Activation of RhoA/ROCK2 signaling by hypoxia-inducible factor 1α in promoting tumor growth and metastasis in human colon cancer.

Background: Recent evidence strongly suggests the profound role of the tumor microenvironment in cancer development and progression. A hypoxic microenvironment is widely acknowledged to be a typical feature of solid tumors, and altered hypoxia-inducible factor 1α (HIF-1α) expression has been associated with the formation and the progression of many solid tumors; however, the underlying mechanism of this relationship remains obscure. Methods: Clinical colorectal cancer tissue samples were collected to detect the differential expression of HIF-1α, Ras homolog family member A (RhoA), and Rho-associated, coiled-coil containing protein kinase 2 (ROCK2). With hypoxic stress, small interfering RNA (siRNA) targeting HIF-1α, lentivirus transfection of RhoA was used to study the mechanism of HIF-1α and RhoA/ROCK2 signaling pathways in the growth and metastasis of colon cancer. Results: According to Cell Counting Kit 8, wound-healing, and Transwell assays, HIF-1α expression activated the RhoA/ROCK2 pathway within colon cancer cell lines, accelerating their growth and expansion. In cells transfected with LV-RhoA, inactivating the RhoA/ROCK2 pathway with the specific inhibitor Y-27632 decreased tumor growth and metastasis under hypoxic conditions, while activating the RhoA/ROCK2 pathway restored these biological properties. The Western blot results showed that the expression levels of pMYPT1, cyclin D1, and MMP2 in the siRNA + LV-RhoA group were also significantly increased compared with those in the siRNA group. Conclusions: For the first time, this study demonstrated that HIF-1α can promote the growth and metastasis of colon cancer via directly affecting RhoA/ROCK2 signaling and thus represents a novel therapeutic target for colon cancer.

Efficacy of surgical staple line reinforcement in Glissonean stapling: A single-center pilot study.

Vascular staplers are routinely used in laparoscopic liver resection, which has become a standard procedure in advanced medical facilities. Although previous reports have outlined the benefits of staple line reinforcement (SLR), its application in Glissonean pedicle transection during hepatic resection remains poorly studied. This study investigated surgical SLR as a tool to enhance staple line strength and improve perioperative hemostasis. Here, 10 patients who underwent laparoscopic liver resection using the Tri-StapleTM2.0 Reinforced Reload were included. Patient characteristics, surgical details, and outcomes were assessed. The results demonstrated successful outcomes with no complications related to bile leakage or injuries during staple insertion. Overall, our findings suggest that SLR can be safely utilized in Glissonean pedicle transection during laparoscopic liver resections. Further studies are required to comprehensively evaluate its benefits compared with conventional surgical staplers.

Impact of the coronavirus disease 2019 pandemic on gastric and colorectal cancer surgeries: a multicenter epidemiologic study from the Kinki region of Japan.

The coronavirus disease 2019 pandemic affected cancer surgeries and advanced cancer diagnoses; however, the trends in patient characteristics in medical institutions during this time, and the surgical approaches used are unclear. We investigated the impact of the pandemic on gastric and colorectal cancer surgeries in the Kinki region of Japan. We grouped 1688 gastric and 3493 colorectal cancer surgeries into three periods: "pre-pandemic" (April 2019-March 2020), "pandemic 1" (April 2020-March 2021), and "pandemic 2" (April 2021-September 2021), to investigate changes in the number of surgeries, patient characteristics, surgical approaches, and cancer progression after surgery. Gastric and colorectal cancer surgeries decreased from the pre-pandemic levels, by 20% and 4%, respectively, in pandemic 1, and by 31% and 19%, respectively, in pandemic 2. This decrease had not recovered to pre-pandemic levels by September, 2021. Patient characteristics, surgical approaches, and cancer progression of gastric and colorectal surgeries did not change remarkably as a result of the coronavirus disease 2019 pandemic.

The Impact of KRAS Status on the Required Surgical Margin Width for Colorectal Liver Metastasis Resection.

Local recurrence after colorectal liver metastasis (CRLM) resection severely affects survival; however, the required surgical margin width remains controversial. This study investigated the impact of KRAS status on surgical margin width and local recurrence rate (LRR) post-CRLM resection. Overall, 146 resected CRLMs with KRAS status (wild-type KRAS (wtKRAS): 98, KRAS mutant (mKRAS): 48) were included. The LRR for each group, R1 (margin positive) and R0 (margin negative), was analyzed by KRAS status. R0 was further stratified into Ra (margin ≥ 5 mm) and Rb (margin < 5 mm). Patients with local recurrence had significantly worse 5-year overall survival than those without local recurrence (p = 0.0036). The mKRAS LRR was significantly higher than wtKRAS LRR (p = 0.0145). R1 resection resulted in significantly higher LRRs than R0 resection for both wtKRAS and mKRAS (p = 0.0068 and p = 0.0204, respectively), and while no significant difference was observed in the Ra and Rb LRR with wtKRAS, the Rb LRR with mKRAS (33.3%) was significantly higher than Ra LRR (5.9%) (p = 0.0289). Thus, R0 resection is sufficient for CRLM with wtKRAS; however, CRLM with mKRAS requires resection with a margin of at least 5 mm to prevent local recurrence.

Amentoflavone inhibits colorectal cancer epithelial-mesenchymal transition via the miR-16-5p/HMGA2/ß-catenin pathway.

Background: Amentoflavone is a type of bioflavonoid that exists in many Chinese medicines and has anti-inflammatory, antioxidant, antiviral, and anticancer effects. However, the effect of amentoflavone on epithelial to mesenchymal transition (EMT) in human colorectal cancer (CRC) has not been studied. In this study, we aim to explore the effect of amentoflavone on EMT in CRC. Methods: The effects of long noncoding RNA (lncRNA) miR-16-5p on proliferation, migration, and invasion were determined by in vitro and in vivo experiments. A luciferase reporter assay was carried out to reveal the interaction between miR-16-5p and targeted genes. Reverse transcription polymerase chain reaction (RT-PCR) was used to evaluate the expression of miR-16-5p. A western blot assay was used to detect the expression of targeted genes in CRC cells. Results: The results showed that amentoflavone significantly inhibited CRC migration, invasion, and EMT by increasing miR-16-5p expression. Mechanistically, amentoflavone induced inactivation of the Wnt/ß-catenin pathway via miR-16-5p, directly targeting 3'-UTR of HMGA2 to suppress HMGA2 expression in CRC. Clinically, combined miR-16-5p and HMGA2 levels may serve as a predictor for poor prognosis in patients with CRC. Furthermore, an in vivo PDX model suggested that amentoflavone exhibited antitumor effects in vivo via the miR-16-5p/HMGA2/ß-catenin pathway. Conclusions: This is the first study to show that amentoflavone inhibits CRC EMT via the miR-16/HMGA2/ß-catenin pathway. Amentoflavone may be beneficial in treating CRC patients in the clinic.

Intracorporeal reinforcing sutures reduce anastomotic leakage in double-stapling anastomosis for laparoscopic rectal surgery.

Introduction: In rectal surgery, double-stapled anastomosis is one of the most common techniques. However, the crossing of the staple line is considered a weakness of this method and could lead to anastomotic leakage (AL), which is one of the major complications of rectal cancer surgery. Aim: To investigate the usefulness of laparoscopic intracorporeal reinforcement suturing for preventing AL in laparoscopic rectal surgery. Material and methods: A total of 153 patients with rectal cancer underwent laparoscopic rectal resection with anastomosis using the double-stapling technique between January 2015 and December 2018. Patient characteristics, surgical data, and outcomes were recorded and retrospectively analysed. Patients who received intracorporeal reinforcing sutures (n = 72) were compared with those who did not receive the reinforcing sutures (n = 81). Results: AL was observed in 11 (7.2%) cases overall and in only 1 case in the group with intracorporeal reinforcing sutures. There were no associations between clinicopathological factors and the use of reinforcing sutures. Multivariate analysis revealed that a distance from the anal verge of less than 6.5 cm, diabetes mellitus, and the non-use of reinforcing sutures were independent risk factors for AL. Conclusions: Laparoscopic intracorporeal reinforcing sutures reduced the incidence of AL. Therefore, laparoscopic reinforcing sutures for double-stapled anastomoses seem useful for the prevention of AL.

Indocyanine green plasma clearance rate and 99mTc-galactosyl human serum albumin single-photon emission computed tomography evaluated preoperative remnant liver.

BACKGROUND: Preoperative evaluation of future remnant liver reserves is important for safe hepatectomy. If the remnant is small, preoperative portal vein embolization (PVE) is useful. Liver volume analysis has been the primary method of preoperative evaluation, although functional examination may be more accurate. We have used the functional evaluation liver using the indocyanine green plasma clearance rate (KICG) and 99mTc-galactosyl human serum albumin single-photon emission computed tomography (99mTc-GSA SPECT) for safe hepatectomy. AIM: To analyze the safety of our institution's system for evaluating the remnant liver reserve. METHODS: We retrospectively reviewed the records of 23 patients who underwent preoperative PVE. Two types of remnant liver KICG were defined as follows: Anatomical volume remnant KICG (a-rem-KICG), determined as the remnant liver anatomical volume rate × KICG; and functional volume remnant KICG (f-rem-KICG), determined as the remnant liver functional volume rate based on 99mTc-GSA SPECT × KICG. If either of the remnant liver KICGs were > 0.05, a hepatectomy was performed. Perioperative factors were analyzed. We defined the marginal group as patients with a-rem-KICG of < 0.05 and a f-rem-KICG of > 0.05 and compared the postoperative outcomes between the marginal and not marginal (both a-rem-KICG and f-rem-KICG > 0.05) groups. RESULTS: All 23 patients underwent planned hepatectomies. Right hepatectomy, right trisectionectomy and left trisectionectomy were in 16, 6 and 1 cases, respectively. The mean of blood loss and operative time were 576 mL and 474 min, respectively. The increased amount of f-rem-KICG was significantly larger than that of a-rem-KICG after PVE (0.034 vs 0.012, P = 0.0273). The not marginal and marginal groups had 17 (73.9%) and 6 (26.1%) patients, respectively. The complications of Clavian-Dindo classification grade II or higher and post-hepatectomy liver failure were observed in six (26.1%) and one (grade A, 4.3%) patient, respectively. The 90-d mortality was zero. The marginal group had no significant difference in postoperative outcomes (prothrombin time/international normalised ratio, total bilirubin, complication, post-hepatectomy liver failure, hospital stay, 90-d, and mortality) compared with the not-marginal group. CONCLUSION: Functional evaluation of the remnant liver enabled safe hepatectomy and may extend the indication for hepatectomy after PVE treatment.

Significance of a calcium-binding protein S100A14 expression in colon cancer progression.

Background: The S100 proteins are characterized by two distinct EF-hand calcium-binding motifs. Several members of the S100 family are involved in cancer progression. S100A14, a member of the S100 family, has been cloned and reported in colon-specific microarray databases. In this study, we assessed the biological and functional significance of S100A14 in normal colon and in colon cancer. Methods: The expression of S100A14 in normal colon and colon cancer was assessed. We used in situ hybridization, reverse transcription polymerase chain reaction (RT-PCR), cell migration assay, cell growth assay, western blotting, and immunohistochemical analysis. Clinicopathological examinations were also performed. Results: S100A14 is expressed in normal colon epithelium and several colon cancer cell lines. However, it is not expressed in SW480 cells. S100A14-overexpressing SW480 cells were established by stable transfection. Interestingly, a decrease in cell motility was observed, as determined using two independent migration assays. S100A14-overexpressing SW480 cells showed increased E-cadherin levels but decreased ability to form colonies in soft agar. Moreover, S100A14 expression was decreased in 95 of 154 human colon cancers, and lower S100A14 expression led to worse prognoses. Conclusions: Our results suggest that S100A14 is involved in cell motility, adhesion, and growth changes in colon cancer and that its expression is inversely correlated with colon cancer progression. S100A14 expression in colon cancer is a useful prognostic marker.

Hepatectomy Followed by Adjuvant Chemotherapy with 3-Month Capecitabine Plus Oxaliplatin for Colorectal Cancer Liver Metastases.

LESSONS LEARNED: Three-month adjuvant capecitabine plus oxaliplatin in combination (CAPOX) appeared to reduce recurrence, with mild toxicity in postcurative resection of colorectal cancer liver metastases (CLM). Recurrence in patients who underwent the 3-month adjuvant CAPOX after resection of CLM was most commonly at extrahepatic sites. BACKGROUND: The role of neoadjuvant and adjuvant chemotherapy in the management of initially resectable colorectal cancer liver metastases (CLM) is still unclear. We evaluated the feasibility of 3-month adjuvant treatment with capecitabine plus oxaliplatin in combination (CAPOX) for postcurative resection of CLM. METHODS: Patients received one cycle of capecitabine followed by four cycles of CAPOX as adjuvant chemotherapy after curative resection of CLM. Oral capecitabine was given as 1,000 mg/m2 twice daily for 2 weeks in a 3-week cycle, and CAPOX consisted of oral capecitabine plus oxaliplatin 130 mg/m2 on day 1 in a 3-week cycle. Primary endpoint was the completion rate of adjuvant chemotherapy. Secondary endpoints included recurrence-free survival (RFS), overall survival (OS), dose intensity, and safety. RESULTS: Twenty-eight patients were enrolled. Median age was 69.5 years, 54% of patients had synchronous metastases, and 29% were bilobar. Mean number of lesions resected was two, and mean size of the largest lesion was 31 mm. Among patients, 20 (71.4%; 95% confidence interval, 53.6%-89.3%) completed the protocol treatment and met its primary endpoint. The most common grade 3 or higher toxicity was neutropenia (29%). Five-year recurrence-free survival and overall survival were 65.2% and 87.2%, respectively. CONCLUSION: Three-month adjuvant treatment with CAPOX is tolerable and might be a promising strategy for postcurative resection of CLM.

Laparoscopic Colectomy for Splenic Flexure Cancer Approached from Four Directions.

Background: Standardized protocols for laparoscopic surgery of splenic flexure cancer (SFC) have not been established yet. We described a standardized laparoscopic procedure for SFCs and examined its safety and feasibility. Methods: Laparoscopic colectomy for SFC was performed as follows. The sigmoid colon was mobilized to the descending mesocolon through the medial approach. After confirming the base of the inferior mesenteric artery, the left colic artery was dissected and resected at the base. Further dissection was carried out between the mesentery of the colon and the renal fascia until it exceeded the upper pole of the left kidney and the splenic flexure. The next dissection reached the white line at the lateral side and the sigmoid-descending colon junction. After making an incision at the greater omentum and gastrocolic ligament from the center of the transverse colon to the splenic flexure, the transverse mesocolon base was dissected from the inside splenic flexure for complete mobilization. This was performed by approaching from four directions toward the splenic flexure. Intestinal resection and anastomosis are performed. Results: This procedure was performed in 70 patients with splenic flexure colon cancer (mean age 70 years). The mean operative time was 190 minutes, and the mean blood loss was 2.0 mL. No notable perioperative or postoperative complications were noted. Conclusions: Safe mobilization of the splenic flexure can be achieved by approaching from four directions, and standardization of left colectomy can facilitate complete mesenteric excision.

Laparoscopic Surgery for Colorectal Cancer in Super-Elderly Patients: A Single-Center Analysis.

BACKGROUND: Super-elderly patients with colorectal cancer are being encountered with increasing frequency in Japan. Laparoscopic surgery is considered a less invasive surgery in these patients; however, it is difficult to conduct controlled clinical trials in this super-elderly population. This study assessed the feasibility and safety of laparoscopic colorectal surgery in patients over 85 years old. MATERIALS AND METHODS: Open and laparoscopic surgeries for colorectal cancer in super-elderly patients (aged 85 y and older) were performed under general anesthesia in a single medical center. Records were retrospectively reviewed, and the clinicopathologic features of each patient and the surgical time and outcomes were recorded and analyzed. RESULTS: Records of colorectal surgery were reviewed for 108 super-elderly patients. Twenty-six open surgeries and 82 laparoscopic surgeries were performed. The mean operation times were 215 and 228 minutes in open and laparoscopic surgeries, respectively. Intraoperative bleeding in laparoscopic surgery was lesser than that in open surgery. There were 2 cases with major postoperative complications in open surgery, and mortality occurred in one case within 1 month after surgery. No major complications were observed in laparoscopic surgery. In survival analysis, disease-free survival did not differ between the 2 groups. The oldest patient was a man aged 102 years and 6 months who underwent laparoscopic anterior resection with lymph node dissection. CONCLUSION: Laparoscopic surgery in super-elderly patients with colon cancer is feasible and safe. The authors report the success of laparoscopic colectomy for rectosigmoid colon cancer in the oldest known patient and the positive outcomes of laparoscopic colectomy in super-elderly patients.

Diaphragm disease associated with nonsteroidal anti-inflammatory drugs mimicking intestinal tumor: A case report.

INTRODUCTION: Diaphragm disease is rare and caused by intestinal obstruction due to nonsteroidal anti-inflammatory drugs (NSAIDs). Given the availability of video capsule endoscopy (VCE) and balloon enteroscopy (BE) this disease will be diagnosed more often. PRESENTATION OF CASE: A 73-year-old man was presented to our hospital for persistent nausea and vomiting. Abdominal ultrasound and computed tomography revealed small-bowel thickening, stricture in the terminal ileum, and dilation of the proximal small intestine. Differential diagnosis included ileal lymphoma and multiple ileal adenocarcinomas, and a diagnostic laparoscopy was performed. Twenty-centimeter of ileum was resected by primary ileo-ileal anastomosis. On pathological examination, fibrosis of the submucosa was identified, and erosions and numerous inflammatory cells reaching the submucosa were also identified from the specimen. DISCUSSION: The preoperative diagnosis of diaphragm disease is sometimes challenging due to its uncharacteristic symptoms; moreover, radiological findings are usually indefinite and distinctive. Currently, the main treatment for diaphragm disease is surgery. CONCLUSION: We have documented a case of intestinal obstruction by NSAIDs. However, it is desirable to determine the course of treatment based on small bowel endoscopic dilatation cases in the future.

Internal hernia of the stomach associated with colostomy after laparoscopic surgery for rectal cancer: a case report.

BACKGROUND: Colostomy via the intraperitoneal route is often performed during laparoscopic Hartmann's operation or abdominoperineal resection. Internal hernia of the small intestine often occurs after colostomy. This report shows a rare case of internal hernia of the stomach associated with sigmoid colostomy after laparoscopic abdominoperineal resection for rectal cancer. CASE PRESENTATION: The patient was a 79-year-old woman with a sigmoid colostomy. Computed tomography scan showed a markedly distended stomach in the space between the lifted sigmoid colon and the lateral abdominal wall. Laparoscopy revealed that the body of the stomach had passed through a hernia orifice located between the lifted sigmoid colon and the left lateral abdominal wall. The dislocated stomach was restored to its normal position, and the lateral defect was closed with the lateral peritoneum and the lifted sigmoid colon laparoscopically. CONCLUSIONS: Internal hernia associated with colostomy can lead to not only obstruction of the small intestine, but also obstruction of the stomach. We reported a successful case of the suture repair for the internal hernia of the stomach associated with colostomy.

Usefulness of laparoscopic posterior rectopexy for complete rectal prolapse: A cohort study.

BACKGROUND: Transabdominal rectopexy for complete rectal prolapse reportedly yields more definitive results than transperineal surgery. Recently, minimally invasive laparoscopic rectopexy has become a popular treatment option for patients with rectal prolapse. Herein, we describe our surgical procedure for correction of rectal prolapse. We further aimed to perform a comparative assessment between perioperative outcomes achieved with open and laparoscopic applications of this technique. MATERIALS AND METHODS: In this cohort study, 65 patients underwent posterior rectopexy (laparoscopic, 50; open, 15) between April 2008 and December 2015. The basic procedure consisted of posterior rectopexy using mesh fixation (modified Wells' method). We assessed and compared perioperative outcomes (duration of surgery and hospitalization, complication rates, blood-loss, degree of fecal incontinence) of laparoscopic and open rectopexy. Furthermore, pre- and post-operative urinary incontinence was measured (using pad test, questionnaire) and compared to determine the effects of the procedure on pelvic organ function. A p-value <0.05 indicated statistical significance. RESULTS: The mean operative time of the laparoscopic and open procedures was 127 and 83.6 min, respectively. The amount of blood-loss was negligible and 77 (range, 18-200) g with the laparoscopic and open approaches, respectively. The mean duration of hospitalization was 4.2 and 7.2 days for the former and latter procedures, respectively (p < 0.05). Rectal prolapse and fecal incontinence (evaluated using Wexner's score) diminished in all patients. Urinary incontinence also decreased postoperatively. There were no recurrences of rectal prolapse. CONCLUSION: Laparoscopic rectopexy can be safely performed in older patients to achieve early postoperative ambulation and significantly shorten the hospital-stay. It may therefore be considered an effective treatment for complete rectal prolapse and urinary dysfunction.

Transperineal abdominoperineal resection for anorectal melanoma: A case report.

INTRODUCTION: Anorectal melanoma is a rare type of cancer characterized by frequent metastasis. We report our experience with a case of anorectal melanoma resected via transperineal abdominoperineal resection and total mesorectal excision. PRESENTATION OF CASE: A 77-year-old woman visited our hospital with the complaint of melena. Colonoscopic examination revealed a black type 1 tumor measuring 5 mm in size on the dentate line of the anal canal circumference. Tumor biopsy revealed malignant melanoma, and positron emission tomography-computed tomography showed tracer accumulation within the mass but not at other sites. We performed a two-stage abdominoperineal resection surgery with lymphadenectomy via transperineal abdominoperineal resection, and pathological diagnosis indicated submucosal tumor depth. The patient was diagnosed with T2 N0 M0 stage I malignant melanoma and was followed on an outpatient basis. A 24-month follow-up computed tomography revealed multiple liver metastases. DISCUSSION: Anorectal melanoma is associated with a very poor prognosis because of its association with early lymph node metastasis and distant metastasis. The tumor may spread beyond the main lesion and involve the surrounding mucosa and draining lymph nodes. Transperineal abdominoperineal resection is a minimally invasive procedure that can be used to achieve curative tumor resection with lymphadenectomy. CONCLUSION: Transperineal abdominoperineal resection appears to be a feasible approach for the treatment of anorectal melanoma.

Hepatic anisakiasis mimicking metastatic liver tumour.

INTRODUCTION: Anisakiasis is a parasitic disease caused by anisakid nematode larvae, which are found in raw or undercooked fish. It occurs more frequently in the digestive tract, but has also been reported outside the gastrointestinal tract. This report details a case of rare hepatic anisakiasis that was initially diagnosed as metastatic rectal cancer. PRESENTATION OF CASE: A 60-year-old male underwent radical resection for stage III rectal cancer followed by adjuvant chemotherapy for six months. Seven months after surgery, a new, 10 mm diameter area of low density was seen in segment 4/8 margin of the liver on enhanced computed tomography (CT) scan. Metastatic liver tumour from rectal cancer was suspected. Laparoscopic partial hepatectomy was performed. The diagnosis was revised to hepatic anisakiasis when pathological examination revealed anisakis simplex larvae in the necrotic tissue. DISCUSSION: Anisakiasis outside of the gastrointestinal tract is a rare finding, but may be seen more frequently with the recent increase in the consumption of raw fish around the world. Hepatic anisakiasis may mimic tumours in the liver. Clinicians should consider dietary inquiry and further evaluation in patients with liver margin tumours less than 20 mm in size that are not positively malignant, as hepatic anisakiasis may be a possible diagnosis. CONCLUSION: We report a rare case of hepatic anisakiasis which initially presented as suspected metastatic cancer. Hepatic anisakiasis should be considered in the differential diagnosis of low density liver tumours less than 20 mm, where the patient's diet includes raw fish.

Safety and effectiveness of FOLFOXIRI plus molecular target drug therapy for metastatic colorectal cancer: A multicenter retrospective study.

INTRODUCTION: FOLFOXIRI plus bevacizumab has a promising efficacy as first-line systemic chemotherapy for metastatic colorectal cancer (mCRC). This study aimed to evaluate the safety and effectiveness of FOLFOXIRI plus antibodies. RESULTS: Fifty-five patients were enrolled (median age: 60 years, males: 25, females: 30). Twenty-six subjects had RAS mutations and 29 had RAS wild-type. Anti-VEGF and anti-EGFR antibodies were administered to 38 and 17 patients, respectively. The most common severe adverse event was neutropenia (51%). The overall response rate (ORR) was 69% (55% with anti-VEGF antibodies and 100% with anti-EGFR antibodies; P = 0.190), and the disease control rate was 98% (stable disease: 16 patients). With a median follow-up period of 18.4 months, the median progression-free survival (mPFS) was 11.0 months and the median overall survival (mOS) was 41.9 months. The mPFS and mOS did not significantly differ between patients treated with anti-EGFR antibodies and those with anti-VEGF antibodies. METHODS: We retrospectively collected data from mCRC patients treated with FOLFOXIRI plus antibodies between March 2014 and December 2017. CONCLUSIONS: FOLFOXIRI plus antibody therapy was effective in patients with mCRC. The response rate was higher in patients treated with anti-EGFR antibodies than in those treated with anti-VEGF antibodies.

Observational study of first-line chemotherapy including cetuximab in patients with metastatic colorectal cancer: CORAL trial.

OBJECTIVE: We aimed to clarify the clinical practice and outcomes of first-line cetuximab-containing chemotherapy in patients with metastatic colorectal cancer. Efficacy and safety were evaluated in each group classified by the European Society for Medical Oncology Guidelines 2012. METHODS: This prospective observational study included patients with previously untreated metastatic colorectal cancer from 158 centers in Japan who started first-line cetuximab-containing chemotherapy from January 2012 to June 2013 and were followed for up to 3 years. The resection rates after chemotherapy were calculated and the overall survival was estimated using the Kaplan-Meier method for Group 1 (G1, potentially resectable), Group 2 (G2, not resectable and tumor-related symptoms) and Group 3 (G3, not resectable and asymptomatic). RESULTS: Of 578 patients, 562 were classified into G1 (n = 165), G2 (n = 224) or G3 (n = 173). The resection rate of any site was higher in G1 (57.0%) than in G2 (11.2%) and G3 (11.6%). G1, G2 and G3 showed median overall survivals (95% confidence interval) of 45.9 (38.1-not available), 16.7 (14.5-18.8) and 30.6 (23.2-34.8) months, respectively (P < 0.0001). The common tumor-related symptoms in G2 were pain, fatigue and anorexia, from which 31.7, 22.2 and 14.8% of the patients suffered at baseline. CONCLUSIONS: The expected efficacy and safety of first-line cetuximab-containing chemotherapy were demonstrated in patients with metastatic colorectal cancer under clinical practice in Japan. REGISTERED CLINICAL TRIAL NUMBERS: UMIN000007275.

Updated 5-year survival and exploratory T x N subset analyses of ACTS-CC trial: a randomised controlled trial of S-1 versus tegafur-uracil/leucovorin as adjuvant chemotherapy for stage III colon cancer.

OBJECTIVE: Adjuvant Chemotherapy Trial of TS-1 for Colon Cancer (ACTS-CC), a randomised phase III trial, demonstrated that adjuvant therapy with S-1 for stage III colon cancer was non-inferior in 3-year disease-free survival (DFS) to that of tegafur-uracil plus leucovorin (UFT/LV). We updated DFS and overall survival (OS) and performed T x N subset analysis. METHODS: A total of 1518 patients with curatively resected stage III colon cancer were randomly assigned to receive S-1 (80-120 mg/day on days 1-28 every 42 days, four courses) or UFT/LV (UFT: 300-600 mg/day and LV: 75 mg/day on days 1-28 every 35 days, five courses). RESULTS: The 5-year DFS rates of the S-1 and UFT/LV group were 70.2 % and 66.9 %, respectively (HR 0.88; 95% CI 0.74 to 1.06; p=0.177), and non-inferiority of DFS was reconfirmed with a median of 63.5-month follow-up. The similarity of OS was also confirmed (HR 0.92; 95% CI 0.72 to 1.17; p=0.488); 5-year OS rates of the S-1 and UFT/LV group were 86.0 % and 84.4 %, respectively. No significant interactions were identified between the major baseline characteristics and DFS of the S-1 and UFT/LV groups, except for histological type; S-1 was more favourable in patients with poorly differentiated adenocarcinoma. Patient outcomes were well separated by TNM-substages (IIIA/IIIB/IIIC). With the patients divided into 20 subsets by T and N factors, the DFS and OS rates of T3 and N1 subset, which accounted for 62 % of stage IIIB patients and 44 % of all studied subjects, were significantly better than those of the other subsets in stage IIIB and similar to those of stage IIIA. CONCLUSIONS: Adjuvant therapy of S-1 for stage III colon cancer was reconfirmed to be non-inferior in DFS to those of UFT/LV after long follow-up. No difference in OS was also demonstrated. T3N1 patients might be considered separately from other patients included in stage IIIB because of its favourable outcome. TRIAL REGISTRATION NUMBER: NCT00660894.