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Dysregulated hepatic steatosis may lead to chronic liver inflammation and nonalcoholic steatohepatitis (NASH). Recent studies have suggested that exendin-4, a glucagon-like peptide-1 agonist, may be a promising therapeutic for hepatic steatosis and NASH. However, the molecular mechanisms underlying the antihepatic steatosis actions of exendin-4 are not fully clear. Here, we demonstrate that autophagy is activated by either palmitic acid (PA) or oleic acid (OA) in HepG2 cells, and exendin-4 further enhances the autophagy-lysosomal pathway. We show that inhibition of autophagy by shLC3 attenuates exendin-4-mediated antisteatotic activity. Furthermore, expression of a key lysosomal marker, lysosome associated membrane protein 1 (LAMP1), is upregulated in OA + exendin -4-treated cells. The colocalization of LAMP1 and LC3 puncta further suggests that autophagic flux was enhanced by the cotreatment. Based on these findings, we conclude that autophagic flux might play an important role in the antisteatotic action of exendin-4.

Pseudomyxoma Peritonei (PMP) and Peritoneal Mesothelioma (PM) are both rare peritoneal malignancies. Currently, affected patients may be treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy offering long-term survival or even cure in selected patients. However, many issues regarding the optimal treatment strategy are currently under debate. To aid physicians involved in the treatment of these patients in clinical decision making, the PSOGI executive committee proposed to create a consensus statement on PMP and PM. This manuscript describes the methodology of the consensus process. The Delphi technique is a reliable method for attaining consensus on a topic that lacks scientific evidence through multiple voting rounds which feeds back responses to the participants in between rounds. The GRADE system provides a structured framework for presenting and grading the available evidence. Separate questionnaires were created for PMP and PM and sent during two voting rounds to 80 and 38 experts, respectively. A consensus threshold of 51.0% was chosen. After the second round, consensus was reached on 92.9%-100.0% of the questions. The results were presented and discussed in the plenary session at the PSOGI 2018 international meeting in Paris. A third round for the remaining issues is currently in progress. In conclusion, using the Delphi technique and GRADE methodology, consensus was reached in many issues regarding the treatment of PM and PMP amongst an international panel of experts. The main results will be published in the near future.

In the era of intensity modulation radiation therapy (IMRT), no prospective randomized trial has evaluated the efficacy of adjuvant therapies such as adjuvant concurrent chemoradiotherapy (CCRT), adjuvant sequential chemotherapy and radiotherapy (CT‐RT), and adjuvant CT alone in resectable pancreatic adenocarcinoma (PA). Through propensity score matching, we designed a nationwide, population‐based, head‐to‐head cohort study to determine the effects of dissimilar adjuvant treatments on resectable PA. We minimized the confounding of various adjuvant treatment outcomes among the following resectable PA groups of patients from the Taiwan Cancer Registry database: group 1, adjuvant CCRT; group 2, adjuvant sequential CT‐RT; and group 3, adjuvant CT alone. All the studied techniques are IMRTs. The matching process yielded a final cohort of 588 patients (196, 196, and 196 patients in groups 1, 2, and 3, respectively). In both univariate and multivariate Cox regression analyses, adjusted hazard ratios (aHRs; 95% confidence interval [CI]) of death derived for the adjuvant CCRT and adjuvant sequential CT‐RT cohorts compared with the adjuvant CT alone cohort were 0.398 (0.314–0.504) and 0.307 (0.235–0.402), respectively. A combination of adjuvant IMRT and CT for resectable PA treatment improves survival to a greater extent than does adjuvant CT alone.

Multiple common variants identified by genome-wide association studies showed limited evidence of the risk of breast cancer in Taiwan. In this study, we analyzed the breast cancer risk in relation to 13 individual single-nucleotide polymorphisms (SNPs) identified by a GWAS in an Asian population. In total, 446 breast cancer patients and 514 healthy controls were recruited for this case–control study. In addition, we developed a polygenic risk score (PRS) including those variants significantly associated with breast cancer risk, and also evaluated the contribution of PRS and clinical risk factors to breast cancer using receiver operating characteristic curve (AUC). Logistic regression results showed that nine individual SNPs were significantly associated with breast cancer risk after multiple testing. Among all SNPs, six variants, namely FGFR2 (rs2981582), HCN1 (rs981782), MAP3K1 (rs889312), TOX3 (rs3803662), ZNF365 (rs10822013), and RAD51B (rs3784099), were selected to create PRS model. A dose–response association was observed between breast cancer risk and the PRS. Women in the highest quartile of PRS had a significantly increased risk compared to women in the lowest quartile (odds ratio 2.26; 95% confidence interval 1.51–3.38). The AUC for a model which contained the PRS in addition to clinical risk factors was 66.52%, whereas that for a model which with established risk factors only was 63.38%. Our data identified a genetic risk predictor of breast cancer in Taiwanese population and suggest that risk models including PRS and clinical risk factors are useful in discriminating women at high risk of breast cancer from those at low risk.

Introduction Peritoneal metastasis (PM) of hepatocellular carcinoma (HCC) without distant spread are rare. The related prognosis is poor without standard treatment available. The role of cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is poorly documented. Methods An international multicentric cohort was constituted by retrospective analysis of 21 patients undergoing CRS/HIPEC for PM of HCC between 1992 and 2016 from 10 reference centers of PSOGI. Data on clinical features, treatment strategies, and survival outcomes were analyzed. Results The median time interval from the diagnosis of PM to the procedure was 4.5 months. The median peritoneal cancer index was 14. Sixteen patients had complete cytoreduction (CCR0-1). Ten patients had grades 3 to 4 complications. The median duration of follow-up was 52.2 months. The median OS was 46.7 months. The projected 3y-OS and 5y-OS were 88.9 and 49.4% respectively. The median OS for patients with CCR0-1 resection was not reached whereas it was 5.9 months for those with CCR2-3 resection after CRS (p = 0.0005). The median RFS was 26.3 months and projected RFS at 3 years of 36.5 months Three prognostic factors were associated with improved RFS in the univariate analysis: preoperative chemotherapy (p = 0.0156), PCI >15 (p = 0.009), Number of chemotherapy agents used for HIPEC (p = 0.005). Conclusion CRS/HIPEC is a safe and effective approach in selected patients with PM of HCC. CRS/HIPEC gives the patient a chance for a good relapse free and overall survival and should be considered as an option.

Purpose In the era of intensity-modulation radiation therapy (IMRT), no prospective randomized trial has evaluated the efficacy of IMRT exclusively, such as concurrent chemoradiotherapy (CCRT), sequential induction chemotherapy followed by radiotherapy (CT-RT), and systemic chemotherapy (CT) alone, for treating unresectable pancreatic adenocarcinomas (PAs) without metastasis. Through propensity score matching, we designed a nationwide, population-based, head-to-head cohort study to determine the effects of various treatments on unresectable PAs. Patients and methods We minimized the confounding effects of various treatment outcomes in patients with unresectable PAs from the Taiwan Cancer Registry database by dividing them as follows: group 1, CCRT; group 2, sequential CT-RT; group 3, nontreatment; and group 4, CT alone. Results The matching process yielded a final cohort of 2960 patients (740 patients each in groups 1, 2, 3, and 4). In both univariate and multivariate Cox regression analyses, the adjusted hazard ratios (95% confidence interval) derived for the definitive CCRT and sequential CT-RT groups compared with the CT alone group were 0.443 (0.397–0.495) and 0.633 (0.568–0.705), respectively. Conclusions A combination of IMRT and systemic CT for the treatment of unresectable PAs might increase survival compared with CT alone.

Arctigenin (ATG), a lignin extracted from Arctium lappa (L.), exerts antioxidant and anti-inflammatory effects. We hypothesized that ATG exerts a protective effect on hepatocytes by preventing nonalcoholic fatty liver disease (NAFLD) progression associated with lipid oxidation-associated lipotoxicity and inflammation. We established an in vitro NAFLD cell model by using normal WRL68 hepatocytes to investigate oleic acid (OA) accumulation and the potential bioactive role of ATG. The results revealed that ATG inhibited OA-induced lipid accumulation, lipid peroxidation, and inflammation in WRL68 hepatocytes, as determined using Oil Red O staining, thiobarbituric acid reactive substance assay, and inflammation antibody array assays. Quantitative RT-PCR analysis demonstrated that ATG significantly mitigated the expression of acetylcoenzyme A carboxylase 1 and sterol regulatory element-binding protein-1 and significantly increased the expression of carnitine palmitoyltransferase 1 and peroxisome proliferator-activated receptor alpha. The 40 targets of the Human Inflammation Antibody Array indicated that ATG significantly inhibited the elevation of the U937 lymphocyte chemoattractant, ICAM-1, IL-1β, IL-6, IL-6sR, IL-7, and IL-8. ATG could activate the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and AMP-activated protein kinase (AMPK) pathways and could increase the phosphorylation levels of Akt and AMPK to mediate cell survival, lipid metabolism, oxidation stress, and inflammation. Thus, we demonstrated that ATG could inhibit NAFLD progression associated with lipid oxidation-associated lipotoxicity and inflammation, and we provided insights into the underlying mechanisms and revealed potential targets to enable a thorough understanding of NAFLD progression.

Our hospital was the first institution to offer cytoreduction surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in Taiwan. Therefore, we report our experience and outcomes among patients who underwent HIPEC. Since 2002, 164 eligible patients underwent HIPEC, and we excluded cases of laparoscopic or prophylactic HIPEC. The cases were categorized according to whether they were treated before 2012 (Period 1: 80 cases) or after 2012 (Period 2: 84 cases). The rates of surgical morbidity were 46.3% during Period 1 and 20.2% during Period 2 (P

Background Prospective randomized trials have not been used to evaluate the efficacy of adjuvant therapies after intrahepatic cholangiocarcinoma (ICC) resection. Methods We analyzed data from the Taiwan Cancer Registry database of ICC patients receiving resection. To compare outcomes, patients with ICC were enrolled and categorized into the following adjuvant treatment modality groups: group 1, concurrent chemoradiotherapy (CCRT); group 2, sequential chemotherapy (CT) and radiotherapy (RT); and group 3, CT alone. Results We enrolled 599 patients with resectable ICC who received surgery without distant metastasis. Of these patients, 174 received adjuvant CCRT (group 1), 146 received adjuvant sequential CT and RT (group 2), and 279 received adjuvant CT alone (group 3). Multivariate Cox regression analysis indicated that pathologic stage and positive margin were significantly poor independent predictors. After adjustment for confounders, adjusted hazard ratios (95% confidence intervals) for overall mortality at advanced pathologic stages III and IV were 0.55 (0.41–0.74) and 0.92 (0.70–1.33) in groups 1 and 2, respectively, compared with group 3. Conclusions Adjuvant CCRT improved survival in resected ICC with advanced pathologic stages or a positive margin in early pathologic stages compared with adjuvant CT alone or adjuvant sequential CT and RT.

The impact of body mass index (BMI) on the outcome of advanced gastric cancer surgery is controversial. Between December 1987 and December 2006, a total of 947 advanced gastric cancer patients receiving curative resection with retrieved lymph node number15 were studied and divided into three groups according to BMI (25, 25-30, and30 kg/m(2)).With regard to comorbidities present prior to surgery, higher BMI patients were more likely to have heart disease, type 2 diabetes, and hypertension than lower BMI patients. Compared with BMI25 kg/m(2), higher BMI patients had longer operative time and more surgery-related morbidity. Multivariate Cox proportional-hazard analysis showed that age, pathological T and N categories, and lymphovascular invasion were independent prognostic factors. The initial recurrence patterns, 5-year overall survival, and cancer-specific survival were similar among the three groups.Only in stage III gastric cancer with BMI less than 25 kg/m(2) patients receiving total gastrectomy had a more advanced pathological N category and a worse prognosis compared to those receiving subtotal gastrectomy. Higher BMI was associated with longer operative time and more surgery-related morbidity than lower BMI. BMI alone is not an independent prognostic factor.

Tumour-associated fibroblasts (TAFs), as a functionally supportive microenvironment, play an essential role in tumour progression. Here we investigate the role of IL-25, an endogenous anticancer factor secreted from TAFs, in suppression of mouse 4T1 mammary tumour metastasis. We show that a synthetic dihydrobenzofuran lignan (Q2-3), the dimerization product of plant caffeic acid methyl ester, suppresses 4T1 metastasis by increasing fibroblastic IL-25 activity. The secretion of IL-25 from treated human or mouse fibroblasts is enhanced in vitro, and this activity confers a strong suppressive effect on growth activity of test carcinoma cells. Subsequent in vivo experiments showed that the anti-metastatic effects of Q2-3 on 4T1 and human MDA-MD-231 tumour cells are additive when employed in combination with the clinically used drug, docetaxel. Altogether, our findings reveal that the release of IL-25 from TAFs may serve as a check point for control of mammary tumour metastasis and that phytochemical Q2-3 can efficiently promote such anticancer activities.

Robotic gastrectomy has become more popular in the treatment of gastric cancer, especially in Asian countries. Until now, few studies have compared robotic surgery with open or laparoscopic surgery for gastric cancer patients.Data were prospectively collected between January 2006 and February 2012. A total of 689 patients underwent curative resection of adenocarcinoma of the stomach. Patients were separated into three groups according to the different surgical approaches used (586 open, 64 laparoscopic, and 39 robotic). The clinicopathological characteristics and surgical outcomes of the three groups were compared.The open group was associated with a larger tumor size, more D2 dissection, more advanced tumor stage, and more blood loss than the groups treated with laparoscopic and robotic methods. Robotic gastrectomy was associated with female predominance, less blood loss, shorter hospital stay, and longer operative time than open and laparoscopic gastrectomy. The retrieved lymph node numbers were similar between the open and robotic groups. Postoperative morbidity rates were similar among the three groups. In terms of the learning curve of robotic gastrectomy, operative time and docking time were significantly reduced in the recent robotic group (n=14) compared to the initial robotic group (n=25).Robotic gastrectomy could achieve extended lymph node dissection similar to open surgery. Our results showed a significant learning curve effect in the initial 25 cases of the robotic group.

BACKGROUND/AIMS The rate of recurrence increases in proportion to the degree of tumor depth, even after curative resection for gastric adenocarcinoma. Serosal exposure is considered as an important risk factor of peritoneal recurrence. However, some patients with serosa-negative cancer were found to have peritoneal recurrence. There are few reports concerning risk factors of peritoneal recurrence in serosa-negative gastric adenocarcinoma. The aim of this study is to evaluate the incidence and risk factors of peritoneal recurrence in serosa-negative gastric adenocarcinoma after curative resection. METHODOLOGY Total 1128 serosa-negative gastric cancer patients (574 pT1, 251 pT2, 303 pT3) diagnosed as gastric adenocarcinoma that underwent R0 resection from 1988 to 2005 were enrolled. RESULTS Peritoneal recurrence was observed in 50 (4.4%) patients, including 3 pT1, 3 pT2 and 44 pT3 patients. The incidence of peritoneal recurrence increased significantly with tumor invading subserosa (pT3). Multivariate analysis showed that the independent risk factor of peritoneal recurrence was tumor depth. CONCLUSIONS The incidence of peritoneal recurrence in serosa-negative cancer is low, and tumor depth is a significant risk factor. We should be aware of peritoneal recurrence during follow-up, especially for patients with subserosal tumor invasion.

Home death has a special cultural meaning for Taiwanese patients who are dying and their family members. However, very limited evidence has been presented on the impact of home death on caregiver bereavement outcomes. The purpose of this study was to explore the preference for place of death by Taiwanese patients dying of cancer and the actual place of death and to investigate the relationship between place of death of a patient and grief reactions of the family caregivers. This study consisted of 46 dying patients and 46 matched family caregivers (N = 92). The grief reaction was measured using the Texas Revised Inventory of Grief. Statistical analyses included descriptive statistics, t tests, logistic regression, and multiple regression. Most of the patients (74%) preferred to die at home; however, only 33% of family caregivers preferred the patient to die at home, and only 17% of patients actually died at home. Of these patients, 43% of their preferences were congruent with the actual place of death, whereas 79% of the family caregivers' preferences were congruent with the patients' actual place of death. Finally, the place of death was not a significant predictor of caregivers' grief reactions immediately after the loss of a loved one or at 1 month after the death occurred. This study provides important implications for future studies and clinical practice.

Pyloric stenosis usually presents with symptoms, and this may lead patients to consult their physician. We evaluate whether distal gastric cancer patients with pyloric stenosis had a better outcome than those without.A total of 551 distal gastric cancer patients who received curative subtotal gastrectomy between January 1988 and December 2003 at Taipei Veterans General Hospital were analyzed. Among them, 174 patients were sorted into the pyloric stenosis group according to obstructive symptoms. Their clinicopathological features, survival and prognostic factors were evaluated.The 5-year overall and disease-free survival rate of distal third gastric adenocarcinoma for the pyloric stenosis group was significantly lower than those without pyloric stenosis. Multivariate analysis revealed the pyloric stenosis group had deeper cancer invasion (relative to pT1, RR of pT2 3.1, p=0.009; pT3 6.1, p0.001; pT4 16.5, p0.001), and more lymph node metastasis (RR 3.6; p=0.001). The pyloric stenosis group had a tendency to lymph node metastasis toward the hepatoduodenal ligament, but this did not reach statistical difference. However, the pyloric stenosis group had significantly higher lymph node metastasis in the retropancreatic region (5.17% vs. 0.53%; p=0.001).Distal gastric cancers with pyloric stenosis have worse biological behavior than those without, and consequently have a poor outcome.

Accumulated evidence indicates that the incidence of early-onset breast cancer has rapidly increased in Taiwan and other Asian compared to Western countries. The mismatch repair (MMR) pathway might be one of the crucial mechanisms of predisposition to early breast cancer. In this study, we explored whether MMR gene polymorphisms contribute to the risk of breast cancer in young women. This was a 2-stage case–control study including 737 cases and 719 controls. After eight single nucleotide polymorphisms (SNPs) were genotyped in MMR pathway genes in the stage I study, a promising SNP, MSH2 rs2303425, was selected for validation in the stage II study. A luciferase reporter assay was used to evaluate the transcriptional activity of MSH2. Logistic regression analysis showed that individuals with the MSH2 rs2303425 C/C genotype had a significantly increased risk of breast cancer compared to those with the T/T genotype (adjusted odds ratio 2.0; 95 % confidence interval 1.1–3.8), particularly in early-onset breast cancer patients with the luminal A subtype. The luciferase assay in three cell lines indicated that the MSH2 rs2303425 T/C substitution decreased MSH2 expression, which is consistent with the finding of an association study. A common variant SNP in MSH2 may contribute to the susceptibility to early-onset breast cancer functionally, particularly for the luminal A subtype.

Recurrence after curative resection for gastric cancer remains high. We examined its incidence and factors related to recurrence pattern, while trying to avoid the interaction of various factors. A total of 611 gastric cancer patients after resection for curative intent (1988-1995) were analyzed. The result showed that 245 patients had recurrence (40.1%). Cumulative recurrence rates were 53.5%, 80%, 89.0%, 94.7%, 96.3%, 98%, and 99.5% at 1, 2, 3, 4, 5, 6, and 7 years, respectively. Over half of patients with recurrence (123; 50.2%) had an initial single recurrence. Taking single and multiple recurrence together, most recurrences (213; 86.9%) were distant metastases, 110 recurrences (44.9%) were local relapses, and 78 recurrences (49.8%) were both local and distant. Among the distant metastases, 131 patients (53.5%) had peritoneal dissemination, 106 patients (43.3%) had hematogenous metastases, and 70 patients (28.6%) had distant lymphatic spread. Scirrhous-type stromal reaction, serosa invasion, and female gender were factors negatively related to peritoneal recurrence. Medullary-type stromal reaction and male gender showed a preference for locoregional recurrence, and expanding growth tumor commonly led to hematogenous metastasis. Patients who had paraaortic lymph node metastasis were at high risk of developing distant lymphatic recurrence. It is conceivable that the patterns of recurrence and the times to recurrence provide a biological basis for clinical monitoring of patients with the aim of modifying therapeutic modalities.

Previous studies indicated that smoking exposure is associated with an increased risk of breast cancer, and α9-nicotine acetylcholine receptors (α9-nAChRs) are involved in breast tumorigenesis. However, no studies have explored the joint effect of α9-nAChRs (CHRNA9) genes and cigarette smoking exposure on breast cancer risk. A case-control study was conducted on 737 breast cancer patients and 719 age-matched healthy controls. Three single-nucleotide polymorphisms (SNPs) of CHRNA9 located in the promoter region were genotyped and compared between cases and controls to identify those SNPs associated with breast cancer susceptibility. A dual-luciferase reporter assay was used to analyze the promoter activities of these SNPs of the CHRNA9 gene. After a Bonferroni correction, the G allele of the CHRNA9 rs7329797 SNP was significantly associated with an increased risk of developing breast cancer compared with A/A genotype carriers (odds ratio, 1.8; 95% confidence interval, 1.2-2.6). A multiplicative interaction between passive smoking exposure and the CHRNA9 rs73229797 SNP on the risk of breast malignancy was observed. A functional assay further showed that rs73229797 was associated with increased promoter activity of the CHRNA9 gene. Our findings support a significant interaction effect existing between the CHRNA9 gene and smoking exposure on the risk of breast cancer development.

An 81-year-old woman had an early carcinoma invading focally into the upper submucosa of the middle-transverse colon, which was accompanied by extensive lymph node metastases and resulted in a poor prognosis. Although her tumor was small and flat, a rim of pale yellow-speckled mucosa adjacent to the tumor enabled its earlier detection. To further study the exceptional lymph node metastases we studied the expression of intestinal trefoil factor and sialyl Tn antigen immunohistochemically on the resected specimen. Their simultaneous expression in lymph node metastasis further supports the aggressive nature of this tumor.

Although there were some studies on clinicopathologic characteristics, operative morbidity, and mortality in elderly patients with gastric cancer, no reports have specifically focused on survival and quality of life after resection. A total of 433 patients aged ≥ 65 years (1987–1994) who underwent gastric resection for gastric adenocarcinoma were studied. Two groups were considered: patients aged 65 to 74 years and those > 74 years. Most of the patients (78.1%) had advanced diseases, and nearly half (41.3%) had associated chronic disease(s). Resections with curative intention were performed in 362 patients (83.6%). The overall operative morbidity rate was 21.7% and mortality rate 5.1%. Although operative procedures were similar in both groups, patients aged >74 years had a higher mortality rate than those aged 65 to 74 years (10.1% vs. 3.5%; p= 0.034). Age and extent of gastric resection were two independent factors negatively affecting mortality. The cumulative survival rates for patients who underwent curative resection were 86.2%, 72.4%, 67.2%, 62.9%, and 60.0% at 1, 2, 3, 4, and 5 years, respectively. Nearly all patients (96%) after surgery had normal work and daily activities. Some patients appeared to lack energy (16%) or experienced a period of anxiety or depression. There was no statistical difference in survival and quality of life assessed by the Spitzer index after curative resection between the two groups. Therefore resection with curative intention can be performed for the elderly with acceptable morbidity and mortality rates, possible long-term survival, and good quality of life, but a limited operation should be considered in the very elderly patients.

Objective: We had previously reported a reasonable categorization of the number of positive lymph nodes (LN: 0, 1–4, 5–8, and > 8) as a prognostic indicator. This study was an extension, to see which factors correlated with number of positive lymph nodes. Methods: A total of 533 patients with gastric adenocarcinoma, who underwent curative surgery between January 1988 and December 1995, were entered into this study. Patients were divided into four groups according to metastatic LN number (0, 1–4, 5–8, and > 8). Their survival and clinicopathological factors were analyzed. Results: A total of 16,457 LNs, with an average of 30.9 per specimen, were removed, of which 1686 (10.2%) showed metastases. The 5-yr cumulative survival rate decreased as the number of metastatic LNs increased, i.e., 91.3% for LN 0; 67.4% for LN 1–4; 37.2 for LN 5–8, and 14.1% for LN > 8. Multivariate analyses showed that depth of cancer invasion (odds ratio: 2.4), gross appearance (odds ratio: 1.9), size (odds ratio: 1.9), and location (odds ratio: 1.4) of tumor were four independent factors correlated with the number of metastatic LNs. Number of metastatic LNs increased with advanced Japanese nodal stage and UICC-TNM stage. Conclusions: Depth of tumor invasion, and gross appearance, size, and location of tumor were four pathological factors independently correlated with number of metastatic LNs in gastric cancer.

Quality of life (QOL) was evaluated in 162 patients having radical gastrectomy for cancer. The results showed that more than half of the patients had a good appetite; they consumed a normal diet and a normal volume of food. Approximately 60% of the patients had weight loss of more than 5 kg. Patients who underwent a total gastrectomy had poor tolerance of normal food and frequent eating and body weight loss versus those who had a subtotal gastrectomy. Patients who underwent Billroth II reconstruction after a distal subtotal gastrectomy lost more body weight than those with a Billroth I anastomosis. The extent of lymphadenectomy did not influence the QOL. Patients under 65 years of age had a better QOL. Nearly all patients had normal work and daily living activities. Some patients appeared to lack energy or had a period of anxiety or depression. These data indicate that radical gastrectomy can be performed with an acceptable QOL for a potentially curable gastric carcinoma.

Methotrexate (MTX) has been widely used for the treatment of cancer and rheumatoid arthritis (RA). Aspirin (ASA) is a non-selective cyclooxygenase (COX) inhibitor that contributes to the treatment of inflammatory conditions such as RA. It has been observed that the antitumor effect of ASA can be attributed to inhibition of cell cycle progression, induction of apoptosis and inhibition of angiogenesis. In the present study, we revealed that the treatment with a combination of MTX and ASA resulted in antagonism of the cytotoxic effect as demonstrated by SRB and colony formation assays. ASA alleviated the MTX-mediated S phase accumulation and recovered the G1 phase. MTX-mediated accumulation of the S phase marker cyclin A was also alleviated by ASA. Notably, FAS protein levels were upregulated by MTX in A549 cells. The antagonism of MTX efficacy caused by ASA was accompanied by altered expression of caspase-3, Bcl-2 and FAS but not dihydrofolate reductase (DHFR). This suggests that the alteration of caspase-3, Bcl-2 and FAS was involved in the antagonism between ASA and MTX. Exogenously added folic acid reversed the MTX-mediated DHFR inhibition following either MTX or MTX + ASA treatments. Most importantly, we demonstrated for the first time that the commonly used non-steroidal anti-inflammatory drug for headache ASA and possibly other COX-1/2 inhibitors can produce a strong antagonistic effect on the growth inhibition of lung cancer cells when administered in combination with MTX. The clinical implication of our finding is obvious, i.e., the clinical efficacy of MTX therapy can be compromised by ASA and their concomitant use should be avoided.

The relationship between the prognosis and age of patients with gastric cancer is controversial. To evaluate whether there is a biological characteristic specific to the age of patients, we examined the clinical characteristics of patients with gastric cancer with special reference to their age. Based on a prospective database, a retrospective study of 419 patients who underwent radical gastrectomy for cure in the past 6 years was conducted. Clinical characteristics including gender, gross appearance of the tumour (Borrmann's classification, tumour location), histopathology (depth of tumour invasion, lymph node status, Lauren's classification and degree of tumour cell differentiation) and TNM tumour stage were analysed in six different age groups (39, 40-49, 50-59, 60-69, 70-79,80 years). The mean age of the 419 patients was 64.6 years (range from 26-91) and the peak age incidence of gastric cancer (46.3%) was in the 60-69 year old age group. The male: female ratio was 4.6:1 on the whole and male gender predominated at ages60. The proportion of diffuse type tumours (68.4%) by Lauren's criteria in the young age group (39 yrs) decreased with age (25% in the80 years group; P0.001). Similarly, the proportion of poorly-differentiated tumours (89.5%) in the young age group (39 yrs) decreased with advancing age (P0.001). These findings suggest that both diffuse type and poorly-differentiated tumours predominate in younger patients and, without considering the factor of delay in diagnosis, may explain the poorer prognosis demonstrated in younger patients.

Supplemental Digital Content is available in the text, In Taiwan, colorectal cancer with peritoneal carcinomatosis is considered a terminal condition. We examined the clinical outcomes of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) treatment for colorectal cancer with peritoneal carcinomatosis in Taiwan. We enrolled patients with colorectal cancer and peritoneal metastasis from Taipei Medical University, Wanfang Hospital between January 1999 and December 2014. Of the enrolled patients, 3 had mucinous-type tumors. In total, we enrolled 31 patients who underwent a total of 33 procedures. Of the 31 patients, 2 received the HIPEC procedure twice. Cytoreductive surgery was performed followed by HIPEC. The hazard ratios of death following cytoreductive surgery and HIPEC were calculated using the Cox proportional hazards model. The 2- and 5-year overall survival rates of these patients following cytoreductive surgery and HIPEC were 57% and 38%, respectively. The completeness of cytoreduction (CC) scores were CC-0, CC-1, CC-2, and CC-3 in 18 (54.5%), 3 (9%), 7 (21.2%), and 5 (15.2%) patients, respectively. The mean peritoneal cancer index (PCI) was 16.20, and the mean postoperative PCI (PPCI) was 4.6. The major risk factors for death in these patients were a total PCI score > 20, total PPCI score > 0, and CC score ≥ 2 (P = 0.022, 0.031, and 0.0001, respectively; log-rank test). Multivariate analysis revealed that the total PPCI score was the strongest predictor of death following cytoreductive surgery and HIPEC in these patients. In Taiwan, performing cytoreductive surgery and administering HIPEC for treating colorectal cancer with peritoneal metastasis are feasible and resulted in long-term survival. In addition, the total PPCI score was related to poor prognosis following cytoreductive surgery and HIPEC in patients with colorectal cancer and peritoneal metastasis.

To investigate the outcomes of the selective neoadjuvant concurrent chemoradiotherapy (CCRT) in lower 3rd rectal cancer patients in different groups (with or without neoadjuvant CCRT), especially in survival rate, local recurrence rate, and sphincter preservation rate. From January 1999 to December 2012, 69 consecutive patients who had histologically proven adenocarcinoma of lower 3rd rectum, defined preoperatively as lower tumor margin within 7 cm from the anal verge as measured by rigid sigmoidoscopy, received total mesorectum excision (TME). Our inclusion criteria of neoadjuvant CCRT are lower 3rd rectal cancer, stage II/III, and large (diameter >5 cm or >1/2 of circumference). Neoadjuvant concurrent CCRT had begun to apply lower 3rd rectal cancer patients or not. The radiation techniques of neoadjuvant CCRT for lower 3rd rectal cancer patients were all conventional fraction intensity modulated radiotherapy (IMRT) and concurrent fluoropyrimidine chemotherapy. Five-year overall survival rate, disease-free survival rate, and local recurrence rate for lower 3rd rectal cancer patients in group I were 51%, 45%, and 25%, respectively. On the contrary, 5-year overall survival rate, disease-free survival rate, and local recurrence rate for lower rectal cancer patients in group II were 70%, 70%, and 3%, respectively. The 5-year sphincter sparing rate was increased from 38.2% to 100% after the beginning of neoadjuvant CCRT. Analyzing local recurrence, overall survival rate, disease-specific survival rate, and sphincter sparing rate in group II were statistically significant superior to group I. Five-year overall survival rate, disease-free survival rate, and sphincter sparing rate for lower 3rd rectal cancer patients were improved after the addition of neoadjuvant CCRT. No unacceptable toxicity was noted after conventional fraction IMRT and concurrent fluoropyrimidine chemotherapy. Our study showed neoadjuvant CCRT could be valuable for lower 3rd rectal cancer patients.

Microsatellite instability (MSI) is one of the leading mechanisms for the carcinogenesis of gastric cancer. Its prognostic value is controversial.Between May 1988 and Oct 2003, a total of 214 gastric cancer patients undergoing curative surgery were enrolled, and their MSI statuses were classified as MSI-H (high) or MSI-L/S (low/stable). The clinicopathologic characteristics of MSI-H and MSI-L/S gastric cancers were compared.The MSI-H tumors accounted for 11.7 % (n = 25) of the 214 total gastric cancers. Although not statistically significant, the MSI-H gastric cancers were more frequently located in the lower third of the stomach (64 % vs. 49.2 %) and were more often the intestinal type (72 % vs. 61.4 %) compared to the MSI-L/S gastric cancers. The MSI-H gastric cancers had a significantly better 5-year overall survival (OS) rate (68 % vs. 47.6 %, p = 0.030) and a trend of a better 3-year disease-free survival rate (71.8 % vs. 55.2 %, p = 0.076) compared to the MSI-L/S gastric cancers. A multivariate analysis revealed that pathologic TNM stage and MSI status were the independent prognostic factors for OS after curative surgery.Compared to MSI-L/S tumors, MSI-H tumors are associated with a better OS rate for gastric cancer patients after R0 resection.

Splenectomy is the most common combined organ resection in the surgical management for gastric cardia cancer. The role of combined splenectomy is still controversial.From January 1998 to December 2006, a total of 174 patients received radical total gastrectomy for advanced adenocarcinoma of cardia. Patients with previous gastric surgery or tumor invasion of pancreas or spleen were excluded. Among them, 115 patients were enrolled in this study. Patients were divided into group 1 (splenectomy, n=47) and group 2 (spleen preservation, n=68). Their clinicopathological characteristics were compared.Multivariate analysis showed that only tumor size and lymphovascular invasion were two independent indicators of survival. The surgically-related morbidity and mortality rates were similar between the two groups. Among the 3 patients with splenic hilar lymph nodes metastasis, all of them had large tumor size (=4cm), advanced stage (stage III and IV) and tumor center located at the posterior wall of stomach. The 5-year overall survival for advanced cancer was similar (57.1% vs. 60.2%, p=0.681).Splenectomy does not improve overall survival in the management of advanced gastric cardia cancer. Splenectomy has limited clinical benefits except for large advanced tumors located at the posterior wall of stomach.

The preliminary results of a prospective double-blind controlled trial of colchicine in 100 patients with hepatitis B virus-related cirrhosis are reported. The patients, 94 males and 6 females, aged 32-80, were assigned to receive either 1 mg of colchicine or an identical placebo orally on a daily basis. The duration of the follow up ranged from 15 to 51 months (median 26 months). Seventy percent had histological proof of cirrhosis. On entry, 80 patients were in Child-Pugh class A, 19 were in class B, and one was in class C. Compared to the placebo group, there was no improvement in the colchicine group after a 24-month follow up in any of the biochemistry data, for example, serum albumin, alkaline phosphatase, alanine and aspartate aminotransferase, bilirubin, and prothrombin time. The difference in the cumulative survival rates at 51 months did not reach statistical significance (p = 0.8) in either group. There was no histological improvement in 30 patients who were willing to undergo repeated liver biopsies. No trend toward improvement of the hepatic pressure gradient was observed in these patients. The serum levels of aminopropeptide of type III procollagen increased significantly in patients in both groups after 24 months of therapy (1.07 +/- 0.06 vs. 1.36 +/- 0.06 U/ml in the colchicine group, 0.93 +/- 0.09 vs. 1.25 +/- 0.07 U/ml in the placebo group; p0.05). In addition, neither the clinical deterioration of cirrhosis nor death was prevented in patients receiving colchicine therapy. This report indicates that colchicine has no effect in the treatment of HBV-related postnecrotic cirrhosis.

The AJCC 7th edition changes the classification of T- and N-factors and the TNM stage of gastric cancer. We evaluated its prognostic impact.From December 1987 to December 2006, a total of 1,380 patients underwent curative surgery for gastric cancer at the Department of Surgery, Taipei Veterans General Hospital, with a retrieved lymph node number ≥ 15. Survival was compared for disease classified according to the AJCC 6th and 7th editions.There is a significant difference in 5-year survival between T2 and T3 gastric cancer classified according to the AJCC 7th edition (75.2 vs. 54.9%, p0.001), as well as between N1 and N2 (71.4 vs. 44.1%, p0.001). Although patients with N3a had a better 5-year survival than did those with N3b (27.6 vs. 11.3%, p0.001), the N3 categories were combined and not applied in the TNM stage in the 7th edition. Multivariate analysis using Cox's proportional hazards model with a forward logistics regression stepwise procedure demonstrates that age, N category of 6th edition, and T and N categories of 7th edition are independent prognostic factors; however, T category of 6th edition is no longer significant. Furthermore, the discriminative power of survival difference between each TNM stage seems to be comparable between the 6th and 7th editions.The AJCC 7th edition provides a more stratified survival difference in staging of gastric cancer. Future division of N3a and N3b in the classification of the TNM stage is recommended.

Despite curative surgery for gastric cancer, many patients die of recurrent cancer. Few studies have investigated the time to recurrence after curative resection for gastric cancer. Data were collected prospectively between December 1987 and December 2006. A total of 1,549 patients underwent curative resection of adenocarcinoma of the stomach at Taipei Veterans General Hospital. Among them, 419 patients had recurrence; they were divided into early recurrence (

Objective: We investigated the role and turn around time of rapid staining and immediate interpretation of fine-needle aspiration cytology (FNAC) for women with palpable breast lesions. Study Design: A total of 408 FNAC specimens from 400 patients with palpable breast lesions was analyzed for immediate interpretation and preliminary cytologic diagnosis. All cytological diagnoses were correlated with subsequent alcohol-fixed Papanicolaou-stained slides, mammographic, ultrasonographic and histopathological findings. Results: Of the 408 specimens, 243 (59.6%) were interpreted as benign, 37 (9.0%) atypical, 22 (5.4%) suspicious, 68 (16.7%) malignant, and 38 (9.3%) unsatisfactory. 132 of 408 (32.4%) had subsequent surgical procedures; the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 88.5, 100, 100, 81.9 and 92.4%, respectively. The average turn around time was 8.6 min. Mammographic results were available in 242 (59.3%) cases, with 112 (46.3%) undergoing surgical excision. In correlation with mammography and surgical pathology, the false-positive rate, false-negative rate, sensitivity, specificity and accuracy were 1.9, 10.5, 98.1, 89.5 and 95.8%, respectively. Conclusions: Rapid FNAC interpretation is a useful, effective diagnostic method for palpable breast lesions in our healthcare environment.

Signet ring cell carcinoma and mucinous carcinoma are mucin-producing gastric cancers. Their clinicopathological difference was obscure.From December 1987 to July 2005, a total of 1612 gastric cancer patients received curative surgery, 128 patients with signet ring cell carcinoma and 48 with mucinous carcinoma were enrolled in this study. Clinicopathological data were compared between the two groups.Early stage (stage I and II) patients with mucinous carcinoma were associated with more male predominant (p = 0.002), larger tumor size (p = 0.020), deeper cancer invasion (p0.001), and a worse 5-year overall survival (63.6% vs 88.2%, p = 0.012) than those with signet ring cell carcinoma. There was no significant difference between the two groups with advanced stage in 5-year overall survival. There is no significant difference in the initial recurrence pattern between the two groups.Patients with mucinous carcinoma had different biological behaviors with those with signet ring cell carcinoma, in particular early stage, hence had a worse survival.

Signal peptide-CUB-epidermal growth factor–like domain-containing protein 2 (SCUBE2), originally identified from the endothelium and several nonendothelial primary cell types, was recently shown to be expressed in invasive breast carcinomas. However, the protein localization and biological significance of SCUBE2 in breast cancer are unknown. In this report, we show by anti-SCUBE2 immunostaining that SCUBE2 is mainly expressed in vascular endothelial and mammary ductal epithelial cells in normal breast tissue. In addition, we observed positive staining for SCUBE2 in 55% (86 of 156) of primary breast tumors. Patients with positive SCUBE2 protein–expressing tumors had better prognosis than those with negative SCUBE2 protein–expressing tumors in terms of disease-free survival. Multivariate analysis confirmed SCUBE2 protein expression as an independent prognostic factor for disease-free survival. Furthermore, overexpression of ectopic SCUBE2 protein resulted in suppression of MCF-7 breast cancer cell proliferation and reduced MCF-7 xenograft tumor growth in nude mice. Molecular and biochemical analyses revealed that the COOH terminal region of SCUBE2 directly bound to and antagonized bone morphogenetic protein activity. Together, our results show for the first time that altered SCUBE2 expression is important in breast cancer progression and SCUBE2 may serve as a useful prognostic marker. [Cancer Res 2009;69(8):3634–41]

The incidence of adenocarcinoma of the esophagogastric junction (AEG) is rapidly increasing. We evaluated the clinicopathological difference and outcomes of Taiwanese patients with AEG according to the Siewert classification.Data were prospectively collected between December 1987 and July 2007. Two hundred thirty-one patients underwent curative resection of AEG at Taipei Veterans General Hospital and were divided into different Siewert types. The clinicopathological characteristics, operative morbidity, survival, and initial recurrence pattern were compared between the different types.Fifty-one type II and 180 type III cancer patients were studied. Subtotal esophagectomy via a left thoracotomy (19.6% vs 2.8%), smaller tumor size (4.43 +/- 2.04 vs. 5.35 +/- 2.03 cm), and more combined organ resection (60% vs. 43.1%) were more common in type II than type III cancer. Multivariate analysis showed that three independent risk factors for death were gender, tumor size, and lymphovascular invasion. There were long-term survivors among the patients with lesser curvature site lymph node metastasis, whereas metastasis to the lymph nodes of the distal stomach and along the greater curvature site was associated with poor prognosis. The 5-year survival was similar between type II and type III cancer (59.6% vs. 63.5%, P = 0.947).Lymphovascular invasion, tumor size, and gender were determined to be three independent factors of survival after curative resection for AEG, and Siewert type was not associated with differences in survival.

Background This study elucidated risk factors and management for intra-abdominal infection after extended radical gastrectomy. Methods From 1988 to 2004, 2,076 patients with gastric cancer underwent extended radical gastrectomy at Taipei Veterans General Hospital. Risk factors for intra-abdominal infection were determined by analyzing clinicopathological factors, operative procedure, combined organ resection, operative time, blood loss, and associated disease(s). Management modalities were summarized. Results The overall complication rate was 18.7%. Eighty (3.9%) patients were found to have intra-abdominal infections. Age, prolonged operation time, and combined organ resection were the precipitating factors. These patients were categorized into 3 groups: intra-abdominal abscess with adequate drainage, intra-abdominal abscess without anastomotic leakage, and intra-abdominal abscess because of leakage. Adequate drainage was the primary treatment. Mortality rate was 22.5% (18), and the most common cause of mortality was intra-abdominal abscess caused by leakage. Conclusions Although expert surgical skills can minimize the incidence of intra-abdominal infection, management also requires experience and training.

Lauren's intestinal type of gastric cancer was proposed to be dependent on long-term environmental factors and is always preceded by chronic premalignant change. A cohort study was performed and demonstrated an increased cancer risk of gastric remnant after gastric surgery for benign disease. It is generally believed that after gastrectomy the residual stomach has an environmental change and, thus, enters a neoplastic process. Based on the carcinogenic theory of intestinal-type tumour, it would be of interest to know whether the intestinal-type tumour is more common in gastric remnant cancer. Forty patients with gastric remnant cancer had gastrectomy in the Veterans General Hospital-Taipei. Another 683 patients with primary gastric carcinoma underwent resection and were used as controls. The clinical characteristics, tumour stage and intestinal-type tumour were analysed in gastric remnant cancer and were compared with the various portions of primary gastric carcinoma. Although the overall distribution of intestinal-type carcinoma in gastric remnant (45%) was no different to that of any other portion of stomach cancer, intestinal-type carcinoma was more common in the early stage of gastric remnant (73%) and distal stomach (73%), but not in the proximal stomach (50%), which was supposed to have the same characteristics as the gastric remnant because of identical anatomic location. More than expected, intestinal-type carcinoma in early gastric remnant cancer together with a long incubation interval between primary surgery and later tumour occurrence were compatible with the theory of carcinogenesis of intestinal-type carcinoma.

Carcinomas of the ampulla of Vater are uncommon, and signet-ring cell carcinoma is rare. We report a case of signet-ring cell carcinoma of the ampulla of Vater with obstructive jaundice in a 53-year-old man. Abdominal ultrasonography and abdominal computed tomographic scan revealed dilatation of the common bile duct, intrahepatic duct, and main pancreatic duct, with the obstruction level in the distal common bile duct near the ampulla of Vater. Duodenoscopy displayed an ampullary tumor protruding from the papilla of Vater with an erythematous and sloughing surface. Endoscopic biopsy of the tumor showed a signet-ring cell carcinoma. The patient received percutaneous transhepatic cholangiographic drainage, and the jaundice gradually improved. A Whipple operation including pancreatoduodenectomy and hemigastrectomy was performed. Pathological examination confirmed signet-ring cell carcinoma of the ampulla of Vater with direct invasion of the periampullary duodenum and distal common bile duct. No gastric lesion or nodal metastasis was found. The postoperative course was uneventful. The patient was alive with no recurrent disease during a follow-up period of 25 months.

Aims We evaluate the influency stage migration in a randomised trial comparing D1 (N 1 lymphadenectomy) and D3 (N 1, 2 and 3 lymphadenectomy) dissections. Methods Two hundred and thirteen curatively resected patients were analysed, with this TNM data. Results After applying D3 patients' data according to simulated D1 staging, D3 resections were associated with up-staging to N2-3 levels in 8% of patients according to the N stage. The likelihood of N-status migration increased with increasing depth of invasion into the gastric wall. The increases in the calculated survival rate after stage migration on known 5-year survival rates were: 2% in stage IB, 1% in stage II, 4% in stage IIIA, and 1% in stage IIIB. Conclusions Stage migration secondary to meticulous lymph node dissection affects stage-specific survival rates. True therapeutic survival benefit of D3 resection can only be assessed in this context.

Prognosis of gastric cancer with concomitant liver metastasis is poor. Gastrectomy and chemotherapy had been reported to be beneficial to this group of patients. Whether all the patients can benefit from that treatment modality and whether the clinical characteristics can give some information about survival have not been evaluated.Eighty-three gastric cancer patients with concomitant liver metastases who had received treatment in the past 10 years were retrospectively studied with special reference to different extent of liver metastases. Clinical characteristics (peritoneal tumor dissemination, tumor markers, clinicopathological factors), treatment modalities (gastrectomy or chemotherapy) and survival were analyzed for their possible relationship with the extent of liver metastases.There were 33 patients with liver metastases limited to one lobe and 50 patients had metastases in both lobes. The clinicopathological characteristics show no difference between uni- and bilobar liver metastases except higher percentage of concomitant peritoneal dissemination in patients with bilobar disease. More unilobar involvement patients underwent gastrectomy (70% vs. 48%, p=0.018). Higher frequency of abnormal CEA level in bilobar metastases (38% vs. 60%, p=0.045). Median survival of unilobar metastasis is 7.8 months and 4.3 months for the bilobar involvement (p=0.001). Gastrectomy might prolong the survival in patients with unilobar metastasis (p=0.005), but not in patients with bilobar diseases (p=0.074). Chemotherapy could prolong the survival in patients without gastrectomy, but not the survival after gastrectomy.The clinicopathological characteristics and tumor markers have no role in predicting the survival among patients with liver metastases. Both gastrectomy and chemotherapy for the patients without gastrectomy could prolong survival, but chemotherapy could not prolong the survival after gastrectomy, the benefit of resection and chemotherapy are probably caused by selection bias.

Death from gastric carcinoma after curative resection is mostly due to recurrence. The most common recurrence is peritoneal dissemination, which represents 33 to 50% of total recurrence after curative gastrectomy. Since survival after peritoneal dissemination is very poor, selection of high-risk patients for further management after resection may contribute to better survival.Based on a prospective database, a total of 1,092 patients with gastric carcinoma who underwent curative resection were included in this study. The incidence of peritoneal recurrence, disease-free interval and survival after peritoneal recurrence were determined. The clinicopathological factors including sex, age, tumor location, size, gross appearance, histological findings, depth of tumor invasion, lymph node status, tumor cell infiltration pattern were analyzed to see if there is any relationship with peritoneal dissemination.The incidence of peritoneal recurrence after curative resection was 13.46%. The mean disease-free interval was 14.2 months and the survival after peritoneal recurrence was 4.9 months in average. Almost all the clinicopathological factors were related with peritoneal recurrence, but only depth of tumor invasion, gross appearance and tumor infiltration pattern are closely associated with peritoneal tumor dissemination after multivariate analyses.Since the prognosis after peritoneal recurrence is so poor, selection of high-risk patients for further management after gastrectomy may be based on these three factors.

Objective This retrospective study evaluated two different modes of nutrition supplementation in premature neonates with respiratory distress syndrome. Methods Data were collected from the medical records of premature infants treated from January 1, 1997 to July 31, 2000. Seventeen infants were given peripheral amino acids and gradual advanced minimal hypocaloric enteral feeding within the first 48 h (early nutrition group), and 19 infants received nutrition supplementation more than 48 h after birth (late nutrition group). Groups were similar with regard to gestational age, birth weight, Apgar score, mode of delivery, and diagnosis. Results Compared with infants in the late nutrition group, those in the early nutrition group required fewer days of parenteral nutrition, fewer days to reach full enteral feeding, fewer days of mechanical ventilation, fewer days of aminophylline use, fewer days to regain birth weight, and had a lower percentage of maximal weight loss. Other physiologic parameters such as age at maximal weight loss, weight gain after day 10, and hospital days required favored the use of early nutrition. Conclusions Early nutrition to maintain a positive energy balance in premature neonates with respiratory distress syndrome is beneficial.

The present study sought to evaluate the clinicopathological features of our gastric cancer patients in terms of a modified Lauren's histological classification and compared the results with those from studies from Japan and Western countries. A total of 536 consecutive patients with gastric cancer were treated surgically between December 1987 and December 1993. A clinicopathological analysis was only performed for intestinal types (IT) and diffuse types (DT) of gastric cancer because patients falling into the 'other' category were too small to produce meaningful data. Of 536 cases of gastric cancer, 268 (50%) were IT, 231 (43.1%) were DT and 37 (6.9%) were of the other type. The overall IT:DT ratio was 1.2. Gastric cancer patients with IT (in contrast to DT) were characterized by older age, male dominance, smaller tumours, the tumour often being located in the lower and upper third of the stomach and less peritoneal metastasis. In both sexes, the peak incidence of gastric cancer patients was in the age group 65-74 years. Men had higher proportions of IT carcinoma than women. The IT:DT ratio for men and women was 1.4 and 0.4, respectively. Although the increased ratio of IT:DT paralleled the advance of age in both sexes, the transitional age (the age at which the IT:DT ratio exceeds 1.0) in male patients (age group 51-64 years) was earlier than for female patients (age group 65-74 years). Patients with IT gastric cancer had a significantly better survival rate than those with DT. However, the type of carcinoma (IT or DT) was not an independent predictor of survival. These data indicate that gastric cancer in Taiwan Chinese has different biological behaviour in terms of IT and DT. The clinicopathological features in IT and DT carcinoma are similar to studies from Japan and from Western countries.

BACKGROUND--No nodal grouping category of gastric cancer has been universally accepted for the grading of the effectiveness of therapeutic regimens. AIMS--To establish an appropriate nodal grouping as a forecaster of distant disease and test its validity as a determinant in survival. PATIENTS--Five hundred and ten patients who underwent curative resections for gastric cancer were studied. METHODS--Retrospectively analyse the prognostic significance of the number of metastatic lymph nodes. RESULTS--A total of 17 176 lymph nodes with an average of 34 per specimen were removed, of which 2811 (16%) showed metastases. Among the 510 patients, 287 (56%) had lymph node metastases, with an average of 9.8 per metastatic case. The survival of all patients was related to their nodal status, an abrupt decrease in survival was seen between 0 and 1 and 4 compared with 5 or more modes while little difference in survival existed among 1, 2, 3, and 4, and among 5, 6, 7, and 8 positive nodes. Multivariate analysis showed that the number of positive nodes (1-4, 5-8 versus > or = 9; relative risk 2.2) and depth of cancer invasion (three levels; relative risk 1.9) were independently correlated with survival. The current nodal stage was not a prognostic factor. CONCLUSIONS--Gastric cancer patients with 0, 1 to 4, 5 to 8, and > 9 positive nodes may represent four appropriate prognostic groups and should be adopted for classification of nodal stage in gastric cancer.

We report that a modified dextran-coated charcoal (DCC) assay, including the addition of sodium molybdate and 5% DCC stripping of endogenous hormone, detected higher estrogen receptors (ERs) than those by the conventional assay. ERs in 21 gastric adenocarcinoma were determined by the modified DCC assay; 13 patients had ERs of 2.5 to 520.2 fmol/mg protein with a mean dissociation constant of 1.9 × 10×10 M. The remaining 8 patients had no detectable amount of the receptor. There were no differences between the ER-positive and ER-negative groups in clinico-pathologic characteristics such as age, sex, tumor size, location, gross appearance, invasive depth, invasion of lymph vessel or vein of stomach wall, nodal involvement, peritoneal dissemination, liver metastasis, and curability. Histological analysis, using Japanese, Lauren's, or Ming's classifications, all revealed no differences between the ER-positive and -negative groups. The survival rate was identical for the 2 study groups. These results suggest that the presence or absence of ERs in gastric adenocarcinoma does not correlate to either biologic or clinicopathologic characteristics of this tumor; the role of ERs in human gastric cancer remains to be elucidated. © 1992 Wiley-Liss, Inc.