, a total of 244 with available preoperative data for these three tumor markers were eligible for this study. The associations of the tumor markers with clinicopathological factors and the prognosis were examined using univariate and multivariate analyses. RESULTS: S-P53Ab positivity was strongly correlated with rectal cancer, depth of tumor invasion, lymph node metastasis, and lymphatic invasion. The ratio of S-P53Ab positivity was higher than that of CEA or CA19-9 in patients with stage 0/I disease. S-P53Ab had no power to predict the prognosis (P = 0.786). The patients with combined CEA and CA19-9 positivity had a significantly poorer overall survival than those with positivity for neither or only one, and combined CEA and CA19-9 positivity was an exclusive independent prognostic factor (P = 0.034). CONCLUSIONS: The clinical significance of S-P53Ab measurement in CRC patients is limited. However, the combination of CEA and CA19-9 levels may be effective for predicting the outcomes of CRC treatment.

Lysine-specific demethylase-1 contributes to malignant behavior by regulation of invasive activity and metabolic shift in esophageal cancer.

Lysine-specific demethylase-1 (LSD1) removes the methyl groups from mono- and di-methylated lysine 4 of histone H3. Previous studies have linked LSD1 to malignancy in several human tumors, and LSD1 is considered to epigenetically regulate the energy metabolism genes in adipocytes and hepatocellular carcinoma. This study investigates the function of LSD1 in the invasive activity and the metabolism of esophageal cancer cells. We investigated whether LSD1 immunohistochemical expression levels are related to clinical and pathological features, including the maximum standard uptake value in fluorodeoxyglucose positron emission tomography assay. The influence of LSD1 on cell proliferation, invasion and glucose uptake was evaluated in vitro by using specific small interfering RNA for LSD1, and an LSD1 inhibitor. We also evaluated two major energy pathways (glycolytic pathway and mitochondrial respiration) by measuring the extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR) with an extracellular flux analyzer. High LSD1 immunohistochemical expression was significantly associated with high tumor stage, lymphovascular invasion, poor prognosis, and high maximum standard uptake value in esophageal cancer patients. In the in vitro analysis, LSD1 knockdown significantly suppressed the invasive activity and glucose uptake of cancerous cells, reduced their ECAR and increased their OCR and OCR/ECAR. LSD1 may contribute to malignant behavior by regulating the invasive activity and metabolism, activating the glycolytic pathway and inhibiting the mitochondrial respiration of esophageal cancer cells. The results support LSD1 as a potential therapeutic target.

CXCL12/CXCR4 activation by cancer-associated fibroblasts promotes integrin ß1 clustering and invasiveness in gastric cancer.

Cancer-associated fibroblasts (CAFs) are reportedly involved in invasion and metastasis in several types of cancer, including gastric cancer (GC), through the stimulation of CXCL12/CXCR4 signaling. However, the mechanisms underlying these tumor-promoting effects are not well understood, which limits the potential to develop therapeutic targets against CAF-mediated CXCL12/CXCR4 signaling. CXCL12 expression was analyzed in resected GC tissues from 110 patients by immunohistochemistry (IHC). We established primary cultures of normal fibroblasts (NFs) and CAFs from the GC tissues and examined the functional differences between these primary fibroblasts using co-culture assays with GC cell lines. We evaluated the efficacy of a CXCR4 antagonist (AMD3100) and a FAK inhibitor (PF-573,228) on the invasive ability of GC cells. High CXCL12 expression levels were significantly associated with larger tumor size, increased tumor depth, lymphatic invasion and poor prognosis in GC. CXCL12/CXCR4 activation by CAFs mediated integrin ß1 clustering at the cell surface and promoted the invasive ability of GC cells. Notably, AMD3100 was more efficient than PF-573,228 at inhibiting GC cell invasion through the suppression of integrin ß1/FAK signaling. These results suggest that CXCL12 derived from CAFs promotes GC cell invasion by enhancing the clustering of integrin ß1 in GC cells, resulting in GC progression. Taken together, the inhibition of CXCL12/CXCR4 signaling in GC cells may be a promising therapeutic strategy against GC cell invasion.