Relapse In Colon Cancer Research Articles

Adjuvant Therapy of Stage II and III Colon Cancer

Up to 50% of patients who undergo curative resection for colon cancer relapse and ultimately die of metastatic disease. Adjuvant chemotherapy given after surgery reduces the risk of disease recurrence in patients with stage II/III disease, and considerable progress of adjuvant chemotherapy in these patients has been reported. Clinical studies evaluating chemotherapy regimens continue, as do trials that use specific, molecularly targeted agents that have shown promising results in patients with advanced colon cancer. Ongoing important issues to be addressed relate to the optimal schedule and/or choice of chemotherapeutic regimens, and the efficacy of the combination of molecular agents with conventional chemotherapy.

Local Anesthetics for Breakthrough Pain in Patients Receiving Intrathecal Treatment for Cancer Pain Management

To the Editor: Neuraxial administration of drugs is often used to optimize the treatment in patients no longer responsive to systemic analgesics (1). Despite optimal analgesia, patients may suffer from fluctuations in pain intensity (breakthrough pain) (2). This condition is challenging for physician, as no specific indications have been provided for patients receiving a continuous spinal drug combination. We report three cases of patients selected for intrathecal therapy, implanted with a port-system and an external pump, and presenting breakthrough episodes treated by the use of local anesthetics as needed. The first patient, a 57-year-old male, with colon cancer was admitted for abdominal pain due to extensive visceral involvement. The second patient was a 40-year-old female, admitted for unbearable pain due to pelvic relapse of colon cancer, presenting multiple metastases (spleen, pancreas, left colon, presacral area, left ischiorectal fossa, bladder, left ala ilii, abdominal wall, ureter, lung, and liver). She complained of abdominal-pelvic pain with irradiation to the left leg, with a mixed component, visceral, neuropathic, and somatic. The third patient, a 76-year-old male with lung cancer, was admitted for vertebral, chest wall, and shoulder pain, irradiated to the left arm, which increased in intensity on movement due to chest wall involvement. An intrathecal catheter was introduced at the level of corresponding segmental area and connected with a subcutaneous port placed in the anterior thoracic wall, after tunneling the catheter subcutaneously. The proper position of the catheter tip was checked by contrast medium injection. These patients received an intrathecal mixture containing morphine and levobupivacaine, in doses of 25–80 mg and 6–40 mg, respectively, with a mean infusion rate of levobupivacaine of 37 mg/day (about 1.5 mg/h), allowing an acceptable basal pain relief (<4 on a numerical scale of 0–10). Episodes of breakthrough pain, unresponsive to large doses of systemic opioids, were relieved by intrathecal boluses of about 1.25 mg (0.5 mL of levobupivacaine), by a three-way stopcock placed in the external system, close to the port. This means that the dose required to treat breakthrough events was approximately the hourly dose. No infection signs or important hemodynamic changes were observed, despite the repeated boluses. Of interest, the treatment was subsequently maintained at home by properly instructed relatives, without reporting complications for a survival time of 10, 45, 32 days, respectively. This is the first report on the use of local anesthetics as an intrathecal bolus for treating breakthrough pain in cancer patients receiving a spinal analgesic treatment. This treatment should be reserved to very selected population, providing the best methods to prevent the risk of infection due to the high rate of manipulations. Sebastiano Mercadante, MD Patrizia Ferrera, MD Patrizia Villari, MD Anesthesia and Intensive Care Unit; Pain Relief and Palliative Care Unit; La Maddalena Cancer Center; Palermo, Italy; [email protected] Edoardo Arcuri, MD Intensive Care and Pain Therapy Unit; National Cancer Institute Regina Elena; Rome, Italy

Down-regulation of CD59 (protectin) expression on human colorectal adenocarcinoma cell lines by levamisole.

The vulnerability of tumour cells to complement-mediated immune attack is regulated by membrane associated molecules. Recently, we have shown that the expression of the membrane attack complex inhibitor CD59 is enhanced on colonic adenocarcinoma cells compared to normal colonic epithelial cells. CD59 was shown, in the same study, to protect the tumour cells from complement-mediated lysis. Levamisole (LMS), used in conjunction with 5-fluorouracil as adjuvant therapy, reduces the incidence of colon cancer relapse following surgical resection. This led to our investigation of the effect of LMS on CD59 expression and function on the human colorectal cell lines HT29 and Caco-2. When cultured in the presence of 10 microM LMS, the cells reduced their expression of CD59 in a time-dependent manner. LMS treated HT29 cells were more sensitive to lysis by complement than control cells, and the reduction in CD59 expression was shown to be partly responsible for this. A reduction in CD59 expression will augment complement-mediated immune surveillance and may contribute to LMSs anti-tumour activity in vivo.

Effect of levamisole on major histocompatibility complex class I expression in colorectal and breast carcinoma cell lines

The antihelminthic drug levamisole (LMS) is used in conjunction with 5-fluorouracil (5-FU) as adjuvant therapy to reduce the incidence of colon cancer relapse following surgical resection. Clinical trials in patients with breast cancer have yielded conflicting results as to its efficacy in the treatment of this malignancy. LMS is thought to act as an immunostimulant, yet its precise mechanism remains unclear. In this study, the effect of LMS on major histocompatibility complex (MHC) class I (MHC I) and MHC class II (MHC II) expressions in human colorectal and breast carcinoma cell lines was examined. The colon cancer cell line CaCo-2 and the breast cancer cell line MDA-MB-435 were cultured for 24-68 hours in the presence or absence of 10-microns LMS followed by staining with antibodies directed against either MHC I or MHC II: After staining, cells were visualized by fluorescent microscopy. When cultured in the presence of LMS, cells from both cell lines exhibited a decreased fluorescent intensity with antibodies directed against MHC I protein. The most significant difference from cells cultured without LMS was apparent after 48 hours of incubation. Neither cell line exhibited fluorescent intensities above background when stained with anti-MHC II antibody. LMS decreases the expression of MHC I on CaCo-2 and MDA-MB-435 tumor cell lines. Prior studies have indicated that natural killer (NK) cells are more efficient in attacking cells with lowered or no MHC I expression. An MHC I deficiency induced by LMS would augment NK-mediated immune surveillance. One mechanism contributing to levamisole's anti-tumor activity in vivo may be reduction of MHC I expression on tumor cells.