YY1-modulated long non-coding RNA SNHG12 promotes gastric cancer metastasis by activating the miR-218-5p/YWHAZ axis.

Long non-coding RNA (lncRNA) small nucleolar RNA host gene 12 (SNHG12) plays important roles in the pathogenesis and progression of cancers. However, the role of SNHG12 in the metastasis of gastric cancer (GC) has not yet been thoroughly investigated. In the present study, we demonstrated that SNHG12 was upregulated in GC tissues and cell lines. In addition, the expression level of SNHG12 in GC samples was significantly related to tumor invasion depth, TNM stage and lymph node metastasis and was associated with disease-free survival (DFS) and overall survival (OS) in GC patients. In vivo and in vitro assays indicated that SNHG12 promotes GC metastasis and epithelial-mesenchymal transition (EMT). Bioinformatics and mechanistic analyses revealed that SNHG12 can directly target miR-218-5p to regulate YWHAZ mRNA, forming an SNHG12/miR-218-5p/YWHAZ axis and decreasing the ubiquitination of ß-catenin. In addition, SNHG12 stabilizes CTNNB1 mRNA by binding with HuR, thus activating the ß-catenin signaling pathway. Further analysis also revealed that the transcription factor YY1 negatively modulates SNHG12 transcription. In conclusion, SNHG12 is a potential prognostic marker and therapeutic target for GC. Negatively modulated by YY1, SNHG12 promotes GC metastasis and EMT by regulating the miR-218-5p/YWHAZ axis and stabilizing CTNNB1 via activation of the ß-catenin signaling pathway.

Emphysematous gastritis after metastatic malignant melanoma: a radiological surprise.

Malignant melanoma is cancer of the skin which commonly metastasises to the stomach. There have been no reported cases of emphysematous gastritis secondary to metastasis of malignant melanomas, to date. However, a 61-year-old woman with metastatic malignant melanoma of the left great toe presented to us with symptoms of severe left hypochondrium pain associated with high-grade fever, gross abdominal distension and recurrent vomiting. Two months earlier, metastasis was observed to have spread to the stomach and inguinal lymph nodes. At this stage, the patient opted for traditional medication instead of definitive surgery and chemotherapy. Radiological imaging revealed an emphysematous change to the stomach which was radiologically consistent with gastric malignant melanoma. Unfortunately, the patient succumbed to this rare condition.

[A Case in Which Eating Ability Was Restored after Chemotherapy for Gastric Metastasis Following Colon Cancer Resection].

We report here a rare case of gastric metastasis after resection ofa transverse colon cancer in which eating ability was restored following mFOLFOX6 (folinic acid plus fluorouracil plus oxaliplatin) plus cetuximab (Cet) chemotherapy. A 56-year-old man with chief complaints of constipation and abdominal fullness was referred to our hospital. In February 2013, he was diagnosed with transverse colon cancer via enema and colonoscopy. We performed transverse colon cancer resection followed by a 6-month course of capecitabine chemotherapy. In July 2014, the patient's serum carcinoembryonic antigen level increased, in October, he was again referred to our hospital with complaints of appetite loss and vomiting. He was diagnosed with multiple lymph node and gastric metastases via ultrasonography, computed tomography, and endoscopy, as well as multiple lung metastases via computed tomography. As the gastric metastases and vomiting rendered him unable to eat, a nasogastric tube was inserted and was administered mFOLFOX6 plus Cet chemotherapy. After 2 courses of chemotherapy his ability to eat was restored. As of March 2015, the patient remains alive following 12 courses of chemotherapy.

[A case of metastatic gastric cancer originating from transverse colon cancer].

Metastatic gastric cancer is uncommon, and metastasis of colorectal cancer to the stomach is extremely rare. We report a case of metastatic gastric cancer that originated from transverse colon cancer. A 52-year-old woman underwent a left hemicolectomy and D3 lymph node dissection based on a diagnosis of transverse colon cancer. The pathology results were as follows: mucinous adenocarcinoma, type 2, 6 × 11 cm, ss, ly1 v1, pm (-), dm (-), n1 (+), P0, H0, M0, Stage IIIa. The patient received XELOX as postoperative adjuvant therapy for 6 months. One year and 3 months after the left hemicolectomy, gastroscopy revealed a submucosal tumor in the lower body of the stomach and an incipient cancer in the cardia of the stomach, and a colonoscopy revealed an incipient cancer in the transverse colon. An endoscopic ultrasonography fine needle aspiration biopsy of the submucosal tumor in the lower body of the stomach was performed. Histology showed that this tumor was a mucinous adenocarcinoma similar to the primary transverse colon cancer, which led to a diagnosis of metastatic gastric cancer originating from transverse colon cancer. Distant metastasis was not detected. Endoscopic submucosal dissection of the incipient gastric cancer was performed, as were distal gastrectomy and partial colectomy. Peritoneal dissemination and para-aortic lymph node recurrence were detected 7 months after the second surgery.

Hepatoid adenocarcinoma of the stomach: an unusual case of elevated alpha-fetoprotein with prior treatment for hepatocellular carcinoma.

Hepatoid adenocarcinoma (HAC) is a rare type of extrahepatic carcinoma whose morphology is similar to that of hepatocellular carcinoma (HCC). Metachronous HCC and HAC in the same patient is extremely rare. The case of a 68-year-old man with chronic hepatitis B infection who had both HCC and HAC of the stomach is reported herein. Nine years previously this patient had been diagnosed with HCC and received a right lobectomy. HCC that recurred at the caudate lobe at 6 months after the operation was successfully treated with transarterial chemoembolization. The patient was followed up regularly thereafter without evidence of tumor recurrence for 9 years. In July 2010 his serum alpha-fetoprotein (AFP) level elevated from 6.5 ng/mL to 625.4 ng/mL, and he developed a probable single metastatic lymph node around the hepatic artery without intrahepatic lesions. Subsequent evaluation with upper endoscopy revealed a 4-cm ulcerative lesion on the antrum of the stomach. Subtotal gastrectomy was performed with lymph-node dissection. Histologic examination revealed a special type of extrahepatic AFP-producing adenocarcinoma-HAC with lymph-node metastasis-which indicates that HAC can be a cause of elevated AFP even in patients with HCC. HAC should be considered if a patient with stable HCC exhibits unusual elevation of AFP.

Tumor interstitial fluid and gastric cancer metastasis: an experimental study to verify the hypothesis of "tumor-phlegm microenvironment".

OBJECTIVE: To extract tumor interstitial fluid (TIF) from MKN-45 gastric cancer which is similar to "muddy phlegm" in Chinese medicine and observe influences of MKN-45 tumor interstitial fluid (MKN-45 TIF) intervention on metastasis of gastric cancer and on the expressions of vascular endothelial growth factor (VEGF), kinase insert domain containing receptor (KDR), epithelial-cadherin (E-cad), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1) and telomerase genes and proteins in primary tumor tissue. METHODS: An MKN-45 tumor-bearing model was established in 50 nude mice. The modeled animals were equally randomized to 5 groups: the simple tumor-bearing group (model group), the normal saline (NS) via tail vein injection (i.v.) group (NS i.v. group), MKN-45 TIF i.v. group (TIF i.v. group), NS intraperitoneal injection (i.p.) group (NS i.p. group), and MKN-45 TIF i.p. group (TIF i.p. group). The TIF and NS intervention groups received injection (i.p. or i.v.) of MKN-45 TIF or NS twice a week, 0.2 mL at a time. After 8 weeks, the primary tumors were removed, weighed and HE stained to observe tumor metastasis. The primary tumor tissues were analyzed by immunohistochemistry and real-time quantitative PCR to detect expressions of VEGF, KDR, E-cad, COX-2, ICAM-1, and telomerase genes and proteins in different groups. RESULTS: There were significant differences in tumor weight between TIF intervention groups and the model and NS intervention groups. Tumor metastasis was observed in all 5 groups, but the tumor metastasis rate in TIF intervention groups was significantly higher than those in the model and NS intervention groups. The gene and protein expressions of gastric cancer-related factors VEGF, KDR, COX-2, ICAM-1 and telomerase were unregulated while the gene and protein expressions of E-cad were downregulated in TIF intervention groups. CONCLUSIONS: TIF promotes tumor growth, invasion and metastasis of gastric cancer. These findings provide preliminary experimental clues for verifying the hypothesis of "tumor-phlegm microenvironment".

Treatment of high-risk gastric cancer postoperatively using intensity-modulated radiotherapy: a single-institution experience.

BACKGROUND/AIMS: The aim of this study was to determine the efficacy and acute toxicity of our early experience with treating postoperatively non-metastatic gastric cancer with intensity-modulated radiotherapy (IMRT). METHODOLOGY: A retrospective review was performed on 47 consecutive patients with gastric cancer and treated with postoperatively adjuvant IMRT at Department of radiation oncology, Zhejiang cancer hospital, China, between January 2007 and August 2009. One patient who did not complete his radiation course was excluded, leaving 46 patients for analyses. The median radiation dose delivered was 4500cGy using 180cGy fractions. Concurrent chemotherapy administered were 5-fluorouracil (n=36), capecitabine (n=9) and none (n=1). RESULTS: The median follow-up time was fifteen months (range 6-28 months). 1-year OS and 2-year OS were 98.0% and 80.0%, assessed by Kaplan-Meier methods. Of the six patients who died, five (83.3%) developed a distant metastases. The overall survival time by tumor size was significantly different (>6cm vs. =6cm, p<0.05). There was no significant survival difference between 5-fluorouracil group and capecitabine group (p=0.80). CONCLUSIONS: The data support the use of IMRT in the adjuvant treatment in high risk gastric cancer postoperatively. Acute toxicity is tolerable. Capecitabine with concurrent IMRT was as effective and tolerable as 5-FU/IMRT. Distant metastasis was the main reason of treatment failure that must be addressed in future trials.

Palliative first-line therapy with weekly high-dose 5-fluorouracil and sodium folinic acid as a 24-hour infusion (AIO regimen) combined with weekly irinotecan in patients with metastatic adenocarcinoma of the stomach or esophagogastric junction followed by secondary metastatic resection after downsizing.

BACKGROUND: The aim of this retrospective study was to evaluate the efficacy and safety of weekly high-dose 5-fluorouracil (5-FU)/folinic acid (FA) as 24-h infusion (AIO regimen) plus irinotecan in patients with histologically proven metastatic gastroesophageal adenocarcinoma (UICC stage IV). MATERIAL/METHODS: From 08/1999 to 12/2008, 76 registered, previously untreated patients were evaluable. Treatment regimen: irinotecan (80 mg/m²) as 1-h infusion followed by 5-FU (2000 mg/m²) combined with FA (500 mg/m²) as 24-h infusion (d1, 8, 15, 22, 29, 36, qd 57). RESULTS: Median age: 59 years; male/female: 74%/26%; ECOG ≤1: 83%; response: CR: 1%, PR: 16%, SD: 61%, PD: 17%, not evaluable in terms of response: 5%; tumor control: 78%; median OS: 11.2 months; median time-to-progression: 5.3 months; 1-year survival rate: 49%; 2-year survival rate: 17%; no evidence of disease: 6.6%; higher grade toxicities (grade 3/4): anemia: 7%, leucopenia: 1%, ascites: 3%, nausea: 3%, infections: 12%, vomiting: 9%, GI bleeding of the primary tumor: 4%, diarrhea: 17%, thromboembolic events: 4%; secondary metastatic resection after downsizing: 16 patients (21%), R-classification of secondary resections: R0/R1/R2: 81%/6%/13%, median survival of the 16 patients with secondary resection: 23.7 months. CONCLUSIONS: Combined 5-FU/FA as 24-h infusion plus irinotecan may be considered as an active palliative first-line treatment accompanied by tolerable toxicity; thus offering an alternative to cisplatin-based treatment regimens. Thanks to efficient interdisciplinary teamwork, secondary metastatic resections could be performed in 16 patients. In total, the patients who had undergone secondary resection had a median survival of 23.7 months, whereas the median survival of patients without secondary resection was 10.1 months (p≤0.001).

Trastuzumab: a new treatment option for HER2-positive metastatic gastric and gastroesophageal junction cancer.

In patients with metastatic gastric cancer, median overall survival with standard chemotherapy remains under 1 year. As such, effective new treatments with acceptable tolerability are urgently needed. Amplification/overexpression of HER2 is reported in approximately 20% of gastric tumors, providing a rationale to investigate trastuzumab, a monoclonal antibody against HER2, in this setting. In the Phase III international Trastuzumab for Gastric Cancer (ToGA) study, the addition of trastuzumab to chemotherapy significantly improved overall survival without compromising safety in patients with HER2-positive metastatic gastric or gastroesophageal junction cancer. The purpose of this review is to discuss clinical data supporting the role of trastuzumab in metastatic gastric cancer, and consider the optimization of gastric cancer-specific HER2 testing and analysis.

Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: the FLAGS trial.

PURPOSE: Patients with advanced gastric or gastroesophageal adenocarcinoma need more efficacious and safer treatments than established today. S-1, a contemporary oral fluoropyrimidine, can provide that advantage. PATIENTS AND METHODS: This study was conducted in 24 countries and 146 centers. One thousand fifty-three patients were stratified (center, number of metastatic sites, prior adjuvant therapy, and measurable cancer) and randomly assigned. Patients received either S-1 at 50 mg/m(2) divided in two daily doses for 21 days and cisplatin at 75 mg/m(2) intravenously on day 1, repeated every 28 days (527 patients) or infusional fluorouracil at 1,000 mg/m(2)/24 hours for 120 hours and cisplatin at 100 mg/m(2) intravenously on day 1, repeated every 28 days (526 patients). The primary end point was superiority in overall survival (OS) from cisplatin/S-1 compared with cisplatin/infusional fluorouracil in patients with advanced, untreated gastric, or gastroesophageal adenocarcinoma. The secondary end points were response rate, progression-free survival, time to treatment failure, and safety. RESULTS: The median OS was 8.6 months in the cisplatin/S-1 arm and 7.9 months in the cisplatin/infusional fluorouracil arm (HR, 0.92; 95% CI, 0.80 to 1.05; P = .20). Significant safety advantages were observed in the cisplatin/S-1 arm compared with the cisplatin/infusional fluorouracil arm for the rates of grade 3/4 neutropenia (32.3% v 63.6%), complicated neutropenia (5.0% v 14.4%), stomatitis (1.3% v 13.6%), hypokalemia (3.6% v 10.8%), and treatment-related deaths (2.5% v 4.9%; P < .05). CONCLUSION: Cisplatin/S-1 did not prolong OS of patients with advanced gastric or gastroesophageal adenocarcinoma compared with cisplatin/infusional fluorouracil, but it did result in a significantly improved safety profile.

The GYMSSA trial: a prospective randomized trial comparing gastrectomy, metastasectomy plus systemic therapy versus systemic therapy alone.

BACKGROUND: The standard of care for metastatic gastric cancer (MGC) is systemic chemotherapy which leads to a median survival of 6-15 months. Survival beyond 3 years is rare. For selected groups of patients with limited MGC, retrospective studies have shown improved overall survival following gastrectomy and metastasectomies including peritoneal stripping with continuous hyperthermic peritoneal perfusion (CHPP), liver resection, and pulmonary resection. Median survival after liver resection for MGC is up to 34 months, with a five year survival rate of 24.5%. Similarly, reported median survival after pulmonary resection of MGC is 21 months with long term survival of greater than 5 years a possibility. Several case reports and small studies have documented evidence of long-term survival in select individuals who undergo CHPP for MGC. DESIGN: The GYMSSA trial is a prospective randomized trial for patients with MGC. It is designed to compare two therapeutic approaches: gastrectomy with metastasectomy plus systemic chemotherapy (GYMS) versus systemic chemotherapy alone (SA). Systemic therapy will be composed of the FOLFOXIRI regimen. The aim of the study is to evaluate overall survival and potential selection criteria to determine those patients who may benefit from surgery plus systemic therapy. The study will be conducted by the Surgery Branch at the National Cancer Institute (NCI), National Institutes of Health (NIH) in Bethesda, Maryland. Surgeries and followup will be done at the NCI, and chemotherapy will be given by either the local oncologist or the medical oncology branch at NCI. TRIAL REGISTRATION: ClinicalTrials.gov ID. NCT00941655.

Feasibility of self-expandable metallic stent plus chemotherapy for metastatic gastric cancer with pyloric stenosis.

BACKGROUND AND AIM: Self-expandable metallic stent placement is accepted as palliative therapy for advanced gastric cancer with gastric outlet obstruction, but data are lacking for chemotherapy after self-expandable metallic stent insertion. This study retrospectively compared results between surgery plus chemotherapy and stenting plus chemotherapy for metastatic gastric cancer with pyloric stenosis. METHODS: Subjects comprised 26 patients who received chemotherapy after surgery or endoscopic stenting for metastatic gastric cancer with pyloric stenosis between April 2000 and December 2007 in four Japanese hospitals. Patients were categorized into two groups: 15 patients who received chemotherapy after surgery for pyloric stenosis (Surgery group); and 11 patients who received chemotherapy after self-expandable metallic stent placement for pyloric stenosis (Stent group). RESULTS: Median survival time and median time to treatment failure were 284 days and 226 days in the Surgery group and 337 days and 247 days in the Stent group, respectively. No significant differences were noted between survival and time to treatment failure. No significant differences were found in median oral intake rate (Surgery, 93.1%; Stent, 93.2%) or median hospital stay rate (Surgery, 24.6%; Stent, 23.7%) during survival. Response rate was 45.5% in the Surgery group and 50% in the Stent group, with no significant difference. Likewise, no significant differences were noted between groups for frequencies of toxicity or complications. CONCLUSIONS: The present results suggest that chemotherapy after stenting is as effective and safe as chemotherapy after surgery. Stents may replace surgery in combination therapy with chemotherapy for metastatic gastric cancer with gastric outlet obstruction.

Pemetrexed in combination with oxaliplatin as a first-line therapy for advanced gastric cancer: a multi-institutional phase II study.

BACKGROUND: This clinical trial assessed the efficacy of pemetrexed combined with oxaliplatin (PEMOX) in patients with advanced gastric cancer (AGC). PATIENTS AND METHODS: Forty-four patients with untreated AGC were enrolled to evaluate response rate (RR). Patients received pemetrexed (500 mg/m(2)) with vitamin supplementation and oxaliplatin (120 mg/m(2)) every 21 days for six cycles or until disease progression occurred. RESULTS: Median age was 62 years (range 26-76). The majority of patients (93%) had metastatic disease. Sixteen of the 44 patients achieved confirmed response [RR 36%; 95% confidence interval (CI) 22% to 52%]; four complete responses and 12 partial responses (complete and partial responses according to the RECIST guidelines are the confirmed-responses observed in the study population). Median time to tumor progression (TTP) was 6.2 months (95% CI 4.3-7.5) and median survival was 10.8 months (95% CI 7.7-17.2). A total of 220 cycles were administered, with a median of six cycles. Most common grade 3/4 toxic effects were neutropenia in 41% of patients (19% of cycles) and thrombocytopenia in 11% of patients (4% of cycles). Treatment delays or dose reductions for toxicity occurred in 10% and 5% of cycles, respectively. CONCLUSIONS: PEMOX is active and well tolerated in AGC. RR, TTP, and survival were comparable to those achieved in studies using different 5-fluorouracil (5-FU)-oxaliplatin combinations, without the inconvenience of prolonged 5-FU schedules.

Gastrostomy-site tumor recurrence is not always fatal.

Percutaneous gastrostomy (PEG) site tumor seeding is a rare occurrence with fewer than 30 reported cases. Reported treatment ranges from observation to wide excision with unanimously poor outcome. We report the first published case of a long-term survivor after resection of a PEG site recurrence and review our treatment approach.

Local injection of M-CH combined with i.p. hyperthermic hypo-osmolar infusion is an effective therapy in advanced gastric cancer.

Treatment failure of surgically treated gastric cancer is attributed to the spread of gastric cancer cells into the abdominal cavity and lymphatic or hematogenic canals. In the present study, local injection of mitomycin C bound to activated carbon (M-CH) combined with i.p. hyperthermic hypo-osmolar infusion (IPHHOI) was intraoperatively administered to prevent lymph node recurrence and peritoneal recurrence of gastric cancer. Between April 1998 and August 1999, 79 patients with advanced gastric cancer were allocated randomly to two groups. Forty patients underwent M-CH plus IPHHOI combined with surgery (M-CH1+IPHHOI group) and the remaining 39 underwent surgery alone (control group). Lymph node and peritoneal recurrence were significantly decreased in the M-CH1+IPHHOI group compared to that in the control group (p<0.05). The 1- and 2-year survival rates for the M-CH1+IPHHOI group were 91.2 and 72.1%, and those for the control group were 78.9 and 45.5%. The M-CH1IPHHOI group reaped a significant survival benefit (p=0.0352) compared to the control group. Although this study was conducted randomly for a small number of patients and short time, compared with the control group, the M-CH1+IPHHOI group had a beneficial effect in preventing lymph node recurrence and peritoneal recurrence after curative gastrectomy for advanced gastric cancer.

[Multiorgan resection in combination with intraoperative, hyperthermic chemotherapy in recurrent fibrolamellar hepatocellular carcinoma. An individual therapeutic concept for a 21-year-old patient]. / Multiviszerale Resektion in Kombination mit intraoperativer, hyperthermer Chemotherapie beim Rezidiv des fibrolamellären, hepatozellulären Karzinoms. Ein individuelles, therapeutisches Konzept bei einem 21jährigen Patienten.

The fibrolamellar karzinoma of the liver (FLC) as an uncommon variant of the hepatocellular karzinoma (HCC) is an indolent growing tumor. In its prior manifestation the FLC occurs at the adolescence and young adult stage. Early stage diagnosis and aggressive surgical treatment achieve better long-term results than usual resection of the HCC. Usually the FLC is, caused by its inconspicuous clinical appearance, diagnosed at a stage too advanced for effective surgical treatment. Especially the young patient's age and the remaining therapeutic options for palliative or curative treatment postulate a difficult decision for the surgeon. When a subtotal hepatectomy cannot be performed, total hepatectomy with liver transplantation is a valuable option. Palliative treatment protocols include systemic chemotherapy, ethanol instillation and chemoembolisation. We report the case of a 21-year-old male patient who presented with a recurrent intrahepatic FLC, peritoneal karzinomatosis confined to the right lower abdomen including gastric, splenic, diaphragmatic and colon transversum metastasis 14 months after primary surgery. We selected this patient as a reasonable candidate for an extended resection in trying to offer the optimal therapeutic modality. Thus we performed a right hemihepatectomy, near complete resection of the right diaphragm, total gastrectomy with lymphadenectomy including en bloc resection of spleen, colon transversum, omentum majus and peritonectomy of the paravesical region. Furthermore hyperthermic intraperitoneal chemotherapy was carried out the next day. The patient's postoperative course remained uncomplicated with fast recovery. Presently, 6 months after surgery, the patient has no evidence of recurrence.

High-dose infusional 5-fluorouracil combination therapy of metastatic gastric and colorectal cancer.

To improve the therapeutic ratio of palliative chemotherapy in patients with metastatic colorectal and gastric cancer 5-fluorouracil (5-FU) was administered as weekly high-dose 24-hour continuous infusion in combination with leucovorin (LV) and interferon-alpha-2b (IFN) as biomodulating agents: Chemotherapy consisted of a weekly schedule of 500 mg/m2 leucovorin as a 2-hour infusion, followed by a 24-hour continuous infusion of 2500 mg/m2 5-FU. IFN was administered subcutaneously at a dose of 3 mio I.E. three times a week. In patients with gastric carcinoma, etoposide (VP) 100 mg/m2 as 30-minute bolus infusion was added. Eighty-five patients (colorectal: 55 points, gastric: 30 points) are evaluable for response, toxicity, and survival analysis. Colorectal: CP+PR: 19/55 (34.5%), NC: 25/55 (45.5%), PD: 11/55 (20.0%). Median duration of remission in months (90% confidence interval): 5.2 (3.1 to 9.2), median survival since the start of salvage chemotherapy: 13.9 months (12.3 to 20.1), from initial diagnosis of metastasis: 30.2 months (26.3 to 44.5). Gastric: CR: 8/30 (26.7%), PR: 14/30 (46.6), NC: 5/30 (16.7), PD: 3/30 (10.0%). Median duration of remission in months (90% confidence interval): 6.75 (1.5 to 16.2), median survival since start of chemotherapy: 15.1 months (90% confidence interval 11.8 to 20.3 months). Hematologic toxicity: hemoglobin: I: 20.0%, II: 10.0%, leukocytes: I: 13.3%, II: 33.3%, III: 16.6%, platelets: I: 10.0% and III: 3.3%. Hematologic toxicity was moderate to negligible, peripheral toxicity consisted mainly of tolerable stomatitis and diarrhea. Dose and schedule intensified weekly 5-FU combination therapy in metastatic colorectal and gastric cancer is highly active in terms of response and median survival time. Chemotherapy pretreated patients with colorectal cancer seem to have a substantial survival benefit with this salvage protocol.

Surgical therapy for gastric cancer.

The aim of any surgical approach to gastric carcinoma should be a complete resection with no residual tumor left behind, that is, a R0-resection according to the UICC. Complete tumor resection in this respect refers to the primary tumor as well as the lymphatic drainage and requires an adequate safety margin. The indications for surgical therapy of gastric cancer and the choice of procedure should consequently be guided by the tumor stage. This requires accurate preoperative staging, which can today be achieved with endoscopic ultrasonography and surgical laparoscopy. Gastric carcinoma stage IA (mucosa carcinoma) can be cured by local excision. In patients with tumor stages IB (submucosa carcinoma), II, and IIIA, lymph node metastases are common. Based on the available data, this group of patients benefits from radical resection and D2 lymph node dissection. In patients with advanced gastric carcinoma, that is, tumor stages IIIB and IV, a complete tumor removal usually can not be achieved by surgical resection. Neoadjuvant therapeutic modalities should consequently be assessed in these patients. Based on tumor location and growth pattern, a total gastrectomy is the procedure of choice in patients with middle and proximal third gastric cancer. A subtotal gastrectomy may be performed in patients with tumors of the distal third and "Laurén's intestinal type" growth pattern. Depending on the individual tumor situation, the gastrectomy can be extended toward varying portions of the distal esophagus or a pancreas, preserving splenectomy and resection of the retroperitoneal lymph nodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Folate biochemical modulation regimen for the treatment of gastric cancer.

Twenty patients with metastatic gastric cancer were treated with methotrexate (MTX, M), 100 to 160 mg/m2 at 0 h, and, in sequence, 5-fluorouracil (FU, F), 600 to 1000 mg/m2 at 4 h; leucovorin (LV, L), 200 mg/m2 at 18 h, then 20 mg/m2 every 6 h x 12; 5-fluorouracil, 600 mg/m2 at 19 h; and high-dose cisplatin (DDP, P), 100 mg/m2 at 20 h. In addition, they were treated with a continuous 5-fluorouracil infusion, 1000 mg/m2/24 h from 18 h to 114. There were 8 complete and 6 partial responses among the 16 patients with measurable tumors. Five patients, each with one remaining clinical site of disease, received supplementary regional therapy: three received intraperitoneal therapy, two received hepatic arterial therapy. Intraperitoneal therapy and hepatic artery therapy each produced one complete response. Median survival was 16 months for all patients, and 25% survived 2 years. In comparison with matched patients, both response rates and survival improved twofold.