Metachronous Signet Ring Cell Bladder Metastasis as First Sing of Cancer Recurrence.

We describe the case of a 74-year-old woman with previous history of gastric signet cell carcinoma who develops bladder metastasis as first sign of recurrence 6 years later. Bladder metastasis due to signet cell carcinoma is extremely rare with only 19 cases reported. Treatment includes radical cystectomy or chemotherapy.

P.R.O.P.S. - A novel Pre-Operative Predictive Score for unresectability in patients with colorectal peritoneal metastases being considered for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

BACKGROUND: Twenty to thirty percent of planned cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) procedures are abandoned intra-operatively. Pre-operative factors associated with unresectability identified previously were used to develop a Pre-Operative Predictive Score (PROPS), which was compared with current selection criteria-Peritoneal Surface Disease Severity Score (PSDSS), Verwaal's Prognostic Score (PS) and Colorectal Peritoneal Metastases Prognostic Surgical Score (COMPASS), to determine which score provides the best prediction for unresectability. METHODS: Fifty-six patients with peritoneal metastases of colorectal origin were included. Beta-coefficient values of significant variables (p < 0.05) were determined from multivariate analysis to develop PROPS. PROPS, PSDSS, PS and COMPASS were compared using a receiver operating characteristic curve to calculate its accuracy, sensitivity and specificity. RESULTS: PROPS consisted of nine patient and tumour factors which were categorised into three groups: (i) poor tumour biology: previous inadequate resection, underwent multiple lines of chemotherapy and poorly differentiated or signet cell histology; (ii) heavy tumour burden: abdominal distension, palpable abdominal mass and computed tomography findings of ascites, small bowel disease and/or omental thickening; and (iii) active tumour proliferation: elevated tumour markers. Overall, PROPS achieved 86% accuracy with 100% sensitivity and 68% specificity, PSDSS achieved 85% accuracy with 100% sensitivity and 63% specificity, PS achieved 73% accuracy with 100% sensitivity and 68% specificity and COMPASS achieved 61% accuracy with 27% sensitivity and 100% specificity. CONCLUSIONS: PROPS is more effective in predicting unresectability as compared to PSDSS, PS and COMPASS, and has the added advantage of using solely pre-operative factors.

Does Primary Tumor Side Matter in Patients with Metastatic Colon Cancer Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy?

BACKGROUND: Primary tumor location has been shown to be prognostic of overall survival (OS) in patients with both locally advanced and metastatic colorectal cancer. The impact of sidedness on prognosis has not been evaluated in the setting of peritoneal-only metastases treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A retrospective review of prospectively maintained databases of patients with peritoneal surface malignancy undergoing CRS/HIPEC from three high-volume centers was performed. RESULTS: A total of 115 patients with metastatic colon cancer to the peritoneum who underwent CRS/HIPEC with mitomycin C were identified. Fifty-one patients (45%) had left-sided primary tumors, and 64 (55%) had right-sided primary tumors. Patients with right-sided tumors were more likely to be older (median age 56 vs. 49 years, p = 0.007) and to have signet ring cell histology (17% vs. 4%, p = 0.026). Patients with right-sided tumors had median disease-free survival (DFS) and OS of 14 months (95% confidence interval [CI] 10.5-17.5) and 36 months (95% CI 27.4-44.6), respectively, versus 16 months (95% CI 11.0-21.0) and 69 months (95% CI 24.3-113.7) for those patients with left-sided tumors. On multivariate analysis, primary tumor side was an independent predictor of both DFS and OS. CONCLUSIONS: In this study, there was a dramatic, clinically significant difference in OS between patients with right- and left-sided tumors, and primary tumor side was an independent predictor of DFS and OS. Primary tumor side should be considered in patient selection for CRS with or without HIPEC.

Preoperative Nomogram to Risk Stratify Patients for the Benefit of Trimodality Therapy in Esophageal Adenocarcinoma.

PURPOSE: To develop a nomogram that estimates 1-year recurrence-free survival (RFS) after trimodality therapy for esophageal adenocarcinoma and to assess the overall survival (OS) benefit of esophagectomy after chemoradiotherapy (CRT) on the basis of 1-year recurrence risk. METHODS: In total, 568 consecutive patients with potentially resectable esophageal adenocarcinoma who underwent CRT were included for analysis, including 373 patients who underwent esophagectomy after CRT (trimodality therapy), and 195 who did not undergo surgery (bimodality therapy). A nomogram for 1-year RFS was created using a Cox regression model. The upper tertile of the nomogram score was used to stratify patients in low-risk and high-risk groups for 1-year recurrence. The 5-year OS was compared between trimodality and bimodality therapy in low-risk and high-risk patients after propensity score matching, respectively. RESULTS: Median follow-up for the entire cohort was 62 months. The 5-year OS in the trimodality and bimodality treatment groups was 56.3% (95% confidence interval [CI] 47.9-64.7) and 36.9% (95% CI 31.4-42.4), respectively. The final nomogram for the prediction of 1-year RFS included male gender, poor histologic grade, signet ring cell adenocarcinoma, cN1, cN2-3, and baseline SUVmax, with accurate calibration and reasonable discrimination (C-statistic: 0.66). Trimodality therapy was associated with improved 5-year OS in low-risk patients (p = 0.003), whereas it showed no significant survival benefit in high-risk patients (p = 0.302). CONCLUSIONS: The proposed nomogram estimates early recurrence risk. The addition of surgery to CRT provides a clear OS benefit in low-risk patients. The OS benefit of surgery in high-risk patients is less pronounced.

External Validation of the Prognostic Nomogram (COMPASS) for Patients with Peritoneal Carcinomatosis of Colorectal Cancer.

BACKGROUND: To optimize outcome, selection of patients for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is critical. Recently, Simkens et al.7 evaluated the peritoneal surface disease severity score (PSDSS) and suggested a new prognostic nomogram, the colorectal peritoneal metastases prognostic surgical score (COMPASS) based on age, peritoneal carcinomatosis index score, locoregional lymph node status, and signet ring cell histology. This COMPASS nomogram had better discriminative ability according to the Harrell c-index than PSDSS (c = 0.72 vs. 0.62). This study aimed to validate the COMPASS nomogram externally. METHODS: Data were retrieved from a prospectively maintained database, and all patients who underwent surgery between May 2005 and May 2016 were included in the study. For each patient, the PSDSS and COMPASS were calculated and then divided into subgroups. The discriminative ability of both scores for overall survival were quantified using Harrell c indices. RESULTS: A total of 153 patients underwent CRS + HIPEC for peritoneal carcinomatosis (PC) of colorectal cancer. The median overall survival (OS) was 46 months, and the mean PSDSS was 7.8 ± 3.7. When the PSDSS was divided into subgroups, the c index was 0.67. The mean COMPASS was 55.5 ± 25.6. When the patients were divided into four groups according to cutpoints of Simkens et al.7 a c index of 0.72 was obtained, showing its significant superiority over the discriminative ability of the PSDSS (p = 0.016). CONCLUSION: External validation of the COMPASS confirms its moderate to good discriminative ability and its superiority over the PSDSS. Nevertheless, discrimination with the COMPASS score remains suboptimal, and further research on prognostic variables is essential for optimal patient selection.

Development of a Prognostic Nomogram for Patients with Peritoneally Metastasized Colorectal Cancer Treated with Cytoreductive Surgery and HIPEC.

BACKGROUND: With the introduction of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), long-term survival can be achieved in selected patients with colorectal peritoneal metastases (PM). Patient selection and outcome may be improved significantly with a tool that adequately predicts survival in these patients. This study was designed to validate the peritoneal surface disease severity score (PSDSS) in patients with colorectal PM treated with CRS + HIPEC. If performance of the PSDSS was suboptimal (c < 0.7), we aimed to develop a new prognostic model. METHODS: Patients were included if they had colorectal PM and underwent CRS + HIPEC with intended complete cytoreduction in a Dutch tertiary hospital between 2007 and 2015. Statistical analyses were performed with R-software. RESULTS: A total of 200 patients underwent CRS + HIPEC. External validation of the PSDSS showed a Harrell's c statistic of 0.62. After analysis, four parameters appeared prognostically relevant factors for overall survival: age, PCI score, locoregional lymph node status, and signet ring cell histology. The weighted relevance of these parameters was turned into a prognostic nomogram that we termed colorectal peritoneal metastases prognostic surgical score (COMPASS). The COMPASS differentiated well and showed a Harrell's c statistic of 0.72 with a calibration plot showing good agreement. CONCLUSIONS: This study externally validated the PSDSS and developed a new prognostic score, the COMPASS. This pre-cytoreduction nomogram was more accurate than PSDSS in predicting survival of patients undergoing CRS + HIPEC. It can be used as tool to assist in the decision about continuing cytoreduction and HIPEC and can provide valuable information in the follow-up period after CRS + HIPEC.

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.

Systemic chemotherapy (SC) before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in patients with peritoneal mucinous carcinomatosis of appendiceal origin (PMCA).

BACKGROUND: The role of SC before CRS/HIPEC for patients with PMCA is unclear. This study explores the effect of SC prior to CRS/HIPEC on overall survival (OS) in patients with PMCA. METHODS: 72 patients with recently diagnosed PMCA who underwent CRS/HIPEC were identified from a prospective database. Thirty patients had SC before CRS/HIPEC (Group 1) and 42 did not (Group 2). Patients who were referred to our center after multiple lines of SC were excluded from this analysis. OS was estimated. RESULTS: Median follow-up was 3.2 years. Groups were similar regarding lymph node positivity, postoperative SC and rate of complete cytoreduction. Twenty-four (80%) patients in Group 1 and 21 (50%) in Group 2 had high grade histology (HG) (p = 0.01). OS from CRS/HIPEC at 1, 2, and 3 years was 93, 68, 51% in Group 1 and 82, 64, 60% in Group 2, respectively (p = 0.74). Among HG patients 3-year survival was 36% in the SC group vs. 35% in the group without SC (p = 0.67). The 3-year OS for patients with low grade (LG) tumors was 100% in the SC group vs. 79% in the group with no prior SC (p = 0.26). Among patients with signet ring cell (SRC) histology, 1, 2 and 3-year survival was 94, 67 and 22% in the SC group vs. 43, 14, 14% in the group with no SC, respectively (p = 0.028). There were only 6 patients with LG PMCA who received prior SC. CONCLUSIONS: Preoperative SC could improve the prognosis of patients with high-grade PMCA with SRC histology.

Poor outcome after cytoreductive surgery and HIPEC for colorectal peritoneal carcinomatosis with signet ring cell histology.

BACKGROUND: Signet ring cell cancer (SRCC) patients have a poor oncologic outcome. The aim of this study was to determine whether the potential drawbacks of hyperthermic intraperitoneal chemotherapy (HIPEC) outweigh the benefits in patients with peritoneally metastasized SRCC. METHODS: Patients with peritoneal carcinomatosis (PC) of colorectal origin referred to two tertiary centers between April 2005 and December 2013 were identified and retrospectively analyzed. Data were compared between SRCC histology and other differentiations. RESULTS: Three-hundred-fifty-one patients were referred for CRS+HIPEC among which 20 (5.7%) patients were identified with SRCC histology. CRS + HIPEC was performed in 16 of these 20 (80%) and 252 out of the 331 remaining patients (76.1%). A higher proportion of patients in the SRCC-group were diagnosed with N2 stage (62.5% vs. 36.1%, P=0.04). A macroscopic complete resection was achieved in 87.5% and 97.2% respectively (P=0.04). Median survival was 14.1 months compared to 35.1 months (P<0.01). Recurrence occurred in 68.8% of the SRCC patients and in 43.7% of the other histology patients (P=0.05). CONCLUSION: Patients with SRCC and PC treated with CRS+HIPEC have a poor median survival only slightly reaching over 1 year. In the presence of other relative contraindications, SRCC histology should refrain a surgeon from performing CRS and HIPEC.

Adjuvant chemoradiation with 5-fluorouracil/leucovorin versus S-1 in gastric cancer patients following D2 lymph node dissection surgery: a feasibility study.

PURPOSE: We retrospectively analyzed the feasibility and adverse events for two regimens, postoperative chemoradiation (CRT) with 5-fluorouracil/leucovorin (5-FU/LV) compared to S-1 in D2-resected gastric cancer patients. PATIENTS AND METHODS: The study included 405 gastric cancer patients who underwent curative gastrectomy with D2 lymph node dissection and received adjuvant therapy between January 2008 and July 2009. Feasibility and adverse events for the CRT and S-1 regimens were analyzed. RESULTS: Out of the 405 patients, 244 (60.2%) had CRT and 161 (39.8%) had S-1 treatment. The regimen was selected based on the preferences of the physician and the patient. S-1 was more frequently administered to patients with older age (age≥70) and those with early-stage disease (stage II). The stage was significantly more advanced in the CRT group compared to the S-1 group (S-1 vs. CRT: stage II, 59.6% vs. 36.1%; stage III/IV, 28.0% vs. 48.3%, respectively; p<0.001). The completion rate of the planned therapy was significantly higher in the CRT group than in the S-1 group (95.1% vs. 72.8%, respectively; p<0.001). Regarding severe adverse events (grade 3-4), neutropenia (CRT vs. S-1; 40.2% vs. 8.7%, respectively, p<0.001), nausea (CRT vs. S-1; 5.7% vs. 0%, respectively; p=0.002) and stomatitis (CRT vs. S-1; 7.4% vs. 2.5%, respectively; p=0.034) were significantly more frequent in the CRT cohort compared to the S-1 group. CONCLUSION: Both adjuvant CRT with 5-FU/LV and adjuvant S-1 are safe and feasible in D2-resected gastric cancer patients. Patients with old age or early stage disease tend to prefer S-1 therapy to chemoradiation.

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.

Metachronous, colitis-associated rectal cancer that developed after sporadic adenocarcinoma in an adenoma in a patient with longstanding Crohn's disease: a case report.

BACKGROUND: Colorectal cancer associated with Crohn's disease (CD) is increasing in proportion to the number of patients with CD in Japan. There are two subtypes of colorectal cancer with CD: sporadic cancer and colitis-associated cancer. Early diagnosis of colitis-associated cancer is sometimes difficult; when colorectal cancer is found in patients with CD, both colitis-associated cancer and sporadic cancer should be kept in mind. Here, we describe a case of metachronous, colitis-associated rectal cancer that developed after the complete resection of an adenoma that became a sporadic adenocarcinoma in a patient with longstanding CD. To the best of our knowledge, this is the first report of colitis-associated cancer in a patient with CD after removal of a sporadic cancer. CASE PRESENTATION: We describe a 51-year old man with CD who had difficulty in defecation. A rectal polyp was detected and a transanal resection of the polyp was performed. A histopathological examination showed an adenoma with sporadic adenocarcinoma. After three years, a follow-up colonoscopy revealed a reddish, elevated lesion in the patient's rectum. A colonoscopic biopsy showed a signet ring cell carcinoma. We performed an abdominoperineal resection of the rectum and a bilateral pelvic lymph node dissection. A histopathological examination revealed a mucinous adenocarcinoma with signet ring cell carcinoma and lymph node metastasis. The patient received adjuvant chemotherapy with oral uracil 224 mg combined with tegafur 100 mg plus leucovorin. No signs of recurrence were noted at a follow-up 18 months after the third surgery and 60 months after the second surgery.

Cytoreduction and HIPEC in the Netherlands: nationwide long-term outcome following the Dutch protocol.

PURPOSE: This nationwide study evaluated results of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastasis of colorectal origin in the Netherlands following a national protocol. METHODS: In a multi-institutional study prospective databases of patients with peritoneal carcinomatosis (PC) from colorectal cancer and pseudomyxoma peritonei (PMP) treated according to the Dutch HIPEC protocol, a uniform approach for the CRS and HIPEC treatment, were reviewed. Primary end point was overall survival and secondary end points were surgical outcome and progression-free survival. RESULTS: Nine-hundred sixty patients were included; 660 patients (69 %) were affected by PC of colorectal carcinoma and the remaining suffered from PMP (31 %). In 767 procedures (80 %), macroscopic complete cytoreduction was achieved. Three-hundred and thirty one patients had grade III-V complications (34 %). Thirty-two patients died perioperatively (3 %). Median length of hospital stay was 16 days (range 0-166 days). Median follow-up period was 41 months (95 % confidence interval (CI), 36-46 months). Median progression-free survival was 15 months (95 % CI 13-17 months) for CRC patients and 53 months (95 % CI 40-66 months) for PMP patients. Overall median survival was 33 (95 % CI 28-38 months) months for CRC patients and 130 months (95 % CI 98-162 months) for PMP patients. Three- and five-year survival rates were 46 and 31 % respectively in case of CRC patients and 77 and 65 % respectively in case of PMP patients. CONCLUSIONS: The results underline the safety and efficacy of cytoreduction and HIPEC for PC from CRC and PMP. It is assumed the uniform Dutch HIPEC protocol was beneficial.

Extensive cytoreductive surgery for appendiceal carcinomatosis: morbidity, mortality, and survival.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) are frequently used to treat appendiceal carcinomatosis. Some patients require multivisceral resection because of the volume of disease. It is unclear whether extent of CRS impacts survival in appendiceal carcinomatosis. METHODS: We analyzed 282 patients undergoing attempted CRS/HIPEC for appendiceal carcinomatosis. Patients were defined as having undergone Extensive CRS (n = 60) if they had >3 organ resections or >2 anastomoses; a subgroup of Extreme CRS patients (n = 10) had ≥5 organ resections and ≥3 anastomoses. Kaplan-Meier survival curves and multivariate Cox-regression models were used to identify prognostic factors affecting outcomes. RESULTS: Relative to the comparison group, patients undergoing Extensive CRS had a higher median peritoneal carcinomatosis index, operative duration, blood loss, and length of stay. No difference in completeness of cytoreduction, severe morbidity, or 60-day mortality was evident. Subgroup analysis of 10 patients undergoing extreme CRS likewise revealed no increase in severe morbidity or mortality. Median progression-free (PFS) and overall survival (OS) were 23.5 and 74 months in the comparison group; 18.5 (p = 0.086) and 51 (p = 0.85) months in the Extensive CRS group; and 40 months and not reached in the Extreme CRS subgroup. In a multivariable analysis, extent of CRS was not independently associated with PFS or OS. CONCLUSIONS: Extensive CRS is associated with greater OR time, blood loss, and length of stay, but is not associated with higher morbidity, mortality, or inferior oncologic outcomes in patients with appendiceal carcinomatosis.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial.

BACKGROUND: This randomized phase III study was to evaluate the efficacy and safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal carcinomatosis (PC) from gastric cancer. METHODS: Sixty-eight gastric PC patients were randomized into CRS alone (n = 34) or CRS + HIPEC (n = 34) receiving cisplatin 120 mg and mitomycin C 30 mg each in 6000 ml of normal saline at 43 ± 0.5°C for 60-90 min. The primary end point was overall survival, and the secondary end points were safety profiles. RESULTS: Major clinicopathological characteristics were balanced between the 2 groups. The PC index was 2-36 (median 15) in the CRS + HIPEC and 3-23 (median 15) in the CRS groups (P = 0.489). The completeness of CRS score (CC 0-1) was 58.8% (20 of 34) in the CRS and 58.8% (20 of 34) in the CRS + HIPEC groups (P = 1.000). At a median follow-up of 32 months (7.5-83.5 months), death occurred in 33 of 34 (97.1%) cases in the CRS group and 29 of 34 (85.3%) cases of the CRS + HIPEC group. The median survival was 6.5 months (95% confidence interval 4.8-8.2 months) in CRS and 11.0 months (95% confidence interval 10.0-11.9 months) in the CRS + HIPEC groups (P = 0.046). Four patients (11.7%) in the CRS group and 5 (14.7%) patients in the CRS + HIPEC group developed serious adverse events (P = 0.839). Multivariate analysis found CRS + HIPEC, synchronous PC, CC 0-1, systemic chemotherapy ≥ 6 cycles, and no serious adverse events were independent predictors for better survival. CONCLUSIONS: For synchronous gastric PC, CRS + HIPEC with mitomycin C 30 mg and cisplatin 120 mg may improve survival with acceptable morbidity.

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.

Significance of occult neoplastic cells on tumor metastasis: a case report of gastric cancer.

BACKGROUND: Occult neoplastic cells (ONCs) are the tumor cells floating in the lymph node sinuses, distant from the primary tumor, and supposed to be one of most reliable marker of prognosis. METHODS: We report here the case of a 52-year-old woman with a gastric cancer associated by numerous ONCs. RESULTS: Postoperative examination of the stomach disclosed an advanced, poorly differentiated adenocarcinoma with frequent lymph node metastases. In addition to ONCs and occasional micrometastases, focal aggregates of ONCs, one of the possible intermediate lesions between the ONCs and the usual metastases, are also observed. CONCLUSIONS: In the present case, at least some of ONCs seem to form the microaggregates of tumor cells in lymph nodes, anchor in the sinuses, and grow up to the large tumorous lesion. Even if most of the ONCs were trapped and disappeared under the influence of tumor immunity, the detection of ONCs could be one of the reliable clues to estimate the prognosis.

[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.

Critical analysis of 33 patients with peritoneal carcinomatosis secondary to colorectal and appendiceal signet ring cell carcinoma.

BACKGROUND: Primary signet-ring cell carcinoma (SRC) of colorectal and appendiceal origin is a rare entity with an aggressive biology and clinical behavior. The majority of patients develop peritoneal carcinomatosis (PC) early in the disease. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may potentially improve survival. METHODS: An observational study of 33 patients with SRC of colorectal or appendiceal origin was identified through a retrospective review of two peritoneal surface malignancy databases between January 1997 and December 2008. Survival analysis was performed using the Kaplan-Meier method. RESULTS: Thirty-three patients (18 women (55%); mean age at diagnosis of carcinomatosis, 49 (standard deviation = 12) years) were identified to have SRC, with 15 cases of colorectal and 18 of appendiceal origin. For patients with colonic SRC who underwent complete CRS and HIPEC versus systemic chemotherapy only, the median survival was 13 and 18 months (P = 0.75). For patients with appendiceal SRC who underwent complete CRS and HIPEC versus systemic chemotherapy only, the median survival was 27 and 15 months (P = 0.12). CONCLUSIONS: There seems to be less survival benefits after a complete CRS and HIPEC as a curative treatment for PC from colorectal SRC compared with that for non-SRC colorectal adenocarcinoma. However, in patients with appendiceal SRC, long-term survival is a reality after treatment.

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.