Prognostic significance of the expressions of metallothionein, glutathione-S-transferase-pi, and P-glycoprotein in curatively resected gastric cancer

OBJECTIVE: To determine the effect of adding a trained intensivist on patient care and educational outcomes in a community teaching hospital. MATERIAL AND METHODS: We retrospectively reviewed outcomes for patients admitted to the medical intensive-care unit (MICU) of a 270-bed community teaching hospital between July 1992 and June 1994. Mortality rates and durations of stay were determined for the year before (BD, 1992 through 1993) and the first year after (AD, 1993 through 1994) introduction of a full-time director of critical care. Performance of resident trainees on a standardized critical-care examination was measured for the same periods. RESULTS: Overall, 459 patients in the BD period were compared with 471 patients in the AD period. The mix of cases and severity of illness (acute physiology and chronic health evaluation or APACHE II scores) on admission were similar for the BD and AD periods. MICU mortality decreased from 20.9% during the BD to 14.9% during the AD period (P = 0.02), and in-hospital mortality decreased from 34.0% to 24.6% (P = 0.002). Disease-specific mortalities were lower during the AD period for most categories of illness. Detailed analysis of a subgroup of patients (those with pneumonia) demonstrated no differences in distribution of patients by gender, race, or acuity of illness (APACHE II scores). The mortality rate due to pneumonia decreased from 46% during the BD period to 31% during the AD period. This decrease was consistent across categories of APACHE II scores. From BD to AD periods, mean durations of total hospital stay decreased from 22.6 +/- 1.4 days to 17.7 +/- 1.0 days, and mean MICU stay decreased from 5.0 +/- 0.3 days to 3.9 +/- 0.3 days (P < 0.05). Critical-care in-service examination scores for 22 residents increased from 53.8 +/- 1.7% to 67.5 +/- 2.2% (P < 0.01), and AD scores were significantly higher than BD scores for residents at similar levels of training. CONCLUSION: Addition of a medical intensivist was temporally associated with improved clinical and educational outcomes in our community teaching hospital.     

Causes of death and recurrence after surgery for early gastric cancer

The analysis of generalized tonic clonic seizures is usually difficult with scalp EEG due to muscle artifact. We applied Gabor Transform to evaluate 20 seizures from 8 consecutive patients admitted for video-EEG monitoring. We studied the relative intensity ratios of alpha, theta and delta bands over time. In 14/20 events we found a significant decremental activity in the delta band at the onset of the seizure indicating that this is dominated by theta and alpha bands. We conclude that GT is a useful auxiliary tool in the analysis of ictal activity that sheds light on the underlying pathophysiological mechanisms.     

Use of a thromboembolic risk score to improve thromboprophylaxis in surgical patients

OBJECTIVE: The correlations between steady-state plasma concentrations of mianserin and its active metabolite desmethylmianserin and those of trazodone and its active metabolite m-chlorophenylpiperazine (m-CPP) were examined in 19 depressed patients. METHODS: Ten patients received first mianserin (30 mg per day) and second trazodone (150 mg per day), while 9 patients received these treatments in the opposite sequence, with at least 2-week intervals between the two phases. Blood was sampled at steady state, 1-3 weeks after initiation of each treatment. Plasma concentrations of mianserin, the separate enantiomers S(+)- and R(-)-mianserin, desmethylmianserin, trazodone and m-CPP were measured by means of high-performance liquid chromatography. RESULTS: There was a significant correlation between steady-state plasma concentrations of trazodone and total mianserin (r = 0.59) or S(+)-mianserin (r = 0.57), but not R(-)-mianserin (r = 0.33). CONCLUSION: The present study thus suggests that the metabolic capacity of mianserin, especially the more active S(+)-enantiomer, and that of trazodone correlate to each other. This finding supports the previous suggestions that cytochrome P4502D6 is involved in the metabolism of mianserin and trazodone.     

与早期胃癌复发有关的临床病理特性及生物指标的分析

Objective: The aim of this study was to identify the correlation between the clinicopathological characteristics and recurrence in early gastric cancer (EGC), what's more, we attempt to look for a predictive biomarker to predict and treat for recurrence of EGC. Methods: This study retrospectively analyzed 178 early gastric cancer patients who had the complete postoperative and follow-up medical records in the First Affiliated Hospital of Yangtze University (China) between January 1995 to December 2005. All of them were followed-up to December 2009 regularly. Computer tomography (CT), endoscopy, and single photon emission computed tomography (SPET-CT) were used to diagnose for recurrence of EGC. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) were used for the detection of cerbB2. Chi-square test was applied to this study for statistics analysis. Results: Fourteen patients had recurrence. Eighteen patients were cerbB2-positive, including twelve recurrence patients and six norecurrence patients. Sex, tumor depth, and lymph node metastasis were related to the recurrence of EGC. Also, cerbB2-positive patients had the higher recurrence rate compared to the cerbB2-negative patients.Conclusion: Recurrence of EGC after curative resection can be predicted by using some clinicopathological characteristics.CerbB2 can be used as a predictive biomarker for recurrence of EGC.     

Increased risk for cancer in patients with the Peutz-Jeghers syndrome

BACKGROUND: Some reports describe an increased risk for cancer in patients with the Peutz-Jeghers syndrome. OBJECTIVE: To characterize occurrences of cancer in a large cohort of patients with the Peutz-Jeghers syndrome. DESIGN: Retrospective cohort study. SETTING: Tertiary care center. PATIENTS: 34 patients with the Peutz-Jeghers syndrome identified from Mayo Clinic records from 1945 to 1996. MEASUREMENTS: Cases of cancer documented by chart review and telephone follow-up. RESULTS: 26 cases of noncutaneous cancer developed in 18 of the 34 patients: 10 cases of gastrointestinal cancer and 16 cases of extraintestinal cancer. With the use of SEER (Surveillance, Epidemiology, and End Results) data for comparison, the relative risk for cancer was 18.5 (95% CI, 8.5 to 35.2) in women with the Peutz-Jeghers syndrome and 6.2 (CI, 2.5 to 12.8) in men with the syndrome (P = 0.001). In women, the relative risk for breast and gynecologic cancer was 20.3 (CI, 7.4 to 44.2). CONCLUSIONS: The Peutz-Jeghers syndrome is associated with an increased risk for cancer. The relative risk for breast and gynecologic cancers is particularly high.     

Clinical result of intraperitoneal hyperthermic chemoperfusion for gastric cancer with serosal invasion to prevent peritoneal recurrence

In order to evaluate clinical effects of intraperitoneal hyperthermic chemoperfusion (IHCP) to prevent peritoneal recurrence in gastric cancer patients with serosal invasion, the clinical outcome was studied in 126 gastric cancer patients with macroscopic serosal invasion. Results of 59 patients who had surgery combined with IHCP (IHCP group) were compared with those of 67 patients who had surgery alone (control group). IHCP was performed for 120 minutes just after surgery under hypothermic general anesthesia with perfusate containing 10 micrograms/ml of mitomycin C. The inflow temperature and the outflow temperature of the perfusate were controlled to be 44.5 approximately 45 degrees C, and 43 approximately 44 degrees C, respectively. The 2-, 4- and 8-year survival rates for the IHCP group were 86%, 74% and 66%, respectively, against 78%, 59% and 50%, respectively, in the control group. The survival rates of the IHCP group were significantly better than those of the control group. Peritoneal recurrences after surgery were encountered in one of 59 patients in the IHCP group and 17 of 67 patients in the control group. The peritoneal recurrence rate of the IHCP group was significantly lower than that of the control group. These results suggest that IHCP treatment is effective in prevention of peritoneal recurrences after surgery for gastric cancer patients with serosal invasion.     

Prevention of gastric ulcer recurrence with tetraprenylacetone

We have carried out an experimental investigation of lesions of the intervertebral disc produced by flexion, lateral bending and rotational forces in an attempt to produce disc herniations. Adult Wistar rats were divided into 4 groups: control and posterior, lateral and rotational herniation. There were 10 rats in each group. The tail between the 5th and 8th vertebral segments was used. A Kirschner wire was inserted into each of 2 adjacent vertebrae and the movement produced had an apex which was anterior or lateral depending on the group involved. Variables such as rupture of the annulus, the cellularity of the nucleus pulposus and the site of the lesion in the disc were studied histologically. The height of the disc, the protrusion, the thickness, and the surfaces of the annulus fibrosus and the nucleus pulposus were measured. In every case we found a nuclear displacement which did not become a protrusion. The surface parameters and the cellularity of the nucleus pulposus are most useful indicators and should be included in any study examining the disc after the injection of substances for treatment.     

Superficial bladder cancer: decreasing the risk of recurrence

Bladder cancer appears to develop through two alternative pathways. Papillary bladder cancer, the most common pathway, has a less aggressive course and is frequently heralded by hematuria, whereas carcinoma in situ appears to be more aggressive and is more difficult to detect. Superficial bladder cancer has a high propensity for recurrence but a low rate of progression. Transurethral resection is frequently employed for both diagnosis and treatment. The risk of tumor recurrence is related to the number of tumors at presentation and the findings on the first follow-up cystoscopy. Even patients with a low risk of recurrence need periodic cystoscopic examinations. Patients with a higher risk of recurrence may benefit from adjuvant intravesical chemotherapy or immunotherapy. Bacillus Calmette-Guérin (BCG) appears to be the most effective drug for intravesical therapy but has the highest rate of side effects. It is the treatment of choice for carcinoma in situ. Newer treatment strategies include perioperative intravesical chemotherapy and chemoprevention.     

Strategies to decrease the incidence of intra-abdominal recurrence in resectable gastric cancer

Two main approaches are suggested to improve treatment results in resectable gastric cancer: extended lymphadenectomy and adjuvant antitumour therapy. Progress is to some extent stalled by the perception of gastric cancer as a pathophysiologically uniform disease; it has been demonstrated, however, that there are variants of gastric cancer associated with predominantly intra-abdominal spread or with haematogenous metastases. Recent clinicopathological studies have provided information about the mechanisms of this metastatic diversity. A review of clinical trials suggests that no single method of treatment can efficiently address all variants of gastric cancer spread, but new treatment strategies may be based on defining the pathophysiological variant of gastric cancer and selecting adjuvant therapy according to the most probable mode of tumour spread. Treatment should start with surgery which includes a 'reasonably' extended lymphadenectomy aimed at achieving an increased rate of curative resection and more accurate staging. Risk factors for peritoneal spread of tumour require the perioperative use of intraperitoneal chemotherapy. Subsequent adjuvant therapy may be indicated in patients at high risk of further cancer spread or occult metastases, as determined by pathological examination of the resected specimen.     

Perigastric lymph node status as a prognostic indicator in patients with gastric cancer

OBJECTIVE: The mismatch negativity, a negative component in the auditory event-related potential, is thought to index automatic processes involved in sensory or echoic memory. The authors' goal in this study was to examine the topography of auditory mismatch negativity in schizophrenia with a high-density, 64-channel recording montage. METHOD: Mismatch negativity topography was evaluated in 23 right-handed male patients with schizophrenia who were receiving medication and in 23 nonschizophrenic comparison subjects who were matched in age, handedness, and parental socioeconomic status. The Positive and Negative Syndrome Scale was used to measure psychiatric symptoms. RESULTS: Mismatch negativity amplitude was reduced in the patients with schizophrenia. They showed a greater left-less-than-right asymmetry than comparison subjects at homotopic electrode pairs near the parietotemporal junction. There were correlations between mismatch negativity amplitude and hallucinations at left frontal electrodes and between mismatch negativity amplitude and passive-apathetic social withdrawal at left and right frontal electrodes. CONCLUSIONS: Mismatch negativity was reduced in schizophrenia, especially in the left hemisphere. This finding is consistent with abnormalities of primary or adjacent auditory cortex involved in auditory sensory or echoic memory.     

Analysis of risk factors for cisplatin-induced ototoxicity in patients with testicular cancer

This study evaluates the degree and relevance of persisting ototoxicity after cisplatin-based standard-dose chemotherapy for testicular cancer, with emphasis on identification of potential factors for an increased risk of this late sequel. Hearing thresholds of 86 patients with a median age of 31 years (range 21-53 years) and a median follow-up time of 58 months (range 15-159 months) were assessed by conventional pure-tone audiometry. Interviews were conducted evaluating the patients' history with special regard to audiological risk factors, as well as circumstances of ototoxic symptoms. Details concerning treatment and patient variables were extracted retrospectively from the patients' charts. An additional screening programme assessed current body functions, blood parameters and other late toxicities. Symptomatic ototoxicity persisted in 20% of patients (59% tinnitus, 18% hearing loss, 23% both), while 10% had experienced completely reversible ototoxic symptoms for a duration of 1-18 months after treatment. Symptoms were bilateral in 81% of patients. Hearing thresholds were compatible with cisplatin-induced hearing loss in 42% of audiograms performed. Subjective (history) and objective (audiogram) findings were not always consistent. The following statistically significant risk factors for ototoxicity were established: high cumulative dose of cisplatin (P < 0.0001); history of noise exposure (P = 0.006). Additionally, high doses of vincristine (P = 0.001) seemed to result in reversible ototoxic symptoms. No other independent risk factors were identified. In conclusion, persisting ototoxicity represents a clinical sequel for approximately 20% of testicular cancer patients treated at standard dose but may affect more than 50% of patients receiving cumulative doses of cisplatin > 400 mg m(-2). Previous noise exposure may also result in a threefold increased risk for cisplatin ototoxicity. Future studies should use these risk factors as important stratification criteria for trials aiming at the evaluation and prevention of cisplatin-induced ototoxicity.     

Adjuvant chemotherapy for patients with resected Dukes' C and high-risk B2 colon cancer with fluorouracil and levamisole

Carcinoma of the large bowel is the second leading cause of cancer mortality in Singapore. Although the great majority of patients are discovered at a stage where resection with curative intent is possible, almost half of the patients afflicted will die of it. The combination of 5-fluorouracil + levamisole used in patients with curatively resected high risk Dukes B2 and all Dukes' C colon cancers has been shown to reduce cancer recurrence rate and improve overall survival. Since 1990 adjuvant chemotherapy has been recommended for this group of patients. This report describes patients treated in Singapore, their toxicities and their outcome. A total of 341 patients were treated between 1990 and 1996. Treatment compliance was 71.8%. Toxicity was moderate with mainly grade 1-2 nausea and vomiting, diarrhoea, stomatitis, alopecia, and neutropenia. There was 1 treatment-related death. Median recurrence-free interval was 81 months and median survival was not reached at 90 months. This regimen is tolerable. Until further randomised reports comparing 5-fluorouracil + levamisole to other combinations are available, this combination chemotherapy is recommended to patients after surgical resection of the high risk Dukes' B2 and Dukes' C colon cancer to reduce cancer recurrence and improve overall survival.     

Surgical management for lymph node recurrence of resected fibrolamellar carcinoma of the liver: a case report

Fibrolamellar carcinoma of the liver (FLC), which is very rare in Japan, is reported to be frequently accompanied by lymph node metastasis in Europe and the United States. We describe a 22-year-old man with recurrent FLC in the lymph nodes after undergoing partial hepatectomy. He underwent a second operation for removal of recurrent lymph node tumors in the mediastinum and abdominal cavity one year after initial surgery. However, a third operation became necessary seven months later, because of recurrence in a lymph node in the abdominal cavity. We discuss the management of lymph node metastasis from FLC.     

Immunonutrition in gastric cancer surgical patients

The aim of this study was to evaluate the potential advantages of perioperative versus postoperative administration of an enteral immune-enhancing diet on host defense and protein metabolism. Thirty subjects, candidates for gastrectomy for cancer, were randomly allocated into two groups. The first group (n = 15) received an enteral formula enriched with arginine, omega-3 fatty acids, and RNA 7 d before and 7 d after surgery; the second group (n = 15) received the same diet but only 7 d after surgery. Postoperative immune and inflammatory responses were investigated by phagocytosis ability of polymorphonuclear cells, interleukin-2 receptors (IL-2R), lymphocyte subsets, interleukin-6 (IL-6), and delayed hypersensitivity response (DHR). Prealbumin (PA), retinol binding protein, albumin, and transferrin were determined as protein synthesis indicators. Perioperative immunonutrition prevented the early postoperative impairment of phagocytosis, DHR, total number of lymphocytes, and CD4/CD8 ratio (P < 0.05 versus postoperative group). The IL-2R levels were significantly higher in the perioperative group (P < 0.05 versus postoperative on postoperative day [POD] 4 and 8). Perioperative group also showed lower levels of IL-6 (P < 0.05 versus postoperative on POD 1, 4, and 8) and higher levels of PA (P = 0.04 versus postoperative on POD 8). The perioperative administration of immunonutrition ameliorated the host defense mechanisms, controlled the inflammatory response, and improved the synthesis of short half-life constitutive proteins.     

Comparative clinical study of adjuvant postoperative chemotherapy (5-FU, Tegafur, 5-FU + MMC) in curatively resected cases of gastric cancer. Study Group on 5-FU Oral Adjuvant Chemotherapy in Gastric Cancer

A multi-center collaborative study was conducted in curatively resected gastric cancer patients at Stages II and III to compare oral 5-FU (Group A), oral Tegafur (Group B) and i.v. MMC + oral 5-FU (Group C). From May 1982 to April 1985, 1,012 cases were enrolled at 55 institutions. Some 138 (13.8%) were excluded, and 874 were analyzable. In the analysis of background factors, Group B had more cases with tumor of large diameter and advanced Stage. Adverse effects were relatively mild in all groups, and there was no problem in drug tolerance. Five-year survival rate was 67.6%, 62.4% and 68.6% in Groups A, B and C, respectively, reflecting no significant difference among them. It was 85.0%, 83.0% and 81.1% in Stage II and 52.5%, 51.0% and 59.0% in Stage III of Groups A, B and C, respectively. No significant difference was found, but Stage III of Group C showed a slightly higher survival rate. Supportive clinical study will be required to assess the usefulness of MMC as an introduction therapy. We found no difference in efficacy between 5-FU and Tegafur as maintenance therapy. The life-prolongation effect of fluoropyrimidines in comparison with surgery alone should be studied separately.     

Prognostic value of immunohistochemically identifiable tumor cells in lymph nodes of patients with completely resected esophageal cancer

BACKGROUND: Current methods of disease staging often fail to detect small numbers of tumor cells in lymph nodes. Metastatic relapse may arise from these few cells. METHODS: We studied 1308 lymph nodes from 68 patients with esophageal cancer without overt metastases who had undergone radical en bloc esophagectomy. A total of 399 lymph nodes obtained from 68 patients were found to be free of tumor by routine histopathological analysis and were studied further for isolated tumor cells by immunohistochemical analysis with the monoclonal anti-epithelial-cell antibody Ber-EP4. This antibody did not stain lymph nodes from 24 control patients without carcinoma. RESULTS: Of the 399 "tumor free" lymph nodes, 67 (17 percent), obtained from 42 of the 68 patients, contained Ber-EP4-positive tumor cells. Fifteen of 30 patients who were considered free of lymph-node metastases by histopathological analysis had such cells in their lymph nodes, and 5 of the 15 had small primary tumors. Ber-EP4-positive cells found in "tumor free" nodes were independently predictive of significantly reduced relapse-free survival (P=0.008) and overall survival (P=0.03). They predicted relapse both in patients without nodal metastases (P=0.01) and in those with regional lymph-node involvement (P=0.007). All 12 patients whose lymph nodes were negative on both histopathological and immunohistochemical analysis and who were available for follow-up survived without recurrence. The presence of micrometastatic tumor cells in bone marrow had no additional prognostic value. CONCLUSIONS: Immunohistochemical examination of lymph nodes may improve the pathological staging of esophageal cancer.     

Detection of micrometastases in the bone marrow in patients with gastric cancer

An immunocytochemical method using an antibody probe to recognise the epithelial membrane antigen was used to screen smears obtained surgically from bone-marrow in 88 patients with gastric cancer. Tumor cells were detected in the bone-marrow of 58 patients (65.9%). The EMA positive cells in the marrow were not correlated with the location and node status of the stomach. In the stage of TNM I, II, III and IV, the positive rates of micrometastases in the bone marrow were 42.9%, 57.1%, 73.7% and 69.0%, respectively. The results showed that the poorer differentiated lesion, the higher rate of positive cells in the bone marrow. The curative surgery and multimodality treatment after operation could result in remission of positive cells in some patients. The method can detect occult metastases in bone marrow, and may be useful to monitor patients for evidence of response. It can measure the efficacy of adjuvant therapy, and predict prognosis of the patients.     

A case report of resected primary duodenal carcinoma associated with early gastric cancer and cumulative results at 21 institutions in Japan

A case of primary duodenal carcinoma simultaneously associated with an early gastric cancer is reported. A 72-year-old woman complaining of appetite loss and nausea was admitted in June 1988. Endoscopic examination showed an ulcerative lesion in the angle of the stomach and a Borrmann type 2 tumor in the bulb of the duodenum. Both lesions were revealed to be adenocarcinomas by histological examination of obtained biopsy specimens. Synchronous carcinoma was diagnosed and pancreatoduodenectomy and lymph node dissection were performed. The primary tumor of the duodenum was histologically a moderately differentiated adenocarcinoma, and the gastric cancer was a tumor limited to the mucosa. Metastasis was recognized in a regional lymph node (No. 14A). There has been no recurrence during the 4-year postoperative follow-up period. This result suggests that pancreatoduodenectomy with systematic regional lymph node dissection can greatly contribute to prolonging the survival of patients with advanced duodenal cancer. This case is very rare, in that curative operation was performed for a primary duodenal carcinoma simultaneously associated with an early gastric cancer.     

Study on Ki-67 immunoreactivity as a prognostic indicator in patients with advanced gastric cancer

BACKGROUND: Cell proliferation characteristics may reflect the aggressiveness of gastric tumors and their eventual prognosis. The aim of this study was to evaluate whether the proliferative activities determined by the antibody Ki-67 could be used as a prognostic predictor in patients affected by advanced gastric cancer. METHODS: The prognostic significance of proliferative activity was investigated in 56 patients who underwent curative gastrectomy (R0) for advanced gastric cancer using the monoclonal antibody Ki-67. The patients were divided into three groups according to the Ki-67 labeling index of the tumors: < 10% (18 cases), 10-40% (21 cases) and > 40% (17 cases). The Cox regression model was used to evaluate the prognostic significance of the Ki-67 index controlling for age, gender, histology, depth of tumor invasion and node metastasis. RESULTS: There was no significant relationship between the Ki-67 index and wall invasion (P = 0.80) or nodal status (P = 0.73). The cumulative 3-year survival rates (95% Cl) were 61.0% (35.3-79.2%) in patients with Ki-67 index < 10%, 52.4% (29.7-70.9%) with Ki-67 index 10-40% and 52.9% (27.6-73.0%) with Ki-67 index > 40% and the differences were not statistically significant (P = 0.93). Also in multivariate analysis the proliferative activity did not independently affect survival (P = 0.98). An interaction between Ki-67 index and age was found and Ki-67 index > 40% was significantly associated with a poor prognosis in patients over 68 years old (P = 0.004). CONCLUSION: Our study indicated that the proliferative activity in gastric cancer, determined with the monoclonal antibody Ki-67, does not influence the survival except in elderly patients (> or = 68 years old).