Endocytoscopic Observation of Non-Ampullary Mucosal Duodenal Cancer.

Our previous study of duodenal adenoma using an endocytoscopy system (ECS) demonstrated that disappearance of goblet cells and spindle-shaped nuclei with loss of polarity were characteristic features. In addition, round duct openings and finger-like projections were observed in tubular adenoma and villous adenoma, respectively. Here, we retrospectively investigated six cases of histologically proven sporadic non-ampullary mucosal duodenal cancer (NAMDC) using ECS. Immunohistochemistry for CD10, MUC2, MUC5AC, and MUC6 was employed to determine the mucin phenotype in addition to conventional HE histology. Immunohistochemistry revealed one case involving the duodenal bulb that was considered to be the mixed type. The other five cases, located in the second or third portion, were considered to be the intestinal type. Vital staining of the mixed-type case was considered insufficient for ECS observation because of surface mucus. However, all five cases of intestinal-type duodenal cancer demonstrated a villous structure, disappearance of goblet cells and enlarged nuclei with loss of polarity. Tubular structures were admixed in four of those cases. Four cases demonstrated oval-shaped nuclei, and one case had spindle-shaped nuclei. Cases showing spindle-shaped nuclei in most of the lesion were diagnosed histologically as cancer in adenoma where the adenomatous component of the tumor was dominant. Oval-shaped nuclei and nuclear enlargement are the characteristic features of NAMDC revealed by ECS and are included among the histological criteria used for diagnosis. ECS offers the potential to perform real-time histological diagnosis of NAMDC in vivo.

[Does Colonic Stenting Affect the Long-Term Prognosis of Colorectal Cancer ?]

The impact of colonic stenting on long-term prognosis has not yet been clarified. We compared background factors, progression-free survival, and overall survival between patients with stents(stent group)who underwent surgery after colonic stenting as a bridge to surgery and patients without stents(non-stent group)who underwent emergency surgery for left-sided colorectal cancer ileus. There was no difference between the 2 groups in the induction of adjuvant chemotherapy, but the use of oxaliplatin-base was highly introduced in the stent group(p=0.03). The 5-year DFS rates were 55.1% and 70.3%(p=0.21)and the 5-year OS rates were 90.7%and 70%(p=0.35)in the stent and non-stent groups, respectively. In the present study, colon stent placement did not affect long-term prognosis.

[A Case of Peritoneal Metastasis of Appendiceal Mucinous Carcinoma Successfully Managed by Multidisciplinary Treatment].

There is no established treatment for appendiceal mucinous adenocarcinoma. When this condition is complicated by pseudomyxoma peritonei(PMP), multidisciplinary treatment is often administered. A 40-year-old woman was diagnosed with right ovarian cancer for which laparotomy was performed. At the time of laparotomy, we considered the tumor to be an appendiceal carcinoma infiltrating the right ovary and performed ileocecal resection with lymph node dissection(D3)and right salpingo-oophorectomy. The pathological diagnosis was stage pT3, pN0, pM0, pStage Ⅱ mucinous adenocarcinoma of the appendix. Fourteen months later, the patient underwent abdominal total hysterectomy and left salpingo-oophorectomy because a CT scan suggested recurrence in the uterus, left fallopian tube, and ovary. Seventeen months after the second operation, despite adjuvant chemotherapy, CT revealed a peritoneal nodule in the pelvic cavity. Therefore, we administered chemotherapy comprising 5 lines for 32 months, which resulted in failure. CT showed an enlarged tumor and ascites and the patient became terminally ill. We repeatedly performed cytoreduction surgery and intraperitoneal chemotherapy, which improved her QOL. One year after discharge, abdominal CT showing an abdominal wall and intraperitoneal mass. We performed again cytoreduction surgery and intraperitoneal chemotherapy. Her postoperative course is good and she is currently an outpatient.

[The Outcome of Preoperative Chemoradiotherapy for Advanced Lower Rectal Cancer-The Possibility of an Omission of the Lateral Dissection].

The objective of this study was to evaluate the outcomes of selective LPLN dissection(LPLD)based on pretreatment imaging in patients with advanced low rectal cancer treated with pre-operative CRT. We reviewed 32 patients without suspected LPLN metastasis based on the MDCT or MRI results before CRT. These patients underwent total mesorectal excision (TME)without LPLD. The clinical characteristics and oncological outcomes were examined. In all cases, the per-protocol treatments were completed. Tumor recurrence occurred in 14 patients at the liver(3 cases), the lung(7 cases)and the local sites(4 cases). Of the 4 cases with pelvic recurrence, no recurrence was found in the lateral lymph node area. Under the condition that pre-operative chemoradiotherapy is to be performed for advanced lower rectal cancer with negative lateral lymph node metastasis, a lateral dissection could be omitted.

[A Case of Low-Grade Appendiceal Mucinous Neoplasm Complicated by Pseudomyxoma Peritoneri Successfully Treated with Cytoreductive Surgery and Intraperitoneal Chemotherapy].

We experienced a case of low-grade appendiceal mucinous neoplasm complicated by pseudomyxoma peritonei that was successfully treated with cytoreductive surgery and early postoperative intraperitoneal chemotherapy. The patient was a 26- year-old man with massive ascites and a swollen appendix on the computed tomography(CT). The appendix was a cystic mass of 5 cm in size. The entire parietal peritoneum, omentum, stomach, spleen, gall bladder, and entire colon were covered with numerous mucous nodules. Total colectomy, total gastrectomy, splenectomy, cholecystectomy, total omentectomy, parietal peritonectomy, ileostomy, and intraperitoneal irrigation were performed. The pathological diagnosis was low-grade appendiceal mucinous neoplasm. Postoperative intraperitoneal chemotherapy with cisplatin and mitomycin C was performed. A residual tumor was found on the dorsal side of the hepatoduodenal ligament 3 months postoperation on the CT. The residual tumor was successfully excised via a concomitant resection of the hepatic caudate lobe. Postoperative intraperitoneal chemotherapy was then performed. No recurrence was found at 8 months postoperation. The addition of early postoperative intraperitoneal chemotherapy improved the patient's quality of life in a short period. This could be one of the treatment options.

[A Case of Giant Retroperitoneal Liposarcoma Resected after Trabectedin Chemotherapy].

The basic treatment for retroperitoneal liposarcoma is surgical therapy. Since the administration of trabectedin for soft tissue sarcoma has been approved, another option for soft tissue sarcoma treatment has been added. We report a case of radical resection after trabectedin therapy for initially unresectable retroperitoneal liposarcoma. A 61-year-old man was admitted to our hospital with an abdominal tumor. A tumor, about 50 cm in maximal diameter, that was not movable throughout the abdomen was observed. Computed tomography revealed a giant tumor almost occupying the entire abdomen, and he was diagnosed with retroperitoneal liposarcoma based on histopathological examination of a puncture specimen. Chemotherapy containing trabectedin was administered. At the end of 8 courses, he achieved stable disease. However, the movability improved, and surgery was performed. The procedure was tumor resection with right kidney, adrenal gland, and inferior vena cava resection. Histopathological examination revealed a mixed type of well differentiated type and dedifferentiated type. The patient is alive without recurrence 10 months after the surgery.

[Benefit of Adjuvant Chemotherapy after Curative Resection of Liver and Lung Metastases in Colorectal Cancer].

The survival benefit of adjuvant chemotherapy after resection of liver and pulmonary metastases in colorectal cancer(CRC) remains controversial. We enrolled9 0 CRC patients who underwent hepatic metastasectomy and2 5 CRC patients who underwent pulmonary metastasectomy between April 2005 and March 2017 to clarify the efficacy of adjuvant chemotherapy after hepatic andpulmonary metastasectomy. Forty-two patients receivedad juvant chemotherapy after hepatic metastasectomy, and1 0 patients receivedad juvant chemotherapy after pulmonary metastasectomy. Patients who underwent hepatic metastasectomy andreceivedad juvant chemotherapy hadlonger overall survival(OS)(p=0.043)andrelapse -free survival (RFS)(p=0.043)than those who underwent surgery alone. There were no significant differences in OS(p=0.84)andRFS (p=0.87)between patients receiving adjuvant chemotherapy after pulmonary metastasectomy and those receiving surgery alone. On multivariate analysis, adjuvant chemotherapy was independently associated with favorable OS in patients who underwent hepatic metastasectomy(hazardratio: 0.473, 95% confidence interval: 0.23-0.97, p=0.04). No prognostic factor associatedwith OS andRFS was identifiedin patients undergoing pulmonary metastasectomy. These results suggest that patients who undergo hepatic metastasectomy couldhave an OS andRFS benefit from adjuvant chemotherapy, but those who undergo pulmonary metastasectomy would not.

[Does the Sidedness of Perforative Colorectal Cancer Influence the Prognosis of Patients ?]

We examined the influence of the sidedness of the primary tumor on survival of patients with colon cancer perforation. The subjects of this retrospective study were 52 patients who underwent surgery for colon perforation between April 2005 and December 2016 at our institution and survived more than 30 days. Patients with perforation of the oral side of the tumor were included. The background data and survival times were compared between 9 patients whose primary tumors were located in the cecum, ascending colon, or transverse colon(right-side group)and 43 patients whose primary tumors were located in the descending colon, sigmoid colon, or rectum(left-side group). There was no significant difference in terms of age, sex, Stage, or rate of chemotherapy, but Hinchey stage was significantly higher in the left-side group(p<0.05). The median survival time tended to be longer in the left-side group(68.2 months vs 21.2 months, p=0.05). These results suggest that right-side perforation might cause a poorer prognosis than left-side perforation in patients with perforative colorectal cancer.

Visualization of stem cell features in human hepatocellular carcinoma reveals in vivo significance of tumor-host interaction and clinical course.

UNLABELLED: Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies because of recurrence and/or metastasis even after curative resection. Emerging evidence suggests that tumor metastasis and recurrence might be driven by a small subpopulation of stemness cells, so-called cancer stem cells (CSCs). Previous investigations have revealed that glioma and breast CSCs exhibit intrinsically low proteasome activity and that breast CSCs also reportedly contain a lower reactive oxygen species (ROS) level than corresponding nontumorigenic cells. Here we visualized two stem cell features, low proteasome activity and low intracellular ROS, in HCC cells using two-color fluorescence activated cell sorting to isolate cells with stem cell features. These cells were then analyzed for their division behavior in normoxia and hypoxia, expression of stem cell markers, tumorigenicity, metastatic potential, specific gene expression signatures, and their clinical implications. A visualized small subpopulation of HCC cells demonstrated asymmetric divisions. Their remarkable tumorigenicity in nonobese diabetic/severe combined immunodeficient mice suggested the cancer initiation potential of these HCC CSCs. Comprehensive gene expression analysis revealed that chemokine-related genes were up-regulated in the CSCs subpopulation. Our identified HCC CSCs facilitated the migration of macrophages in vitro and demonstrated metastatic potential by way of recruitment of macrophages in vivo. In patients who undergo curative operation for HCC, the CSC-specific gene signature in the liver microenvironment significantly correlates with recurrence. CONCLUSION: Based on these findings, the stem cell feature monitoring system proposed here is a promising tool to analyze the in vivo significance of CSC microenvironments in human HCCs.

Identification of pancreatic cancer stem cells and selective toxicity of chemotherapeutic agents.

BACKGROUND & AIMS: Identification and purification of cancer stem cells (CSCs) could lead to new therapeutic targets, but their heterogeneous expansion is an obstacle to their study. We investigated whether it is possible to monitor pancreatic CSCs in real time, based on their intrinsic low level of proteasome activity. METHODS: We engineered human pancreatic adenocarcinoma cells (PANC1, MIAPaCa2, BxPC3, and KLM1) to express a green fluorescent molecule fused to the degron of ornithine decarboxylase (Gdeg) from a retroviral vector; the fluorescent Gdeg accumulates in CSCs as a result of low activity of the 26S proteasome. Cells with high and low levels of fluorescence (Gdeg(high) and Gdeg(low)) were isolated by flow cytometry; tumor growth was analyzed in immunocompromised mice. We performed a screen for agents that were specifically toxic to pancreatic CSCs, in a synthetic lethal manner. RESULTS: Gdeg(high) cells, but not Gdeg(low) cells, formed spheres and underwent asymmetric division-features of CSCs. Injection of as few as 10 Gdeg(high) cells led to tumor formation in mice. Gemcitabine was toxic to cultured Gdeg(low) cells, whereas Gdeg(high) cells were resistant. We observed that quercetin was toxic to Gdeg(high) cells in culture and in pre-established tumors grown from these cells in mice. Nuclear accumulation of ß-catenin was detected in Gdeg(high), but not Gdeg(low), and lost after exposure to quercetin. CONCLUSIONS: We used a fluorescence marker system for level of proteasome activity to identify pancreatic cancer cells with features of cancer stem cells. We identified quercetin as a compound that is specifically toxic to pancreatic CSCs.