[Laparoscopic Resection of a Liver and Ovarian Metastasis of Transverse Colon Cancer-A Case Report].

A 60s woman was diagnosed to transverse colon cancer and she underwent laparoscopic right hemicolectomy. Localized peritoneal dissemination surrounding tumor was detected during surgery. She was administrated to chemotherapy due to a hepatic metastasis in S2/3 postoperatively. Subsequently, PET-CT revealed a left ovarian metastasis in addition to a liver metastasis during chemotherapy. Laparoscopic hepatic left lateral segmentectomy and bilateral adnexectomy was performed at 1 year and 9 months after the first surgery and histopathological examination showed a metastasis of transverse colon cancer. The growth of liver and lung metastases and peritoneal disseminations was detected at 6 months later after the second surgery and the patient is currently receiving palliative treatment. Previous literatures described that ovarian metastasis of colon cancer showed bilateral metastasis and resistance to chemotherapy frequently and ruptured in some cases. We should consider to resect bilateral ovary even if unilateral metastasis alone was detected by imaging examination.

A case of esophageal squamous cell carcinoma accompanied by pancreatic and bile duct metastases: Successful treatment starts with an accurate diagnosis.

ABSTRACT: Pancreatic and bile duct metastases from esophageal cancer are extremely rare. We report a case of advanced esophageal cancer successfully treated with chemotherapy, selected on the basis of an accurate pathologic diagnosis. A 69-year-old man with chronic renal dysfunction presented with persistent abdominal pain and anorexia. Upper gastrointestinal endoscopy revealed an irregular-shaped tumor in the lower esophagus. Computed tomography and ultrasonography revealed swollen para-aortic lymph nodes, a pancreatic mass, and distal bile duct stenosis. Histopathological examination showed that all of the lesions were squamous cell carcinoma with unique immunohistochemical characteristics of p40+ and cytokeratin 7+. The final diagnosis was esophageal squamous cell carcinoma accompanied by lymph node, pancreas, and bile duct metastases. Taking his renal dysfunction into consideration, modified FOLFOX was administered as the first-line chemotherapy. The patient survived for 15 months since his first presentation. The favorable outcome was attributed to the accurate diagnosis based on comprehensive tissue sampling.

Clinical Factors of Delayed Perforation after Endoscopic Submucosal Dissection for Gastric Neoplasms.

BACKGROUND: Delayed perforation is a rare but severe complication of endoscopic submucosal dissection (ESD) for early gastric neoplasm (EGN). The aim of this study was to clarify clinical factors related to delayed perforation after ESD. METHODS: A total of 1158 consecutive patients with 1199 EGNs underwent ESD at our hospital between January 2000 and December 2015. Univariate analysis was used to identify clinicopathological factors related to delayed perforation. Moreover, duration of cautery needed for hemostasis was measured by comparison between perforated and nonperforated points in patients with delayed perforation. RESULTS: Delayed perforation occurred in 5 of 1158 consecutive patients with 1199 EGNs who underwent ESD (0.42%). All cases were diagnosed within 24 h after ESD and recovered with conservative management. On univariate analysis, location in the upper stomach was the factor most significantly associated with delayed perforation (P < 0.01). Duration of cautery needed for hemostasis was significantly longer at perforated points (9 s) than at nonperforated points (3.5 s) in five patients. CONCLUSIONS: Location in the upper stomach was the risk factor most prominently associated with delayed perforation after ESD for EGNs. In addition, delayed perforation appears associated with excessive electrocautery for hemostasis.

Polypoid leiomyosarcoma of the esophagus treated by endoscopic submucosal dissection.

We report a rare case of polypoid leiomyosarcoma of the esophagus that was treated by endoscopic submucosal dissection (ESD). A 63-year-old man with complaints of progressive dysphagia was referred to Hyogo Cancer Center for treatment of esophageal tumor. Esophagoscopy revealed a polypoid tumor 25 mm in diameter on the left side of the upper esophagus. Despite several biopsy specimens, the diagnosis could not be confirmed. Computed tomography showed a protruded, homogeneously enhancing mass in the upper esophagus, but no lymph node enlargement or metastasis. After 1.5 months, the esophagogram showed a filling defect 47 mm in diameter in the upper esophagus. Given this rapid tumor growth, en bloc resection was done by ESD for therapeutic diagnosis. After this treatment, the tumor seemed to grow larger, showing a short stalk and occupying the esophageal lumen. Histopathologically, the tumor comprised pleomorphic spindle cells with mitosis. Tumor invasion involved the lumina propria mucosae and contact with the muscularis mucosae, but not involving the submucosa. Immunohistochemical examination showed positive staining for smooth muscle actin and HHF35, but negative for desmin, caldesmon, CD34, c-kit, DOG1, ALK, S-100 protein and cytokeratin. These histopathological findings were compatible with a diagnosis of esophageal leiomyosarcoma derived from the muscularis mucosae.

Influence of endoscopic submucosal dissection on additional gastric resections.

BACKGROUND: Widespread application of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) results in noncurative resection in some patients. The influence of preceding ESD on additional gastric resections has not been completely evaluated. METHODS: Endoscopic, surgical, and pathological records of 255 patients who underwent additional gastrectomy after noncurative ESD at a single prefectural cancer center from September 2002 to December 2010 were reviewed. The estimated gastric resection based on endoscopic images before ESD was compared with the actual gastric resection performed after ESD. RESULTS: Altered gastric resection was performed in 4 (1.6%) of the 255 patients. In 3 patients, total gastrectomy was performed instead of distal gastrectomy; in 1 patient, distal gastrectomy was performed instead of pylorus-preserving gastrectomy because of an insufficient distance from the cardia or pylorus caused by contraction of the ESD scar. Standard gastrectomy including total or distal gastrectomy with D2 lymph node dissection was performed in 33 patients because of deep submucosal invasion with positive/indefinite vertical margins. The final pathology revealed pT2 or deeper in 10 patients. CONCLUSIONS: In conclusion, 98.4% patients underwent the scheduled gastric resection before ESD, and the preceding gastric ESD had almost no influence on changing the gastric resection of the additional surgery. Although rare, the preceding ESD may necessitate alterations in gastric resection to widen the surgical area because of contraction of ESD scar for lesions near the cardia or pylorus. MINI ABSTRACT: A retrospective study of additional gastrectomy after noncurative ESD showed that the preceding ESD had almost no influence on changing the gastric resection of the additional surgery.

Percutaneous endoscopic gastrostomy for decompression of malignant bowel obstruction.

BACKGROUND: Previous reports on percutaneous endoscopic gastrostomy (PEG) for bowel decompression have included a relatively small number of patients and the details of post-procedural outcomes and complications are lacking. The aim of the present study was to evaluate the outcomes and safety of PEG for bowel decompression in a relatively large number of patients with malignant bowel obstruction. PATIENTS AND METHODS: Over a 10-year period, 76 patients with malignant bowel obstruction were referred to the main referral cancer center in Shizuoka prefecture for PEG to obtain decompression. The method for gastrostomy was carried out by the pull-method, the modified introducer method and the percutaneous endoscopic gastrojejunostomy method. Patient demographics, procedural success, complications, elimination of nasal intubation, and survival were reviewed. RESULTS: Successful placement was achieved in 93% of patients (71/76). Procedure-related complications occurred in 21% ofpatients (15/71), of which the majority involved stomal leakage (eight patients), and wound infection (six patients). There were no procedure-related deaths. Among the 55 patients who required nasal intubation before PEG, a trans-gastrostomy intestinal tube was inserted in 16 patients. The need for further nasal intubation was eliminated in 96% of the patients (53/55). The median survival time was 63 days (range, 8-444 days) after PEG placement. CONCLUSIONS: PEG for bowel decompression in patients with malignant obstruction can be carried out with an acceptable risk of minor complications. In combination with a trans-gastrostomy intestinal tube insertion, the elimination of nasal intubation can be achieved in most patients.

Gastric obstruction after endoscopic submucosal dissection.

BACKGROUND: Bleeding and perforation are two major complications of gastric endoscopic submucosal dissection (ESD). There are only a few reports concerning gastric obstruction related to ESD in the stomach. OBJECTIVE: The aim of this study was to clarify the clinicopathological features of patients who experienced gastric obstruction after gastric ESD. METHODS: Clinicopathological data of 1878 patients who underwent gastric ESD from September 2002 to December 2010 were retrospectively reviewed. Data of lesion location, circumference, circumferential extent of ESD ulcer, specimen diameter, depth of cancer, ulcer findings within the lesion, curability of ESD, number of simultaneous lesions, and occurrence of post-operative bleeding and perforation were collected. The risk of gastric obstruction regarding lesion and procedure related factors were assessed, and treatment for these patients was studied. RESULTS: Gastric obstruction was observed in 2.5% of the patients (47/1878). Symptoms occurred in a median of 24 days after ESD. The incidence among patients with lesions in the upper part of the stomach was 4.7% (17/316), 0.36% (3/818) in the middle, and 3.8% (27/699) in the lower part. In relation to the circumferential extent, the incidence was 50% (33/66) among patients with a resection of >75% of the circumference. Stenosis was observed in 87% (41/47) of patients with gastric obstruction. Endoscopic balloon dilation was performed in 45 patients. Perforation due to EBD occurred in four patients; one was referred to surgery. CONCLUSIONS: Patients with a wide resection of >75% of the circumference should be considered for early repeat endoscopy after ESD, and dilation should be performed with caution if found to have stenosis.

Endoscopic submucosal dissection for early gastric cancer in cases preoperatively contraindicated for endoscopic treatment.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is an optimal treatment for early gastric cancer (EGC) with negligible risk of lymph node metastasis; however, ESD is sometimes performed to treat lesions preoperatively contraindicated for the procedure due to various reasons. Here we aim to evaluate the treatment outcomes of ESD for lesions that were preoperatively contraindicated for ESD. PATIENTS AND METHODS: Clinicopathological data of 104 EGC lesions in 104 patients were reviewed retrospectively. The demographic characteristics of patients, reasons for ESD, treatment results, complications, and outcomes were assessed. RESULTS: The major reasons for undergoing ESD included advanced age, desire to undergo ESD, and the existence of comorbidities. En-bloc and complete resection rates were 97 and 71%, respectively. Perforation and postoperative bleeding rates were 13 and 9%, respectively. Resection was beyond the expanded Japanese criteria for endoscopic treatment of EGC in 87 patients (84%), 41 (47%) of whom underwent additional therapy, including subsequent gastrectomy (29 patients) and photodynamic therapy (12 patients). The median follow-up period was 47 months, during which seven patients died from recurrent disease. The 5-year overall and disease-specific survival rates were 70 and 91.5%, respectively. CONCLUSIONS: ESD is a technically demanding procedure for lesions preoperatively contraindicated for endoscopic resection. The curative resection rate was low, but the 5-year disease-specific survival rate of 91.5% was favourable. In experienced hands, ESD may be a treatment option for patients not suitable for radical surgery, and the relevant risk of complications must be considered before treatment.

Characteristics of autoimmune pancreatitis based on serum IgG4 level.

BACKGROUND: Autoimmune pancreatitis is categorized as an IgG4-related autoimmune disease, mostly associated with serological alterations, however characteristics of autoimmune pancreatitis based on serum markers have not been fully evaluated. METHODS: We evaluated demographics, symptoms, imaging and therapeutic outcome in 27 cases of autoimmune pancreatitis stratified by serum IgG4 level. RESULTS: Twenty patients (74%) had elevated serum IgG4 and 7 (26%) had normal IgG4 levels. Compared to patients with normal serum IgG4 levels, patients with elevated IgG4 had higher incidence of jaundice at onset (14.3% vs. 80%, respectively; P=0.002), more frequent diffuse pancreatic enlargement at imaging (14.3% vs. 60%, respectively; P=0.04), significantly higher 18F-2-fluoro-2-deoxy-d-glucose uptake of pancreatic lesions (SUV max: 4.0 vs. 5.7, respectively; P=0.02), more frequent extrapancreatic lesions (42.9% vs. 85%, respectively; P=0.03). Response to steroids was recognized regardless of serum IgG4 level, however maintenance therapy was required more frequently amongst patients with elevated compared to normal IgG4 (85.7% vs. 33.3%, respectively; P=0.04). CONCLUSIONS: Clinical features of autoimmune pancreatitis are different based on level of serum IgG4. Further studies are needed to clarify if normal serum IgG4 cases are a precursor of active type 1 or type 2 autoimmune pancreatitis.

A case of sclerosing cholangitis without pancreatic involvement thought to be associated with autoimmunity.

Sclerosing cholangitis (SC) is one of the lesions frequently seen in IgG4-related systemic diseases, causing biliary stricture and mimicking bile duct carcinoma and primary sclerosing cholangitis (PSC). Although it often accompanies autoimmune pancreatitis (AIP), autoimmune-related SC without a pancreatic lesion is very rare. A 79-year-old woman was referred to our institution with suspected diagnosis of bile duct carcinoma in the previous hospital. The patient was not icteric and fever free, but with an elevated level of serum biliary enzyme, which lead us to detect this disease. Clinical images including computed tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP) and intraductal ultrasonography (IDUS) demonstrated multiple strictures at the intrahepatic bile duct and enhanced wall thickness at the upper common bile duct, however her pancreas was normal. Repeated endoscopic procedures with multiple biopsies from the biliary strictures demonstrated fibrous ductal tissues with lymph-plasma cell infiltration (>10 IgG4(+) cells/HPF). By positron emission tomography using (18)F-fluorodeoxyglucose (FDG-PET), the uptake of FDG was not remarkable in areas other than the biliary lesions. Additional laboratory tests showed elevated levels of serum IgG (2,571 mg/dL), and γ-globulin (29%), and positive autoantibodies, but normal IgG4 (53.2 mg/dL). Together with clinical images, laboratory and histological findings, we diagnosed this patient as sclerosing cholangitis which was thought to be associated with autoimmunity. After one year of follow-up without steroid therapy, idiopathic thrombocytopenic purpura (ITP) developed with an increased level of serological markers. We encountered a rare case of sclerosing cholangitis expected to be associated with autoimmunity, which showed biliary strictures mimicking bile duct carcinoma and needed careful diagnosis. Unlike the typical AIP, the current case demonstrated distinct serological findings and no other organ involvement. Further study is needed to clarify the characteristics of sclerosing cholangitis associated with autoimmunity with a large number of cases.

Proximally migrated pancreatic stent successfully removed using needle-knife and forceps: complication after precut papillotomy assisted by pancreatic stenting.

Pancreatic stent-assisted ampullary precut papillotomy is a rescue method for cases with difficult bile duct cannulation during endoscopic retrograde cholangiopancreatography (ERCP). We describe a case in which post-ERCP pancreatitis (PEP) developed due to the proximal migration of pancreatic stent, after precut papillotomy. Removal of the migrated pancreatic stent was achieved after needle-knife incision of the pancreatic duct's orifice followed by retrieval of the stent using rat-tooth forceps, which resulted in rapid resolution of the PEP. Caution is needed when pancreatic stent is placed after papillary incision. Needle-knife incision of the pancreatic duct orifice followed by forceps removal is an effective technique for rescuing pancreatic stent migration.

Synthesis of modified siRNA bearing C-5 polyamine-substituted pyrimidine nucleoside in their 3'-overhang regions and its RNAi activity.

Short interfering RNA (siRNA) induces specific gene silencing by the RNA interference (RNAi) pathway. Nucleosides in the 3'-overhang regions of siRNAs were replaced with 5-bis(aminoethyl)aminoethylcarbamoylmethyl-2'-deoxyuridine or thymidine. siRNA bearing modified nucleoside was more active in silencing the gene expression of hepatocyte nuclear factor 4α (HNF4α) compared with siRNA bearing thymidine.

Study on suitability of KOD DNA polymerase for enzymatic production of artificial nucleic acids using base/sugar modified nucleoside triphosphates.

Recently, KOD and its related DNA polymerases have been used for preparing various modified nucleic acids, including not only base-modified nucleic acids, but also sugar-modified ones, such as bridged/locked nucleic acid (BNA/LNA) which would be promising candidates for nucleic acid drugs. However, thus far, reasons for the effectiveness of KOD DNA polymerase for such purposes have not been clearly elucidated. Therefore, using mutated KOD DNA polymerases, we studied here their catalytic properties upon enzymatic incorporation of nucleotide analogues with base/sugar modifications. Experimental data indicate that their characteristic kinetic properties enabled incorporation of various modified nucleotides. Among those KOD mutants, one achieved efficient successive incorporation of bridged nucleotides with a 2'-ONHCH2CH2-4' linkage. In this study, the characteristic kinetic properties of KOD DNA polymerase for modified nucleoside triphosphates were shown, and the effectiveness of genetic engineering in improvement of the enzyme for modified nucleotide polymerization has been demonstrated.

Effect of 3'-end capping of aptamer with various 2',4'-bridged nucleotides: Enzymatic post-modification toward a practical use of polyclonal aptamers.

The capping of the 3'-ends of thrombin binding aptamers (TBAs) with bridged nucleotides increased the nuclease resistances and the stabilities in human serum. The binding abilities of the aptamers were not affected by the capping. The capping could be simply executed via a one step enzymatic process using 2',4'-bridged nucleoside 5'-triphosphate and terminal deoxynucleotidyl transferase.

A case of autoimmune pancreatitis with metachronous appearance of idiopathic thrombocytopenic purpura.

Autoimmune pancreatitis (AIP) is often associated with systemic disorders, but a case accompanied with idiopathic thrombocytopenic purpura (ITP) is very rare. A 67-year-old man was referred to our institution with complaints of abdominal pain and jaundice. Multiple images showed diffuse enlargement of the pancreas, narrowing of the main pancreatic duct, stenosis of the lower common bile duct and thickness of the anterior wall of the abdominal aorta. Serum levels of IgG and IgG4 were elevated and a diagnosis of AIP was made based on the Japanese criteria. The pancreatic lesion and serum markers responded well to steroid therapy. A year after withdrawal of steroids, the peripheral blood platelet levels gradually decreased to 5.8 × 10(4)/µl. With elevated serum PAIgG levels and exclusion of other causes, we diagnosed ITP. Immediately after restarting steroid therapy, the platelet level in the peripheral blood recovered.

Transcription and reverse transcription of artificial nucleic acids involving backbone modification by template-directed DNA polymerase reactions.

Oligodeoxyribonucleotides (ODN) where the phosphodiester linkage had been replaced with an amide-type linker [-CH(2)C=ONH-] or an amine-type linker [-CH(2)CH(2)NH-] were synthesized to investigate the effect of these backbone modifications on polymerase reactions. In addition, a triphosphate analogue of thymidine dinucleotide with the amide-type linker was synthesized and enzymatic insertion of the amide linkage into ODN was attempted using this analogue for the polymerase reaction. Primer extension reactions using three types of thermostable DNA polymerases, KOD(exo-), Vent(exo-) and Taq were performed for the assays. Analysis of these data indicate that (i) the polymerase reaction tends to be affected much more by insertion of the cationic flexible amine-type linker than by insertion of the neutral rigid amide-type linker; (ii) the backbone modification has a greater effect on the polymerase reaction when it is adjacent to the 3'-end of a primer as the elongation terminus than when it is on the template, as well as in base or sugar modification; (iii) although the modified linker in the modified DNA template is passed beyond by the polymerase, it still affects the extension reaction several bases downstream from its location; (iv) the modified linker in the template, in some cases, also affects the extension reaction upstream from its location; (v) further improvement of the chemical structure is required for dinucleotide-mimic incorporation.

Smart conferring of nuclease resistance to DNA by 3'-end protection using 2',4'-bridged nucleoside-5'-triphosphates.

Incorporation of 2',4'-bridged nucleotides into the 3'-end of oligodeoxyribonucleotide (ODN) was examined using terminal deoxynucleotidyl transferase (TdT). The three types of 2',4'-bridged nucleoside-5'-triphospates with different bridging structures used were incorporated efficiently into the 3'-end of DNA by TdT, although only single nucleotide incorporation was observed. Nuclease resistance was conferred on DNA, depending on the types of bridging nucleotides added.

Synthesis and properties of oligodeoxyribonucleotides bearing a polyamino group at the 2' position via 2'-O-carbamoylmethyl and 2'-S-carbamoylmethyl groups.

An oligodeoxyribonucleotide containing 2 '-O-methoxycarbonylmethyluridine was synthesized and converted into several 2 '-modified oligodeoxyribonucleotides by a postsynthetic modification method. Using this method, oligodeoxyribonucleotides bearing a polyamine at the 2 ' position were easily prepared, which could form duplexes with either complementary DNA or RNA.