Anaplastic carcinoma of the pancreas diagnosed by endoscopic ultrasound-guided fine-needle aspiration: a case report and review of the literature.

BACKGROUND: Anaplastic carcinoma of the pancreas is a rare pancreatic neoplasm with a poor prognosis. It is classified as a variant of ductal adenocarcinoma, but the clinical features and treatment of it remain unknown because of its rarity and aggressiveness. Endoscopic ultrasonography and endoscopic ultrasound-guided fine-needle aspiration are useful techniques for the diagnosis of pancreatic tumors with high sensitivity and specificity. CASE PRESENTATION: A 72-year-old Japanese woman presented with a diagnosis of acute pancreatitis, and a cystic lesion with slightly high density area was observed by computed tomography in her pancreatic head. In addition, endoscopic ultrasound revealed a heterogeneous lesion. Endoscopic ultrasound-guided fine-needle aspiration showed pleomorphic atypical cells. We diagnosed anaplastic carcinoma of the pancreas. We resected the lesion, and she has shown no sign of recurrence for > 6 months. There are few reports of anaplastic carcinoma of the pancreas diagnosed by endoscopic ultrasound-guided fine-needle aspiration and treated by surgery. Our analysis indicates that anaplastic carcinoma of the pancreas is more likely than typical ductal carcinomas to have cystic lesions with the tumor. CONCLUSIONS: We report a case of anaplastic carcinoma of the pancreas diagnosed by endoscopic ultrasound-guided fine-needle aspiration and subsequently resected with a clear margin. We speculate that anaplastic carcinoma of the pancreas is more likely to have cystic changes than pancreatic ductal adenocarcinoma. When we diagnose pancreas tumor as having cystic changes, anaplastic carcinoma of the pancreas should be considered one of the differential diagnoses.

[A Distal Bile Duct Carcinoma Patient Who Underwent Surgical Resection for Liver Metastasis].

A 70-year-old man with distal bile duct carcinoma underwent a subtotal stomach-preserving pancreaticoduodenectomy without adjuvant chemotherapy. One and a half years after the surgery, elevated levels of serum SPan-1(38.1 U/mL)were observed and CT scans demonstrated a solitary metastasis, 25mm in size, in segment 8 of the liver. The patient received 2 courses of gemcitabine-cisplatin combination chemotherapy. No new lesions were detected after chemotherapy and the patient underwent a partial liver resection of segment 8. The pathological examination revealed a metachronous distant metastasis originating from the bile duct carcinoma. Subsequently, the patient received S-1 adjuvant chemotherapy for 6 months. Following completion of all therapies, the patient survived without tumor recurrence for 3 years and 10 months after the initial operation. Thus, surgical interventions might be effective in improving prognosis among selected patients with postoperative liver metastasis of bile duct carcinoma.

Regeneration of peritoneum using amniotic membrane to prevent postoperative adhesions.

BACKGROUND/AIMS: Adhesions following intraperitoneal surgery are frequent causes of small bowel obstruction. Attempts to prevent postoperative adhesions have mostly proven disappointing clinically. Currently used by ophthalmologists in ocular surface disorders, amniotic membrane transplantation can reduce inflammation and promote re-epithelization. We used amniotic membrane for facilitating peritoneal regeneration and prevention of adhesions with surgical trauma. METHODOLOGY: 20 rats were randomized in equal number into treatment or control groups. Seven days after operation, the incidence and severity of adhesions were evaluated. Histologic and immunohistochemical analyses were examined at 1, 4, 10 weeks after operation. RESULTS: While severe adhesions were observed after 1 week between the cecum and surrounding organs in the control group, adhesion formation was significantly reduced in the amniotic membrane group. Histologic examination demonstrated that free-floating myofibroblasts in the peritoneal cavity attached to surfaces of amniotic membrane grafts to form a layered structure. Free-floating mesothelial cells were incorporated into the regenerating mesothelium on the myofibroblast layer in 4 weeks, while implanted amniotic membrane grafts were absorbed by 10 weeks. In the amniotic membrane group the cecum appeared nearly normal. CONCLUSIONS: Amniotic membrane grafts reduced intraperitoneal adhesions after surgical trauma, were well absorbed, and served as a substrate for regenerating mesothelium.

Endocrine cell and nerve regeneration in autologous in situ tissue-engineered small intestine.

BACKGROUND: The purpose of this study was to regenerate a larger size of small intestinal tissue than that of our previous study and to evaluate the regeneration of the endocrine cells (ECC) and nerve system of autologous tissue-engineered small intestine. The effect of implantation of large numbers of smooth muscle cells (SMC) for the regeneration of small intestine was also investigated. METHODS: Two types of scaffolds with different cell densities were fabricated: low density (LD) of SMC in the scaffold and high density (HD) of SMC in the scaffold. Both scaffolds were implanted into defects of isolated ileum in a canine model. Animals were sacrificed at 8, 12, 18, and 24 weeks. RESULTS: The area of engineered small intestine in the HD group was four times larger than that in the LD group, although that was smaller in size than the original size of the defect. There were no significant changes in the thickness of regenerated smooth muscle layer (SML) in the LD and HD groups. The numbers of endocrine cells gradually increased after implantation. At 18 weeks of regeneration, the number of ECC reached levels comparable to that of normal mucosa. The nerve fibers extended to the center of the graft area and were observed in regenerated SML and regenerated villi at 24 weeks. CONCLUSIONS: The ECC and nerve fibers were regenerated in autologous in situ tissue-engineered small intestine. Seeding a large number of SMC was not sufficient for the regeneration of the small intestine in a tubular configuration.

Monoclonal antibody conjugated to gadolinium as a contrast agent for magnetic resonance imaging of human rectal carcinoma.

BACKGROUND AND OBJECTIVES: Local disease is the most frequent recurrence pattern of rectal carcinoma, and its prognosis is not good. One reason for the poor prognosis is the difficulty of making the diagnosis at an early stage. To detect local recurrence as early as possible, we produced the monoclonal antibody, A7-gadolinium (Mab A7-Gd), conjugate as a contrast agent for magnetic resonance imaging to distinguish between carcinoma and normal tissue. METHODS: We examined the in vitro immunoreactivity of Mab A7 coupled to Gd by chelate, and stability of Mab A7-EDTA-Gd in human serum. Its in vivo distribution in nude mice with human colorectal carcinoma was also examined. RESULTS: Mab A7-Gd retained binding activities that were nearly identical to intact Mab A7. Mab A7-Gd was stable in human serum. More radiolabeled Mab A7-Gd accumulated in the tumor than normal mouse IgG-Gd. Both Mab A7-Gd and normal mouse IgG-Gd disappeared from blood linearly over time. Accumulation levels in normal tissues decreased linearly over time but were lower than those in tumors. CONCLUSIONS: Mab A7 conjugated to gadolinium selectively accumulated in the tumor. Our results suggest that it is potentially suitable as a contrast agent for MR imaging to detect local rectal carcinoma recurrence.

Tissue engineering of small intestinal tissue using collagen sponge scaffolds seeded with smooth muscle cells.

In a previously reported attempt to regenerate small intestine with autologous tissues, collagen scaffolds were used without cell seeding or with autologous mesenchymal stem cell seeding. However the regenerated intestine lacked a smooth muscle layer. To accomplish regeneration of a smooth muscle layer, this present study used collagen scaffolds seeded with the smooth muscle cells (SMC) in a canine model. Autologous SMC were isolated from stomach wall and cultured. Two types of scaffolds were fabricated: in SMC (+), cultured SMCs were mixed with collagen solution and poured into a collagen sponge; and in SMC (-), SMCs were omitted. Both scaffolds were implanted into defects of isolated ileum as a patch graft. Animals were euthanized at 4, 8, and 12 weeks; for the last time point, the ileal loop had been reanastomosed at 8 weeks. At 12 weeks, the SMC (-) group showed a luminal surface covered by a regenerated epithelial cell layer with very short villi; however only a thin smooth muscle layer was observed, representing the muscularis mucosae. In the SMC (+) group, the luminal surface was covered completely by a relatively well-developed epithelial layer with numerous villi. Implanted SMCs were seen in the lamina propria and formed a smooth muscle layer. Thus, we concluded that collagen sponge scaffolds seeded with autologous SMCs have a potential for small intestine regeneration.

Intratumoral administration of methotrexate bound to activated carbon particles: antitumor effectiveness against human colon carcinoma xenografts and acute toxicity in mice.

We previously developed a new formulation of methotrexate (MTX) that is adsorbed onto a suspension of activated carbon particles (MTX-CH) and reported the usefulness of local administration in murine tumors. The present study examines the effects of human colon carcinoma (LoVo) xenografts and the acute toxicity of MTX-CH compared with MTX aqueous solution (MTX-AQ) in mice. In therapeutic experiments, LoVo cells were implanted into the backs of BALB/c nude mice. When the cells had developed into tumors, we performed an intratumoral administration of a weekly dose of 30 mg/kg. The MTX concentration in the tumor was compared between the MTX-CH group and MTX-AQ group. In experiments on acute toxicity, MTX-CH and MTX-AQ were injected subcutaneously in BDF1 mice, and intoxication symptoms, changes in body weight, and date of death were recorded. In the therapeutic experiments, intratumoral administration of MTX-CH was much more effective in suppressing the tumor growth compared with MTX-AQ. In experiments of acute toxicity, the death time of the MTX-CH group was delayed to a greater extent, and the 50% lethal dose (LD(50)) values of MTX-CH were lower than those of MTX-AQ. The LD(50) values of MTX-CH are 75 times higher than the efficacious dose of 30 mg/kg. The present results suggest that intratumoral administration of MTX-CH is useful for local therapy and the therapeutic dose of MTX-CH can be safely injected subcutaneously.

[Intratumoral administration of methotrexate bound to activated carbon particles (MTX-CH) inducing antitumor effect in vivo].

Methotrexate is one of the anticancer drugs that can be safely administered subcutaneously, but locally injected MTX in aqueous solution form does not function in the administration site for very long. We developed a new dosage formulation: methotrexate bound to activated carbon particles (MTX-CH), and can report that it controlled tumor growth through its long-acting effect at the administration site. In this study, we investigated the effect of local administration of MTX-CH compared with MTX aqueous solution in tumors from transplanted human colon cancer cells (LoVo) into the back of nude mice. MTX-CH is superior to MTX aqueous solution in terms of its long-acting effect at the administration site and antitumor effect. We suggest that intratumoral injection therapy of MTX-CH is useful for patients in poor condition and with high surgical risk due to cardiac disease or old age, and patients who are diagnosed positive for cancer after endoscopic mucosal resection of early colorectal cancer.