[A Case of BRAF Mutant Cecal Cancer Treated with Encorafenib, Binimetinib, and Cetuximab Triple Therapy].

A Japanese woman in her early 70's presented to our hospital with abdominal pain and nausea. Abdominal computed tomography showed irregular wall thickening of the ileocecal region and small intestine dilatation. Colonoscopy revealed a tumor lesion at the ileocecal valve and adenocarcinoma was detected in the biopsy specimen. Accordingly, the diagnosis was cecal cancer and bowel obstruction. Right hemicolectomy was performed as palliative surgery, and laparotomy findings revealed peritoneal dissemination. The final staging was pT4a, pN2b, pM1c, pStage Ⅳc, harboring a BRAFV600E mutation. Rapid postoperative tumor progression occurred, leading to multiple liver metastases and ascites. Encorafenib, binimetinib, and cetuximab triple therapy was started as a second line regimen. The therapy was extremely effective. CA19-9 level decreased to within normal range, and the liver tumor size was visibly diminished. After receiving treatment for 2 months in outpatient care, she had to discontinue the treatment due to carcinomatous peritonitis. Unfortunately, she died 6 months after initial diagnosis. BRAF-mutated colon cancer is associated with poor prognosis. In Japan, encorafenib, binimetinib, and cetuximab triple therapy is a new BRAF targeting regimen approved in 2020. We report this clinical course in hopes of eventually achieving better outcomes for patients with this aggressive disease.

[A Case of Cecal Cancer Diagnosed from Sister Mary Joseph's Nodule].

A metastatic tumor of the umbilicus is called"Sister Mary Joseph's nodule", and patients with this tumor show a poor prognosis. Sister Mary Joseph's nodule is a rare occurrence, and there are few case reports. We report a case of cecal cancer first presented with the metastatic tumor in the umbilicus. A 90-year-old woman, complained umbilical induration and foul-smelling discharge, had been treated as omphalitis for 2 months. Because her symptom didn't improve, biopsy of the umbilical tumor was performed, and the findings revealed an adenocarcinoma. She was referred to our hospital. Abdominal CT showed wall thickening in the cecum, and multiple liver metastases. Therefore, we performed lower gastrointestinal endoscopy, which revealed a cecal tumor. We performed biopsy of the tumor and the findings were consistent with adenocarcinoma. Based on these results, we diagnosed the umbilical tumor as a metastasis from the colorectal cancer. Umbilical resection and ileocecal resection were performed, and multiple peritoneal metastases was detected. Post operative course was uneventful, she died 11 months after surgery. Umbilical metastases may worsen the patient's quality of life; thus, the local resection of umbilicus was recommended positively.

[A Case of Two-Stage Radical Resection with Neoadjuvant Chemotherapy for Cecal Cancer with Synchronous Peritoneal Metastasis(P3)].

A 63-year-old female patient was diagnosed with cecal cancer(cT3, N2a, M0)and underwent surgery for the first time. Only laparoscopic ileocecal resection(D3 dissection)was performed because intraperitoneal observation revealed peritoneal metastasis around the tumor and uterus. We decided to perform a radical resection because the peritoneal metastasis was localized by FDG-PET/CT. Five courses of neoadjuvant chemotherapy(mFOLFOX6)were performed to shrink the tumor. Unrecognized peritoneal metastases were found in other areas during the second surgery. Although the extent of the peritoneal metastasis was P3, all lesions had been resected. No perioperative complications occurred, and adjuvant chemotherapy was administered to the patient. Recurrence was not observed until 6 months postoperatively.

Feasibility of endoscopic submucosal dissection for cecal tumors involving the ileocecal valve or appendiceal orifice.

BACKGROUND AND AIM: Endoscopic resection of the ileocecal valve lesions (ICVL) and peri-appendiceal orifice lesions (PAOL), is challenging. This study aimed to evaluate the feasibility of endoscopic submucosal dissection (ESD) for ICVLs and PAOLs compared with other cecal lesions (OCEL). METHODS: This was a multicenter, retrospective cohort study conducted at a cancer center hospital and two community hospitals. Non-pedunculated cecal lesions that were intended to be treated by ESD followed by at least one surveillance colonoscopy were included. The main outcome was curative resection defined as en-bloc resection and R0 resection without risk factors of metastases. The secondary outcome was co lon preservation. RESULTS: A total of 206 patients with 206 cecal lesions, including 37 ICVL, 27 PAOL, and 142 OCEL, who were to be treated with ESD were included in this study. Curative resection rates were 75.7% for ICVL, 70.4% for PAOL, and 77.5% for OCEL (P = 0.67). In the multivariate analysis of predictors of curative resection, tumor size (<40 mm) (odds ratio [OR] 2.40; 95% confidence intervals [CI], 1.14-5.04; P = 0.02) and a negative non-lifting sign (OR 6.12; 95% CI, 2.55-14.60; P < 0.01) were significant. Colon preservation was achieved for 91.9% of the ICVL, 92.6% of the PAOL, and 90.8% of the OCEL (P = 0.947). CONCLUSIONS: Based on curative resection and colon preservation rates, ESD was found to be feasible for ICVL and PAOL. Large tumor size (≥ 40 mm) and positive non-lifting signs were significant factors for non-curative resection.

Cecal Tumorigenesis in Aryl Hydrocarbon Receptor-Deficient Mice Depends on Cecum-Specific Mitogen-Activated Protein Kinase Pathway Activation and Inflammation.

The aryl hydrocarbon receptor (AhR) is a transcription factor known as a dioxin receptor. Recently, Ahr-/- mice were revealed to develop cecal tumors with inflammation and Wnt/ß-catenin pathway activation. However, whether ß-catenin degradation is AhR dependent remains unclear. To determine whether other signaling pathways function in Ahr-/- cecal tumorigenesis, we investigated histologic characteristics of the tumors and cytokine/chemokine production in tumors and Ahr-/- peritoneal macrophages. AhR expression was also assessed in human colorectal carcinomas. Of the 28 Ahr-/- mice, 10 developed cecal lesions by 50 weeks of age, an incidence significantly lower than previously reported. Cecal lesions of Ahr-/- mice developed from serrated hyperplasia to adenoma/dysplasia-like neoplasia with enhanced proliferation. Macrophage and neutrophil infiltration into the lesions was also observed early in serrated hyperplasia, although adjacent mucosa was devoid of inflammation. Il1b, Il6, Ccl2, and Cxcl5 were up-regulated at lesion sites, whereas only IL-6 production increased in Ahr-/- peritoneal macrophages after lipopolysaccharide + ATP stimulation. Neither Myc (alias c-myc) up-regulation nor ß-catenin nuclear translocation was observed, unlike previously reported. Interestingly, enhanced phosphorylation of extracellular signal-regulated kinase, Src, and epidermal growth factor receptor and Amphiregulin up-regulation at Ahr-/- lesion sites were detected. In human serrated lesions, however, AhR expression in epithelial cells was up-regulated despite morphologic similarity to Ahr-/- cecal lesions. Our results suggest novel mechanisms underlying Ahr-/- cecal tumorigenesis, depending primarily on cecum-specific mitogen-activated protein kinase pathway activation and inflammation.

Competitive Risk Analysis of Prognosis in Patients With Cecum Cancer: A Population-Based Study.

BACKGROUND: The presence of competing risks means that the results obtained using the classic Cox proportional-hazards model for the factors affecting the prognosis of patients diagnosed with cecum cancer (CC) may be biased. OBJECTIVE: The purpose of this study was to establish a competitive risk model for patients diagnosed with CC to evaluate the relevant factors affecting the prognosis of patients, and to compare the results with the classical COX proportional risk model. METHODS: We extracted data on patients diagnosed with CC registered between 2004 and 2016 in the Surveillance, Epidemiology, and End Results (SEER) database. The univariate analysis utilized the cumulative incidence function and Gray's test, while a multivariate analysis was performed using the Fine-Gray, cause-specific (CS), and Cox proportional-hazards models. RESULTS: The 54463 eligible patients diagnosed with CC included 24387 who died: 12087 from CC and 12300 from other causes. The multivariate Fine-Gray analysis indicated that significant factors affecting the prognosis of patients diagnosed with CC include: age, race, AJCC stage, differentiation grade, tumor size, surgery, radiotherapy, chemotherapy and regional lymph nodes metastasis. Due to the presence of competitive risk events, COX model results could not provide accurate estimates of effects and false-negative results occurred. In addition, COX model misestimated the direction of association between regional lymph node metastasis and cumulative risk of death in patients diagnosed with CC. Competitive risk models tend to be more advantageous when analyzing clinical survival data with multiple endpoints. CONCLUSIONS: The present study can help clinicians to make better clinical decisions and provide patients diagnosed with CC with better support.

Adult Intestinal Intussusception: Practical Issues and Concerns.

CASE SUMMARY: A 37-year-old woman with no relevant past medical history presented to the emergency department after a 2-day-long period of crampy abdominal pain with an inability for oral intake because of persistent vomiting. The physical examination was unremarkable. Abdominal CT scan with water-soluble oral contrast revealed an ileocecal intussusception (Fig. 1). Because the patient was hemodynamically stable and no abdominal tenderness was found, a delayed surgical intervention was planned with laparoscopic approach. During intervention, the intestinal invagination was reduced, a cecal neoplasm suspected, and a right hemicolectomy with complete mesocolic excision was performed (Fig. 2). Postoperative recovery was uneventful, with discharge on postoperative day 5. The definite pathological report showed well-differentiated colon adenocarcinoma pT2N1aMx, with 1 of 49 positive lymph nodes.

[Prognostic analysis of colon and rectal neuroendocrine neoplasm in different stages].

Objective: To explore the survival difference of patients with colon and rectal neuroendocrine neoplasm (NEN) at different stages. Methods: We identified 8 679 patients with colorectal NEN diagnosed between 1988 and 2014 from the Surveillance, Epidemiology, and End Results (SEER) registry, including 5 437 rectal NEN and 3 242 colon NEN ( 1 681 cecum NEN ). Survival curve was drawn by Kaplan-Meier method. Prognostic factors were analyzed by univariate analysis and multivariate Cox regression model. Results: The ratio of male patients with colon and rectal NEN was similar to female (P=0.095). Rectal NEN patients were younger (P<0.001), more highly differentiated (P<0.001), and with earlier stage (P<0.001). Survival analysis showed that the survival of rectal NEN was superior to that of colon NEN, with 10-year tumor-specific survival rates of 86.8% and 44.8% respectively (P<0.001). Multivariate Cox analysis showed that age, gender, marital status, primary tumor site, grade, stage and surgery were independent prognostic factors of colorectal NEN (all P<0.01). The most important factor was stage (HR=3.531), followed by differentiation grade (HR=1.856). Stratified analysis displayed that the survival of rectal NEN in stage Ⅰ, Ⅱ and Ⅳ were better than those of corresponding stage of colon NEN (all P<0.05), but worse in stage Ⅲ (P=0.012). While the survival of rectal NEN were significantly better than those of colon NEN within all stages after excluding 1681 cases of cecal NEN (all P<0.05). Among the patients with well-differentiated NEN, the survival of rectal NEN in stage Ⅰ, Ⅲ and Ⅳ were better than those of corresponding stage of colon NEN (all P<0.05) while there was no significant difference in stage Ⅱ(P=0.169). For poor-differentiated NEN, only the survival of rectal NEN patients in stage Ⅳ (P=0.001) was significant longer than those of colon NEN, while there was no significant difference in stage Ⅰ, Ⅱ and Ⅲ (stage Ⅰ: P=0.760; stage Ⅱ: P=0.181; stage Ⅲ: P=0.313). Conclusions: The survival of NEN patients in colon and rectum is different. Cecum NEN should be considered as a separated tumor for prognostic analysis due to its special clinicopathologic characteristics.

A granular cell tumor: an unusual colon polyp.

We read with interest the article by Sevilla Ribota et al1 that described an unexpected finding of a granular cell tumour (GCT) of the rectum, which was removed by band ligation-assisted mucosectomy. We present a similar case of a GCT of the cecum, which was resected using a different endoscopic procedure.

Mantle cell lymphoma of the cecum.

The authors have read with great interest the recently published article "Colon lymphomas: an analysis of our experience over the last 23 years" by Martín Domínguez V et al., a single center retrospective review of 29 patients diagnosed with colon lymphoma. The present report describes a case of mantle cell lymphoma (MCL) of the cecum that aims to improve the knowledge regarding this unusual clinical and endoscopic entity.

Primary colon mantle lymphoma: a misleading macroscopic appearance!

Mantle cell lymphoma (MCL) of the colon is a rare entity, usually presenting as lymphomatous polyposis. We report the case of a 43-year-old male with an unusual colonic MCL in the form of a single exophytic and ulcerous lesion with necrotic areas associated with an ileo-cecal intussusception. The endoscopic appearance suggested adenocarcinoma. However, the diagnosis was made by histology and immunohistochemistry studies of the endoscopic biopsies.

[A Case of Anastomotic Stage â Cecal Cancer Recurrence after Functional End-To-End Anastomosis].

An 83-year-old woman was referred to our hospital for cecal cancer, and ileocecal resection(D3 lymph node resection) with functional end-to-end anastomosis. Since the tumor was of histological Stage Ⅰ, no adjuvant chemotherapy was performed. One year and 9 months after the operation, an anastomotic recurrence was identified alongthe staple line using colonoscopy. We performed a resection of the anastomotic recurrence. At present, 6 months after the second operation, the patient remains in good health without evidence of recurrence. A few cases of anastomotic recurrence after surgery for Stage Ⅰcolon cancer have been reported in the literature available in Japanese. We report a rare case of an anastomotic recurrence of Stage Ⅰ cancer after functional end-to-end anastomosis.

[A Case of Gastric Large-Cell Neuroendocrine Carcinoma Combined with Adenocarcinoma in the Cecum].

A 74-year-old man with anemia visited our department. Esophagogastroduodenoscopy showed a type 2 lesion from the angulus to the antrum. Histopathological findings indicated gastric neuroendocrine carcinoma. Colonoscopy showed a type 1 lesion at the cecum. Distal gastrectomy was performed with D1+lymph node dissection, Roux-en-Y reconstruction, and ileocecal resection with D3 lymph node dissection. The patient was pathologically diagnosed with large-cell neuroendocrine carcinoma in the stomach, pT4a(SE), med, INF a>>b-c, ly1-2, v1(SM, EVG), pN0, pM0, pStageⅡB, and adenocarcinoma (tub1>tub2)of the cecum, pT2(MP), ly1(HE), v1(EVG, SM), pN0, pM0, pStageⅠ. Postoperatively, he received oral S-1 as an adjuvant chemotherapy. His postoperative course was uneventful without any recurrence over 18 months.

EMR of laterally spreading lesions around or involving the appendiceal orifice: technique, risk factors for failure, and outcomes of a tertiary referral cohort (with video).

BACKGROUND AND AIMS: EMR of sessile periappendiceal laterally spreading lesions (PA-LSLs) is technically demanding because of poor endoscopic access to the appendiceal lumen and the thin colonic wall at the base of the cecum. We aimed to assess the feasibility and safety of EMR for PA-LSLs. METHODS: Consecutive LSLs ≥20 mm and PA-LSLs ≥10 mm detected at 3 academic endoscopy centers from September 2008 until January 2017 were eligible. Prospective patient, procedural, and lesion data were collected. PA-LSLs were compared with LSLs in other colonic locations. RESULTS: Thirty-eight PA-LSLs were compared with 1721 LSLs. Referral for surgery without an attempt at EMR was more likely with PA-LSLs (28.9% vs 5.1%, P < .001), and those that involved a greater percentage of the appendiceal orifice (AO) were less likely to be attempted (P = .038). Most PA-LSLs (10/11) were not attempted because of deep extension into the appendiceal lumen; 2 of 11 of these surgical specimens contained invasive cancer. Once attempted, complete clearance of visible adenoma (92.6% PA-LSLs vs 97.6% LSLs, P = .14), adverse events, and rates of adenoma recurrence did not vary significantly between PA-LSLs and LSLs. All 7 patients with prior appendicectomy achieved complete adenoma clearance. There were no cases of post-EMR appendicitis. Twenty of 22 PA-LSLs (91%) eligible for surveillance avoided surgery to longest follow-up. CONCLUSIONS: EMR is a safe, effective, and durable treatment for PA-LSLs when specific criteria are fulfilled. If the distal margin of the PA-LSL within the AO cannot be visualized or if more than 50% of the circumference of the orifice is involved, surgery should be considered. (Clinical trial registration number: NTC01368289.).

Endoscopic features and clinical outcomes of colorectal mucosa-associated lymphoid tissue lymphoma.

BACKGROUND AND AIMS: Colorectal mucosa-associated lymphoid tissue (MALT) lymphoma is a rare disease. The purpose of this study was to investigate the clinical and endoscopic features of colorectal MALT lymphoma. METHODS: Patients diagnosed with colorectal MALT lymphoma at Asan Medical Center from 2002 to 2016 were eligible. Medical records were reviewed to investigate clinical features and treatment outcomes. Endoscopic pictures were assessed to characterize the endoscopic features of colorectal MALT lymphoma. RESULTS: A total of 51 patients were enrolled. The median age was 60 years (interquartile range, 55-71), and 21 (41%) were men. Twenty-six patients (51%) were asymptomatic. Forty-four patients (86%) were in early disease stages, namely Lugano stages I, II, and IIE. Endoscopic appearances were classified as 4 distinct types: subepithelial tumor type (26 patients, 51%), polyposis type (10 patients, 20%), epithelial mass type (7 patients, 14%), and ileitis type (8 patients, 16%). The rectum (20 patients, 39%) was the most common location, followed by the ileocecal area (15 patients, 30%). An initial endoscopic impression of lymphoma was made in only 7 patients. Forceps biopsy sampling as the initial tissue acquisition method could histologically diagnose MALT lymphoma in 28 of 35 patients (80%). Polypectomy as the initial histologic diagnosis could diagnose MALT lymphoma in 16 of 16 patients. Progression-free and overall survival rates at 5 years were 92% and 94%, respectively. CONCLUSIONS: Colorectal MALT lymphomas show various endoscopic appearances, complicating the endoscopic suspicion of colorectal MALT lymphoma. The prognosis of colorectal MALT lymphoma was excellent.

Feasibility of endoscopic submucosal dissection for cecal lesions.

BACKGROUND: The treatment results of endoscopic submucosal dissection (ESD) for colorectal lesions have improved markedly, but some lesions remain difficult to treat. Hence the cecum is considered a technically challenging site for ESD. We examined the feasibility of ESD for cecal lesions. METHODS: Among a total of 708 colorectal ESD performed in our hospital between March 2006 and December 2016, 549 procedures performed after April 2012 were studied, at a time when the techniques of ESD had stabilized and the procedure was covered by health insurance in Japan. Among 549 cases, 61 were cecal lesions and 488 were noncecal lesions. The treatment outcomes were analyzed. RESULTS: For cecal lesions, the en bloc resection rate was 95.1%, R0 resection rate was 91.8%, perforation rate was 0%, delayed bleeding rate was 6.6%, median diameter of resected specimen was 32 mm (16-65 mm), median time of the procedure was 44 minutes (8-140 min). The corresponding results for noncecal lesions were 97.3%, 95.5%, 0.4%, 2.7%, 30 mm (10-109 mm), and 37 min (7-225 min). No significant differences were observed and the good treatment results were seen. When the outcomes were analyzed for cecal sites considered to be particularly challenging; proximity to appendiceal orifice, the ileocecal valve, and the bottom of cecum, the treatment results were not inferior to other sites. CONCLUSIONS: ESD is safe and effective even for cecal lesions considered challenging to treat. ESD is feasible for cecal lesions.

Discovery of a neuroendocrine tumor of the caecum by mammary metastasis using 18F-DOPA-PET.

Neuroendocrine tumors (NET) develop from the diffuse endocrine system. These are rare tumors that can affect diverse organs. We present here the case of a 42-year-old female patient in whom a NET of the breast was discovered that was likely not of mammary origin. The main challenge was finding the primary tumor using immunohistochemistry and specific medical imaging modalities for NET. The primary tumor was localized at the last ileal loop upstream of the Bauhin valve thanks to the use of 18F-DOPA-PET. Ileocaecal resection by laparoscopy was performed. A WHO grade 2 NET of the ileum measuring 2.2 cm × 1.5 cm was found that infiltrated the submucosa with six metastatic lymph nodes of the eight removed (6N+/8). This unusual clinical case is the first one of a digestive NET of the ileum-caecal junction by mammary metastasis.