Most total pancreatectomies for ductal adenocarcinoma potentially can Be replaced by whipple over the splenic artery: a before and after study.

INTRODUCTION: Recently, more and more total pancreatectomy (TP) has been performed for central-located pancreatic ductal cell adenocarcinoma (PDCA) which abuts or involves both gastroduodenal and splenic arteries and demands transaction of both of them for a complete resection. Spiked by Warshaw's procedure (spleen-preserving distal pancreatectomy with excision of splenic vessels), we developed a new procedure "Whipple over the splenic artery (WOTSA)" to replace TP by leftward extension of pancreatic parenchyma transaction line and preservation of pancreatic tail and spleen after excision of splenic artery. This uncontrolled before and after study assesses the safety and efficacy of a new technique "Whipple over the splenic artery (WOTSA)" as a treatment for PDAC which traditionally requires total pancreatectomy (TP) for a complete excision. METHODS: The study group comprised 40 consecutive patients who underwent WOTSA for PDAC between August 2019 and September 2022. Their clinicopathological characteristics and survival were compared with those of a historical control group comprising 30 consecutive patients who underwent TP between January 2016 and July 2019. RESULTS: None of the 40 patients in the WOTSA group required reoperation due to infarction of the pancreas and/or spleen remnant. DM medication after WOTSA were none in 19, oral hypoglycemic agents in 19, and insulin preparations in 2 patients. Compared with TP, patients who underwent WOTSA exhibited similar rates of major operative complications, clear pancreatic parenchyma transaction margin, and number of harvested positive lymph nodes, but higher rate of adjuvant chemotherapy completion and a trend toward better median disease free survival (14 vs. 7.5 mo, P=0.023). CONCLUSIONS: Compared to TP, WOTSA can be safely performed and have much better postoperative glycemic status without cost of higher operative risk or impaired surgical radicality. These findings indicate that most TPs for PDAC potentially can be replaced by WOTSAs.

Ramucirumab plus triplet chemotherapy as an alternative salvage treatment for patients with metastatic colorectal cancer.

BACKGROUND: Ramucirumab is indicated for salvage treatment after failure of first-line treatment for metastatic colorectal cancer (mCRC). However, the application of ramucirumab at later-line treatment in real-world practice has not received much discussion. METHODS: In this retrospective study, we enrolled 70 patients with mCRC who received ramucirumab plus chemotherapy at National Taiwan University Hospital between 2018 and 2019. RESULTS: Compared with those who received third- or later-line ramucirumab treatment, patients who received second-line ramucirumab treatment had significantly longer median time to treatment discontinuation (mTTD; 6.7 vs 3.6 months, P = .004) and median overall survival (mOS; not reached vs 7.6 months, P = .009). Multivariate analyses revealed that second-line ramucirumab and triplet chemotherapy backbone were the only independent predictive factors for long mTTD and mOS. Patients who received ramucirumab with triplet chemotherapy had a significantly longer mOS than did patients who received ramucirumab with doublet chemotherapy (not reached vs 5.6 months, P = .002). Among those receiving second-line ramucirumab treatment, combination with triplet chemotherapy led to a longer mTTD than did combination with doublet chemotherapy, but the difference was non-significant (not reached vs 4.4 months, P = .108). By contrast, in patients receiving fourth- or later-line ramucirumab, combination with triplet chemotherapy led to significantly longer mTTD than did combination with doublet chemotherapy (8.0 vs 2.9 months, P = .032). CONCLUSION: Ramucirumab plus triplet chemotherapy may be an alternative regimen in patients with mCRC, particularly as a later-line treatment modality.

Proteasome inhibitors restore the STAT1 pathway and enhance the expression of MHC class I on human colon cancer cells.

BACKGROUND: A new strategy, particularly a novel combination, for immunotherapy in microsatellite stable metastatic colorectal cancer (mCRC) treatment needs to be formulated. Studies on the interferon-γ (IFN-γ)/ Janus kinase (JAK)/ signal transducer and activator of transcription (STAT)1 pathway provide new directions in this regard. METHODS: Our study applies three colon cancer cell lines, including microsatellite stable (MSS) cell lines, which are SW480 and SW620, and microsatellite instability-high (MSI-H) cell line, which is DLD-1. We compared the expressions of immune surface markers on colon cancer cells in response to IFN-γ. We elucidated these mechanisms, which involved the upregulation of immune surface markers. Furthermore, we examined real-world clinical samples using the PerkinElmer Opal multiplex system and NanoString analysis. RESULTS: We established that the baseline expression of major histocompatibility complex (MHC) class I alleles and programmed death-ligand 1 (PD-L1) were generally low in cell line models. The immune surface markers were significantly increased after IFN-γ stimulation on SW480 but were notably unresponsive on the SW620 cell line. We discovered that STAT1 and phosphorylated STAT1 (pSTAT1) were downregulated in the SW620 cell line. We verified that the STAT1/pSTAT1 could be restored through the application of proteasome inhibitors, especially bortezomib. The expression of MHC class I as downstream signals of STAT1 was also up-regulated by proteasome inhibitors. The similar results were reproduced in DLD-1 cell line, which was also initially unresponsive to IFN-γ. In real-world samples of patients with mCRC, we found that higher STAT1 expression in tumor cells was strongly indicative of a highly immunogenic microenvironment, with significantly higher expression levels of MHC class I and PD-L1, not only on tumor cells but also on non-tumor cells. Furthermore, tumor infiltrating lymphocytes (TILs) were increased in the positive-STAT1 group. Through NanoString analysis, we confirmed that the mRNA expressions of IFN-γ, human leukocyte antigen (HLA)-A, HLA-E, and HLA-G were also significantly higher in the positive-STAT1 group than those in the negative-STAT1 group. CONCLUSION: Our study provides a novel rationale for the addition of bortezomib, a proteasome inhibitor, into new immunotherapy combinations.

Chemotherapy agents stimulate dendritic cells against human colon cancer cells through upregulation of the transporter associated with antigen processing.

Single immunotherapy fails to demonstrate efficacy in patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Research on immune reactions before and after systemic agents for mCRC is warranted. Our study examined cell line models to compare the expression of immune surface markers on colon cancer cells before and after chemotherapy agents. We also elucidated mechanisms underlying the effects of chemotherapy agents on immune surface markers. We used real-world clinical samples with NanoString analysis and the Perkin-Elmer Opal multiplex system. We established that chemotherapy agents, particularly 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan, stimulated the expression of stimulatory MHC class I alleles through stimulation the pathway of transporters associated with antigen processing 1 and 2 (TAP1 and TAP2) in cell line models. Application of infected cell protein 47 (ICP-47), a specific inhibitor of the TAP1/TAP2, significantly inhibited expression of TAP1/TAP2 and also inhibited the expression of the downstream MHC class I. In the functional assay, SN-38 significantly promoted the phagocytosis of colon cancer cells by monocyte-derived dendritic cells (MoDCs). We confirmed that the expression of major histocompatibility complex (MHC) class I, significantly increased after first-line chemotherapy and targeted therapy in the samples of real-world patients with de novo mCRC. Our study provides new insights for novel immunotherapy combinations.

Exploring the roles of interaction and flow in explaining nurses' e-learning acceptance.

BACKGROUND: To provide safe and competent patient care, it is very important that medical institutions should provide nurses with continuing education by using appropriate learning methods. As compared to traditional learning, electronic learning (e-learning) is a more flexible method for nurses' in-service learning. Hence, e-learning is expected to play a pivotal role in providing continuing education for nurses. OBJECTIVES: This study's purpose was to explore the role and relevance of interaction factors, intrinsic motivator (i.e., flow), and extrinsic motivators (i.e., perceived usefulness (PU) and perceived ease of use (PEOU)) in explaining nurses' intention to use the e-learning system. DESIGN: Based on the technology acceptance model (TAM) with the flow theory, this study's research model presents three types of interaction factors, learner-system interaction, instructor-learner interaction, and learner-learner interaction to construct an extended TAM to explore nurses' intention to use the e-learning system. SETTINGS: Sample data were gathered from nurses at two regional hospitals in Taiwan. PARTICIPANTS: A total of 320 questionnaires were distributed, 254 (79.375%) questionnaires were returned. Consequently, 218 usable questionnaires were analyzed in this study, with a usable response rate of 68.125%. METHODS: First, confirmatory factor analysis was used to develop the measurement model. Second, to explore the causal relationships among all constructs, the structural model for the research model was tested by using structural equation modeling. RESULTS: First, learner-system interaction, instructor-learner interaction, and learner-learner interaction respectively had significant effects on PU, PEOU, and flow. Next, flow had significant effects on PU and PEOU, and PEOU had a significant effect on PU. Finally, the effects of flow, PU, and PEOU on intention to use were significant. CONCLUSIONS: Synthetically speaking, learner-system interaction, instructor-learner interaction, and learner-learner interaction can indirectly make significant impacts on nurses' usage intention of the e-learning system via their extrinsic motivators (i.e., PU and PEOU) and intrinsic motivator (i.e., flow).

The effects of information systems quality on nurses' acceptance of the electronic learning system.

BACKGROUND: To ensure the quality of healthcare provision, nurses must continuously enhance their professional knowledge and competencies via continuing education. As compared with traditional learning, electronic learning (e-learning) is a more flexible method for nurses' in-service learning. Hence, e-learning is expected to play a key role in providing continuing education for nurses. PURPOSE: The main purpose of this study was to examine whether system quality, information quality, service quality, and user-interface design quality as the antecedents to nurse beliefs can affect nurses' intention to use the e-learning system. METHODS: A cross-sectional design was used to investigate the effects of information systems quality on nurses' acceptance of the e-learning system. This study gathered sample data from nurses at 3 hospitals in Taiwan. A total of 450 questionnaires were distributed, and 320 effective questionnaires were analyzed in this study, indicating an effective response rate of 71.1%. Collected data were analyzed using structural equation modeling. RESULTS: System quality, information quality, and user-interface design quality had significant effects on perceived usefulness (PU), perceived ease of use (PEOU), and perceived enjoyment (PE), and service quality had significant effects on PU and PEOU. Moreover, PEOU had significant effects on PU and PE, and the effects of PU, PEOU, and PE on intention to use were significant. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: User-interface design quality is the most key antecedent that can make significant impacts on nurses' PU and PE, and more efforts should be made to develop a friendlier user interface via designing useful and enjoyable features to induce nurses to use the e-learning system. Moreover, system quality can make the greatest impact on nurses' PEOU; thus, medical institutions should effectively enhance system quality to deliver benefits and pleasure to boost nurses' usage intention of the e-learning system via reducing the complexity.

Association between color doppler vascularity index, angiogenesis-related molecules, and clinical outcomes in gastric cancer.

PURPOSE: This study was conducted to evaluate the correlation between color Doppler vascularity index (CDVI), clinical outcomes and five angiogenesis-related molecules including vascular endothelial growth factor (VEGF), placenta growth factor (PlGF), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and calreticulin (CRT) in gastric cancer, and to develop an effective model selected from these five molecules to predict patient survival. PATIENTS AND METHODS: CDVI could be obtained preoperatively by transabdominal ultrasound from 30 patients. Enzyme immunoassay was adopted to determine protein level of VEGF and PlGF, and immunohistochemistry was used to detect COX-2, iNOS and CRT expression. Correlation between CDVI and five individual molecules was assessed. Multiple molecules model was developed using classification and regression tree (CART) analysis from five molecules, and was tested for patient survival in another 45 patients. RESULTS: CDVI was significantly correlated with patient survival (P = 0.00907) and absolute number of metastatic lymph nodes (P = 0.01). There was no significant association between CDVI and any individual molecule. The model, developed by CART consisting of VEGF and PlGF, could differentiate high and low CDVI and survival in testing group (P = 0.00257). CONCLUSIONS: CDVI was associated with lymph node metastasis, combined VEGF and PlGF expression status and patient survival in gastric cancer.

Expression of eukaryotic initiation factor 4E in gastric adenocarcinoma and its association with clinical outcome.

BACKGROUND AND OBJECTIVES: Overexpression of eIF4E can result in oncogenic transformation and uncontrolled growth of mammalian cells, presumably by facilitating the expression of growth-control gene products, which are normally translationally repressed. Overexpression of eIF4E was present in human breast carcinoma and human head and neck squamous cell carcinoma, and may be of prognostic value in breast carcinomas. In order to elucidate the clinical significance of eIF4E expression, this study was conducted to quantify expression of eIF4E in human gastric cancer tissue and correlate them with clinicopathological factors and patient survival. METHODS: Specimens from sixty-nine patients with gastric adenocarcinoma were analyzed and eIF4E overexpression was quantified by Western blot analysis. Quantification of eIF4E levels in cancer was expressed relative to controls from non-tumorous mucosa of the same patients. Confirmation of eIF4E overexpression at the cellular level was performed using immunohistochemical staining. The association of clinicopathologic factors and survival with eIF4E expression was analyzed. RESULTS: In non-tumorous parts of specimens, overexpression of eIF4E was always present in gastric glands but not in gastric pits lining mucosa, and it was also expressed in the areas of intestinal metaplasia and dysplasia. In the 69 specimens, the mean eIF4E expression was 5.77 +/- 8.55-fold (mean +/- standard deviation), ranged from from 0.1-fold to 38-fold. The degree of eIF4E expression appeared to be independent of invasion depth of tumor, lymph node metastasis, Lauren classification, Borrmann types, and Helicobacter pylori infection. Marked overexpression of eIF4E (more than seven-fold) was correlated with tumor vascular invasion (P = 0.046, Fisher exact-test). The survival rate of the patients with underexpression or mild overexpression of eIF4E (less than sevenfold) was significantly higher than that with marked eIF4E overexpression (more than sevenfold) (P = 0.01734, log rank test). CONCLUSIONS: Marked eIF4E overexpression in gastric cancer was found to be associated with vascular invasion. The prognosis for gastric cancer patients with marked overexpression of eIF4E was worse than those with underexpression. It may serve as an additional prognostic and therapeutic factor in gastric cancer, and deserves further investigation.

High-frequency microsatellite instability predicts better chemosensitivity to high-dose 5-fluorouracil plus leucovorin chemotherapy for stage IV sporadic colorectal cancer after palliative bowel resection.

The influence of MSI on treatment outcome of colorectal cancers remains unclear and deserves further investigation. We recruited 244 patients with stage IV sporadic colorectal cancers for our study, based on appropriate eligibility criteria. Patients were nonrandomly allocated to 2 treatment groups of either with or without high-dose 5-FU plus leucovorin chemotherapy (HDFL, 5-FU 2,600 mg/m(2) leucovorin 300 mg/m(2) maximum 500 mg). Each treatment group was further divided into 2 subgroups according to high-frequency MSI (MSI-H) status. MSI-H was defined as the appearance of MSI in at least 2 of the 5 examined chromosomal loci (BAT-25, BAT-26, D5S346, D2S123, D17S250). We compared clinicopathologic parameters, p53 overexpression and overall survival between the groups. In addition, 4 subgroups were identified as follows: MSI-H(+)HDFL(+), n = 35; MSI-H(-)HDFL(+), n = 134; MSI-H(+)HDFL(-), n = 17; MSI-H(-)HDFL(-), n = 58. There was no significant difference of background clinicopathologic data between the HDFL(+) and HDFL(-) treatment groups (p > 0.05). Survival analyses indicated that the patients of subgroup MSI-H(+)HDFL(+) survived significantly longer than those of subgroup MSI-H(-)HDFL(+), with median survival times of 24 (95% CI 20.2-27.9) and 13 (95% CI 11.6-14.4) months, respectively (p = 0.0001, log-rank test). In contrast, in patients without chemotherapy, the prognosis was poor irrespective of MSI status, with median survival times of 7.0 (95% CI 4.6-9.4) and 7.0 (95% CI 6.1-7.9) months in the MSI-H(+)HDFL(-) and MSI-H(-)HDFL(-) subgroups, respectively (p = 0.8205, log-rank test). MSI-H cancers responded significantly better to HDFL (p = 0.001), with a mean response rate of 65.71% (95% CI 49.98-81.44%) in subgroup MSI-H(+)HDFL(+) compared to 35.07% (95% CI 26.99-43.15%) in subgroup MSI-H(-)HDFL(+). There appeared to be no preferential metastatic site where response to HDFL can be predicted based on the MSI status of the primary tumor. Toxicity to HDFL was similarly minimal between MSI-H(+) and MSI-H(-) patients (p > 0.05). Multivariate analysis of all patients further indicated that MSI-H and chemotherapy were independent favorable prognostic parameters (p < 0.05). Thus, the better prognosis of stage IV sporadic colorectal cancers with MSI-H may be associated with better chemosensitivity, rather than lower aggressiveness in biologic behavior.

Association of overexpressed proline-directed protein kinase F(A) with chemoresistance, invasion, and recurrence in patients with bladder carcinoma.

BACKGROUND: It has been shown previously that proline-directed protein kinase F(A) (PDPK F(A)) is overexpressed in various human malignancies compared with its expression in normal controls, and the suppression of overexpressed PDPK F(A) is capable of inhibiting the growth of various types of human carcinoma cells, suggesting a role for this PDPK in human malignancies. In this report, the authors combine immunohistologic, molecular, cellular, and clinicopathologic studies to demonstrate further an essential critical role for overexpressed PDPK F(A) in bladder carcinoma invasion, chemoresistance, and poor prognosis. METHODS: The expression and localization of PDPK F(A) were analyzed by the immunohistochemical staining of specimens obtained from patients with primary transitional cell carcinoma (TCC) of the bladder. The stable antisense clones of human bladder carcinoma cells with specific suppression of overexpressed PDPK F(A) were established for invasion and chemosensitivity studies. RESULTS: The immunohistochemical study revealed that PDPK F(A) was overexpressed preferentially in the invasive bladder carcinoma tissues. It was found that the stable antisense clones with specific suppression of overexpressed PDPK F(A) to approximately 40% of the parental control level were capable of inhibiting the invasive activity and simultaneously enhancing the chemosensitivity of bladder carcinoma cells to various therapeutic drugs, such as vinblastine, vincristine, paclitaxel, and bleomycin. Clinicopathologic studies also revealed a correlation between overexpressed PDPK F(A) and disease recurrence/survival in patients with primary TCC (P < 0.05). CONCLUSIONS: Taken together, the results demonstrate an essential critical role of overexpressed PDPK F(A) in invasion, chemoresistance, and poor prognosis. Suppression of overexpressed PDPK F(A) may provide a new potential target for therapeutic intervention aimed at preventing chemoresistance, disease progression, and recurrence in patients with bladder carcinoma.

Association of color Doppler vascularity index and microvessel density with survival in patients with gastric cancer.

OBJECTIVE: The purpose of this study was to investigate the clinical usefulness of microvessel density (MVD) and an in vivo angiogenesis parameter, color Doppler vascularity index (CDVI), in patients with gastric cancer. SUMMARY BACKGROUND DATA: Many studies have reported a significant association between the degree of MVD-evaluated angiogenesis with the clinicopathologic factors and prognosis of patients with various solid tumors. All these studies were accomplished on tissue sections retrospectively obtained from surgical specimens. However, an in vivo method to assess tumor angiogenesis for human malignancies is highly desirable for diagnostic purpose, treatment planning, and follow-up. The CDVI is a new ultrasound parameter for evaluating in vivo angiogenesis, has a good correlation with status of lymph node metastasis in cervical carcinoma, and can predict distant metastasis and survival in colon cancer patients. Therefore, the CDVI may also be useful to assess in vivo angiogenesis in human gastric cancer. METHODS: A total of 79 patients with gastric cancer were enrolled in this study, and microvessel density was evaluated by using immunohistochemical staining of surgical specimens with anti-CD-34 antibody. Tumors were sonographically visible in 31 patients. The CDVI of each tumor was determined using transabdominal color Doppler ultrasound. The CDVI was defined as the ratio of the number of the colored pixels within a tumor section to the number of total pixels in that specific tumor section, and was calculated by using Encomate software (Electronic Business Machine Co. Ltd., Taipei, Taiwan). Correlation between MVD, CDVI and clinicopathologic factors and patient survival was studied. RESULTS: The MVD was significantly correlated with vascular invasion by multiple linear regression analysis. Although the survival of patients with high MVD (> 32) was significantly worse than those with low MVD (< 32) by univariate analysis, vascular invasion was an independent prognostic factor by Cox proportional hazard model. There was a linear correlation between CDVI and MVD (r =.495, P =.005). Moreover, in patients with a high CDVI (> 11%), the survival rate was significantly lower than that in those with low CDVI (< or = 11%, P =.005). None of the patients with high CDVI (> 11%) survived 2 years after curative resection. In addition to vascular invasion, the CDVI was another independent prognostic factor in the patients with stage III gastric cancer. CONCLUSIONS: Vascular invasion was an important prognostic indicator in gastric cancer. The high CDVI was a good preoperative indicator of early death in stage III gastric cancer patients. Thus, the CDVI may be helpful in selecting patients with gastric cancer for neoadjuvant chemotherapy and/or anti-angiogenic therapy.

Prospective evaluation of laparoscopy-assisted colectomy versus laparotomy with resection for management of complex polyps of the sigmoid colon.

Laparoscopy-assisted colectomy is technically feasible, but objective evidence of its benefits remains scarce. This study was done to evaluate the outcomes and operative stress of laparoscopy-assisted colectomy versus the traditional open method in the management of sigmoid complex polyps that cannot be safely or adequately removed by colonofibroscopy. Between January 1997 and December 1999, a total of 42 patients were equally randomized to the laparoscopy group and the laparotomy group by the blocked randomization method. Three patients randomized to the laparoscopy group did not complete the trial; therefore 18 patients treated by laparoscopy-assisted sigmoidectomy and the other 21 treated by the open method were prospectively evaluated. These two groups of patients were well matched in age, gender, symptoms, tumor location, localization method, tumor size, morphology, histopathology, and the accuracy of the clinical diagnosis. Two standardized surgical strategies, the lateral-to-medial and medial-to-lateral dissection sequences, were performed in 14 and 4 patients of the laparoscopy group, respectively, according to whether their tumors were located above or below 20 cm above the anal verge. After evaluating the surgical outcomes, we found that the laparoscopy group was significantly better than the laparotomy group in regard to parameters that included severity of postoperative pain, wound size, postoperative complication rate, and the duration of postoperative ileus, hospitalization, and disability. There was no significant difference in the operating times for these two groups. However, the costs of the laparoscopy group were significantly higher. To evaluate the surgical stress, we measured the serum C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), total lymphocyte count, and CD4+/CD8+ ratio 24 hours before and after surgery. We found that the postoperative serum CRP level and the ESR were significantly less elevated and the total lymphocyte counts and CD4+/CD8+ ratio were significantly less depressed in the laparoscopy group than in the laparotomy group. We thus concluded that laparoscopy-assisted sigmoidectomy can be safely performed with shorter convalescence and less operative stress but at a higher cost. We strongly recommended the use of this technique in the management of sigmoid complex polyps if the patient's economic status permits.

P53 overexpression predicts poor chemosensitivity to high-dose 5-fluorouracil plus leucovorin chemotherapy for stage IV colorectal cancers after palliative bowel resection.

Our study aims to further clarify the prognostic significance of p53 overexpression in stage IV colorectal cancer. Between January 1994 and June 1997, we recruited 144 patients with stage IV colorectal cancers for our study, based on appropriate eligibility criteria. The patients were nonrandomly allocated to 2 treatment groups of either with or without high-dose 5-fluorouracil plus leucovorin chemotherapy (HDFL: 5-Fu: 2,600 mg/m(2) leucovorin 300 mg/m maximum 500 mg). Each treatment group was further divided into 2 subgroups according to the status of p53 overexpression. Therefore, 4 subgroups were allocated in our study and were designated as p53 (overexpression) HDFL (+), n = 65; p53 (normal) HDFL (+), n = 37; p53 (overexpression) HDFL (-), n = 27; and p53 (normal) HDFL (-), n = 15, respectively. All patients were prospectively followed until April 2001. There was no significant difference of the background clinicopathologic data of these 4 allocated subgroups of patients (p > 0.05). Multivariate analysis of various clinicopathologic factors of the whole group of patients indicated that age > or = 60 years, poor differentiation, mucin production, CEA > 100 ng/ml, p53 overexpression and without chemotherapy were the significant independent poor prognostic factors (p < 0.05). Survival analyses indicated that the patients of subgroup p53 (normal) HDFL (+) survived significantly longer than those of subgroup p53 (overexpression) HDFL (+), with mean survival time (95% confidence interval [CI]) of 20.24 (16.24-24.25) and 13.29 (10.98-15.60) months, respectively (p = 0.0043, log-rank test). In contrast, in patients without chemotherapy, the prognosis was poor regardless of their p53 status, with mean survival time (95% CI) of 6.85 (5.47-8.23) and 5.87 (4.48-7.26) months in p53 (overexpression) HDFL (-) and p53 (normal) HDFL (-) subgroups of patients, respectively (p = 0.2820, log-rank test). Cancers of normal p53 expression responded significantly better to HDFL (p < 0.05), with mean response rate (95% CI) being 65.57% (52.18-82.96%) in subgroup p53 (normal) HDFL (+) as compared to 35.38% (23.52-47.24%) in subgroup p53 (overexpression) HDFL (+). The toxicity to HDFL was similarly minimal between p53-normal and p53-overexpression patients (p > 0.05). We thus concluded that the poorer prognosis of stage IV colorectal cancers with p53 overexpression was associated with their poorer chemosensitivity rather than the more biologic aggressiveness.