Presence of CD44v9-Expressing Cancer Stem Cells in Circulating Tumor Cells and Effects of Carcinoembryonic Antigen Levels on the Prognosis of Colorectal Cancer.

Circulating tumor cells (CTCs) are cancer cells released from the primary tumor into the bloodstream, and contain cancer stem cells that influence tumor survival, recurrence, and metastasis. Here, we investigated CD44v9 expression in CTCs and impact of preoperative carcinoembryonic antigen (CEA) levels on colorectal cancer (CRC) prognosis. We analyzed the expression of CD44v9 mRNA in CTCs using reverse transcription-polymerase chain reaction and preoperative CEA levels in blood samples obtained from 300 patients with CRC. Subsequently, we evaluated the association of CD44v9 expression and CEA levels with clinicopathological factors. CD44v9 mRNA was expressed in 31.3% of the patients, and was significantly associated with liver metastasis. Patients with positive CD44v9 expression had a lower 5-year survival rate (62.3%) than those with negative CD44v9 expression (82.8%, p < 0.001). Cox regression analysis identified CD44v9 expression and high CEA levels (≥5 ng/mL) as poor prognostic factors, while negative CD44v9 expression and low CEA levels (<5 ng/mL) were associated with favorable prognosis (hazard ratio = 0.285, p = 0.006). These results suggest that a combination of CD44v9 mRNA expression in CTCs and serum CEA levels could serve as a valuable prognostic marker for CRC, potentially enhancing the accuracy of prognosis predictions.

Monitoring Metastatic Colorectal Cancer Progression According to Reactive Oxygen Metabolite Derivative Levels.

Oxidative stress has been implicated in the development, proliferation, and metastasis of colorectal cancer, but few studies have considered how oxidative stress changes in relation to treatment response. In this study, we investigated whether the rate of change in reactive oxygen metabolite derivatives (d-ROM)-serum markers of oxidative stress-could predict treatment response in metastatic colorectal cancer. We enrolled 53 patients with metastatic colorectal cancer who were treated with 3 months of chemotherapy. We measured d-ROM levels and performed computed tomography before and after chemotherapy, and we examined the change in d-ROM levels for each anticancer treatment. Factors influencing the d-ROM ratio (post-treatment: pre-treatment levels) were examined using linear regression analysis. d-ROM levels decreased in patients showing a partial response (p < 0.001) and increased in those showing disease progression (p = 0.042). An increasing d-ROM ratio was associated with disease progression (regression coefficient: 0.416, 95% confidence interval: 0.279-0.555, p < 0.001). Our study indicates that d-ROM levels are useful markers of tumor progression and that the d-ROM ratio is useful for predicting treatment response in patients with metastatic colorectal cancer.

Follicular cholangitis mimicking a common bile duct cancer: a case report.

BACKGROUND: Follicular cholangitis (FC) is a benign bile duct disease that was first reported 2003. Pathologically, it is characterized by lymphoplasmacytic infiltration with multiple lymphoid follicle formations under the mucosal layer of the biliary tract. However, as this disease is extremely rare, little is known about its etiology and pathogenesis. CASE PRESENTATION: A 77-year-old woman was diagnosed with middle bile duct stenosis and potential increases in alkaline phosphatase (ALP) and γ-glutamyl transpeptidase levels (γ-GTP). Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and IgG4 levels were all within the normal limits. Contrast-enhanced computed tomography (CE-CT) and magnetic resonance imaging (MRI) revealed bile duct dilation from intrahepatic to upper common bile duct and an irregular mass lesion in distal bile duct. Additionally, multiple overlapping leaf-like folds were detected. 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT) did not demonstrate fluorodeoxyglucose uptake. Subtotal stomach-preserving pancreaticoduodenectomy with regional lymph node dissection was performed because common bile duct cancer could not be ruled out. The resected specimen showed diffuse homogeneous middle bile duct wall thickening. Microscopically, the lesion exhibited thick fibrosis with several invaded lymphoplasmacytic cells, and lymphoid follicle formations were detected under the mucosal layer. Immunohistochemical staining (IHC) revealed positive for CD3, CD4, CD20 and CD79a, and these findings led to a final diagnosis of FC. The patient has not experienced recurrence to date (42 months postoperatively). CONCLUSIONS: Currently, accurate preoperative diagnosis of FC is difficult. More cases must be accumulated to generate additional knowledge on its precise diagnosis and proper treatment.

[Short-Term Outcomes of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer].

In recent years, an increasing number of reports have demonstrated the usefulness of neoadjuvant chemoradiotherapy (NACRT). In our department, we consider cT3-4 and/or cN-positive locally advanced rectal cancer as an indication for NACRT. We have retrospectively evaluated the efficacy and safety of NACRT in 11 patients who underwent NACRT from November 2018 to July 2022. All patients were male, with a median age of 69 years, and cStage was Ⅱa: 1, Ⅱc: 1, Ⅲb: 5, Ⅲc: 3, and Ⅳa: 1. All patients completed NACRT, and there were no cases of CTCAE Grade 3 or higher adverse events or treatment interruptions. The response rate was 72.7%, and histological response grade were Grade 3: 1(9.1%), 2: 4 (36.4%), 1b: 6(54.5%), and surgical margin was negative in all cases. Pathological down stage was obtained in 45.5% of cases, and pCR was obtained in 1 case(9.1%). The median observation period was 17 months, and during the period, 2 cases(18.2%)developed recurrence, both of which were pulmonary metastases, and no local recurrence including pelvic lymph node recurrence was observed. NACRT for locally advanced rectal cancer is considered a relatively safe and highly locally controllable preoperative treatment.

[A Case of BRAF V600E-Mutant Colorectal Cancer Treated Effectively by Encorafenib, Binimetinib, and Cetuximab Triple Therapy].

A 76-year-old woman was diagnosed with left-sided transverse colon cancer invading the pancreatic tail with multiple liver metastases and peritoneal dissemination. Preoperative diagnosis was cT4b(SI)N2aM1c(H3, P1), cStage Ⅳc, harboring BRAF V600E mutation. Transverse colostomy was performed, and FOLFOXIRI plus bevacizumab(BEV)was administered. After 12 chemotherapy cycles, the primary tumor and metastatic lesions showed partial response. Because of CEA elevating after 5-FU plus LV plus BEV as maintenance therapy was changed, the regimen was switched to encorafenib plus binimetinib plus cetuximab as the second-line chemotherapy. The patient developed dermatitis around the colostomy after the start of the second-line chemotherapy, resulting in temporally cetuximab monotherapy. After improvement of dermatitis, the patient resumed encorafenib plus binimetinib, improving liver metastases. Eight months after the start of the second- line, the patient has been administered with triple therapy and had stable disease status.

Oxidative Stress as a Biomarker for Predicting the Prognosis of Patients with Colorectal Cancer.

INTRODUCTION: Excess oxidative stress is generated by inflammation and cancer, and it is involved in the development and metastasis of colorectal cancer. However, there are few reports on the relationship between blood oxidative stress and prognosis. This study examined the usefulness of derivatives of reactive oxygen metabolites (d-ROMs), a measure of oxidative stress, and the neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, as prognostic markers in colorectal cancer. METHODS: The study enrolled 163 patients who underwent colorectal cancer resection at our institution between 2013 and 2018. Blood samples were taken preoperatively to measure d-ROMs and NLR. Spearman's correlation analysis was used to examine the relationships between d-ROMs and NLR, and Cox regression analysis was performed to identify factors associated with d-ROMs and NLR. The Kaplan-Meier method was used to calculate disease-specific survival (DSS). RESULTS: There was no correlation between d-ROMs and NLR. Tumor size was significantly associated with d-ROMs and NLR. DSS was significantly worse among patients with high d-ROMs or high NLR, although patients with high d-ROMs and high NLR had the worst DSS. In the multivariate analysis, distant metastasis and the high d-ROM/NLR combination were significant factors associated with DSS (p < 0.001, hazard ratio [HR] = 22.880 and p = 0.049, HR = 2.391, respectively). CONCLUSION: Preoperative d-ROMs and NLR reflect the tumor size among patients with colorectal cancer. The combination of d-ROMs and NLR may effectively predict prognosis in patients with colorectal cancer.

Stage IV anal canal squamous cell carcinoma with long-term survival: a case report.

BACKGROUND: Currently, no established standard treatment exists for metastatic anal squamous cell carcinoma. We report a case of complete response in a patient with stage IV anal squamous cell carcinoma after undergoing multidisciplinary treatment. CASE PRESENTATION: A 62-year-old woman visited a nearby doctor with a chief concern of severe pain associated with a firm mass in the anus. The patient was diagnosed with anal canal squamous cell carcinoma and liver metastases and referred to First Department of Surgery Faculty of Medicine University of Fukui for treatment. The patient received a TNM classification of T4N0M1 and stage IV. Rectal amputation was performed; however, postoperative complications hindered immediate anticancer therapy and the liver metastases exacerbated. Radiofrequency hyperthermia and systemic chemotherapy were performed 3 months postoperatively. A prominent reduction in the liver metastasis was observed. Lung metastases appeared during the course of systemic chemotherapy. Radiotherapy was performed to treat the lung lesion and resolved. Radiotherapy was also performed for liver metastasis. The lesion in the liver showed resolution after 54 months postoperatively, and treatment with the anticancer drug was discontinued. Ten-year follow-up findings suggested complete resolution of the lesion in response to the treatment protocol followed in this case. This long-term survival was achieved through a multidisciplinary treatment. CONCLUSIONS: The present case suggests that multidisciplinary treatment approach is effective for resolving stage IV anal squamous cell carcinoma, and addition of new anticancer drug therapy may improve the overall prognosis of squamous cell carcinoma.

Feasibility of [18F]FDG PET/MRI with Early-Delayed and Extended PET as One-Stop Imaging for Staging and Predicting Metastasis in Rectal Cancer.

BACKGROUND: We aimed to evaluate the diagnostic accuracy of 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography/magnetic resonance imaging ([18F]FDG PET/MRI) for preoperative staging and usefulness of the detection of extramural vascular invasion (EMVI) for predicting metastasis in rectal cancer. METHODS: Twenty-three patients underwent pretreatment [18F]FDG PET/MRI, including early-delayed and extended PET and dedicated pelvic MRI without using anticonvulsant or contrast agents. Seven patients received preoperative treatment and all subsequently underwent surgery. Clinical cancer stages were evaluated using postoperative histopathology as a reference. PET/MR-defined EMVI (pmrEMVI) and pathological (p) TN stages were correlated with disease progression for a maximum of 2 years. RESULTS: Of 16 patients without preoperative treatment, 10 had pT3, 4 tumors, 7 had pN1-3 lymph nodes, and 5 had synchronous metastases (SM; liver, lung, inguinal node). The sensitivity, specificity, and accuracy of PET/MRI were 90%, 67%, and 81% for T staging (T1, 2 vs. T3, 4), and 89%, 100%, and 94% for N staging (N0 vs. N1-3), respectively. Patient-based accuracy for SM staging was 100% (4/4). Of 23 patients, 6 were positive for pmrEMVI and 4 had metachronous metastases or local recurrence (MM; pelvic node, brain, lung, skin) during the follow-up periods. Five of the 6 pmrEMVI-positive patients had SM and/or MM (odds ratio = 37.5). Among pT, pN, and pmrEMVI, pmrEMVI-positivity was the only significant predictor for poorer progression-free survival (p < 0.05). CONCLUSIONS: [18F]FDG PET/MRI according to our suggested protocol is a one-stop, non-contrast, and valid diagnostic method for rectal cancer staging, and pmr-EMVI can be used as an imaging biomarker for predicting metastases.

[A Long Term Survival Case of Gastric Cancer with Peritoneal Dissemination Responding to Intraperitoneal Chemotherapy].

A 32-year-old woman was admitted our hospital due to epigastric discomfort. The patient diagnosed as having scirrhous carcinoma of the stomach by upper gastrointestinal scope. Peritoneal dissemination and ovarian metastasis were confirmed by the diagnostic laparoscopy. Therefore, combination chemotherapy with S-1 and intraperitoneal chemotherapy(ip)with docetaxel (DTX) was started. After 2 courses chemotherapy, laparoscopy was performed again. Peritoneal dissemination was scarred, but biopsy showed altered AE1/AE3 positive cells, and increased left ovarian metastasis, so systemic chemotherapy was changed to DCS chemotherapy and added DTX ip. After 4 courses chemotherapy and 7 months after the first diagnosis, subtotal gastrectomy, hysterectomy and bilateral adnexectomy were performed because the cytology and tumor marker remained within normal range. In histopathological diagnosis, the effect of chemotherapy was Grade 2 at the primary site and Grade 3 at the metastatic site. Nine years have passed since the initial diagnosis and she has no relapse with postoperative adjuvant chemotherapy.

[Examination of Prognosis and Adjuvant Chemotherapy in Stage â ¡ and Stage â ¢ Resected Colorectal Cancer in the 9th Edition Japanese Classification of Colorectal Carcinoma].

In the 9th edition Japanese Classification of Colorectal Carcinoma, Stage Ⅱ and Stage Ⅲ colorectal cancer(CRC)were subdivided by TNM classification on invasion and number of lymph node metastases. We studied prognostic comparison and relation of adjuvant chemotherapy at the new classification. We included 400 cases with resected Ⅱ and Ⅲ CRC from 2007 to 2014. Ⅱa/Ⅱb/Ⅱc/Ⅲa/Ⅲb/Ⅲc were 97/68/20/24/124/67 cases. Adjuvant chemotherapy was performed at 19/32/45/66/59/70% in Ⅱa/Ⅱb/Ⅱc/Ⅲa/Ⅲb/Ⅲc, with or without adjuvant chemotherapy at each stage survival rates were compared. In Ⅱa/Ⅱb/Ⅱc, DSS was 97/97/82% and DFS was 89/88/76%, and the prognosis of Ⅱc was significantly worse. In Ⅲa/Ⅲb/Ⅲc, DSS was 95/86/57% and DFS was 82/77/41%. By the presence or absence of adjuvant chemotherapy, significantly differences were obtained at Ⅲb and Ⅲc. Prognosis of Ⅱc was almost same as Ⅲb, and prognosis of Ⅲa was almost same as Ⅱb. Therefore, we considered adjuvant chemotherapy with oxaliplatin should be performed to Ⅱc, Ⅲb, and Ⅲc.

Acute Small Bowel Perforation Caused by Obstruction of a Novel Tag-Less AgileTM Patency Capsule.

A 74-year-old man visited our hospital complaining of abdominal pain. An abdominal computed tomography scan showed multiple wall thickness of the small bowel. Capsule endoscopy was recommended for further evaluation, and patency capsule examination was performed. Eighteen hours after patency capsule ingestion, he experienced small bowel perforation with severe peritonitis caused by intestinal pressure rising because of the patency capsule trapped in his terminal ileum. An ileocolic resection was performed, including the removal of the sclerotic ileum as an emergency surgery. A pathological examination showed transmural inflammation and multiple ulcers with perforation of the small intestine, consistent with Crohn's disease. Here, we report a rare and valuable case of novel tag-less AgileTM patency capsule (Given Imaging Ltd., Yoqneam, Israel) retention leading to small bowel perforation.

[A Case of Pathological Complete Response Following Neoadjuvant Chemotherapy with Gemcitabine plus Nab-Paclitaxel in Borderline Resectable Pancreatic Cancer].

We report a resected case with a pathological complete response(pCR)after neoadjuvant chemotherapy for borderline resectable pancreatic cancer(BRPC). A 67-year-old woman who had been treated for type 2 diabetes mellitus in our hospital presented with an exacerbation of diabetes. An abdominal CT scan confirmed a hypovascular mass in the pancreas body consistent with BRPC. After 3 courses of chemotherapy with gemcitabine plus nab-paclitaxel(GnP), her elevated DUPAN-2 level normalized. A follow up CT scan revealed that the tumor had decreased in size, and no distant metastasis was detected. Distal pancreatectomy with en-bloc celiac axis resection was performed. Histopathological examination of the resected specimens showed no evidence of residual cancer cells(pCR). The patient remains disease-free 8 months after surgery. Neoadjuvant GnP chemotherapy may be useful for BRPC.

Measures for preventing wound infections during elective open surgery for colorectal cancer: scrubbing with gauze.

In addition to the general surgical-site infection prevention measures in colorectal cancer surgery, we performed a simple subcutaneous scrubbing procedure with gauze at the time of abdominal closure, which reduced the incidence of wound infections. There are 289 patients whose primary colon cancer lesions were removed by elective surgeries. They were divided into Group A (74 patients with no wound infection prevention measures who were treated from 2002 to 2003), Group B (76 patients with wound infection prevention measures who were treated from 2007 to 2008), and Group C (139 patients with subcutaneous scrubbing with gauze plus the measures in Group B who were treated from 2009 to 2012). The incidence in Group A was 23%, while the corresponding values in Group B and Group C were 14.5% and 2.9%, respectively. The incidence of wound infections was substantially reduced by additional subcutaneous scrubbing with a saline solution and gauze during closure of a surgical incision. This very simple procedure was considered useful for surgical site infection prevention.

Partial response after transcatheter arterial infusion chemotherapy in a patient with systemic chemotherapy-resistant unresectable colon cancer and hepatic metastasis: (case report).

We report here a case of partial response to hepatic arterial infusion chemotherapy in a patient who developed serious hepatic failure due to unresectable colorectal cancer and hepatic metastasis and showed resistance to systemic chemotherapy with molecular targeted drugs, mFOLFOX6, and FOLFIRI. The patient was a 60-year-old woman who underwent sigmoidectomy for sigmoid colon cancer, lateral posterior hepatic segmentectomy for metastatic liver cancer, and postoperative radiation therapy for metastatic lung cancer. As first-line systemic chemotherapy, mFOLFOX6 (oxaliplatin, 5-fluorouracil, and leucovorin), bevacizumab + FOLFIRI (irinotecan, 5-fluorouracil, leucovorin), and anti-epidermal growth factor receptor antibody + irinotecan were administered, in that order. However, recurrent hepatic metastasis was exacerbated, which induced serious hepatic failure manifested by general malaise, jaundice, abnormal hepatic function, difficulty in walking due to bilateral lower extremity edema, and decreased appetite. The patient was admitted in a serious condition. After hospitalization, the patient received hepatic arterial infusion chemotherapy with 5-fluorouracil and l-leucovorin. After two complete courses, the symptoms improved. The patient's performance status also improved, and she was discharged from the hospital. Four months after discharge, the patient had continued outpatient chemotherapy and maintained excellent performance status. Although HAIC is not presently considered an alternative to systemic chemotherapy, it is sometimes effective in patients who show resistance to molecular targeted drug therapy, FOLFOX, and FOLFIRI, and in whom hepatic metastasis is a key factor in determining prognosis and serious hepatic failure. Further studies should be performed in the future to verify these findings.

Five-year survival of alpha-fetoprotein-producing gastric cancer with synchronous liver metastasis: a case report.

Alpha-fetoprotein-Producing gastric cancer is associated with poor prognosis because of frequent liver and lymph node metastasis. We present a case with synchronous liver metastasis who survived for 5 years. A 69-year-old man with upper abdominal pain was referred to our hospital. Gastrointestinal endoscopy revealed a Borrmann II-like tumor in the lower part of the stomach. Computed tomography revealed a tumor in the left lobe of the liver. Serum alpha-fetoprotein levels were markedly increased. We performed distal gastrectomy after administering oral tegafur/gimeracil/oteracil potassium and administered hepatic intra-arterial cisplatin injection. Liver metastasis showed partial response on computed tomography. Despite left hepatic lobectomy, further metastases to the liver and mediastinal lymph nodes became difficult to control. After sorafenib tosylate administration, stabilization of the disease was observed for 4 months. We conclude that hepatic intra-arterial chemotherapy and oral administration of sorafenib tosylate may potentially improve the prognosis in such cases.

A rare congenital anomaly, bridge-like appendiceal fistula to the terminal ileum, demonstrated by MDCT.

Although appendiceal anatomical anomalies are very rare, understanding of the anatomical details of these anomalies is important for surgery. In this case report, we present images from multi-detector row computed tomography (MDCT) and histological findings of a rare anatomical appendiceal anomaly originating from the cecum and opening into the terminal ileum like a bridge. These anatomical details were clearly depicted on MDCT with multi-planar reconstruction. MDCT demonstrated a communication between the appendix and terminal ileum. Histological analysis revealed that a normal mucosal layer was maintained from the appendix to the connected ileum, without any evidence of inflammatory or neoplastic changes, and only thickening of the muscular layer of the appendix was identified. Based on these histological findings, the appendix was considered to represent an anatomical anomaly rather than secondary fistula caused by inflammation or neoplasm, which has not yet been reported.

[A case of response to panitumumab as third-line chemotherapy for multiple liver metastases and portal venal tumor embolus of rectal cancer].

A 64-year-old man who underwent rectal amputation for rectal cancer was diagnosed with multiple liver metastases and tumor embolus in the portal vein 6 months after operation. Though the patient underwent chemotherapy, mFOLFOX6, and bevacizumab+FOLFIRI, liver metastases were diagnosed as progressive disease (PD). After panitumumab+FOLFIRI was administered for three months as third-line chemotherapy, the tumor embolus completely disappeared, and liver metastases became cytoreductive on CT. The patient was judged to have achieved a partial response (PR). This case indicated that panitumumab was effective as third-line chemotherapy for unresectable recurrent rectal cancer.

Survivin-3B gene decreases the invasion-inhibitory effect of colon cancer cells with 5-fluorouracil.

The expression of survivin molecules has been confirmed in many types of cancer cells, including colon cancer cells, and they are considered important antiapoptotic molecules. Recent studies have revealed the existence of different splicing forms of survivin molecules; however, no studies have examined their expression in gastrointestinal cancers. In 2004, we reported the existence of the survivin-3B gene, a novel splice variant of survivin. In this study, we investigated the relationship between human colon cancer and our recently cloned survivin-3B gene with a coding region of 594 bp. In the first examination, survivin-3B expression was analyzed by RT-PCR in human colon cancer and adjacent normal mucosal tissues. The associations of its expression status with clinicopathological parameters and the prognosis were also examined. Survivin-3B mRNA expression was observed in 37 (46.3%) of 80 primary colon cancers, but not in the adjacent normal colonic mucosal tissue. The rate of survivin-3B gene expression was significantly higher in colon cancer with serosal invasion. The 5-year survival rate of patients with survivin-3B gene-positive primary colon cancer was significantly poorer, at 48.7%, than that (75.4%) of survivin-3B gene-negative patients. In the second examination, after the introduction of the survivin-3B gene into cells of the colon cancer cell line DLD-1, 5-fluorouracil-induced changes in their invasive capacity was examined. The invasion-inhibitory effect of 5-fluorouracil on survivin-3B gene-transfected DLD-1 cells was significantly lower than their empty vector gene-transfected counterparts. We speculate that survivin-3B expression in colon cancer is an important factor involved in the invasive capacity of cancer cells in the presence of anticancer drug.