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1.
J Clin Med ; 12(22)2023 Nov 15.
Article in English | MEDLINE | ID: mdl-38002734

ABSTRACT

(1) Background: Colorectal cancer (CRC) is a global health concern, particularly among the elderly population. This study aimed to assess the impact of laparoscopic surgery on CRC patients aged ≥80 years. (2) Methods: We conducted a retrospective analysis of prospectively collected data from consecutive CRC patients who underwent surgery at our institution between July 2018 and July 2023. The patients were categorized into three groups: those aged over 80 who underwent laparoscopic surgery (Group A), those aged over 80 who underwent open surgery (Group B), and those under 80 who underwent laparoscopic surgery (Group C). We examined various clinical and surgical parameters, including demographic data, medical history, surgical outcomes, and survival. (3) Results: Group A (N = 113) had shorter hospital stays than Group B (N = 23; p = 0.042), with no significant differences in complications or 30-day outcomes. Compared to Group C (N = 269), Group A had higher comorbidity indices (p < 0.001), more emergency admissions, anemia, low hemoglobin levels, colonic obstruction (p < 0.001), longer hospital stays (p < 0.001), and more medical complications (p = 0.003). Laparotomic conversion was associated with obstructive neoplasms (p < 0.001), and medical complications with ASA scores (p < 0.001). Both the medical and surgical complications predicted adverse 30-day outcomes (p = 0.007 and p < 0.001). Survival analysis revealed superior overall survival (OS) in Group A vs. Group B (p < 0.0001) and inferior OS vs. Group C (p < 0.0001). After a landmark analysis, the OS for patients aged 80 or older and those under 80 appeared to be similar (HR 2.55 [0.75-8.72], p = 0.136). (4) Conclusions: Laparoscopic surgery in very elderly CRC patients shows comparable oncological outcomes and surgical complications to younger populations. Survival benefits are influenced by age, comorbidities, and medical complications. Further prospective multicenter studies are needed in order to validate these findings.

2.
Clin Colorectal Cancer ; 11(4): 268-74, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22658458

ABSTRACT

BACKGROUND: Currently there is no reliable technique for predicting clinical or pathologic complete tumor response after radiochemotherapy (RCT) in patients with rectal cancer. We applied reverse phase protein microarray (RPMA) technology to find a signal pathway that may predict the response to preoperative treatment. PATIENTS AND METHODS: Fifteen rectal cancer samples were collected during preoperative RCT. Seven patients had a good response to preoperative therapy (Mandard grade I-II) and 8 patients had a poor response (Mandard grade III-V). Using laser capture microdissection (LCM) and RPMA analysis, we measured the phosphorylation level of nearly 80 end points and analyzed the signaling pathways. RESULTS: We identified 4 signaling proteins whose phosphorylation levels were significantly different (P < .05) between the good vs. poor responders; CHK2 and ß-catenin were more highly phosphorylated in poor responders, whereas PDK1 and glycogen synthase kinase (GSK)-3α/ß had lower phosphorylation levels in poor responders. Interestingly GSK-3α/ß, ß-catenin, and PDK1 are all present in the phosphatidylinositol-3-kinase (PI3K)-AKT signaling pathway. CONCLUSIONS: Based on our results, we hypothesize that the activating state of the PI3K-AKT pathway can stratify patients who could benefit most from neoadjuvant treatment. Moreover, identification of theranostic targets has the potential to pinpoint new therapeutic strategies for the nonresponsive population.


Subject(s)
Biomarkers, Tumor/metabolism , Neoadjuvant Therapy , Rectal Neoplasms/metabolism , Signal Transduction , Adult , Aged , Checkpoint Kinase 2 , Female , Follow-Up Studies , Glycogen Synthase Kinase 3/metabolism , Humans , Male , Middle Aged , Neoplasm Grading , Phosphorylation , Prognosis , Protein Array Analysis , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Pyruvate Dehydrogenase Acetyl-Transferring Kinase , Rectal Neoplasms/drug therapy , Rectal Neoplasms/pathology , beta Catenin/metabolism
3.
Ann Surg Oncol ; 19(2): 402-8, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22071867

ABSTRACT

BACKGROUND: Although surgery is the gold standard treatment of hepatic metastasis from colorectal cancer (CRC), many patients ultimately die of their disease. We tested the hypothesis that the detection of circulating tumor cells (CTC) might identify patients at high risk of dying of disease recurrence after apparently radical liver surgery. METHODS: We considered 50 patients undergoing radical surgery for liver-confined hepatic metastasis from CRC. The expression of a panel of cancer-related genes, as assessed by quantitative real-time PCR, was used to detect CTC in the peripheral blood of these patients immediately before surgery. Survival analysis was performed by the Cox regression model. RESULTS: Univariate analysis of the expression levels of CD133 (a marker of colon cancer stem cells) and survivin (an antiapoptotic factor) resulted in statistically significant association with patient survival [hazard ratio (HR) 2.7, 95% confidence interval (CI) 1.9-3.7, P < 0.0001; and hazard ratio 2.1, 95% CI 1.4-3.2, P < 0.0001, respectively]. Remarkably, multivariate analysis found that only the transcriptional amount of CD133 resulted in statistical significance (HR 2.6, 95% CI 1.9-3.6, P < 0.0001), indicating that this biomarker can independently predict the survival of these patients. CONCLUSIONS: CD133-positive CTC may represent a suitable prognostic marker to stratify the risk of patients who undergo liver resection for CRC metastasis, which opens the avenue to identifying and potentially monitoring the patients who are most likely to benefit from adjuvant treatments.


Subject(s)
Biomarkers, Tumor/genetics , Colorectal Neoplasms/surgery , Liver Neoplasms/surgery , Neoplasm Recurrence, Local/diagnosis , Neoplastic Cells, Circulating/metabolism , Neoplastic Stem Cells/metabolism , Aged , Biomarkers, Tumor/metabolism , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Female , Follow-Up Studies , Hepatectomy , Humans , Liver Neoplasms/mortality , Liver Neoplasms/secondary , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Neoplastic Cells, Circulating/pathology , Neoplastic Stem Cells/pathology , Prognosis , Real-Time Polymerase Chain Reaction , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction , Survival Rate
4.
Anticancer Res ; 29(10): 4139-44, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19846962

ABSTRACT

BACKGROUND: The hypothesis was tested that systemic chemotherapy might contribute to improving overall survival (OS) of patients with unresectable colorectal liver metastases treated with hepatic arterial infusion (HAI). PATIENTS AND METHODS: We considered 153 consecutive patients retrospectively divided into group A (n=72) treated with HAI alone (floxuridine [FUDR] + leucovorin [LV]), and group B (n=81) treated with HAI combined with systemic chemotherapy (5-fluorouracil [5FU] + LV). RESULTS: No significant difference in OS was observed between the two groups. Median OS was better in patients with <50% of liver involvement (21.3 vs. 13.2 months; p<0.0001) and in responders vs. non-responders (24.4 vs. 13.4 months; p<0.0001). The combination of low tumor load with good tumor response to HAI was the only variable retained on multivariate survival analysis, associated with a better clinical outcome (median OS: 34.2 months). CONCLUSION: Our study does not support the use of FUDR-based HAI combined or not with 5FU-based systemic chemotherapy as the first-line therapeutic approach to unresectable colorectal cancer liver metastases. The identification of responsive patients would improve the therapeutic index of this HAI regimen.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Adult , Aged , Cohort Studies , Dexamethasone/administration & dosage , Female , Floxuridine/administration & dosage , Fluorouracil/administration & dosage , Hepatic Artery , Humans , Infusions, Intra-Arterial , Leucovorin/administration & dosage , Male , Middle Aged , Retrospective Studies , Survival Rate , Treatment Outcome
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