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Background: The purpose of this study was to investigate the incidence, origin, and clinical significance of liver atrophy during chemotherapy for colorectal cancer., Methods: This study included 103 patients who underwent chemotherapy before resection for colorectal liver metastases (training set) and 171 patients who underwent adjuvant or first-line chemotherapy without liver resection (validation set). A greater than 10% decrease (atrophy) or increase (hypertrophy) of the liver volume from the baseline was defined as a significant change., Results: In the training set, the numbers of patients who developed atrophy, no change of volume, and hypertrophy of the liver after chemotherapy were 15 (14.6%), 73 (70.9%), and 15 (14.6%), respectively. Liver atrophy was associated with impaired hepatic function, and the postoperative morbidity rate and refractory ascites/pleural effusion were higher in the patients with liver atrophy than those without (60.0% vs. 31.8%, P = 0.045 and 46.7% vs. 8.0%, P < 0.001, respectively). Histopathological examination revealed a strong association between sinusoidal injury and liver atrophy (P < 0.001). The cumulative incidence of liver atrophy increased with increasing duration of chemotherapy, whereas the incidence of liver atrophy was less frequent in patients who had received bevacizumab than those who had not in both the training set (odds ratio [OR], 0.13; P = 0.001) and the validation set (OR, 0.31; P = 0.007)., Conclusions: Liver atrophy is associated with impaired hepatic functional reserve and observed at an increasing frequency as the duration of chemotherapy increases with frequent histopathological evidence of sinusoidal injury in the liver. Bevacizumab may protect against the development of liver atrophy.

Background: Regorafenib is a multi-kinase inhibitor, which was shown to be effective for patients with metastatic colorectal cancer refractory to standard therapies. However, its patterns of response has not yet been fully understood., Methods: Clinical records of 10 patients who received regorafenib for evaluable colorectal liver metastases were reviewed. Response to chemotherapy was evaluated with the RECIST and morphologic response criteria, and its clinical relevance was analyzed., Results: All patients received multiple lines of fluorouracil-based chemotherapy before regorafenib. The median follow-up duration after introduction of regorafenib was 4.9 months (range, 2 to 12.5 months). Median number of chemotherapy cycles was 2 (range, 1 to 15). In size-based response evaluation, 4 patients presented SD and 6 patients showed PD according to the RECIST. In non-size-based response evaluation, 3 patients were classified as optimal morphologic response and 7 patients were categorized as suboptimal morphologic response. Patients who presented optimal morphologic response showed significantly longer progression-free survival compared with those presented suboptimal response (median, 4.9 months vs. 0.7 months; P = 0.028), while size-based response evaluation could not well stratify patient prognosis., Conclusion: Non-size-based CT morphologic response could be a potential alternative response marker for patients treated with regorafenib.

Background: Although the usefulness of adjuvant chemotherapy has been established in the treatment for stages II/III colorectal cancer, its prognostic advantage for colorectal liver metastases (CLM) remains controversial., Methods: Two hundred and nine patients who underwent curative resection for CLM were reviewed. The potential advantage of adjuvant chemotherapy was investigated in 3 groups stratified by disease-free interval (DFI): synchronous CLM (S-CLM), early metachronous CLM (EM-CLM, DFI ≤1 year), and late metachronous CLM (LM-CLM, DFI >1 year)., Results: Of the 105 patients who underwent adjuvant chemotherapy after surgery, 47 received uracil-tegafur and leucovorin (UFT/LV) while 58 received the oxaliplatin-based regimen. Five-year recurrence-free survival (RFS) rates in patients with/without adjuvant chemotherapy were 32.8/11.2% in S-CLM (p = 0.002), 43.7/15.2% in EM-CLM (p = 0.002), 44.1/29.6% in LM-CLM (p = 0.163), respectively. Five-year overall survival (OS) rates were 77.9/44.5% in S-CLM (p = 0.021), 81.5/39.5% in EM-CLM (p = 0.015), 76.1/65.4% in LM-CLM (p = 0.411), respectively. Multivariate analyses in S-CLM and EM-CLM indicated that adjuvant chemotherapy is correlated with better RFS and OS irrespective of the regimens, while the incidence of severe adverse event was significantly different between UFT/LV and oxaliplatin (6.8 vs. 50.9%, p < 0.0001)., Conclusion: Adjuvant chemotherapy might improve the clinical outcomes in S-CLM and EM-CLM. UFT/LV might be a choice for CLM in adjuvant settings in selected patients., (© 2017 S. Karger AG, Basel.)

We present a case of bilateral lymph node metastases of rectal cancer treated with chemotherapy and surgery. The patient was a 65-year-old man with upper rectal cancer. Laparoscopic low anterior resection(LAR)was performed. Pathological findings were tub2>por>muc, pT3, ly2, v3, pN2, pM0. Six months after surgery, the CEA level was elevated. CT and PET-CT confirmed bilateral metastasis to the lymph nodes. Five courses of FOLFOX4 plus bevacizumab were administered, and then, we performed laparoscopic bilateral lymph node dissection. Pathological assessments confirmed scarring and fibrosis, that is, a pathological complete response(pCR)was achieved. Two years and 6 months after surgery, no recurrence was detected. After chemotherapy or chemoradiotherapy, we should perform surgery to prevent local recurrence, especially to the lateral lymph nodes.

Hepatitis C virus (HCV) infection is one of the most common blood-borne infections worldwide. Little is known with respect to changes in HCV status during chemotherapy for colorectal cancer (CRC), and the influence of HCV infection on chemotherapy remains unclear. Between 2001 and 2012, 3,260 patients were diagnosed with CRC in our institute. We studied 77 patients who were positive for anti-HCV antibodies. We retrospectively reviewed changes in HCV load and chemotherapy toxicities. Twenty-four of 77 HCV-infected patients with CRC received chemotherapy. Their median age was 66 years, and four patients had liver cirrhosis. The remaining 20 patients were diagnosed with chronic hepatitis, and their liver function tests and blood cell counts at baseline were normal. Serum HCV ribonucleic acid level before and after chemotherapy was evaluated in ten patients, with medians of 4.0 and 3.05 log IU/ml at baseline before and after chemotherapy, respectively. Two patients demonstrated elevated transaminase levels during chemotherapy. Among the 24 HCV patients received chemotherapy, no patients suffered from febrile neutropenia or treatment delay; two required chemotherapy dose reduction. Our results indicated that chemotherapy for CRC patients with HCV infection can be performed safely without changing the viral load.

Objective: To perform a retrospective analysis of UFT and oral leucovorin combination adjuvant chemotherapy for Stage III colon cancer patients over 76 years old, in order to evaluate both treatment efficacy and toxicity., Subjects: Between 2002 and 2011, 333 Stage III colon cancer patients had surgery performed in our institute, and we studied 25 of them on our chemotherapy regimen., Results: Patients'median age was 78 years old, with 12 men and 13 women. Of all the patients, 19 had Stage IIIa and 6 had Stage IIIb. The 3-year disease-free survival rates for Stage III and Stage IIIa patients were 65. 1% and 83. 1%, respectively, and the 3-year overall survival rate for Stage III was 79. 9%. With regard to toxicity, liver function disorder was observed in 8% of the patients, being the adverse event that occurred the most, but there was no Grade 3 or 4 toxicity., Conclusion: UFT and oral leucovorin combination adjuvant chemotherapy for Stage III colon cancer patients over 76 years showed a good response, especially for Stage III a.

Objective: To perform a retrospective analysis of UFT and oral leucovorin plus PSK combination adjuvant chemotherapy for stage III colon cancer in order to evaluate both treatment efficacy and toxicity., Subjects: Between 2003 and 2009, 273 stage III colon cancer patients underwent surgery in our institute, and we studied 156 of them., Results: Patients' median age was 72 years old; 87 men and 69 women. Of all patients, 119 had stage IIIa and 37 had stage IIIb. The 3-year disease, free survival rates for stage III, stage IIIa and stage IIIb patients were 73. 9%and 80. 6%and 51. 4%, respectively, and the 3-year overall survival rates for stage III was 97. 6%. With regard to toxicity, liver function disorder was observed in 9. 6%of the patients as the most frequent adverse event, but there was no grade 3 or 4 toxicity., Conclusion: UFT and oral leucovorin plus PSK combination adjuvant chemotherapy for stage III colon cancer showed a good response especially for stage III a.

Since pharmacokinetics in patients undergoing hemodialysis differs from that in patients with normal renal function, chemotherapy for a hemodialysis patient should be considered with due care. We administered chemotherapy of modified FOLFOX6 to a patient on hemodialysis with inoperable metastatic colorectal cancer, and measured his plasma concentration of total platinum and non-protein-bound platinum. Since there is no reported case of oxaliplatin use in patients on hemodialysis so far, we evaluated whether it could be safely used for such patients. We made a dose escalation study with 40, 50, 60, 70 and 85 mg of oxaliplatin, and evaluated the pharmacokinetics at each dose. AUC was 5.67-10.21 mg/L x h. The dialysis removal rate was 84.0%. Although this patient could accept it relatively safely without any severe side effect, the optimal dosage and the timing of hemodialysis for inoperable metastatic colorectal cancer patients should be determined by a further study using more cases.