Development and external validation of a nomogram for overall survival after curative resection in serosa-negative, locally advanced gastric cancer.

BACKGROUND: Few nomograms can predict overall survival (OS) after curative resection of advanced gastric cancer (AGC), and these nomograms were developed using data from only a few large centers over a long time period. The aim of this study was to develop and externally validate an elaborative nomogram that predicts 5-year OS after curative resection for serosa-negative, locally AGC using a large amount of data from multiple centers in Japan over a short time period (2001-2003). PATIENTS AND METHODS: Of 39 859 patients who underwent surgery for gastric cancer between 2001 and 2003 at multiple centers in Japan, we retrospectively analyzed 5196 patients with serosa-negative AGC who underwent Resection A according to the 13th Japanese Classification of Gastric Carcinoma. The data of 3085 patients who underwent surgery from 2001 to 2002 were used as a training set for the construction of a nomogram and Web software. The data of 2111 patients who underwent surgery in 2003 were used as an external validation set. RESULTS: Age at operation, gender, tumor size and location, macroscopic type, histological type, depth of invasion, number of positive and examined lymph nodes, and lymphovascular invasion, but not the extent of lymphadenectomy, were associated with OS. Discrimination of the developed nomogram was superior to that of the TNM classification (concordance indices of 0.68 versus 0.61; P < 0.001). Moreover, calibration was accurate. CONCLUSIONS: We have developed and externally validated an elaborative nomogram that predicts the 5-year OS of postoperative serosa-negative AGC. This nomogram would be helpful in the assessment of individual risks and in the consideration of additional therapy in clinical practice, and we have created freely available Web software to more easily and quickly predict OS and to draw a survival curve for these purposes.

Endoscopic submucosal dissection as a staging measure may not lead to worse prognosis in early gastric cancer patients with additional gastrectomy.

BACKGROUND: Endoscopic submucosal dissection is a novel endoluminal technique that enables resection of early stage gastrointestinal malignancies in an en bloc fashion. AIM: To assess whether preceding endoscopic submucosal dissection affected the prognoses of patients who underwent additional gastrectomy with lymph node dissection due to suspicion of nodal metastasis from endoscopic submucosal dissection specimens. PATIENTS AND METHODS: Thirty-one patients with early gastric cancer who underwent gastrectomy after endoscopic submucosal dissection were retrospectively investigated in terms of their survival and tumour recurrence. Additional gastrectomy was performed when histology of the endoscopic submucosal dissection specimens revealed that the tumours did not meet the criteria for node-negative cancers. RESULTS: Twenty-three (74%) and eight (26%) patients had undergone endoscopic submucosal dissection previously due to clinical diagnoses of node-negative cancers and possible node-positive cancers, respectively. Histology of the resected stomachs and lymph nodes revealed residual carcinoma of the stomach in two (6.5%) patients and nodal metastases in four (13%) patients. All patients remain alive without recurrence (median follow-up, 3.4 years; range, 0.6-5.2 years). CONCLUSIONS: Based on the histology of endoscopic submucosal dissection specimens, preceding endoscopic submucosal dissection itself had no negative influence on a patient's prognosis when additional gastrectomy was performed. It may be permissible to resect some early gastric cancers by endoscopic submucosal dissection as a first step to prevent unnecessary gastrectomy, if technically resectable.

A single institutional non-randomized retrospective comparison between definitive chemoradiotherapy and radical surgery in 82 Japanese patients with resectable esophageal squamous cell carcinoma.

This retrospective study was conducted to compare the treatment results between radical surgery and definitive chemoradiotherapy for resectable squamous cell carcinoma of the esophagus. Between June 2000 and May 2005, 82 consecutive patients were selected for this study in which 33 were treated with chemoradiotherapy and 49 with surgery. The patients in the chemoradiotherapy (CRT) group received 2-4 cycles of 5-fluorouracil (1000 mg/m(2)/day, day 1-4, continuous) combined with cisplatin (75 mg/m(2), day 1, bolus) plus 50.4 Gy of radiation, while those in the surgery group were treated by an esophagectomy with radical node dissection. Eighteen surgical patients received postoperative chemotherapy. The baseline clinical TNM stage was similar between the two groups. With a median follow-up period of 36 months (range: 23-84 months) with 47 survivors (57%), the 3-year overall survival rates (P = 0.22) and disease-free survival rates (P = 0.16) were 48% and 44% in the chemoradiotherapy group versus 65% and 59% in the surgery group, and lacked statistical significance. This non-randomized study on patients with resectable squamous cell carcinoma of the esophagus showed that chemoradiotherapy could result in survival comparable with conventional surgery in spite of selection bias of patients. There is a trend toward improved survival with surgery versus definitive CRT.

Ex vivo pilot study using computed analysis of endo-cytoscopic images to differentiate normal and malignant squamous cell epithelia in the oesophagus.

BACKGROUND AND STUDY AIMS: An endo-cytoscopy system allows acquisition of optical biopsies that are quite similar to conventional histology. To simplify discrimination between normal and malignant tissue in the oesophagus using endo-cytoscopy system, we analysed the nuclear (dark staining) area in the obtained images with the goal of an accurate, automatic diagnosis. PATIENTS AND METHODS: Ex vivo endo-cytoscopic observation was performed using endoscopically or surgically resected oesophagus from 10 enrolled patients. Oesophageal tissues were stained using 1% methylene blue, and endo-cytoscopic images were obtained at normal and malignant areas (two areas of each) in each oesophagus. The centre of each image (4x10(-2) mm(2)) was processed by computer, and the area occupied by the total nuclei in each selected field and its ratio to the entire field were calculated. RESULTS: The mean area of the total nuclei was 0.10x10(-2)+/-0.03x10(-2) mm(2) (range 0.05x10(-2) to 0.18x10(-2) mm(2)) in the normal group and 0.40x10(-2)+/-0.06x10(-2) mm(2) (range 0.33x10(-2) to 0.55x10(-2) mm(2)) in the malignant group (P<0.001). The mean ratio of total nuclei to the entire selected field was 6.4+/-1.9% (range 3.1-11.3%) in the normal tissues and 25.3+/-3.8% (range 20.5-34.5%) in the malignant samples (P<0.001). CONCLUSIONS: Endo-cytoscopy system allowed automatic differentiation of normal and malignant tissues in the oesophagus, which could simplify endo-cytoscopic diagnosis. Further study will elucidate whether such analysis is applicable to inflammatory or pre-malignant epithelia in the oesophagus or other gastrointestinal organs.

Differential expression of peroxisome proliferator-activated receptor in histologically different human gastric cancer tissues.

Gastric cancer cell lines express peroxisome proliferator-activated receptor gamma (PPARgamma), and treatment with PPARgamma ligands suppresses growth of subgroup of these cell lines. However, expression and subcellular distribution of PPARgamma in human gastric cancer tissues is still unknown. Therefore, expression and subcellular localization of PPARgamma were examined among different histological types of gastric cancer tissues. Immunohistochemical staining for PPARgamma was performed using biopsy specimens of human gastric cancer of various histological types, gastric adenomas, and intestinal metaplasia. All samples of intestinal metaplasia and most samples of gastric tumors, except for signet ring cell carcinoma, expressed PPARgamma in the epithelial cells. Most samples of signet ring cell cancer lacked PPARgamma expression. All samples of intestinal metaplasia expressed PPARgamma only in the cytosol. For adenoma, 90% was positive for PPARgamma in cytosol, and 40% was positive in nuclei, for well-differentiated adenocarcinoma, 80% was positive in cytosol, and 20% was positive in nuclei. For moderately differentiated adenocarcinomas, 70% was positive for cytosol, and 80% was positive for nuclei; for poorly differentiated adenocarcinoma, 30% was positive in cytosol, and 70% was positive in nuclei. The frequency of samples with positive cytosolic staining decreased as the differentiation stage turned from intestinal metaplasia to adenoma, well-, moderately-, and poorly-differentiated cancers. Simultaneously, there was a tendency toward an increased frequency of samples with positive nuclear PPARgamma staining as the differentiation stage transformed from intestinal metaplasia to poorly-differentiated cancer. There was a striking difference in subcellular localization according to the differentiation levels of gastric dysplastic cells. The findings also supported an intestinal metaplasia-adenoma-well-differentiated gastric cancer sequence, and signet ring cell cancer was suggested to be of a different lineage from other types of gastric cancers.

Eradication diminishes enhancing effects of Helicobacter pylori infection on glandular stomach carcinogenesis in Mongolian gerbils.

To investigate the nature of the link between Helicobacter pylori (Hp) infection and stomach carcinogenesis, a study of the glandular stomach of Mongolian gerbils (MGs) was performed. MGs were treated with N-methyl-N-nitrosourea (MNU), followed by inoculation with Hp (groups 1 and 2) or without Hp (group 3), or infected with Hp (groups 4 and 5) or inoculation without Hp (group 6) followed by MNU administration. At week 21, the animals in groups 2 and 5 underwent an eradication procedure. At week 50, the incidences of adenocarcinomas in group 1 (15 of 23) and group 4 (9 of 26) were significantly higher than in group 3 (1 of 15) and group 6 (1 of 18), respectively. Moreover, those in group 2 (5 of 24) and group 5 (2 of 22) were lower than in groups 1 and 4, respectively. This study shows that Hp eradication may be useful as a prevention approach against stomach cancer.

Increased serum angiogenin concentration in colorectal cancer is correlated with cancer progression.

We have previously demonstrated that the increased expression of angiogenin (ANG) in pancreatic cancer is related to cancer aggressiveness; however, the relationship between ANG expression and its clinical relevance in colorectal cancer has not been demonstrated. We therefore investigated the correlation between serum ANG (sANG) concentration and colorectal cancer progression or the changes in sANG concentrations before and after cancer resection. To determination sANG concentration by ELISA, sera were obtained from colorectal cancer patients (the cancer group) preoperatively (n = 34) and postoperatively (n = 25), from hernia patients (the nonneoplastic group) preoperatively (n = 9) and postoperatively (n = 4), and from 23 healthy volunteers. The amount of ANG in the colorectal cancer tissues (n = 19) was determined by the same method. Before surgery, the mean sANG concentration in the cancer group (411.8 +/- 106.3 ng/ml) was significantly higher than that in both the nonneoplastic group (344.0 +/- 60.7 ng/ml; P = 0.04) and in the healthy volunteers (321.7 +/- 59.7 ng/ml; P = 0.0001). The degree of elevation of sANG concentration in the cancer group was more significant in the more progressed subgroups as compared with that in the normal group (versus T(is) + T1 + T2 cancer, P = 0.01; versus T3 + T4 cancer, P = 0.002; versus stage 0 + I cancer, P = 0.02; versus >stage III cancer, P = 0.001; versus Dukes' A cancer, P = 0.02; versus Dukes' C cancer, P = 0.006). After cancer resection, the mean sANG concentrations in each subgroup decreased to the same levels as those of the normal group; the degrees of reduction were more significant in the more progressed subgroups. The tissue ANG amount correlated significantly with sANG concentration (P = 0.007). These results suggest that the increased concentration of sANG that is derived from colorectal cancer correlates with cancer progression.

Pathophysiological relevance of the CD14 receptor in surgical patients: biological activity of endotoxin is regulated by the CD14 receptor.

Endotoxins (lipopolysaccharides, LPSs) are potent bacterial poisons, and they are always present in the intestine in considerable numbers. Stress, such that as a resulting from multiple injuries, burns, hypovolemia, hypoxia, intestinal ischemia, and surgery can lead to a breakdown of the gut barrier, allowing endotoxins to enter the systemic circulation via translocation. However, estimating the biological activity of translocated circulating endotoxins and identification of the mechanisms regulating their biological activities remain complex problems. CD14 has been found to exist as a soluble protein in the serum and as a glycosylphosphatidylinositol (GPI)-anchored protein of myeloid lineage cells. It plays key roles in both LPS-induced activation and in LPS internalization by cells. In this article, we outline: (i) the biological activity of circulating endotoxin; and (ii) the role of membrane and/or soluble CD14 regulating the bioactivity of circulating endotoxin in a human model of postoperative endotoxemia.

Telomerase activity and telomere length in benign and malignant human thyroid tissues.

Several studies have demonstrated that telomerase is activated and telomere length is altered in various types of tumors. In this study, we investigated telomerase activities and telomere length in 21 thyroid tumors. Telomerase activity was detected in 11 of 12 thyroid cancers and three of nine follicular adenomas. The mean telomere lengths in the cancers tissue and follicular adenomas were lower than in the respective background tissues, the differences being significant (P=0.0055 and P<0.006), respectively. Our findings suggest that change in telomerase activity and telomere length may be important for development of thyroid tumors.

Helicobacter pylori promotes development of pepsinogen-altered pyloric glands, a preneoplastic lesion of glandular stomach of BALB/c mice pretreated with N-methyl-N-nitrosourea.

H. pylori is thought to be a stomach carcinogen. Since no experimental model has hitherto been established to clarify the relationship between H. pylori and stomach carcinogenesis, the effects of infection with the bacteria on experimental carcinogenesis in the glandular stomach of mice were investigated. BALB/c mice were given salty diet or N-methyl-N-nitrosourea (MNU) and administered broth culture of H. pylori. The incidence of pepsinogen-altered pyloric glands, considered as precancerous lesions, was increased in the H. pylori inoculated group pre-treated with MNU. The findings provide the new experimental model demonstrating the relationship between stomach cancer and H. pylori.

Gender differences in cytokine secretion by human peripheral blood mononuclear cells: role of estrogen in modulating LPS-induced cytokine secretion in an ex vivo septic model.

Clinical studies demonstrate a better outcome of sepsis in females. Elevated estrogen levels and plasma cytokine imbalance occur in septic patients. We propose that gender-different cytokine secretion by the peripheral blood mononuclear cells (PBMCs) in sepsis determines the clinical outcome. A 2 x 10(6) PBMC sample from healthy volunteers (10 males and 10 females) was incubated with 1 ng/mL of lipopolysaccharide (LPS), estradiol (E2; 0, 0.03, 0.3, 3.0, 30 ng/mL), or 1 ng/mL of LPS + E2 (0, 0.03, 0.3, 3.0, 30 ng/ml), and supernatant cytokine levels were measured. Tumor necrosis factor alpha (TNF alpha) and interleukin (IL)-6 production by PBMCs from both sexes was time-dependently stimulated by LPS. At 6 h after LPS challenge, the TNF alpha level of male PBMCs was significantly higher but IL-6 secretion by female PBMCs was higher (two-way ANOVA: P < 0.05). E2 alone stimulated cytokine secretion by male PBMCs. Addition of the same E2 concentration as in sepsis patients' plasma modulated LPS-induced cytokine production. No significant sex differences in LPS-stimulated TNF alpha or IL-6 secretion by PBMCs were found, but IL-10 secretion by male PBMCs was significantly suppressed. This study demonstrated a gender difference in PBMCs responsiveness to LPS and E2 stimulation and E2-modulated cytokine secretion. In this PBMCs model of sepsis, only the supernatant IL-10 level was significantly lower in males. These ex vivo findings may partially explain the mechanism underlying the poorer outcome of male sepsis patients.

Increased angiogenin expression in gastric cancer correlated with cancer progression.

PURPOSE: The purpose of this study is to elucidate the expression of angiogenin and its previously undemonstrated clinical significance in gastric cancer (GC). METHODS: Angiogenin expression was examined immunohistochemically in 21 GC tissues and 21 corresponding normal gastric tissues. The serum concentration was determined by enzyme-linked immunosorbent assay (ELISA) in GC patients preoperatively (n = 48) and postoperatively (n = 41), in nonneoplastic patients preoperatively (n = 23) and postoperatively (n = 19), and in 32 healthy volunteers. The amount of angiogenin in the tissue of 21 GC patients was also determined by ELISA. RESULTS: Angiogenin expression was observed in GC cells as well as in some fundic glandular cells and some inflammatory cells. The mean serum concentration in GC patients (407.8 +/- 105.2 ng/ml) was significantly higher than that in the nonneoplastic patients (345.7 +/- 58.3 ng/ml; P < 0.003) and in the healthy volunteers (333.0 +/- 59.3 ng/ml; P < 0.0002). The mean serum angiogenin concentrations were progressively higher in the order T1 + T2 (P < 0.04) < T3 + T4 (P < 0.0001) < recurrent GC (P < 0.05) subgroups, in the order node-negative (P < 0.05) < node-positive (P < 0.0002) subgroups, and in the order stage I +II (P < 0.02) < stage III and over (P < 0.0005) subgroups as compared with those in the healthy volunteers. These elevated serum angiogenin concentrations in each subgroup were significantly (P < 0.0003) reduced after cancer resection. The amounts of angiogenin in GC tissues correlated significantly with the serum angiogenin concentration (P < 0.01). CONCLUSIONS: These results suggest that angiogenin expression is increased in GC and that the increased serum concentration in GC patients correlates with cancer progression.

Feasibility of pylorus-preserving gastrectomy with a wider scope of lymphadenectomy.

OBJECTIVE: To demonstrate the feasibility and safety of pylorus-preserving gastrectomy (PPG) accompanied by complete suprapyloric and infrapyloric lymph node dissection. DESIGN: Retrospective review. SETTING: A university hospital in Japan. PATIENTS: Fifteen patients underwent PPG, and 28 patients underwent conventional distal gastrectomy (CDG) with Billroth I anastomosis. All patients had early gastric cancer, with either limited invasion in the mucosal layer or invasion into the submucosal layer. INTERVENTIONS: In the PPG procedure, the distal part of the stomach was resected while retaining a 1.5-cm pyloric cuff. The right gastroepiploic artery, the right gastric artery, and hepatic and pyloric branches of the vagus nerve were divided, and the infrapyloric artery was preserved. A modified D1 or D2 lymphadenectomy accompanied the PPG. MAIN OUTCOME MEASURES: Patients undergoing the PPG and CDG procedures were assessed 1 year after their surgical procedure. Changes in body weight, serum total protein levels, and serum albumin levels, the incidence of dumping syndromes, and endoscopic findings in the gastric remnant were compared between the 2 groups. RESULTS: Weight loss was significantly less in the PPG group than in the CDG group (P=.02). The incidences of early dumping syndromes, especially vasomotor symptoms, were significantly lower in the PPG group than in the CDG group (P=.03 and P=.02, respectively). The pyloric sphincter function was preserved, and there was no anastomotic leakage in the PPG group. CONCLUSIONS: The PPG procedure with complete D2 lymphadenectomy can be performed safely with a low incidence of major complications and a better postoperative outcome than the CDG procedure. The PPG procedure can be recommended for the treatment of early gastric cancer with broader indications.

Stomach-partitioning gastrojejunostomy for unresectable gastric carcinoma.

OBJECTIVES: To analyze the results of a new type of bypass procedure, stomach-partitioning gastrojejunostomy (SPGJ), for unresectable gastric carcinoma and to compare these results with those of conventional gastrojejunostomy (GJ). DESIGN: Retrospective review. SETTING: A university hospital in Japan. PATIENTS: Eight patients underwent SPGJ in 1 group, and 13 underwent conventional GJ in the other group. Staging was determined using preoperative diagnostic imagings and intraoperative findings. MAIN OUTCOME MEASURES: Assessment of food intake and mean survival rates. RESULTS: There were no significant differences between the 2 groups regarding male-female ratio, mean age, and histological type of carcinoma. All patients had stage IV cancers according to the classification of the Union Internationale Contre le Cancer. The rates of taking a regular meal at 2 weeks after an operation were 88% in the SPGJ group and 31% in the GJ group (P < .05). The mean 1-year survival rates for SPGJ and GJ groups were 42.9% and 7.7%, respectively (P < .05). The mean survival times were 13.4 months in the SPGJ group and 5.8 months in the GJ group (P < .05). CONCLUSIONS: Stomach-partitioning gastrojejunostomy achieved an improved quality of life and a better prognosis for patients, and it is the preferred bypass procedure for unresectable gastric carcinoma.

Increased angiogenin expression in obstructive chronic pancreatitis surrounding pancreatic cancer but not in pure chronic pancreatitis.

We previously demonstrated the increased expression of angiogenin (ANG) in pancreatic cancer and its relation to cancer aggressiveness; however, the expression patterns and the roles of angiogenin in chronic pancreatitis are still unknown. We investigated the expression of ANG both in the tissues and in the sera of chronic pancreatitis patients (pure chronic pancreatitis) by using in situ hybridization, Western blot analysis, and enzyme-linked immunosorbent assay. In situ hybridization revealed no detectable ANG messenger RNA (mRNA) signals in all tissues of pure chronic pancreatitis and normal pancreas. Only a small amount of protein band expression was obtained in all of the protein lysates of pure chronic pancreatitis and normal pancreas. Accordingly, there was no significant difference between the mean serum ANG concentration of chronic pancreatitis patients (352.1+/-72.5 ng/ml) and that of healthy volunteers (357.6+/-45.2 ng/ml). By contrast, acinar cells and interstitial fibroblasts in the tissues surrounding pancreatic cancer showed increased ANG mRNA expression. Strong protein band expression was obtained in the protein lysates of pancreatic cancer surrounding tissue, and mean serum ANG concentration was increased in pancreatic cancer patients. These findings suggest that ANG expression is increased in pancreatic cancer surrounding tissue but is not increased in pure chronic pancreatitis, and that ANG is potentially involved in the pancreatic cancer microenvironment rather than the establishment of pure chronic pancreatitis.

A rare case of gastric cancer in an acromegalic patient.

Although it has been demonstrated that acromegalic patients have an increased risk of neoplasms, especially colon neoplasms, gastric cancer with acromegaly is very rare--only five cases have been reported to date in Japan. We report here a rare case of gastric cancer with acromegaly in a 58-year-old woman, whose acromegalic change began at age 44. This patient showed typical clinical features of acromegaly, with increased concentrations of blood growth hormone (GH) and insulin-like growth factor I (IGF-I); she had four types of neoplasms; gastric cancer, colon tubular adenoma with moderate atypia, pancreatic mucinous cystadenoma, and subcutaneous lipoma. The gastric cancer was macroscopically 0-IIc type, 3.0 x 2.5 cm in size, and histologically diagnosed as a poorly differentiated adenocarcinoma with limited invasion of the mucosal layer. The previously documented stimulatory effects of GH and/or IGF-I on tumorigenesis and cell proliferation may have been responsible for the development of the multiple neoplasms in our patient.

New animal model of glandular stomach carcinogenesis in Mongolian gerbils infected with Helicobacter pylori and treated with a chemical carcinogen.

In 1994 WHO/IARC concluded that "Helicobacter pylori is a definite carcinogen" based on epidemiological studies, but there have been few reports demonstrating a relation between H. pylori and stomach cancer in animal models. We have succeeded in producing adenocarcinomas in the glandular stomachs of Mongolian gerbils with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or N-methyl-N-nitrosourea as carcinogens and hope to establish an experimental stomach carcinogenesis model using H. pylori. Male Mongolian gerbils, 7 weeks old, were infected with H. pylori followed by MNNG administration at a concentration of 100ppm administration or treated with MNNG at a concentration of 300ppm in their drinking water followed by inoculation with H. pylori. They were then killed sequentially, and their excised stomachs underwent microbiological and histopathological examinations. H. pylori were detected in all infected gerbils. Hyperplastic change of pyloric mucosa was observed with high 5-bromo-2'-deoxyuridine incorporation in affected animals. H. pylori infection persists on administration of MMNG and enhances glandular stomach proliferation in Mongolian gerbils. Whether long-term colonization promotes carcinogenesis in the glandular stomach of Mongolian gerbils is a matter of great interest.

Immunohistochemical prognostic indicators of gastrointestinal carcinoid tumours.

AIMS: The aim of this study was to determine whether expression of the oncoproteins p21, p53, E-cadherin (EC), cyclin D1, bcl-2 and Rb and the proliferation marker Ki-67 is predictive of malignant behaviour in gastrointestinal carcinoid tumours. METHODS: Immunohistochemical (IHC) staining was performed on carcinoid tumours from 41 patients (31 rectal, eight gastrointestinal, two appendiceal lesions). The six tumours that had invaded deeply into the muscularis propria or beyond, had metastasized to regional lymph nodes or had metastasized to a distant site were classified as the malignant group, and the other 35 tumours formed the benign group. IHC expression was compared between the two groups, and the prognostic value of each marker was assessed. RESULTS: Of the six tumours in the malignant group, 66.7% were p21 positive, 0% were p53 positive, 33.3% were EC positive, 100% were cyclin D1 positive, 33.3% were Rb positive, 16.7% were bcl-2 positive and 50% were Ki-67 positive. Of the 35 tumours in the benign group, 17.1% were p21 positive, 0% were p53 positive, 100% were EC positive, 94.3% were cyclin D1 positive, 8.6% were Rb positive, 17.1% were bcl-2 positive and 0% were Ki-67 positive. CONCLUSIONS: These data show that p53, cyclin D1, Rb, bcl-2 and Ki-67 staining does not correlate with malignant behaviour but that overexpression of p21 (P=0.02) and reduced staining of EC (P=0.005) do correlate with malignant behaviour. These two parameters may therefore be useful as prognostic indicators for gastrointestinal carcinoid tumours.

Results of local resection with regional lymphadenectomy for early gastric cancer.

BACKGROUND: In 1999, the authors reported preliminary results of local resection with regional lymphadenectomy(LR) for early gastric cancer. METHODS: Twenty-four patients underwent LR until May 2000. Laparoscopic techniques were recently applied. The dissected area for lymphadenectomy depended on the lymphatic flow from the tumor. Local gastric resection was performed with a 2 cm cancer-free margin. Among the 24 patients, 14 who had been followed up for more than 1 year were eligible for the nutritional study, and the nutritional parameters were compared with those for patients undergoing pylorus-preserving gastrectomy (PPG). RESULTS: Twenty-two patients not receiving additional gastrectomy needed no restriction of food intake and had neither postgastrectomy symptoms nor recurrence. All nutritional parameters remained stable between the preoperative and the subsequent period. Nutritional superiority of LR over PPG was observed. CONCLUSIONS: For selected patients with early gastric cancer, LR can be a treatment of choice to provide a good quality of life.

Catecholamine and cytokine response to laparoscopic adrenalectomy in patients with pheochromocytoma.

This study assesses the surgical stress of laparoscopic adrenalectomy (LA) in patients with pheochromocytoma using catecholamine and cytokine. The study was conducted on one patient who had laparoscopic adrenalectomy performed for pheochromocytoma, and three patients as controls who had undergone laparoscopic cholecystectomy (LC) for cholecystolithiasis. Catecholamines, tumor necrosis factor alpha (TNFalpha) and interleukin 6 (IL-6) were measured at 30-minute intervals intraoperatively, and on the first, third and fifth postoperative days (POD) respectively. Plasma TNFalpha and IL-6 were measured by a commercially available sandwich enzyme-linked immunosorbent assay test. During the operation. changes of catecholamine concentration in LA were far larger than those in LC. The changes of TNFalpha concentration in LA were also larger than those in LC. TNFalpha returned to basal value at the end of the operation in LC, but it did not in LA. TNFalpha concentration in LC changed a little after the surgery, whereas that in LA sharply increased and was maintained at a high level from 1 POD until 5 POD. Enhanced cytokine responses were observed in LA compared to LC during and after the surgery. We concluded that laparoscopic adrenalectomy may give those patients with pheochromocytoma more surgical stress than laparoscopic cholecystectomy for cholecystolithiasis, during and after the operation.