Survival outcomes of patients with stage III colorectal cancer aged ≥ 80 years who underwent curative resection: the HiSCO-04 prospective cohort study.

BACKGROUND: The efficacy of adjuvant chemotherapy in elderly patients aged ≥ 80 years with stage III colorectal cancer remains unclear. In parallel with a multicenter prospective phase II trial evaluating the efficacy of uracil-tegafur and leucovorin as adjuvant chemotherapy (HiSCO-03), we conducted a prospective observational study of these patients to assess survival outcomes, including those ineligible for chemotherapy. METHODS: This multi-institutional prospective cohort study included 17 institutions in Hiroshima, Japan. Patients aged ≥ 80 years with stage III colorectal cancer who underwent curative resection were enrolled. The primary endpoint was 3-year disease-free survival, and the secondary endpoints were 3-year overall and relapse-free survival. Propensity score matching was used to assess the effects of adjuvant chemotherapy on survival outcomes. RESULTS: A total of 214 patients were analyzed between 2013 and 2018, including 99 males and 115 females with a median age of 84 years (range 80-101 years). Recurrence occurred in 58 patients and secondary cancers were observed in 17. The 3-year disease-free, overall, and relapse-free survival rates were 63.3%, 76.9%, and 62.9%, respectively. Adjuvant chemotherapy was administered to 65 patients with a completion rate of 52%. In a study of 80 patients that adjusted for background factors using propensity score matching, patients who completed the planned treatment showed improved disease-free survival (3-year disease-free survival: completed, 80.0%; not received, 65.5%; and discontinued, 56.3%; p = 0.029). CONCLUSIONS: Completion of adjuvant chemotherapy may improve the prognosis of patients with colorectal cancer aged ≥ 80 years, although the number of patients who would benefit from it is limited.

Association between social background and implementation of postoperative adjuvant chemotherapy for older patients undergoing curative resection of colorectal cancers, sub-analysis of the HiSCO-04 study.

PURPOSE: Adjuvant chemotherapy is recommended following colorectal cancer resection based on risk of recurrence. In older patients, treatment decisions should consider recurrence rates and tolerability, as well as functional prognosis, residual disease, and social factors. This study aims to investigate factors, including social background, influencing implementation of postoperative adjuvant chemotherapy in older patients undergoing curative resection for colorectal cancer. METHODS: This multi-institutional prospective cohort study included 15 institutions belonging to the Hiroshima Surgical study group for Clinical Oncology. We analyzed 159 older patients aged ≥ 80 years, who underwent curative resection for stage III colorectal cancer between December 2013 and June 2018, as sub-analysis of the HiSCO-04 study. RESULTS: In total, 62 (39.0%) patients underwent postoperative adjuvant chemotherapy. Four factors were significantly associated with its implementation: performance status < 2, Charlson Comorbidity Index < 2, prognostic nutritional index ≥ 40, and presence of a spouse or siblings as lifestyle supporters. No significant difference was found in the backgrounds between complete and incomplete postoperative adjuvant chemotherapy patients. CONCLUSION: Performance status, Charlson Comorbidity Index, nutritional status, and presence of a spouse or siblings as lifestyle supporters are possible factors influencing the implementation of postoperative adjuvant chemotherapy in older patients. To select appropriate treatment options, including postoperative adjuvant chemotherapy, it is essential to consider physical condition and comorbidities of older patients, thoroughly explain the situation to their families, and establish a support system to enhance understanding of the available treatment options.

Prolapse of duodenal bulb from esophageal hiatal hernia: A case report.

INTRODUCTION: The number of patients with hiatal hernia has increased. Paraesophageal and mixed hiatal hernias are absolute indications for surgical treatment due to the possibility of blood flow disturbances to the stomach and other organs. CASE PRESENTATION: A 77-year-old woman with a history of type IV esophageal hiatal hernia (under observation), multiple operations presented with a chief complaint of vomiting. She was diagnosed with a type IV esophageal hiatal hernia with incarceration of the duodenal bulb into the mediastinum. Although the incarceration was relieved with conservative treatment, the patient was at a high risk for recurrence; therefore, surgical hernia repair was performed. Intraoperatively, the hernia portal was severely dilated and the duodenal bulb was easily accessible to the mediastinum due to its high mobility. Fundoplication was performed using the Toupet procedure. No stenosis at the fundoplication site was observed on intraoperative upper gastrointestinal endoscopy. DISCUSSION: The causes of prolapse and incarceration of the duodenal bulb into the mediastinum were speculated to be weakening of the tissue due to aging, adhesion of the omentum to the hernia portal due to chronic prolapse of the stomach toward the mediastinum, increased intra-abdominal pressure due to a rounded back, and anatomical shortening of the distance between the esophageal hiatus and the duodenal bulb. The Toupet method was used as it is associated with a lower incidence of dysphagia. CONCLUSION: Further investigation is needed to determine the best surgical technique.

Predictive factors associated with anastomotic leakage after resection of rectal cancer: a multicenter study with the Hiroshima Surgical study group of Clinical Oncology.

PURPOSE: Several factors have been reported as risk factors for anastomotic leakage after resection of rectal cancer. This study aimed to evaluate the risk factors for anastomotic leakage, including nutritional and immunological indices, following rectal cancer resection. METHODS: This study used a multicenter database of 803 patients from the Hiroshima Surgical study group of Clinical Oncology who underwent rectal resection with stapled anastomosis for rectal cancer between October 2016 and April 2020. RESULTS: In total, 64 patients (8.0%) developed postoperative anastomotic leakage. Five factors were significantly associated with the development of anastomotic leakage after rectal cancer resection with stapled anastomosis: male sex, diabetes mellitus, C-reactive protein/albumin ratio ≥ 0.07, prognostic nutritional index < 40, and low anastomosis under peritoneal reflection. The incidence of anastomotic leakage was correlated with the number of risk factors. The novel predictive formula based on odds ratios in the multivariate analysis was useful for identifying patients at high risk for anastomotic leakage. Diverting ileostomy reduced the ratio of anastomotic leakage ≥ grade III after rectal cancer resection. CONCLUSIONS: Male sex, diabetes mellitus, C-reactive protein/albumin ratio ≥ 0.07, prognostic nutritional index < 40, and low anastomosis under peritoneal reflection are possible risk factors for developing anastomotic leakage after rectal cancer resection with the stapled anastomosis. Patients at high risk of anastomotic leakage should be assessed for the potential benefits of diverting stoma.

Validation of appendiceal stump invagination in laparoscopic appendectomy.

INTRODUCTION: There are various methods for appendiceal stump dissection, but the necessity for stump invagination remains unclear. This study aimed to assess the efficacy of appendiceal stump invagination in patients with acute appendicitis after laparoscopic appendectomy (LA). METHODS: We enrolled 327 patients with acute appendicitis who underwent LA between 2012 and 2020. Perioperative variables and surgical outcomes were analyzed between the invagination of the appendiceal stump and noninvagination groups. Propensity score-matched analysis (PSM) was performed. RESULTS: More patients experienced severe inflammation and severe intra-abdominal contamination in the noninvagination group than in the invagination group. Patients in the noninvagination group had an older age, higher body mass index, and poorer American Society of Anesthesiologists physical status than the invagination group. Severe inflammation in the noninvagination group was associated with longer hospital stays and poorer postoperative complications than in the invagination group. PSM analysis was performed to minimize bias in the two groups. After PSM analysis, there were no significant differences in surgical site infection, postoperative intra-abdominal abscess, Clavien-Dindo class ≥IIIa, or postoperative stay between the two groups. During the follow-up period, the postoperative adhesive ileus was not significantly different between the invagination and noninvagination groups. CONCLUSION: Invagination of the appendiceal stump during LA is not necessary to prevent short- and long-term complications. Even in cases dissected using a laparoscopic endostapler, the appendiceal stump per se is not related to postoperative adhesive ileus.

Duodenal diverticula perforation caused by an impacted bezoar successfully treated by endoscopic drainage and lithotripsy: A case report and literature review.

Duodenal diverticula perforation due to an impacted bezoar is a rare disease. Surgical treatment is associated with high rates of complications and mortality; therefore, treatment strategies must be carefully decided. Endoscopic treatment offers significant benefits to patients over surgery.

High-Output Stoma Leading to the Diagnosis of Antiphospholipid Syndrome.

Diverting stoma (DS) is widely created in colorectal surgery. High-output stoma (HOS) is a major complication of DS, which can lead to dehydration and thrombosis. Additionally, antiphospholipid syndrome (APS) is a risk factor for thrombosis, and it rarely occurs in men. Herein, we describe a case of multiple thromboses caused by chronic dehydration after HOS. A 48-year-old man visited our hospital with fever and lower abdominal pain; he was diagnosed with sigmoid diverticulitis. He underwent laparoscopic high anterior resection for relapsing diverticulitis and diverting ileostomy during the same operation. On postoperative day 1, an output of 3,000 mL/day was observed from the ileostomy. The stoma output exceeded 2,000 mL/day, which was diagnosed as HOS, and chronic dehydration persisted despite supplementation and restriction of oral water intake. Three months postoperatively, a computed tomography scan before ileostomy closure showed multiple thrombi in the inferior vena cava, right common iliac vein, and pulmonary artery. After antithrombotic therapy, ileostomy closure was performed. As lupus anticoagulant was positive twice and APS was diagnosed, antithrombotic therapy was changed from warfarin to direct oral anticoagulants. Thrombosis did not recur 6 months postoperatively. This is the first report of a case wherein APS was present in the background of thrombosis caused by HOS or chronic dehydration. It is important to be cautious about APS when there is thrombosis after HOS to select appropriate therapeutic agents.

Laparoscopic resection of schwannoma in the hepatoduodenal ligament: a case report.

BACKGROUND: The occurrence of schwannomas in the hepatoduodenal ligament is rare, and its preoperative accurate diagnosis is difficult. Only few cases have been treated with laparoscopic surgery. CASE PRESENTATION: A 54-year-old man visited our hospital following abnormal abdominal computed tomography findings. He had no complaints, and his laboratory investigations were normal. Abdominal contrast-enhanced computed tomography revealed a tumor with enhancement at the margin of the hepatoduodenal ligament. The abdominal magnetic resonance imaging findings of the tumor showed hypointensity on the T1-weighted images and mixed hypointensity and hyperintensity on the T2-weighted fat-suppression images. Positron emission tomography showed localized accumulation of fludeoxyglucose only in the hepatoduodenal ligament tumor. The patient underwent laparoscopic tumor resection for accurate diagnosis. Histopathologically, the tumor was mainly composed of spindle cells, which were strongly positive for S-100 protein on immunohistochemical staining. The patient was discharged without any postoperative complications on day 5. CONCLUSIONS: Complete tumor resection is essential for schwannomas to avoid recurrence. Laparoscopic surgery is useful for schwannomas occurring in the hepatoduodenal ligament and can be performed safely by devising an appropriate surgical method.

Risk Factors for Anastomotic Leakage after Colorectal Surgery with Double-staple Technique Anastomosis: Impact of the Agatston Score.

OBJECTIVES: Anastomotic leakage is associated with severe morbidity, mortality, and functional defects. Its risk factors remain unclear. However, blood perfusion may be a potential major risk factor. It has been reported that the Agatston score is an index for blood flow perfusion evaluation. Therefore, we evaluated the clinical indicators associated with anastomotic leakage, including the Agatston score, in patients who underwent colorectal surgery. METHODS: We retrospectively analyzed 147 patients who underwent elective colorectal surgery with the double-staple technique anastomosis for colorectal cancer between April 2015 and March 2020. The primary outcome was the presence or absence of anastomotic leakage. Univariate and multivariate analyses were employed to identify pre- and intraoperative risk factors. RESULTS: Of the 147 patients analyzed, anastomotic leakage occurred in 12 (8.16%). Male gender, history of angina and myocardial infarction, preoperative white blood cell count, the Agatston score, extent of bleeding, operation time, and intraoperative fluid volume were significantly related to a higher incidence of anastomotic leakage in univariate analysis. Multivariate analysis demonstrated that the incidence of anastomotic leakage was high in patients with a high Agatston score. CONCLUSIONS: The Agatston score can predict the incidence of anastomotic leakage in patients following colorectal surgery. Thus, perioperative measures to prevent anastomotic leakage are recommended when a high Agatston score is observed. A prospective trial is required to demonstrate, with a high level of evidence, that the Agatston score can be useful as a risk score for anastomotic leakage following colorectal surgery.

Imaging diagnosis of aberrant proper hepatic and gastroduodenal arteries prior to pancreaticoduodenectomy: A case report.

In hepatobiliary and pancreatic surgery, an understanding of hepatic artery anomalies is of great importance to surgeons. Cases of the proper hepatic artery originating from the superior mesenteric artery and the gastroduodenal artery originating from the celiac trunk are extremely rare. To our knowledge, there are no reports of these arterial variants being diagnosed before hepatobiliary and pancreatic surgery. A 73-year-old woman underwent subtotal stomach-preserving pancreaticoduodenectomy and lymphadenectomy for duodenal carcinoma. Preoperative vascular construction with 3-dimensional computed tomography showed variants of the proper hepatic artery and gastroduodenal artery. The proper hepatic artery originated from the superior mesenteric artery, and the gastroduodenal artery originated from the celiac trunk. Intraoperative findings and preoperative vascular construction from 3-dimensional computed tomography were found to be matched exactly; both the proper hepatic artery and gastroduodenal artery were preserved. By diagnosing a rare arterial variant preoperatively, we were able to perform the surgery safely. In hepatobiliary and pancreatic surgery, understanding any potential variation of the hepatic artery before surgery is crucial to ensure the best patient outcomes.

Appendicitis with submucosal fecalith mimicking a submucosal tumor: a case report.

BACKGROUND: Submucosal fecalith(s) mimicking submucosal tumors of the gastrointestinal lumen are rare. Moreover, accurate preoperative diagnosis of these entities is exceedingly difficult, and the mechanism(s) of their formation remains unclear. CASE PRESENTATION: A 40-year-old woman visited the authors' hospital due to lower abdominal pain and diarrhea. She had previously been treated for endometriosis. Laboratory investigation revealed increased C-reactive protein levels. Abdominal contrast-enhanced computed tomography revealed thickening of the appendix wall and dilation of the small intestine. The patient was diagnosed with paralytic ileus caused by appendicitis, and interval appendectomy was scheduled. She underwent laparoscopic-assisted appendectomy after conservative treatment. Partial cecal resection was selected due to the presence of an elastic mass in the cecum. The final pathological diagnosis was submucosal fecalith, not submucosal tumor. On day 5, the patient was discharged without any postoperative complications. CONCLUSIONS: In cases of appendicitis with fecalith(s) that appear as submucosal tumor(s) on colonoscopy, submucosal fecalith mimicking submucosal tumor should be considered in the differential diagnosis.

Alpha-fetoprotein-producing Colon Carcinoma with Rapidly Increasing Liver Metastases That Resulted in Death: A Case Report.

Alpha-fetoprotein (AFP) has been widely used as a tumor marker for detecting hepatocellular carcinoma and yolk sac tumors. Recently, cases of gastrointestinal cancer with elevated serum AFP levels have been reported. However, AFP-producing colon cancer is considered rarer than other AFP-producing gastrointestinal cancers. In this study, we report on a case of a 47-year-old woman who was diagnosed with sigmoid colon cancer and underwent sigmoidectomy and lymph node dissection. Postoperative adjuvant chemotherapy (AC) was performed after the curative surgery. After the seventh course of AC, multiple liver masses and enlarged systemic lymph nodes were detected; these were later diagnosed as liver metastases from sigmoid colon cancer. Laboratory examination revealed high AFP levels (14,657.8 ng/mL). After confirming the recurrence, her condition worsened rapidly, and she eventually died 8 months after the operation. Autopsy and histopathological findings showed that the liver mass was positive for AFP staining, but the sigmoid colon cancer tissue was not. We then determined that liver metastases of the colon cancer were more likely than germ cell carcinoma according to the clinical course and pathological findings. We assumed that colon cancer cells can rapidly expand by dedifferentiation, and we diagnosed AFP-producing colon cancer with liver metastases. Despite curative surgery and AC for AFP-producing colon cancer, the patient died of liver and systemic lymph node metastases.

Branching form of celiac artery to be aware of in laparoscopic surgery: A case report using MDCT angiography.

The anomalies of the celiac artery have been reported and reviewed in literature. Hence, it is not uncommon to clinically encounter its various types. This report presents the case of a 76-year-old male who underwent laparoscopic distal gastrectomy. Preoperative abdominal contrast-enhanced computed tomography showed an anomaly of the celiac artery, which was extremely rare, with various other anomalies of the artery.

Clinical Complete Response after Chemotherapy and Palliative Surgery for Unresectable Gastric Cancer.

Gastric cancer incidence is high in several countries, and management of advanced gastric cancer remains a challenge. Chemotherapy for unresectable gastric cancers is still evolving, and achieving a complete cure is difficult. Although a clinical complete response to chemotherapy has been reported in patients with unresectable gastric cancer, the chemotherapy duration for these patients is unclear. Here, we report the case of a 71-year-old man who presented with abdominal discomfort. Upper endoscopy revealed advanced gastric cancer on the upper gastric body. Histopathological examination revealed a poorly differentiated adenocarcinoma. Computed tomography revealed regional lymph node and multiple bilobar hepatic metastases. Radical surgery was not possible; therefore, palliative resection of the primary lesion was planned for symptomatic improvement. Tegafur, 5-chloro-2,4-dihydro-pyrimidine, and potassium oxonate were administered prior to surgery, and proximal gastrectomy was performed. Tegafur, 5-chloro-2,4-dihydropyrimidine, and potassium oxonate administration was reinitiated after surgery. A clinical complete response was achieved in the 8th postoperative month, with no hepatic metastases noted on radio imaging. Computed tomography performed in the 1st postoperative year revealed ascites; however, the cytological examination findings were negative. The initial chemotherapy was discontinued, and paclitaxel administration was commenced. Computed tomography performed annually thereafter demonstrated no recurrence, and paclitaxel was discontinued in the 9th postoperative year. The patient remained recurrence free at 12 years postoperatively. For elderly patients like the one presented here, it may be necessary to consider ceasing chemotherapy; however, because it is possible for a complete clinical response over the long term, it should be continued if the patient is well.

Oncogenic mutation in RAS-RAF axis leads to increased expression of GREB1, resulting in tumor proliferation in colorectal cancer.

BRAFV600E mutation accounts for up to 90% of all BRAF mutations in human colorectal cancer (CRC), and constitutively activates the MEK-MAPK pathway. It is recognized that neutralizing mAbs for epidermal growth factor receptor alone are not effective for CRC with BRAFV600E mutation. Therefore, there is increasing interest in identification of the possible therapeutic targets in downstream of BRAF mutation in CRCs. To address this, we studied genome engineered mouse models for colonic neoplasia that has BrafV600E mutation on the basis of Apc inactivation, induced in 2 distinct Cre mouse models, CDX2P-G22Cre and CDX2P-CreERT2 mice. We carried out oligonucleotide microarray analysis for colonic neoplasia generated in these mouse models, and compared gene expression profiles among Kras/Braf WT, Kras-mutated, and Braf-mutated mouse colon tumors to seek new molecular targets corresponding to the KRAS-BRAF-MAPK axis. We found that the expression of the growth regulation by estrogen in breast cancer protein 1 (Greb1) was the most upregulated gene in Braf-mutated mouse tumors compared to Kras/Braf WT counterparts. The silencing of GREB1 significantly reduced the proliferation and tumorigenesis of CRC cell lines, whereas the overexpression of GREB1 promoted cell proliferation. Although GREB1 was first identified as a hormone-responsive gene mediating estrogen-stimulated cell proliferation in endometriosis, breast, and ovarian cancers, these results suggest that RAS-RAF-MAPK signaling upregulates GREB1 expression in CRC, resulting in cellular proliferation. Thus, GREB1 is a possible therapeutic target for CRCs with BrafV600E mutation.

Synbiotics suppress colitis-induced tumorigenesis in a colon-specific cancer mouse model.

Although synbiotics may be effective in maintaining remission of inflammatory bowel disease, their anticarcinogenic effects are still debated. To address this issue, we evaluated the effects of synbiotics, probiotics, and prebiotics on tumorigenesis using a CDX2P-Cre; Apc+/flox mouse model harboring a colon-specific Apc knock out, which develops adenoma and adenocarcinoma of the colon. Dextran sodium sulfate (DSS)-administration promoted colonic tumor development in CDX2P-Cre; Apc+/flox mice, and these tumors were associated with loss of Apc heterozygosity, as confirmed by observation of well-differentiated adenocarcinomas with ß-catenin accumulation in tumor cell cytoplasm. Synbiotics-treatment suppressed dextran sodium sulfate-induced colitis in CDX2P-Cre; Apc+/flox mice, thereby reducing mortality, and inhibited tumorigenesis accelerated by DSS-administration. Conversely, neither probiotics nor prebiotics had any effect on inflammation and tumorigenesis. Lactobacillus casei and Bifidobacterium breve were detected in the fecal microbiota of probiotics-treated mice. Synbiotics-treatment suppressed DSS-induced expression of IL-6, STAT-3, COX-2, and TNF-α gene transcripts in normal colonic epithelium, indicating the possibility of suppressing tumor development. Importantly, these genes may be potential therapeutic targets in inflammation-associated colon cancer.

Usefulness of intraoperative neuromonitoring for preservation of an extralaryngeal bifurcation of the recurrent laryngeal nerve: A case report.

INTRODUCTION: Recurrent laryngeal nerve injury is a major complication of thyroid surgery. An endotracheal tube with electromyography electrodes attached to it was recently developed for intraoperative neuromonitoring during thyroid surgery. Here we describe the successful identification and preservation of an extralaryngeal bifurcation of the recurrent laryngeal nerve by intraoperative neuromonitoring in a patient undergoing thyroid surgery. PRESENTATION OF CASE: A 56-year-old woman presented for evaluation of a neck swelling found during a medical examination. Computed tomography (CT) revealed a tumor with a 5-cm diameter in the left thyroid lobe. Fine needle aspiration cytology revealed a Bethesda category III finding. Left thyroid lobe resection was scheduled. During surgery, the left recurrent laryngeal nerve was found to be adhered to the tumor. Careful exploration and intraoperative neuromonitoring allowed us to identify and preserve an extralaryngeal bifurcation of the recurrent laryngeal nerve. DISCUSSION: The recurrent laryngeal nerve can demonstrate various anomalies and bifurcations. Failure to notice and correctly identify extralaryngeal bifurcation leads to recurrent laryngeal nerve injury. Motor branch injury has a particularly large effect. Intraoperative neuromonitoring has been reported to be useful for identifying and preserving the recurrent laryngeal nerve and its aberrations as well as the external branch of the superior laryngeal nerve during thyroid surgery. CONCLUSION: The findings from this case suggest that an extralaryngeal bifurcation of the recurrent laryngeal nerve can be identified and safely preserved by intraoperative neuromonitoring.

Gallbladder metastasis of renal clear cell carcinoma 15 years after primary cancer excision: a case report.

BACKGROUND: Renal cell carcinoma is well-known for its propensity to metastasize to unusual sites. However, metastasis to the gallbladder has been rarely reported in the literature. CASE PRESENTATION: A 75-year-old Japanese (Asian) woman presented for further evaluation of a gallbladder polyp, 15 years after right radical nephrectomy for renal cell carcinoma. Computed tomography revealed a 12 mm enhancing pedunculated tumor in the gallbladder fundus. Open simple cholecystectomy was performed and the tumor was histologically confirmed as a metastasis of renal cell carcinoma to the gallbladder. Our patient is alive and has been disease-free for 3 years after cholecystectomy. CONCLUSIONS: Although metastasis of renal cell carcinoma is a rare differential diagnosis of gallbladder tumors, simple cholecystectomy is likely to offer a chance of long-term survival for patients with gallbladder metastases of renal cell carcinoma.

Gasdermin C Is Upregulated by Inactivation of Transforming Growth Factor ß Receptor Type II in the Presence of Mutated Apc, Promoting Colorectal Cancer Proliferation.

Mutations in TGFBR2, a component of the transforming growth factor (TGF)-ß signaling pathway, occur in high-frequency microsatellite instability (MSI-H) colorectal cancer (CRC). In mouse models, Tgfbr2 inactivation in the intestinal epithelium accelerates the development of malignant intestinal tumors in combination with disruption of the Wnt-ß-catenin pathway. However, no studies have further identified the genes influenced by TGFBR2 inactivation following disruption of the Wnt-ß-catenin pathway. We previously described CDX2P-G19Cre;Apcflox/flox mice, which is stochastically null for Apc in the colon epithelium. In this study, we generated CDX2P-G19Cre;Apcflox/flox;Tgfbr2flox/flox mice, with simultaneous loss of Apc and Tgfbr2. These mice developed tumors, including adenocarcinoma in the proximal colon. We compared gene expression profiles between tumors of the two types of mice using microarray analysis. Our results showed that the expression of the murine homolog of GSDMC was significantly upregulated by 9.25-fold in tumors of CDX2P-G19Cre;Apcflox/flox;Tgfbr2flox/flox mice compared with those of CDX2P-G19Cre;Apcflox/flox mice. We then investigated the role of GSDMC in regulating CRC tumorigenesis. The silencing of GSDMC led to a significant reduction in the proliferation and tumorigenesis of CRC cell lines, whereas the overexpression of GSDMC enhanced cell proliferation. These results suggested that GSDMC functioned as an oncogene, promoting cell proliferation in colorectal carcinogenesis. In conclusion, combined inactivation of both Apc and Tgfbr2 in the colon epithelium of a CRC mouse model promoted development of adenocarcinoma in the proximal colon. Moreover, GSDMC was upregulated by TGFBR2 mutation in CRC and promoted tumor cell proliferation in CRC carcinogenesis, suggesting that GSDMC may be a promising therapeutic target.

Risk Factors for the Development of Desmoid Tumor After Colectomy in Patients with Familial Adenomatous Polyposis: Multicenter Retrospective Cohort Study in Japan.

BACKGROUND: Desmoid tumor (DT) is the primary cause of death in patients with familial adenomatous polyposis (FAP) after restorative proctocolectomy. This study aimed to identify risk factors for DT in a Japanese population. METHODS: Clinical data for 319 patients with FAP undergoing first colectomy from 2000 to 2012 were reviewed retrospectively. RESULTS: Two hundred seventy-seven FAP patients were included in this study. Thirty-nine (14.1 %) patients developed DT. Occurrence sites were the intraperitoneal region in 25 (64.1 %) cases, intraperitoneal region and abdominal wall in three (7.7 %), and abdominal wall in nine (23.1 %). The mean period from surgery to DT development was 26.3 months (range 4-120 months). Gender (female vs. male, p = 0.03), age at surgery (>30 vs. ≤30 years, p = 0.02), purpose of surgery (prophylactic vs. cancer excision, p = 0.01), and surgical procedure (proctocolectomy [ileoanal anastomosis (IAA), ileoanal canal anastomosis (IACA), total proctocolectomy (TPC)] vs. total colectomy [ileorectal anastomosis, partial colectomy]; p = 0.03) significantly influenced the estimated cumulative risk of developing DT at 5 years after surgery. Conversely, approach (laparoscopic vs. open, p = 0.17) had no significant effect on the increased risk of DT occurrence. In multivariate analysis, female gender, with a hazard ratio of 2.2 (p = 0.02,) and proctocolectomy (IAA, IACA, TPC), with a hazard ratio of 2.2 (p = 0.03), were independent risk factors for DT incidence after colectomy. CONCLUSIONS: Female gender and proctocolectomy (IAA, IACA, TPC) were independent risk factors for developing DT after colectomy in patients with FAP.