Clinical benefits of FOLFOXIRI combined with bevacizumab for advanced-stage primary signet ring cell carcinoma of the appendix: A case report.

RATIONALE: Signet-ring cell carcinoma, which is an infrequent type of colorectal cancer. Abdominal pain is the primary presenting complaint of patients with acute appendicitis. It is difficult to diagnose patients with appendiceal carcinomas accompanying with symptoms of acute appendicitis. PATIENT CONCERNS: A 33-year-old female patient was admitted to our hospital, with chief complaints of "bilateral pelvic space-occupying lesions for 1 month, aggravated abdominal distension, and she accompanied with diarrhea for 3 days." DIAGNOSIS: The patient was with primary signet ring cell carcinoma of the appendix, presented with acute appendicitis, as well as bilateral ovarian metastasis and peritoneal implantation metastasis. INTERVENTIONS: She was then treated with irinotecan, oxaliplatin, calcium folinate, 5-FU combined with bevacizumab, surgical treatment, and postoperative adjuvant treatment with oxaliplatin, capecitabine regimen to consolidate the efficacy. OUTCOMES: The patient is in good conditions, and postoperative adjuvant chemotherapy is in progress as well. CONCLUSION: The outcomes highlighted the importance of strict histopathologic assessment for appendiceal adenocarcinoma, and provided new ideas for the diagnosis and treatment of advanced-stage signet ring cell carcinoma of the appendix.

Alternative medicine: therapeutic effects on gastric original signet ring carcinoma via ascorbate and combination with sodium alpha lipoate.

BACKGROUND: Gastric signet ring cell carcinoma (SRCC) is an aggressive gastric adenocarcinoma with a poor prognosis when diagnosed at an advanced stage. As alternative medicine, two natural supplements (ascorbate (AA) and sodium alpha lipoate (LA)) have been shown to inhibit various cancers with mild side effects. METHODS: These two natural supplements and a series of combinations (AA&LA, AA+LA and LA + AA) were incubated with non-SRCC cells (GPM-1), patient-derived gastric origin SRCC (GPM-2), gastric-origin SRCCs (HSC-39 and KATO-3), human pancreatic (MIA PaCa-2) and ovarian (SKOV-3) cells for evaluating their therapeutic effects. Moreover, these treatments were applied in 3D-cultured organoids to reveal the feasibility of these approaches for in vivo study. RESULTS: Analyzing their antioxidant capabilities and dose-response curves, we observed that all four gastric cell lines, including three patient-derived cell lines were sensitive to ascorbate (~ 10 mM). The influence of ascorbate incubation time was studied, with a 16-h incubation found to be optimal for in vitro studies. Moreover, a simultaneous combination of AA and LA (AA&LA) did not significantly inhibit cell proliferation, while prior LA treatment increased the growth inhibition of AA therapy (LA + AA). Anti-cancer efficacy of AA was further confirmed in 3D-cultured SRCC (KATO-3) organoids. CONCLUSIONS: This study highlights the potential of AA and LA + AA in treating gastric origin SRCC, and demonstrates the influence of order in which the drugs are administered.

CRS + HIPEC combined with IP + IV chemotherapy for gastric signet-ring cell carcinoma: Case report of long-term survival.

RATIONALE: Signet ring cell carcinoma of the stomach is prone to relapse and metastasis after traditional surgical treatment, and the prognosis is also poor. We improved the concept of treatment and conducted cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) combined with intraperitoneal (IP) and intravenous (IV) chemotherapy for a gastric signet-cell carcinoma patient. PATIENT CONCERNS: A 65-year-old male patient with complaint of intermittent hematemesis for over 10 days was referred to our hospital for treatment. The patient developed hematemesis of 800 mL without obvious causes on May 27, 2015, accompanied by dizziness and amaurosis fugax. After the bleeding was stopped with medicinal treatment, diagnostic gastroscopy revealed an ulcer at the less curvature of the stomach, with biopsy pathology diagnosis as severe atypical hyperplasia, which was confirmed to be poorly differentiated adenocarcinoma by a second biopsy. In past medical history, the patient had 5 coronary stents implanted because of coronary atherosclerotic heart disease 3 years ago. DIAGNOSIS: Gastric cancer (cT4NxMx) according to the patient's history and biopsy pathology. INTERVENTIONS: the patient was treated surgery-based multidisciplinary treatments integrating CRS + HIPEC and IP + IV adjuvant chemotherapy. The CRS was curative distal gastrectomy with D2 lymphadenectomy, and HIPEC was cisplatin 120 mg plus mitomycin C 30 mg at 43 °C, for 60 minutes. Final pathological diagnosis of after surgery was: poorly differentiate adenocarcinoma with signet-ring cells, with invasion beyond the serosal layer and into the duodenum, 10/23 lymph nodes positive, nerve invasion, vascular tumor thrombi, Borrmann type IV, Lauren type diffuse. TNM stage was pT4aN3M0, IIIC. After operation, the patient received 6 courses of IV chemotherapy with oxaliplatin and 5-fluorouracil/Tegafur Gimeracil Oteracil Potassium capsules, and IP chemotherapy with docetaxel and carboplatin. OUTCOMES: Regular follow-up till July 20, 2020, revealed that the patient has a disease-free survival of over 61+ months. LESSONS: CRS + HIPEC combined with IP + IV chemotherapy achieved long-term disease-free survival for this patient with gastric signet-ring cell carcinoma and deserve further study. This new treatment modality deserves appropriate consideration in routine clinical practice for patients with advanced gastric cancer.

Impact of adjuvant chemotherapy on outcomes in appendiceal cancer.

BACKGROUND: The impact of using adjuvant chemotherapy following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with appendiceal adenocarcinoma is not known. The aim of this study was to assess the impact of adjuvant chemotherapy following complete cytoreduction in patients with appendiceal adenocarcinoma. METHODS: Retrospective medical record review of all patients with appendiceal adenocarcinoma treated at our institution between 2006 and 2015. Kaplan-Meier plots were used to summarize overall survival (OS) and relapse-free survival over time, and log-rank tests and Cox proportional hazards models were used to test for differences in survival between groups. RESULTS: A total of 103 patients with appendiceal adenocarcinoma received care at our institution during the study period. Complete cytoreduction (cytoreductive score 0-1) was achieved in 68 patients (66%). Of these 68 patients, 26 received adjuvant chemotherapy. The most common regimens were capecitabine (n = 11), capecitabine plus oxaliplatin (n = 7), and 5-FU plus oxaliplatin (n = 6). Tumor histopathology and grade, and the ability to achieve complete cytoreduction were significant predictors of overall survival. The median OS for non-low-grade and well-differentiated tumor patients who received adjuvant chemotherapy following complete cytoreduction was 9.03 years, compared to 2.88 years for patients who did not receive adjuvant chemotherapy (P = .02). Among low-grade and well-differentiated tumor patients who underwent complete cytoreduction, there was no statistically significant difference in OS between those who received adjuvant chemotherapy and those who did not. CONCLUSION: Adjuvant chemotherapy seems to have benefit in appendiceal cancer patients with non-low-grade or well-differentiated tumor type but not in low-grade or well-differentiated tumors.

Nuclear PRMT1 expression is associated with poor prognosis and chemosensitivity in gastric cancer patients.

BACKGROUND: Metastatic and refractory gastric cancer (GC) are associated with a poor prognosis; therefore, the identification of prognostic factors and chemosensitivity markers is extremely important. Protein arginine methyltransferase 1 (PRMT1) may play a role in chemosensitivity/apoptosis induction via activation of the tumor suppressor forkhead box O1 (FOXO1). The purpose of this study was to clarify the expression of and relationship between PRMT1 and FOXO1 to evaluate the applicability of PRMT1 as a prognostic marker and a therapeutic tool in GC. METHODS: We investigated the clinical and functional significance of PRMT1 and FOXO1 in 195 clinical GC samples using immunohistochemistry. We performed suppression analysis of PRMT1 using small interfering RNA to determine the biological roles of PRMT1 in chemosensitivity. RESULTS: PRMT1 and FOXO1 in GC samples were predominantly expressed in the nucleus. Patients with lower PRMT1 expression (n = 131) had suppressed nuclear accumulation of FOXO1, higher recurrence after adjuvant chemotherapy, and poorer prognosis than those with higher PRMT1 expression (n = 64). PRMT1 downregulation in GC cells by RNA interference inhibited cisplatin and 5-fluorouracil sensitivity. The expression of phosphorylated FOXO1 and phosphorylated BCL-2 antagonist of cell death was upregulated in PRMT1 small interfering RNA groups. CONCLUSION: Our data suggest that the evaluation of PRMT1 expression in GC is a useful predictor of poor prognosis and recurrence after adjuvant chemotherapy. Moreover, these data suggest that PRMT1 is a promising therapeutic tool for overcoming refractory GC.

T4 stage and preoperative anemia as prognostic factors for the patients with colon cancer treated with adjuvant FOLFOX chemotherapy.

BACKGROUND: FOLFOX-based adjuvant chemotherapy is a benefit for high-risk stage II and stage III colon cancer after curative resection. But, the prognostic factor or predictive marker for the efficacy of FOLFOX remains unclear. This study was aimed to identify the prognostic value and cumulative impact of adjuvant FOLFOX on the stage II and III colon cancer patients. METHODS: A total of 196 stage II and III colon cancer patients were retrospectively enrolled in prospectively collected data. They underwent curative resection followed by FOLFOX4 adjuvant chemotherapy. The oncological outcomes included the 5-year disease-free survival (DFS) rate and 5-year overall survival (OS) rate. Cox-regression analysis was performed to identify the prognostic value, and its cumulative impact was analyzed. RESULTS: The 5-year DFS rate of the patients was 71.94% and the 5-year OS rate was 81.5%. The prognostic values for the 5-year DFS rate and 5-year OS rate were T4 stage and preoperative anemia in a multivariate analysis. Each patient group who had no prognostic value, single, or both factors revealed 95.35%, 69.06%, and 28.57% in the 5-year DFS rate, respectively (p < 0.0001). The 5-year OS rate also showed the significant differences in each group who had no prognostic value, single, or both factors revealed 100%, 79.3%, and 45.92%, respectively (p < 0.0001). CONCLUSION: Our results showed similar efficacy to MOSAIC study in stage II and stage III colon cancer patients treated with adjuvant FOLFOX chemotherapy after curative resection. Patients who had T4 stage and/or preoperative anemia showed worse prognosis than patients without any prognostic value. These findings suggest that FOLFOX could not be effective in the patients with T4 stage colon cancer accompanied by preoperative anemia.

Adjuvant radiotherapy for gastric carcinoma: 10 years follow-up of 244 cases from a single institution.

BACKGROUND: Postoperative chemoradiotherapy (CRT) of gastric carcinoma improves survival among high- risk patients. This study was undertaken to analyse long-term survival probability and the impact of certain covariates on the survival outcome in affected individuals. MATERIALS AND METHODS: Between January 2000 and December 2005, 244 patients with gastric cancer underwent adjuvant radiotherapy (RT) in our institution. Data were retrieved retrospectively from patient files and analysed with SPSS version 21.0. RESULTS: A total of 244 cases, with a male to female ratio of 2.2:1, were enrolled in the study. The median age of the patients was 52 years (range, 20-78 years). Surgical margin status was positive or close in 72 (33%) out of 220 patients. Postoperative adjuvant RT dose was 46 Gy. Median follow-up was 99 months (range, 79-132 months) and 23 months (range, 2-155 months) for surviving patients and all patients, respectively. Actuarial overall survival (OS) probability for 1-, 3-, 5- and 10-year was 79%, 37%, 24% and 16%, respectively. Actuarial progression free survival (PFS) probability was 69%, 34%, 23% and 16% in the same consecutive order. AJCC Stage I-II disease, subtotal gastrectomy and adjuvant CRT were significantly associated with improved OS and PFS in multivariate analyses. Surgical margin status or lymph node dissection type were not prognostic for survival. CONCLUSIONS: Postoperative CRT should be considered for all patients with high risk of recurrence after gastrectomy. Beside well-known prognostic factors such as stage, lymph node status and concurrent chemotherapy, the type of gastrectomy was an important prognostic factor in our series. With our findings we add to the discussion on the definition of required surgical margin for subtotal gastrectomy. We consider that our observations in gastric cancer patients in our clinic can be useful in the future randomised trials to point the way to improved outcomes.

Impact of aggressive histology and location of primary tumor on the efficacy of surgical therapy for peritoneal carcinomatosis of colorectal origin.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) for peritoneal carcinomatosis (PC) of colorectal origin increases survival (OS) compared to systemic chemotherapy alone. Signet ring histology demonstrates aggressive behavior with poor survival. We sought to determine whether CRS/HIPEC increases survival in this subset of patients. METHODS: We reviewed 67 patients with PC of appendiceal (AP, n = 37) or colorectal origin (CRC, n = 30) with signet cell histology from a prospective database between May 2001 and August 2011. Survival analysis and multivariate Cox regression were used to determine prognostic factors for survival. RESULTS: Complete CRS (CC-0/1) was achieved in 77 % (CRC) and 73 % (AP) of patients. Progression-free survival (PFS) and OS were 9 and 12 months in CRC and 12 and 21 months in AP patients. In the CRC group, univariate predictors of poor survival included female gender, age, American Society of Anesthesiologists score, preoperative albumin, completeness of cytoreduction, and morbidity. In a multivariate Cox regression model, incomplete cytoreduction (CC-2/3) and female gender were joint significant predictors of poor survival. In the AP group, significant univariate predictors of poor survival included higher EBL and PCI score. In a multivariate Cox regression model, blood loss of >500 ml and a body mass index of <25 kg/m(2) were joint significant predictors of poor survival. CONCLUSIONS: AP signet cell tumors demonstrate a more favorable outcome than CRC signet cell tumors after CRC/HIPEC for carcinomatosis, suggesting an underlying difference in biology. CRS/HIPEC does not confer survival benefit in colorectal signet ring carcinomatosis unless complete cytoreduction can be achieved, whereas appendiceal signet ring carcinomatosis may benefit, regardless of resectability.

[Impact of clinicopathological features and extent of lymph node dissection on the prognosis in early gastric cancer patients].

OBJECTIVE: To explore the impact of clinicopathological features and extent of lymph node dissection on the prognosis in early gastric cancer (EGC) patients. METHODS: A total of 142 EGC cases screened from database of gastric cancer of Sun Yat-sen University, from Aug. 1994 to Jan. 2010, were included in this study. According to the lymph node metastasis status, they were divided into lymph node negative (n = 116) and lymph node positive (n = 26) groups. The clinicopathological features of the two groups and the impact of extent of lymph node dissection on the prognosis were analyzed. RESULTS: There were no significant differences in age, gender, tumor size and location, Borrmann typing, WHO TNM staging, histological typing, and CEA value between the two groups (P > 0.05). The TNM stages in the lymph node positive group were higher than that in the lymph node negative group (P < 0.001). Between the cases who underwent D1 (n = 21) and D2 (n = 121) dissection, there were no significant differences in postoperative hospital days, blood transfusion volume, and operation time (P > 0.05). The median numbers of LN dissected in D1 and D2 cases were 4 (0 to 16) and 20 (12 to 30), with a significant difference (P = 0.000), but the number of positive LN without significant difference (P = 0.502). The postoperative complication rates were 9.5% in the D1 and 3.3% in the D2 dissection groups, without a significant difference (P = 0.128). The median survival time of the lymph node negative and positive groups was 156 vs. 96 months (P = 0.010). In cases who received D2 and D1 lymph node dissection, the median survival time (MST) was 156 vs. 96 months (P = 0.0022). In the lymph node positive group, D2 dissection prolonged survival time significantly than D1 dissection (96 vs. 27months) (P = 0.001). Cox regression analysis showed that the extent of lymph node dissection and LN metastasis were independent prognostic factors for EGC patients. CONCLUSIONS: It is not able to accurately assess the LN metastasis status preoperatively according to the routine clinicopathological features. For the patients with unknown LN metastasis status, D2 dissection should be the first choice. Comparing with D1 dissection, the morbidity of D2 dissection are not increased, but survival time is prolonged.

Phase II/III multicentre randomised controlled trial evaluating a strategy of primary surgery and adjuvant chemotherapy versus peri-operative chemotherapy for resectable gastric signet ring cell adenocarcinomas - PRODIGE 19 - FFCD1103 - ADCI002.

BACKGROUND: A dramatic increase in the incidence of the diffuse form of gastric adenocarcinomas and particularly signet ring cell carcinomas has been observed in Western countries. Evidence is accruing that signet ring cell carcinomas may have inherent chemo resistance leaving many clinicians unsure of the benefits of delaying surgery to pursue a neoadjuvant approach. METHODS/DESIGN: PRODIGE-19-FFCD1103-ADCI002 is a prospective multicentre controlled randomised phase II/III trial comparing current standard of care of perioperative chemotherapy (2x3 cycles of Epirubicin, cisplatin, 5-fluorouracil) with a strategy of primary surgery followed by adjuvant chemotherapy (6 cycles of Epirubicin, cisplatin, 5-fluorouracil) in patients with a stage IB-III gastric signet ring cell tumour. The principal objective of the phase II study (84 patients) is to determine if the experimental arm (primary surgery followed by adjuvant chemotherapy) has sufficient interest in terms of percentage of living patients at 24 months to be evaluated in a phase III trial. If 7 or less patients in the experimental arm are alive at 24 months, phase III will not be initiated. The primary objective of phase III (230 additional patients) is to demonstrate superiority of the experimental arm in terms of overall survival. Secondary endpoints include overall survival at 36 months, disease free survival at 24 and 36 months, R0 resection rates, treatment tolerance, postoperative mortality and morbidity evaluated by Clavien-Dindo severity index, the prognostic impact of positive peritoneal cytology and the assessment of quality of life. An ancillary study will assess the emotional and cognitive impact of surgery and perioperative chemotherapy for both the patient and their partner. DISCUSSION: As inherent chemo resistance of signet ring cell tumours and delay in definitive surgery may favour tumour progression we hypothesise that a policy of primary surgery followed by adjuvant chemotherapy will improve overall survival compared to a standard perioperative chemotherapeutic strategy. This randomised phase II/III trial is the first dedicated to this histological subtype. Whilst the development of new biomarkers and targeted therapies are awaited, the results of this trial should further help in devising individualised protocols of patient care in a tumour group whose diversity increasingly demands assessment of alternative strategies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01717924.

Phase II study on safety and efficacy of Yadanzi® (Javanica oil emulsion injection) combined with chemotherapy for patients with gastric cancer.

OBJECTIVE: To investigate the efficacy and safety of Yadanzi® (Javanica oil emulsion injection) combined with chemotherapy for treatment of patients with advanced gastric cancer. METHODS: From January 2011 to December 2012, we recruited 75 patients with advanced gastric cancer, who received javanica oil emulsion injection together with chemotherapy. After two cycles of treatment, efficacy and safety of the combined therapies were evaluated. RESULTS: Overall response rate of 75 patients after treatment was 85.3% (CR+PR+SD). Treatment related side effects were recorded. No treatment related death occurred. CONCLUSIONS: Javanica oil emulsion injection combined with chemotherapy could be considered as a safe and effective regimen in treating patients with advanced gastric cancer. Further randomized clinical trials should be conducted to confirm whether the addition of Yadanzi® to chemotheraphy could be associated with reduced toxicity, enhanced tolerability and improved quality of life for patients with advanced gastric cancer.

Expression of pyruvate dehydrogenase kinase-1 in gastric cancer as a potential therapeutic target.

In contrast to mitochondria in healthy cells, which utilize oxidative phosphorylation, malignant cells undergo elevated glycolysis for energy production using glucose. The objectives of this study were to evaluate whether the expression of various molecules, including pyruvate dehydrogenase kinase-1 (PDK-1), is involved in the altered glucose metabolism associated with gastric cancer prognosis and to assess the role of a therapeutic agent in targeting glucose metabolism in gastric cancer. Immunohistochemistry was performed on gastric cancer tissues obtained from 152 patients who underwent curative resection to assess the expression of hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (GLUT-1), hexokinase-2 (HK-2) and PDK-1. In an in vitro analysis, the lactate production and glucose uptake levels, cellular viability and 5-fluorouracil (5-FU) responses were evaluated before and after treatment with dichloroacetate (DCA), a PDK-1 inhibitor, in the MKN45 and AGS gastric cancer cell lines and in the non-cancerous HEK293 cell line. GLUT-1 and PDK-1 expression was significantly associated with tumor progression, although only PDK-1 expression was an independent prognostic factor for patients who received 5-FU adjuvant treatment. There was no significant difference in cell viability between the HEK293 and gastric cancer cell lines following DCA treatment. However, DCA treatment reduced lactate production and increased responsiveness to 5-FU in MKN45 cells, which expressed high levels of PDK-1 in comparison to the other cell lines. Thus, PDK-1 may serve as a biomarker of poor prognosis in patients with gastric cancer. In addition, PDK-1 inhibitors such as DCA may be considered an additional treatment option for patients with PDK-1-expressing gastric cancers.

Metastatic lymph node targeted chemosensitivity test for gastric cancer.

BACKGROUND: The objective of this study was to compare the chemosensitivity of primary tumor and metastasized lymph node from patient with gastric adenocarcinoma. MATERIALS AND METHODS: We studied 26 gastric cancer patients with lymph node metastasis who underwent gastric resection at the Korea University Guro Hospital from Feb 2007 to July 2008. The chemosensitivity of primary tumor and metastatic lymph node were studied using an adenosine triphosphate-based chemotherapy response assay (ATP-CRA). RESULTS: The concordance rate of the ATP-CRA test was 30.8% (8/26). The concordance rate between primary tumor and metastatic N2 group lymph node was only 9.1% (1/11). The metastatic tumor inhibition rates with 5-fluorouracil, cisplatin, doxorubicin, and oxaliplatin were higher than the inhibition rates for primary tumor. Tumor inhibition rates was significantly different between primary tumor and metastatic tumor after doxorubicin treatment (27.734±20.95 versus 38.403±26.87, P=0.021). We detected simple correlations of tumor inhibition rates between primary and metastatic tumors with cisplatin (r=0.661, P<0.001) and doxorubicin (r=0.475, P=0.031). CONCLUSIONS: We observed differences between first choice chemotherapeutic agents based on ATPCRA tests of primary tumor and metastatic tumor in lymph node. Therefore, chemotherapeutic agents should be carefully selected for adjuvant chemotherapy using a chemosensitivity test.

A case of signet ring carcinoma of the appendix: dilemmas in differential diagnosis and management.

PURPOSE: Signet ring carcinoma (SRC) of the appendix consists one of the most biologically virulent cancers. We present the case of a patient with primary SRC complicated by the development of acute inflammation of the appendix. CASE REPORT: A 78-year-old man was admitted due to a 5-day history of increasing colicky abdominal pain and vomiting. Clinical examination revealed a firm, tender mass in the right ileac fossa. Laparotomy confirmed a tumor mass which appeared to originate from the appendix. The affected part of the bowel was resected and a right hemicolectomy with an end-to-side ileotransverse anastomosis was performed. The appendix was notably thickened with an ulcerated wall containing sinus tracts, chronic inflammation, and scarring. Moreover, a focus of SRC was detected. CONCLUSIONS: Appendiceal SRC is a rare entity, which may sometimes be confused with other pathologies providing difficulties in differential diagnosis, having an impact on therapeutic decisions and affecting prognosis.

[Impact of adjuvant chemotherapy duration on 3-year disease-free survival of colorectal carcinoma patients after radical resection].

BACKGROUND AND OBJECTIVE: Adjuvant chemotherapy has become a standard postoperative treatment for stage III and high risk stage II colorectal carcinoma patients. However, only a few patients can finish 6-month adjuvant chemotherapy. This study was to find out whether the duration of adjuvant chemotherapy would affect the 3-year disease-free survival. METHODS: Clinical data of 276 colorectal carcinoma patients, receiving at least two cycles of adjuvant chemotherapy including xeloda, 5-fluorouracil/calcium folinate (5-FU/CF) or Tegafur with or without oxaliplatin after radical operation in Sun Yat-sen University Cancer Center from April, 2003 to December, 2007, were analyzed for the impact of adjuvant chemotherapy duration on the 3-year disease-free survival. RESULTS: Of the 276 patients, 216 received chemotherapy including oxaliplatin, 60 received xeloda, 5-FU/CF or tegafur as adjuvant chemotherapy. Of the 216 patients, only 49 finished the 6-month adjuvant chemotherapy. Both univariate and multivariate analyses showed that chemotherapy duration (P=0.032), sex (P=0.001), N stage (P=0.002), and pathologic differentiation (P=0.043) were independent prognosis factors for 3-year disease-free survival. CONCLUSION: Duration of adjuvant chemotherapy is an independent prognosis factor for 3-year disease-free survival of colorectal carcinoma patients.

[FOLFOX regimen in the patients with locally advanced or metastatic gastric cancer].

OBJECTIVE: The aim of this study is to investigate the efficiency and toxicity of the FOLFOX regimen, the combination of oxaliplatin (L-OHP), 5-fluorouracil (5-Fu) and calcium folinate (CF), for patients with locally advanced or metastatic gastric cancer. METHODS: Ninety-six patients with locally advanced or metastatic gastric adenocarcinoma, including 72 males and 24 females, were treated with FOLFOX regimen: L-OHP 85 mg/m(2) iv in 2 hours on D1, CF 200 mg/m(2) iv in 2 hours on D1 and D2, 5-Fu 400 mg/m(2) iv on D1 and D2, and then continuous infusion of it at a dose of 600 mg/m(2) for 44 hours. This regimen was repeated every 2 weeks. The first evaluation was done after four cycles. The median cycle of the chemotherapy was 6 (range: 1 to 12 cycles). RESULTS: Of the 96 patients with gastric cancers, 21 underwent R0 resection and afterward received adjuvant FOLFOX chemotherapy. Ten of those were still alive, while the other 11 died of the disease, with a median disease free survival time of 24.0 months and 3-year survival rate of 51.8%. The other 75 received only palliative chemotherapy due to non-operable advanced disease. Thirty of those achieved partial response (PR), the other 20 had a stable disease (SD), but the remaining 25 experienced disease progression (PD), with an overall response rate of 40.0%. The median TTP and overall survival in those 75 patients was 5.9 and 12.0 months, respectively. All 96 patients were evaluable for toxicity according to NCI criteria. The patients of grade 3 vomiting and neural toxicity were 6 and 4, respectively. CONCLUSION: In terms of efficacy and safety, the FOLFOX regimen is effective and well tolerable for patients with locally advanced or metastatic gastric cancers either as adjuvant or palliative chemotherapy.

The management of gastric adenocarcinoma with postoperative chemoirradiation. A non-randomized comparison of oral UFT and 5-FU.

AIMS AND BACKGROUND: We assessed the therapeutic results and tolerability of postoperative chemoradiotherapy with either oral UFT or 5-fluorouracil for carcinoma of the stomach. METHODS AND STUDY DESIGN: Forty-six patients treated with chemoradiotherapy following total or subtotal gastrectomy for gastric carcinoma formed the cohort evaluated. The group included 39 males and 7 females whose ages ranged from 21 to 74 years (median, 53 years). In all patients, surgical therapy was the initial approach with a curative intent. The types of operations performed were total gastrectomy in 11 or subtotal gastrectomy in 35 patients. Radiotherapy began from 14 to 161 days after surgery (median, 55 days). Twenty patients received concomitant oral UFT (200 mg/m2), and 26 patients were given 5-fluorouracil (425 mg/m2, iv bolus) concurrently with irradiation consisting of one or two cycles, usually as a 3-day bolus at the start and last 3 days of irradiation therapy for radiosensitizing purposes. The patients were treated using either cobalt-60 or 6 MV photons, and irradiation doses delivered to the tumor bed and regional lymphatics ranged from 40 to 50 Gy (median, 46 Gy). RESULTS: Median follow-up for the entire group was 24 months (range, 2-67). The 2-year overall survival of the entire group of patients was 64%. The 2-year overall survival rates for 5-fluorouracil and oral UFT groups were 72% and 66%, respectively (P = 0.3). Treatment-related factors were reviewed to identify any impact on survival. Analyses included type of surgery and dissection, fraction size, the total dose of irradiation and the type of chemotherapy. A significant detrimental effect in survival in the patients treated with D2 dissection compared to the patients treated with D1 dissection was noted (P = 0.01). Overall grade II-III toxicity of oral UFT was significantly lower than 5-FU (4 patients vs 14 patients, P = 0.03). CONCLUSIONS: Concomitant use of oral UFT with radiation seems to be more tolerable and an equally effective regimen in the treatment of locally advanced gastric cancer compared with 5-fluorouracil. D2 dissection was found to have detrimental effects on survival in this cohort.

Treatment of metastatic urachal carcinoma in an elderly woman.

BACKGROUND: A 67-year-old woman with a history of smoking presented with abdominal pain and hematuria. On physical examination, she had a palpable pelvic mass. Imaging revealed a large pelvic mass situated on the dome of the bladder, extending from the urachus, without evidence of other sites of metastases. After resection, urachal adenocarcinoma was histologically confirmed. No adjuvant therapy was administered. Repeat imaging obtained 3 months after resection revealed a large left pelvic mass consistent with recurrence. INVESTIGATIONS: Physical examination, pelvic and complete lymph-node examination, laboratory tests, urine analysis, CT scan of the abdomen and pelvis, chest X-ray, bone scan, cystoscopy, histologic examination of tumor morphology, and MRI of the abdomen and pelvis. DIAGNOSIS: Metastatic urachal adenocarcinoma. MANAGEMENT: Surgical excision combined with cystectomy and pelvic lympadenectomy, chemotherapy with 5-fluorouracil, leucovorin, and irinotecan.

Aberrant methylation of p16 predicts candidates for 5-fluorouracil-based adjuvant therapy in gastric cancer patients.

BACKGROUND: Aberrant methylation of some cancer-related genes has been reported to correlate with sensitivity to chemotherapeutic agents. The present study was designed to determine whether DNA methylation in six cancer-related genes affects recurrence of gastric cancer in patients who received 5-fluorouracil-based adjuvant chemotherapy. METHODS: The methylation status of six genes, MGMT, CHFR, hMLH1, p16INK4a, E-cadherin, and Runx3, was analyzed in 56 surgically resected gastric cancer tissue specimens by methylation-specific polymerase chain reaction. Of the 56 patients who underwent surgical resection, 38 received 5-fluorouracil (5-FU)-based adjuvant chemotherapy postoperatively (adjuvant group), whereas the other 18 (32%) did not (surgery group). RESULTS: There were no significant differences between the two groups with respect to sex, cancer differentiation, depth of tumor invasion, lymph node metastasis, lymphatic invasion, vascular invasion and tumor stage. Among the genes, methylation of p16INK4a showed a significant correlation with longer survival in the 38 patients of the adjuvant group, but not in the 18 patients of the surgery group. A multivariate analysis identified p16INK4a methylation to be an independent factor predicting a longer recurrence-free period under 5-FU-based adjuvant chemotherapy. CONCLUSIONS: The present study demonstrated for the first time that gastric cancer patients with p16INK4a methylation specifically benefit from 5-FU-based adjuvant chemotherapy.

Hyperthermic intraperitoneal chemoperfusion is an option for treatment of peritoneal carcinomatosis in children.

BACKGROUND: Gastrointestinal carcinomas in childhood are rare and frequently present at an advanced stage. Besides lymphatic and distant organ metastasis, peritoneal carcinomatosis may be detected and has a poor prognosis. In addition to surgery and intravenous chemotherapy, hyperthermic intraperitoneal chemoperfusion (HIPEC) may be an option for selected patients. Our aim was to demonstrate the feasibility of the method and to discuss possible indications. METHODS: After treating a series of adult patients, HIPEC for peritoneal carcinomatosis from a signet cell carcinoma of the colon was performed intraoperatively in a 12-year-old boy. We gave mitomycin C at a dose of 30 mg/m2 over 90 minutes at maximum temperature of 41.2 degrees C. We performed intraoperative drug level monitoring and daily postoperative liver and kidney function tests and differential blood counts. RESULTS: Hyperthermic intraperitoneal chemoperfusion was performed according to protocol without complications. Perfusate and venous drug levels were similar to those in an adult case. The patient had an uneventful recovery, and serum chemistry and blood count returned to normal after a week. The boy lived for 36 months after initial presentation. Sixteen months after HIPEC, still with excellent quality of life, an elevated carcinoembryonic antigen (CEA) indicated recurrence. Thirty months after HIPEC, he died of progressive recurrent disease. CONCLUSIONS: Hyperthermic intraperitoneal chemoperfusion as performed in adults may be beneficial to children with peritoneal carcinomatosis and merits further study.