Local steroid injection into the artificial ulcer created by endoscopic submucosal dissection for gastric cancer: prevention of gastric deformity.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) of large gastric lesions results in an extensive artificial ulcer that can lead to marked gastric deformity. The aim of the current study was to evaluate therapeutic efficacy in the prevention of gastric deformity of local triamcinolone acetonide (TCA) injection into the extensive artificial ulcer following ESD. PATIENTS AND METHODS: A total of 45 patients who were diagnosed with early gastric cancer were enrolled. Patients were randomly assigned by the sealed-envelope randomization method to either local TCA injections (n = 21) or sham-control (n = 20) groups. Two clips were placed at the two maximum outer edges of the artificial ulcer after the lesion had been resected (Day 0). Local TCA injections were performed on postoperative Day 5 and Day 12. The distance between the two clips was measured by endoscopic measuring forceps on Days 5, 12, 30, and 60. Granulation formation and gastric deformity were evaluated by visual analog scale (VAS) on Days 30 and 60. RESULTS: Local TCA injection did not alter clip-to-clip distance on postoperative Day 60, and formation of flat granulation tissue over the ulcer was followed by regenerative mucosa without any gastric deformity. The sham-control group showed significant shortening of clip-to-clip distance compared with the local steroid-injected group and protruded forms of granulation tissue with mucosal convergence. Histological evaluation revealed prominent growth of neovessels, swelling, and marked increases in endothelial cells in the local steroid-injected group compared with the sham-control group. CONCLUSIONS: Local steroid injection into the floor of a post-ESD artificial ulcer promotes the formation of granulation tissue at an early stage of the healing process leading to regeneration of gastric mucosa without mucosal convergence or gastric deformity.

Establishment of pure NOTES procedure using a conventional flexible endoscope: review of six cases of gastric gastrointestinal stromal tumors.

An increasing number of reports have recently been published on hybrid natural orifice transluminal endoscopic surgery (NOTES). These reports do not address how to complete an operation with a flexible endoscope alone (pure NOTES), but rather how to combine use of an endoscope and a laparoscope. Surgical procedures using flexible and rigid endoscopes have been developed using different processes and concepts. Recognizing this conceptual difference, we conducted a study to address how to establish a pure NOTES procedure. Six patients with gastric gastrointestinal stromal tumors (GISTs) underwent hybrid NOTES. Each case was retrospectively reviewed to determine the appropriateness of the treatment and the usefulness of the endoscopic submucosal dissection (ESD) method, double-scope method, spaced perforation method, duodenal balloon occlusion method, and loop clip technique. The development of operative procedures that take advantage of the characteristics of flexible endoscopes, even with conventional flexible endoscopic devices and conventional endoscopes alone, may contribute to the realization of pure NOTES.

The role of prostaglandins in liver ischemia-reperfusion injury.

Ischemia reperfusion (IR) of the liver is a multifactorial process that, at least in part, is responsible for the morbidity associated with major liver surgery under occlusion of the portal triad with the Pringle maneuver, total vascular exclusion or after liver transplantation. Surgeons are confronted with IR injury (IRI) more often than they anticipate. Although the human body has its own defense system, understanding the pathophysiology of IRI is essential for the surgeon in preventing and/or treating the reperfusion injury in common clinical practice. Several endogenous mechanisms exist to overcome IRI and a large number of pharmacological agents have also been found to confer protection against ischemic injury in the liver. They either blocked the injurious pathways directly or they subjected the liver to preconditioning. Prostaglandins (PGs) are a group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase (COX) pathway. They are short-lived, hormone-like chemicals that regulate cellular activities on a moment-to-moment basis and are produced in most tissues of the body, although the liver has emerged as the major organ participating in the synthesis, degradation and elimination of arachidonate products of systemic origin. PGs are released through the prostaglandin transporter on the cell's plasma membrane. During the last decade intensive work on the cytoprotective effects of PGs on livers suffering from IRI have been well documented. Prostaglandins confer their protective effects on IR-injured livers mainly by inhibiting the generation of reactive oxygen species, preventing leukocyte migration, reducing the synthesis or production of membrane degradation products, improving hepatic insulin and lipid metabolism, and regulating the production of inflammatory cytokines and cell adhesion molecules. Production of PGs have been found essential also soon after partial hepatectomy for hepatocyte proliferation.

Significance of fluorodeoxyglucose PET imaging in the diagnosis of malignancies in patients with biliary stricture.

AIM: This study was performed to evaluate the significance of positron emission tomography using fluorodeoxyglucose (FDG-PET) in diagnosing malignancy in patients with biliary stricture by comparing the sensitivity and specificity of FDG-PET with those of CT scans and cytological examination of the bile. METHODS: Thirty patients who underwent FDG-PET for differential diagnosis of the disease causing biliary stricture were included in this study. The sites of the strictures were as follows: in the intrahepatic bile duct in five patients, in the peripheral extrahepatic bile duct in 17 patients, and in the distal extrahepatic bile duct in eight patients. The sensitivity and specificity (%) of FDG-PET in diagnosing malignancies were evaluated and compared with those of CT scans and cytological examination using obtained bile. Final diagnoses were based on surgical or biopsy findings. Data was collected and analysed in a retrospective fashion. RESULTS: Malignant diseases were diagnosed in 21 patients, as follows: cholangiocarcinoma including Klatskin tumour in 10 patients, gallbladder cancer in eight, duodenal and ampulla cancer in two, and pancreatic cancer in one. In diagnosing malignancy in patients with biliary stricture, overall sensitivity and specificity were 85.7 (18/21) and 55.6 (5/9), respectively, for CT, 64.7 (11/17) and 100 (7/7), respectively, for cytological examination of the bile, and 90.5 (19/21) and 77.8 (7/9), respectively, for FDG-PET. CONCLUSIONS: In diagnosing malignant diseases in patients with biliary stricture, FDG-PET was superior to CT examination in both sensitivity and specificity, and superior to cytological examination of the bile in sensitivity. However, in patients with inflammatory disease, such as primary sclerosing cholangitis and cholecystitis, false positive rates were found. Therefore, a multidisciplinary diagnostic approach using FDG-PET in conjunction with conventional modalities seems essential to a precise differential diagnosis.

Use of multislice helical computed tomography cholangiography in the diagnosis of biliary disease.

A recent advance in computed tomography (CT) technology, multislice helical CT, has enabled production of clearer three-dimensional (3D) images and has drawn interest. We report the usefulness of CT cholangiography using a multislice helical CT scanner for the diagnosis and preoperative imaging of the biliary duct in a case of peculiarly shaped gallbladder with cholecystitis. A 34-year-old woman admitted to our hospital presented with chronic hypochondralgia. A CT scan showed that the gallbladder was normal without wall thickening or stones. However, there appeared to be a tumor, containing a stone approximately 1 cm in diameter, attached under the gallbladder in front of the right kidney and extending up to its lower level. Magnetic resonance cholangiography also depicted a normal gallbladder without wall thickening or stones. Hence, gallbladder stones were not diagnosed by previously the mentioned investigations. In contrast, a 3D image produced by multislice helical CT cholangiography was very clear. From the bottom of the gallbladder, a narrow canal continued to a stone. We diagnosed that the wall of the lower part of the long gallbladder had become thick and elongated because of chronic cholecystitis caused by a gallbladder stone, and laparoscopic cholecystectomy was performed. Macroscopically, the resected gallbladder showed an extremely thickened wall from the lower body to the fundus, in which a stone was located in the center. Multislice helical CT cholangiography has the potential to become one of the most significant examinations for diagnosis and anatomical analysis of biliary disease prior to laparoscopic cholecystectomy.

Partial pancreatic head resection for intraductal papillary mucinous carcinoma originating in a branch of the duct of santorini.

We report partial pancreatic head resection of intraductal papillary mucinous carcinoma originating in a branch of the duct of Santorini. The tumor was located in the ventral part of pancreatic head at a distance from the Wirsung duct. Magnetic resonance cholangiopancreatography accurately showed the communication between the duct of Santorini and the cystic tumor, and was useful for determining the part of the pancreas to be resected. Both the duct of Wirsung and the duct of Santorini were preserved. Partial pancreatic head resection would play an important role in surgical management of low-grade malignant neoplasm.

Is preoperative portal vein embolization effective in improving prognosis after major hepatic resection in patients with advanced-stage hepatocellular carcinoma?

BACKGROUND: The impact of the use of preoperative portal vein embolization (PVE) on long-term survival after surgery was evaluated by retrospective analysis of prognostic factors in patients with advanced-stage hepatocellular carcinoma (HCC) who had undergone hepatic resection with or without PVE. METHODS: The portal embolization group (Group P) consisted of 26 patients who had undergone major hepatectomy (more extensive than right hepatectomy) with PVE, and the nonembolized group (Group N) consisted of 43 patients who had undergone major hepatectomy without PVE. All patients were diagnosed with advanced HCC graded as Stage III or IV according to the International Union Against Cancer TNM classification system. Patient survival rates, recurrence rates, and recurrence sites after surgery in the two groups were evaluated and compared. RESULTS: The 1-year, 3-year, and 5-year cumulative disease specific survival rates in patients with TNM Stage III HCC, respectively, were 96.0%, 64.4%, and 52.7% in Group N and 92.9%, 57.1%, and 45.7% in Group P, whereas the corresponding values in patients with Stage IV HCC were 53.5%, 40.1%, and 26.8% in Group N and 63.5%, 50.8%, and 19.1% in Group P. There were no statistically significant differences in survival rates between Group P and Group N. Multivariate analysis showed that PVE was not a significant prognostic factor. The 1-year, 3-year, and 5-year cumulative recurrence rates for patients with both stages of disease combined were 44.1%, 80.2%, and 86.8% in Group N, respectively, and 39.9%, 72.2%, and 72.2% in Group P, respectively, with no statistically significant differences between the two groups. To date, 35 patients in Group N and 16 patients in Group P have had tumor recurrences in the liver remnant; of these, 27 patients in Group N and 12 patients in Group P had multiple recurrence foci in the liver remnant. No significant difference was seen between the two groups; however, 10 of 16 patients in Group P (62.5%) had remote organ metastasis in addition to recurrence in the liver remnant compared with only 6 of 35 patients in Group N (17.1%): This difference was significant statistically (P = 0.012). CONCLUSIONS: PVE during major hepatic resection neither improves nor worsens long-term prognosis but allows resection in a patient group that, otherwise, is considered as unresectable. Remote metastasis involving the lung, bone, or stomach was seen more frequently postoperatively in Group P compared with Group N, raising a possibly important issue regarding the use of this approach for the treatment of patients with hepatic malignancies, especially HCC.

Spatial assessment by magnetic resonance cholangiopancreatography for preoperative imaging in partial pancreatic head resection.

BACKGROUND: Partial pancreatic head resection has been recommended for intraductal papillary mucinous tumor (IPMT). We report the usefulness of preoperative assessment by magnetic resonance cholangiopancreatography (MRCP) compared with endoscopic retrograde cholangiopancreatography (ERCP). METHODS: We studied 12 cases of surgically resected IPMT in the pancreatic head. The MRCP and ERCP images were interpreted, and we examined the detection rate of each imaging technique for the Wirsung duct, the Santorini duct, the entire cystic tumor, and the communication between the tumor and the ducts. RESULTS: In all cases MRCP correctly identified the entire cystic tumor, and the communication between the tumor and the pancreatic ducts was seen in 64% of cases. In contrast, the detection rate by ERCP of the entire cystic tumor and of the communication between the cystic tumor and the ducts was only 8% and 18%, respectively. CONCLUSION: MRCP clearly showed the relationship of the cystic tumor and the pancreatic ducts and was very useful for preoperative imaging for partial pancreatic head resection.

Remarkable tolerance of tumor cells to nutrient deprivation: possible new biochemical target for cancer therapy.

We hypothesized that the tolerance for nutrient deprivation as well as angiogenesis might be an important factor for tumor progression under hypovascular conditions. When normal human fibroblasts were subjected to extreme nutrient starvation by culturing in a medium without serum, glucose, and amino acids, cells died within 24 h. When substituted with liver cancer cell lines HepG2, Hep3B, HLE, and HuH-7, cell death occurred within 36 h. In contrast, four of six pancreas cancer cell lines, PANC-1, AsPC-1, BxPC-1, and KP-3, survived for remarkably longer periods; >50% of the cells survived, even after starvation for 48 h. Among three gastric cancer cell lines, MKN28, MKN45, and MKN74, only the most poorly differentiated MKN45 cells survived >36 h. More than 50% of the cells in colon cancer cell lines SW480, WiDr, and DLD-1 survived after 36 h, and the most undifferentiated SW480 cell line survived longest. We examined the possible involvement of PKB/Akt expression in the survival of various cell lines under nutrient starvation conditions. High expression of PKB/Akt was found to be associated with tolerance for nutrient starvation. When Akt antisense RNA expression vectors were introduced into PANC-1 cells, the tolerance was partially but significantly diminished by vectors for Akt1 and Akt2 but not Akt3. Because elimination of the tolerance might serve as a new strategy for cancer therapy, several compounds were tested for this purpose, and troglitazone, an insulin sensitizer, as well as LY294002, a phosphatidylinositol 3-kinase inhibitor, were found to kill PANC-1 cells only under nutrient starvation conditions.

Spontaneous total necrosis of hepatocellular carcinoma: report of a case.

We report on a 50-year-old man with a liver mass that, when surgically resected, was found to be a hepatocellular carcinoma that had undergone spontaneous complete necrosis without previous treatment. Histologically, no viable tumor cells were observed. The postoperative course was uneventful, and the patient is alive without evidence of recurrence about 5 years after surgery. Spontaneous total necrosis of hepatocellular carcinoma without previous treatment is rare. In particular, spontaneous total necrosis of a hepatocellular carcinoma that has been proven by histologic examination of a surgically resected liver specimen is extremely rare; only three cases of spontaneous complete necrosis of hepatocellular carcinoma have been reported previously. In this report, we present our unusual case and discuss possible causes of spontaneous total necrosis or regression of hepatocellular carcinoma.

Correlation of in vitro autofluorescence endoscopy images with histopathologic findings in stomach cancer.

BACKGROUND AND STUDY AIMS: There is increasing interest in the use of autofluorescence endoscopic imaging systems for the detection of malignancies in the gastrointestinal tract. The purpose of this study was to investigate the autofluorescent color of cancer lesions, and the detection rate of cancer areas using an autofluorescence endoscopic imaging system. Concurrent histopathologic examination was used for comparison. PATIENTS AND METHODS: This study involved a total of 50 stomach cancer patients (with a total of 61 lesions) undergoing surgery. Immediately after the resection, each lesion was observed using an autofluorescence endoscopic imaging system (LIFE-GI system, Light-Induced Fluorescence Endoscopy in the Gastrointestinal Tract). A total of 429 evaluation points in the specimens were selected according to tumor size. The images obtained in this way were assessed by comparison with histopathologic findings in terms of depth of invasion, thickness of the mucosa that had been invaded by cancer cells, and the histologic type of each cancer. RESULTS: Detection with the LIFE-GI system was possible in 58 of the 61 stomach cancer lesions (95.1%). When examined in detail with reference to sampling points, the detection rates of cancer areas according to depth of cancer cell invasion were 57.5 % for invasion to the mucosa, 74.3 % for invasion to the submucosa, and 88.1% for invasion to the muscularis propria or deeper. The detection rates increased as the depth of invasion increased, and they increased significantly as the mucosa invaded became thicker. Detection rates according to histologic type were 82% for differentiated cancer, and 61% for undifferentiated cancer. Most of the cancer areas appeared dark red. Light blue, brilliant red, and white areas were also observed. CONCLUSIONS: Mucosal thickening as a result of cancer cell invasion had a large impact on the detection rate of the LIFE-GI system. As a result, this method may not be useful for the detection of undifferentiated cancer, which may invade in a more dispersed manner, without altering the mucosal thickness.

Lidocaine-metabolizing activity after warm ischemia and reperfusion of the rat liver in vivo.

The effect of warm ischemia on lidocaine-metabolizing activity was examined in vivo. Total liver ischemia was produced for 1 hr in Sprague-Dawley rats by clamping the portal vein and hepatic artery at the hilum. Livers were then reperfused, and liver microsomes were prepared before and 0, 2, 6, and 24 hr, and 3, 6, and 10 days after reperfusion. Microsomal lidocaine-metabolizing activity and cytochrome P-450 content were examined. Lidocaine N-deethylase activity was decreased from 2.25 +/- 0.33 to 0.97 +/- 0.21 nmol/mg protein/min (mean +/- SD) 24 hr after reperfusion. This inhibition was prolonged, and activity gradually recovered after 10 days. The cytochrome P-450 content showed the same tendency. On the other hand, serum levels of alanine aminotransferase increased significantly 2 hr after reperfusion and returned to control levels 3 days after reperfusion. Liver blood flow recovered rapidly after unclamping and reached baseline levels within 6 hr. Our results suggest that after warm ischemia, prolonged hepatic dysfunction in drug metabolism, which cannot be detected by evaluating serum enzymes or liver blood flow, exists at the microsomal level.

The histological basis of detection of adenoma and cancer in the colon by autofluorescence endoscopic imaging.

BACKGROUND AND STUDY AIMS: The reason for the difference in fluorescence between normal and diseased tissues (carcinoma and adenoma) in the colon observed on autofluorescence endoscopy is unclear, flavins, NADPH and collagen being regarded as possible major sources of fluorescence. The purpose of this study was to identify the reason for this difference in fluorescence. PATIENTS AND METHODS: Samples of human colonic tissues (adenoma: n = 6, cancer: n = 11, normal: n = 11) were obtained from resected specimens. The flavin content of human colonic tissue was measured by high performance liquid chromatography. Fluorescence microscopy under blue light excitation (400-440 nm) was performed using frozen sections of normal, adenomatous and cancerous tissues, and examining them for the presence and characteristics of fluorescence. RESULTS: The flavin content of normal and diseased tissue was not significantly different. Fluorescence microscopy of normal colonic tissue revealed strong fluorescence in the submucosal layer, which corresponded to collagen. Tissue fluorescence did not decrease in reducing agent or acid solution. No difference in fluorescence was detected in normal mucosa, adenoma or cancerous tissue on fluorescence microscopy. These findings indicate that flavins and NADPH do not affect tissue fluorescence, and that submucosal collagen is the main source of tissue fluorescence in the colon. CONCLUSION: The reason for the decreased fluorescence in diseased tissues appears to be a decrease in collagen fluorescence due to the screening effect of mucosal thickening or replacement of submucosa by cancer cells.