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Introduction Functional and morphologic heterogeneity exists in a tumor with a hierarchy in which tumor growth is driven by a small subset of cancer stem cells (CSCs) (1). Like normal [...], Cancer stem cells (CSCs) are generally dormant or slowly cycling tumor cells that have the ability to reconstitute tumors. They are thought to be involved in tumor resistance to chemo/radiation therapy and tumor relapse and progression. However, neither their existence nor their identity within many cancers has been well defined. Here, we have demonstrated that CD13 is a marker for semiquiescent CSCs in human liver cancer cell lines and clinical samples and that targeting these cells might provide a way to treat this disease. [CD13.sup.+] cells predominated in the [G.sub.0] phase of the cell cycle and typically formed cellular clusters in cancer foci. Following treatment, these cells survived and were enriched along the fibrous capsule where liver cancers usually relapse. Mechanistically, CD13 reduced ROS-induced DNA damage after genotoxic chemo/radiation stress and protected cells from apoptosis. In mouse xenograft models, combination of a CD13 inhibitor and the genotoxic chemotherapeutic fluorouracil (5-FU) drastically reduced tumor volume compared with either agent alone. 5-FU inhibited [CD90.sup.+] proliferating CSCs, some of which produce [CD13.sup.+] semiquiescent CSCs, while CD13 inhibition suppressed the self-renewing and tumor-initiating ability of dormant CSCs. Therefore, combining a CD13 inhibitor with a ROS-inducing chemo/radiation therapy may improve the treatment of liver cancer.

Introduction: The clinical significance of laparoscopic cholecystectomy (LC) for acute cholecystitis in elderly patients aged 80 years or older has not been determined. This study aimed to investigate surgical outcomes of LC for acute cholecystitis in elderly patients compared to non‐elderly patients. Methods: Patients who underwent urgent LC for acute cholecystitis were enrolled. Older (≥80 years) and younger patients (<80 years) were compared for perioperative factors to assess surgical outcomes of LC. Results: A total of 351 patients were included; 52 (14.8%) and 299 (85.2%) were categorized as older and younger, respectively. The older group had a significantly higher proportion of patients with concomitant physiological diseases than the younger group and a significantly higher ASA classification. No significant differences between the two groups were found in operation time, intraoperative blood loss, or conversion rate to open surgery. Incidence of postoperative complications and duration of postoperative hospital stay also were not significantly different between the two groups. Conclusion: Surgical outcomes of LC for acute cholecystitis in older patients are comparable to those in younger patients, which confirms the feasibility of LC for acute cholecystitis in elderly patients. [ABSTRACT FROM AUTHOR]

A 64-year-old man presented with epigastric discomfort and nausea. Laboratory analyses revealed increased levels of total and direct bilirubin, and increased levels of aminotransferases. Computed tomography revealed the presence of a mass in the distal common bile duct. Endoscopic retrograde cholangiopancreatography and intraductal ultrasonography revealed a 25 mm filling defect in the distal common bile duct, and biopsy of the lesion disclosed the presence of tubular adenoma. Using fluorine-18 fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET) revealed an increased accumulation of the tracer in the lesion, with a maximum standard uptake value (SUV max ) of 3.3. The patient received a pylorus-preserving pancreatoduodenectomy. The histopathological examination revealed a tubular adenoma with low-grade atypia. The patient remains alive 15 months following the surgery, with no evidence of recurrence of the adenoma. 18 F-FDG PET has been successfully applied in clinical practice to detect a wide variety of tumor types, including lymphoma, lung, colon and bile duct cancer. In the present study, a case of bile duct adenoma with low-grade atypia was reported, revealing the uptake of 18 F-FDG. 18 F-FDG PET may be able to detect premalignant tumors of the bile duct, although whether 18 F-FDG PET is able to differentially discriminate between diagnoses of adenoma and carcinoma of the bile duct remains to be fully elucidated, and the assessment of further case studies is required.

A 56-year-old woman was referred to our hospital because of epigastric discomfort and jaundice. Contrast-enhanced computed tomography and gastrointestinal endoscopy revealed an ampullary tumor. A biopsy specimen showed adenocarcinoma of the ampulla of Vater. The carbohydrate antigen (CA19-9) level was elevated, but insulin and glucagon levels were in the normal range. Based on a diagnosis of adenocarcinoma of the ampulla of Vater, we performed subtotal stomach-preserving pancreatoduodenectomy with regional lymph node dissection. Postoperative histopathological examinations indicated both neuroendocrine carcinoma (40%) and adenocarcinoma (60%) components in the ampulla of Vater and regional lymph node metastasis. According to the 2010 WHO Classification of Tumours of the Digestive System, the diagnosis of mixed adenoneuroendocrine carcinoma (MANEC) of the ampulla of Vater was confirmed. The patient was treated for 6 months with oral administration of TS-1 as adjuvant chemotherapy. Currently, the patient is alive without recurrence 8 months after surgery. MANEC of the ampulla of Vater is rare. It is a highly malignant tumor, and the standardization of its treatment, including surgery, chemotherapy, and radiotherapy requires further study.

We report a case of a 71-year-old man with liver metastases from a rectal neuroendocrine tumor(NET). The patient's chief complaint was melena. He was diagnosed with rectal carcinoma with liver metastases during his initial visit. Therefore, we started UFT/LV as first-line chemotherapy. After 2 courses, the patient's disease had progressed, so the treatment was changed to S-1 as second-line chemotherapy. The patient showed a partial response. In February 2010, we performed an anterior resection, and in April 2010 we performed a posterior segment and S2/8 partial hepatectomy. Histopathological examination showed rectal NET with liver metastases. In December 2011, multiple liver metastases were found, and multimodal treatment including TACE, RFA and somatostatin analogues was selected to treat the recurrent tumor. The patient survived for 10 years after his first visit and for 3 years and 6 months after the recurrence. Multidisciplinary therapy was effective for treating rectal NET with liver metastases.

A 60-year-old male patient underwent curative surgical resection for gastric cancer. After the surgery, the patient was diagnosed with T4b, N3b, ly3, v2, CY0, fStageⅢc gastric cancer, and adjuvant systemic chemotherapy using S-1 and CDDP was administered. However, follow-up computed tomography (CT) scan examination taken 2 months after surgery revealed a pancreatic fistula and retroperitoneal abscess, and percutaneous drainage was performed. After 1 month, the enhanced CT scan detected liver metastasis measuring 25 mm in diameter at segment 7. The CT-guided percutaneous radiofrequency ablation (RFA) combined with transcatheter arterial chemoembolization (TACE) procedure was performed on the liver metastasis using degradable starch microspheres (DSM). Two months after the RFA, a follow-up CT scan revealed local recurrence of the lesion in the medial side of the ablated area in segment 7. A second CT-guided RFA, which was combined with DSM-TACE, was performed on the recurrent lesion. The patient has since survived more than 2 years after the second treatment without any further recurrences. This case report suggests that RFA treatment combined with DSM-TACE might be a safe and feasible treatment for liver metastasis from gastric cancer.

An 83-year-old man underwent extended cholecystectomy for gallbladder cancer. On postoperative day 13, he developed fever and computed tomography (CT) revealed fluid collection at the cut surface of the liver. Ultrasound-guided fluid drainage was conducted, and he was diagnosed with biliary leakage. Radiological examination using a contrast agent revealed that the anterior branch of the bile duct (B5) was completely interrupted. Simple drainage and ethanol injections into the bile duct proved ineffective. Thus, we performed transcatheter arterial embolization (TAE) in the anterior segmental artery (A5) to stop the production of bile in the injured part of anterior segment. The treatment was effective, and he was discharged 15 days after TAE. TAE might be a useful method for treating intractable interrupted-type bile leakage.

Objective: To examine the effect of S-1 adjuvant chemotherapy on muscle volume after curative gastrectomy in gastric cancer patients., Patients: Forty-eight gastric cancer patients (31 men and 17 women) who underwent curative gastrectomy (distal gastrectomy: n=37, and total gastrectomy: n=11) between April 2010 and July 2011 were enrolled in this study. Sixteen patients underwent S-1 adjuvant chemotherapy (S-1 group) for 1 year after the operation, and 32 patients did not (NT group)., Methods: The psoas muscle areas were measured at the fourth lumbar vertebrae on CT images obtained before the operation, and at 6, 12, and 24 months after the operation. Muscle areas was statistically examined by comparing the preoperative and postoperative ratios., Results: The muscle areas 12 months after the operation decreased to 0.86 ± 0.11 in the S-1 group and to 0.96 ± 0.08 in the NT group (p<0.05), and the significant difference disappeared at 24 months (0.93 ± 0.10 vs. 0.93 ± 0.11, NS). In the patients who underwent distal gastrectomy, the muscle areas decreased to 0.90 ± 0.05 in the S-1 group and to 0.96 ± 0.09 in the NT group at 12 months (p<0.05). Meanwhile, in those who underwent total gastrectomy, the muscle areas decreased to 0.80 ± 0.15 and 0.93 ± 0.03, respectively (NS)., Conclusions: S-1 adjuvant chemotherapy affected muscle volume loss after gastrectomy in the gastric cancer patients, but the patients recovered from the adverse effect by 12 months after chemotherapy.

The patient was a 73-year-old male with advanced gastric cancer in the lesser curvature of the antrum.Abdominal computed tomography revealed multiple liver metastases(S5, S8).He was diagnosed with clinical Stage IV gastric cancer (cT3N0M1H1).He received 3 courses of combined neoadjuvant chemotherapy with capecitabine, cisplatin, and trastuzumab because immunostaining indicated the tumor was human epidermal growth factor receptor 2(HER2)-positive.The therapeutic response, as assessed by imaging studies, was partial for the primary lesions and stable for liver metastases.Distal gastrectomy, D2 lymph node dissection, and S5 extended subsegmentectomy of the liver were performed.Histopathological findings indicated that both the primary tumor and liver metastases were neuroendocrine carcinoma.The patient declined post-operative adjuvant chemotherapy and he is alive 6 months after the surgery with no evidence of recurrence.Surgery with neoadjuvant chemotherapy appears to be a promising option for advanced gastric cancer with liver metastases.

The patient was a 74-year-old woman with advanced gastric cancer in the greater curvature of the antrum and lesser curvature of the angle.Abdominal computed tomography revealed bulky lymph node metastases of No. 3, 8a, and 11p.She was diagnosed with clinical Stage IIIA gastric cancer (cT3N2M0) and underwent surgery.Laparotomy findings revealed invasion of bulky lymph nodes to the common hepatic artery and pancreas.Since radical resection was not feasible, exploratory laparotomy was performed.After the surgery, she received 1 course of S-1 monotherapy and 3 courses of S-1/cisplatin (CDDP) therapy.The therapeutic response, as assessed by imaging studies, was partial for the primary lesions and complete for the enlarged lymph nodes.Distal gastrectomy and D2 lymph node dissection were performed.Histopathological findings showed no evidence of lymph node involvement, allowing the patient to undergo radical surgery.The patient received postoperative adjuvant chemotherapy with S-1.She is alive 11 months after the surgery, with no evidence of recurrence.Induction chemotherapy appears to be a promising option for advanced gastric cancer with significant lymph node involvement.

A 74-year-old man with chronic hepatitis C was diagnosed with liver tumors. Contrast-enhanced computed tomography (CT) and ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) revealed hepatocellular carcinomas(HCC) in segments 8 (S8)and 5/8 (S5/8), and detected a lymph node (LN) swelling of 75 mm diameter in the posterior aspect of the pancreatic head. Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) was positive for the swollen LN (SUVmax 12.3), but negative for the intrahepatic HCCs. The alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) values were elevated, and soluble interleukin- 2 receptor levels were also increased (1,440 U/mL). Based on a diagnosis of HCCs with either LN metastasis, or with malignant lymphoma, partial hepatectomy (S8 and S5/8), lymphadenectomy (#13LN), and cholecystectomy were performed. Histopathological examination indicated well differentiated HCC in S5/8, and moderately to poorly differentiated HCC in S8, while poorly differentiated HCC was detected in the LN. Therefore, the final diagnosis was HCCs with metastasis to #13LN originating from the HCC in S8. At present, the patient is alive without further extrahepatic recurrence. The extent of FDG accumulation is related to the degree of differentiation of the HCC; furthermore, there are discrepancies between the FDG uptake in intrahepatic and extrahepatic lesions.

Background/aims: Early cholecystectomy is recommended for patients with acute cholecystitis, particularly when less than 72 hours have passed since symptom onset. The safety of early laparoscopic cholecystectomy for patients receiving anticoagulants or antiplatelet agents is unclear. We retrospectively analyzed the safety of early laparoscopic cholecystectomy for patients with acute cholecystitis undergoing antiplatelet or anticoagulation therapy., Methodology: Between 2005 and 2012, a total of 239 patients were diagnosed with acute cholecystitis, 183 of whom underwent early laparoscopic cholecystectomy. We compared the clinical features and surgical outcomes of 21 patients undergoing antiplatelet or anticoagulation therapy with those of 162 patients not undergoing antiplatelet or anticoagulation therapy., Results: Of the 21 patients, 15 patients took aspirin and four took clopidogrel sulfate. Three patients received dual therapy with two agents. The distributions of the severity of acute cholecystitis, a past history of abdominal operations, body mass index, blood test results, operation time, and blood loss were not significant between the two groups. Neither conversion to open surgery nor bleeding-related complications occurred in the patients undergoing antiplatelet and anticoagulation therapy., Conclusions: Early laparoscopic cholecystectomy for selected patients with acute cholecystitis undergoing antiplatelet and anticoagulation therapy is feasible and safe.

We report a case of a patient in whom a giant mucinous cystadenocarcinoma was treated with distal pancreatectomy. A 37-year-old woman was admitted to the hospital complaining of intermittent epigastric pain. The laboratory data revealed a marked increase in serum levels of carcinoembryonic antigen( CEA 22 ng/mL), cancer antigen( CA) 19-9( 258,129 U/ mL), and CA125 (53 U/mL). A computed tomography (CT) scan revealed a cystic tumor, 15 cm in diameter, in the body of the pancreas. The tumor presented as a multilocular cyst with enhanced nodules. On positron emission tomography (PET)-CT,[ 18F] fluorodeoxyglucose uptake by the nodules of the cyst was noted. Under the diagnosis of malignant mucinous cystic neoplasm, we performed distal pancreatectomy, splenectomy, partial gastrectomy, and left adrenalectomy because the tumor was suspected to be invading the stomach and left adrenal gland. The tumor was histologically diagnosed as invasive mucinous cystadenocarcinoma with ovarian-like stroma. The patient survived for 14 months after surgery without tumor recurrence. Invasive mucinous cystadenocarcinoma of the pancreas has high rates of lymph node metastasis and early recurrence after surgery. We believe that we would have had to perform complete tumor resection equivalent to that of invasive ductal carcinoma of the pancreas if the mucinous cystic neoplasm was found to be malignant preoperatively.

We report a case of long-term survival of a patient who underwent hepatic resection for metastatic gastric cancer. The patient was a 75-year-old man who underwent distal gastrectomy for gastric cancer in 2004. On pathological examination, the tumor was diagnosed as T4a (SE) N0M0, stage IIB. A metastatic lesion was detected in segment 6 of the liver at 2 years after gastrectomy. With regard to radiological findings, a single metastatic lesion and no lymph node metastasis or peritoneal recurrence was observed. The hepatic lesion was curatively resected. Another metachronous liver metastasis was identified in segment 7 of the liver at 3 years after gastrectomy. We resected the remnant liver metastasis, after which the patient has not exhibited any evidence of tumor recurrence for more than 5 years. This case suggests that patients could survive for a long period after undergoing resection of hepatic metastasis because no lymph node metastasis was observed during the operation of the primary gastric cancer, only a single hepatic metastasis without any metastasis to other organs was observed, and the metastatic lesion of the liver could be curatively resected.

We report a case of successful multimodal treatment for combined hepatocellular and cholangiocarcinoma with portal venous tumor thrombus. A 66-year-old man was diagnosed with hepatocellular carcinoma with Vp3 by abdominal enhanced CT. He underwent a complete tumor resection and following interferon and 5-FU combined intra-arterial chemotherapy as an adjuvant setting. The histological findings were consistent with combined hepatocellular and cholangiocarcinoma. At 9 months after the surgery, lymph node metastases were detected. Then we started an oral fluoropyrimidine anticancer agent S-1, because the recurrence was suspected to be originated from the cholangiocarcinoma component. Thereafter, sustained partial remission was achieved. In case of combined hepatocellular and cholangiocarcinoma, we need to create a treatment strategy against characteristics of both components.

We report herein a case of advanced hepatocellular carcinoma (HCC) with gastric cancer and rectal cancer. A 68-year-old man was diagnosed with advanced HCC and gastric cancer. At first, he was planned to be treated by trans-catheter arterial chemoembolization (TACE). After TACE, he was diagnosed with rectal cancer by following abdominal computed tomography (CT) and colonoscopy. Then, he was diagnosed with synchronous triple cancer. To avoid bleeding and obstruction, a resection of rectal cancer was performed secondly. After the surgery, he was treated by TACE for three times. HCC was well-controlled, but there remained a small active HCC lesion. Gastric cancer had little progressed, but was still resectable. Finally, we performed a partial hepatectomy and a distal gastrectomy simultaneously. Both of cancer stage and progression-related multimodal treatment is necessary in synchronous cancer.

We performed chemotherapy with combination of S-1 and CDDP for two patients with progressive gastric cancer accompanied by disseminated carcinomatosis of bone marrow due to bone metastasis with DIC, which was successfully controlled, and they had about one-year prognosis. We think it is worth trying the chemotherapy for the patients with such a severe condition like DIC.

A 70-year-old man was presented with esophageal and gastric cancer pointed by his personal doctor in November 2002. Both of the esophageal and gastric cancer were diagnosed as multiples with cStage II and cStage IA, respectively. In consideration of the patient's quality of life (QOL), chemo-radiotherapy (CRT) for esophageal cancer was preceded, and then total gastrectomy was done. Although esophageal cancer was responded as being complete response (CR), 14 courses of FP therapy were added as supportive chemotherapy. Ten months following CRT, pericardial effusion was noticed, so that pericardiocentesis was performed. Also diuretic has been administered up to the present. Nineteen months following CRT, pleural effusion was noticed and thoracentesis was performed several times into both of the pleural cavities, and that was depending on the degree with OK-432 infusion. Consequently, the patient has been controlled well. As a treatment for esophageal and gastric double cancer, we chose CRT rather than esophagectomy because of the excessive invasiveness. Despite of CR, we have had a difficulty with pleural and pericardial effusions due to the late toxicity of radiotherapy. We need to pay attention to the late toxicity in the case of long-term survival following CRT.

The patient is an 86-year-old man who was presented with right submandibular mass and tarry stool. He was diagnosed having right buccal carcinoma with right cervical lymph node metastasis, gastric cancer with double lesions, and suspected right superior lung cancer by endoscopy and computed tomography. We started with an operation for the right buccal carcinoma. After the operation, superficial-esophageal carcinoma was found. Due to his old age and a lack of physical strength in the operation, we performed an endoscopic mucosal resection for esophageal cancer and argon plasma coagulation for gastric cancer. Symptomatic therapy was only performed for lung cancer. He died from lung cancer 18 months later. However, he had a good quality of life during the progress without recurrence, and the gastric cancer was also controllable without symptoms. It was difficult to decide the treatment for duplicated multiple organ cancers caused by numerous factors such as in our case. We assume that patient's quality of life is the most appropriate factor to be considered in selecting the treatment for elderly patients.