Oxaliplatin-Induced Chronic Peripheral Neurotoxicity: A Prospective Analysis in Patients with Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Oxaliplatin-induced chronic peripheral neurotoxicity (OXCPN) manifests as a loss of sensation and dysesthesia in the distal extremities, which may impair daily activities and increase in incidence with the amount of oxaliplatin delivered. The variation in the reported incidence and severity of OXCPN may be a consequence of differences in the baseline characteristics of patients. MATERIALS AND METHODS: This was a prospective study (ClinicalTrials.gov, NCT00977717) in which OXCPN was recorded for all consecutive colon cancer patients treated at Samsung Medical Center (Seoul, Korea) with oxaliplatin-based combination chemotherapy. The primary endpoint was the incidence of severe OXCPN (grade 2 lasting for >7 days, or grade 3). The association of severe OXCPN and pretreatment parameters was evaluated using a multivariate regression model. RESULTS: Between Jan 2008 and Feb 2010, 100 patients treated with adjuvant folinic acid/fluorouracil plus oxaliplatin (FOLFOX) and 266 patients treated with capecitabine plus oxaliplatin (XELOX) or FOLFOX for advanced disease were registered into our study. The median cumulative dose of oxaliplatin was 796 mg/m2 (range, 85 to 1,583 mg/m2). Severe OXCPN was observed in 126 (34%) patients. Overall, 43 patients discontinued chemotherapy due to toxicity: 23 without severe OXCPN and 20 with severe OXCPN. In univariate analysis, severe OXCPN was frequently observed in patients with age > or =55 years (p<0.01), stage II or III (p<0.01), adjuvant setting (p=0.01), FOLFOX (p<0.01), performance status of 0 (p=0.02), and those with no prior chemotherapy (p<0.01). In a multivariate regression model, the number of chemotherapy cycles and the cumulative oxaliplatin dose were not associated with the development of severe OXCPN. CONCLUSION: We failed to find a significant association between patient characteristics at baseline and the development of severe OXCPN after oxaliplatin-based combination chemotherapy. Pharmacogenomic profiling using genome-wide association study in these patients is underway.

Oncologic Outcome after Cessation or Dose Reduction of Capecitabine in Patients with Colon Cancer

PURPOSE: Oral capecitabine has been used as adjuvant therapy for colorectal cancer patients since the 1990s. Patient-initiated cessation or reduced use of capecitabine occurs widely for various reasons, yet the consequences of these actions are unclear. The present study sought to clarify treatment outcomes in such patients. METHODS: The study included 173 patients who had been diagnosed with stage II or III colon cancer according to the pathologic report after radical surgery at Samsung Medical Center from May 2005 to June 2007 and who had received capecitabine as adjuvant therapy. The patients were divided into groups according to whether the dose was reduced (I, dose maintenance; II, dose reduction) or stopped (A, cycle completion; B, cycle cessation). Recurrence and disease-free survival rates between the two groups each were analyzed. RESULTS: Of the 173 patients, 128 (74.6%) experienced complications, most frequently hand-foot syndrome (n = 114). Reduction (n = 35) or cessation (n = 18) of medication was most commonly due to complications. Concerning reduced dosage, both groups displayed no statistically significant differences in recurrence rate and 3-year disease-free survival rate. Concerning discontinued medication use, the cycle completion group showed an improved recurrence rate (P = 0.048) and 3-year disease-free survival rate (P = 0.028). CONCLUSION: The results demonstrate that maintaining compliance with capecitabine as an adjuvant treatment for colon cancer to preventing complications positively affects patient prognosis.

Neuroanatomy of Sleep-Wake Regulation and its Application to Pharmacotherapy / 대한정신약물학회지

A current hypothesis of sleep-wake regulation proposes that the sleep process starts with the activation of sleep-promoting neurons located in the preoptic area of the anterior hypothalamus. This activation leads to the inhibition of wake-promoting neurons located in the posterior hypothalamus, basal forebrain, and mesopontine tegmentum, which, in turn removes inhibition from the sleep-promoting structures(i.e., disinhibition) to initiate the sleep process. Mutual inhibition between these wake- and sleep-promoting neurons results in switching properties that define discrete wakeful and sleep states with sharp transitions between them. Wake-promoting nuclei include the orexinergic lateral hypothalamic/perifornical area, the histaminergic tuberomammillary nucleus, the cholinergic pedunculopontine tegmental nucleus, the noradrenergic locus coeruleus, the 5-hydroxytryptaminergic raphe nuclei, and possibly the dopaminergic ventral tegmental area. The major sleep-promoting nucleus is the GABAergic ventrolateral preoptic nucleus of the hypothalamus. The regulation of sleep is classically viewed as the dual interaction of circadian(SCN-based) and homeostatic processes, and the propensity to be asleep or awake at any given time is a consequence of a sleep debt and its interaction with signals from the SCN circadian clock. To better understand the mechanisms of sleep and wakefulness, the focus of pharmacotherapy is on targeting specific therapies to the particular defect in sleep-wake regulation.

Effect of Biofeedback Treatment in Patients with Fecal Incontinence

PURPOSE: We aimed to assess the efficacy of biofeedback therapy for patients with fecal incontinence (FI) according to the etiology. METHODS: Twenty-nine patients with fecal incontinence were treated with biofeedback therapy using a EMG-based system. The efficacy was assessed by using changes in the FI score (Cleveland Clinic, Florida: 0~20) and satisfaction based on a subjective evaluation score from 0 to 100. The median follow up duration was 12 (3~25) months. RESULTS: Ten patients had idiopathic fecal incontinence. Fourteen patients had fecal incontinence due to a sphincter saving operation for rectal cancer. Four cases had spinal cord injury and one patient had a major external sphincter tearing due to trauma. The mean age was 52 (16~78) years. The median number of biofeedback sessions was 10 (3~15) overall. The mean efficacy was 42.8%, and the mean satisfaction score was 56.6. Improvements in the FI score and in the patients' satisfaction varied according to the etiology, 69.5% and 71.5 in the idiopathic group, 28.5% and 49.3 in the postoperative group, and 35% and 24 in the spinal cord injury group. In the idiopathic group, 50% of the patients showed an improvement in the FI score of more than 75%, and 90% of the patients showed an improvement of more than 50%. The number of liquid incontinence episodes was improved 78.3% later in the biofeedback group, and this result was much better than in the postoperative incontinence group (31.8%, p=0.03). CONCLUSIONS: The success rate of the biofeedback therapy for fecal incontinence is acceptable. Subjective satisfaction is relatively higher than the improvement in the ecal incontinence score. Idiopathic fecal incontinence may be the best indication for biofeedback therapy.

Surgical Treatment of the Colonic Diverticulosis

PURPOSE: In Asia including Korea, colonic diverticulosis is a relatively uncommon disease. Recently, the incidences of left colonic diverticulosis in Korea has been increasing, mainly due to a westernized diet and life-style. This study was performed to analyze the clinical manifestations and surgical outcomes of patients with colonic diverticulosis. METHODS: We retrospectively reviewed the medical records of 39 patients with colonic diverticulosis who underwent surgery at Asan Medical Center during July 1989 and December 2001. RESULTS: The male to female ratio was 30:9, and the mean age was 52 (26~78) years. The most prevalent age group was people in fifth decade (13 cases, 33%). Twenty-three cases (59%) were in the right colon, 14 cases (36%) in the left and 2 cases (5%) were bilateral. The relative incidence of left colonic diverticulosis was higher in the elderly patients group (>or=50 years old) (57% vs 15%; P=0.002). Of the three diagnostic tools, the barium enema showed a 63% accuracy, the colonofiberscopy 62% and the abdomen-pelvic CT scan 59%. Bowel perforation (19 cases, 49%) and recurrent abdominal pain (10 cases, 16%) were the common surgical indications. Among 11 cases with bowel perforation accompanying the left colonic diverticulosis, two cases (18%), which underwent one-stage operation, developed complications, while 3 cases (27%) among the other 9 that underwent multi-staged operations, did so. CONCLUSION: The incidences of left colonic diverticulosis were relatively high (36%), especially in the elderly patients (P= 0.002). This study indicates that a tailored surgical procedure, depending on the severity of inflammation, is important in reducing postoperative complications.

Optimal Scheme of Postoperative Chemoradiotherapy in Rectal Cancer: Phase III Prospective Randomized Trial / 대한방사선종양학회지

PURPOSE: To determine the optimal scheme of postoperative chemoradiotherapy in rectal cancer by comparing survival, patterns of failure, toxicities in early and late radiotherapy groups using a phase III randomized prospective clinical trial. MATERIALS AND METHODS: From January 1996 to March 1999, 307 patients with curatively resected AJCC stage II and III rectal cancer were assigned randomly to an 'early (151 patients, arm I)' or a 'late (156 patients, arm II)' and were administered combined chemotherapy (5-FU 375 mg/m2/day, leucovorin 20 mg/ m2, IV bolus daily, for 3 days with RT, 5 days without RT, 8 cycles with 4 weeks interval) and radiation therapy (whole pelvis with 45 Gy/25 fractions/5 weeks). Patients of arm I received radiation therapy from day 1 of the first cycle of chemotherapy and those of arm II from day 57 with a third cycle of chemotherapy. The median follow-up period of living patients was 40 months. RESULTS: Of the 307 patients enrolled, fifty patients did not receive scheduled radiation therapy or chemotherapy. The overall survival rate and disease free survival rate at 5 years were 78.3% and 68.7% in arm I, and 78.4% and 67.5% in arm II. The local recurrence rate was 6.6% and 6.4% ( p=0.46) in arms I and II, respectively, no significant difference was observed between the distant metastasis rates of the two arms (23.8% and 29.5%, p=0.16). During radiation therapy, grade 3 diarrhea or more, by the NCI common toxicity criteria, was observed in 63.0% and 58.2% of the respective arms ( p=N.S.), but most were controlled with supportive care. Hematologic toxicity (leukopenia) greater than RTOG grade 2 was found in only 1.3% and 2.6% of patients in each respective arm. CONCLUSION: There was no significant difference in survival, patterns of failure or toxicities between the early and late radiation therapy arms. Postoperative adjuvant chemoradiation was found to be a relatively safe treatment but higher compliance is needed.

Effectiveness of Gastric Resection in Stage IV Gastric Cancer with Hepatic Metastasis, Peritoneal Seeding, or Distant Lymph Node Metastasis

BACKGROUND : The prognosis for patienys with stage IV gastric cancer is very poor. However, recently, some studies have reported benefits from a gastric resection for metastatic gastric cancer. This clinical study was performed to evaluate the effectiveness of a noncurative gastrectomy in treating stage IV gastric cancer with hepatic metastasis, peritoneal seeding, or distant lymph-node metastasis. METHODS : A retrospective analysis of 114 gastric cancer patients who had undergone a gastric resection, in spite of distant metastasis, between May 1989 and March 1998 at the Department of Surgery, College of Medicine, University of Ulsan, was performed. RESULTS : The average age was 53 years old, and male-to-female ratio was 73 : 41. A total gastrectomy was performed in 48 cases and a distal gastrectomy in 66 cases. Lymph-node dissection was performed to D0, D1, and D2 in 42, 37, and 35 cases, respectively. Postoperative adjuvant chemotherapy was done, mainly by 5-FU and cisplatin. The complication rate was low. The median follow- up was 19 months. The overall average survival times of all patients was 25 months, and the average survival time of patients with hepatic metastasis, peritoneal seeding, and distant lymph-node metastasis, were 28 months, 21 months, and 34 months, respectively. However, there were no statistically significant differences between these survival times. There were six long-term survivors, more than 3 years. The causes of death, in descending order, were renal failure, intestinal obstruction due to peritoneal seeding, hepatic failure due to hepatic metastasis and pneumonia, and sepsis due to lung metastasis. CONCLUSIONS : An aggressive gastric resection for stage IV gastric cancer with hepatic or distant lymph-node metastasis and peritoneal seeding might be useful to lengthen the survival period. A prospective study is needed, especially one with an exact evaluation and analysis of the quality of life.