Is Preoperative Chemotherapy Safe for Patients with Colorectal Liver Metastases Undergoing Metastasectomy?

PURPOSE: Controversies regarding preoperative versus postoperative chemotherapy for patients having hepatic metastases of colorectal primary made us elucidate the safety of chemotherapy. By examining the histopathologic changes in the liver following preoperative chemotherapy and analyzing the relation between surgical outcomes and preoperative chemotherapy, we were able to answer whether preoperative chemotherapy is safe. METHODS: We analyzed 38 patients who underwent chemotherapy before resection of hepatic metastasis from colorectal primary, retrospectively. Types of chemotherapy regimen were FL (5-FU+leucovorin), FOLFOX4 (oxaliplatin+5-FU+leucovorin), and FOLFIRI (irinotecan+5-FU+leucovorin). Results of liver function tests were compared before and after preoperative chemotherapy. One pathologist reviewed the degree of hepatic injury from resected specimens. Associations between the histological findings of hepatic injury and surgical outcomes and chemotherapeutic agents were examined. RESULTS: Histopathologic analysis revealed severe liver injury was present in 12 patients (31.6%). In further detail, moderate to severe sinusoidal dilatation was found in 3 patients (25%), steatosis of more than 30% was identified in 9 patients (75%), and steatohepatitis Kleiner score of > or =4 in 5 patients (41.7%). Preoperative chemotherapy did not affect the biochemical profiles of liver function. The overall perioperative complication rate was 5.3% (n=2). There was no difference in postoperative morbidity or mortality from reported results following hepatectomy. CONCLUSION: We found preoperative chemotherapy definitely induced histopathologic changes of hepatotoxicities. Even so, preoperative chemotherapy did not increase morbidity or mortality after hepatic metastasectomy. Preoperative chemotherapy seems to be safe in performing curative hepatic resection for the metastases.

Microsatellite Instability-low Colorectal Carcinomas: Are They Comparable with Microsatellite Stable Cancer?

PURPOSE: Microsatellite instability-high (MSI-H) colorectal cancer (CRC) displays a well-described distinct phenotype, but the true biological significance of MSI-low (L) is still uncertain. To clarify the significance of this MSI-L, we studied the differences between patients with CRC with MSI-H, MSI-L, and microsatellite stability (MSS). METHODS: A total of 723 consecutive patients (429 males and 294 females) who had undergone resections between September 2002 and August 2007 were studied. We analyzed the clinicopathological features, the MSI statuses, and the prognoses of the 723 CRC patients. RESULTS: MSI-H was observed in 54 (7.5%), MSI-L in 27 (3.7%), and MSS in 642 (88.8%) of the 723 colorectal cancer patients. MSI-L and MSS CRC share similar clinicopathological features. A univariate analysis showed no significant differences in overall survival between MSI-L, MSS, and MSI-H. In the multivariate Cox regression analysis, MSI-L was significantly (P=0.036) associated with poorer prognosis compared with MSS tumors, after adjustment for factors previous shown to be associated with the survival based on potentially relevant variables. CONCLUSION: In conclusion, the current study showed no difference in the clinicopathological features of MSI-L versus MSS CRCs. However, in the multivariate analysis, patients with MSI-L CRCs had significantly poorer overall survival. Finally, these findings support the existence of MSI-L CRCs as a distinct category. Thus, further studies are required to explore possible reasons for the adverse prognosis associated with MSI-L cancers.

Gastrointestinal Stromal Tumors of the Colon and Rectum

PURPOSE: This study was designed to review the clinical characteristics of gastrointestinal stromal tumors (GISTs) of the colon and rectum and to evaluate their immunohistochemical and pathologic features based on the current National Institutes of Health criteria. METHODS: Patient and disease characteristics, pathologic features, surgical or endoscopic management, and clinical outcomes of 11 patients with GISTs diagnosed and primarily treated at our institution between March 1995 and February 2009 were evaluated. RESULTS: Colorectal GISTs accounted for 4.4% of all GISTs. The primary location was the rectum (8 cases). Four patients had high-risk GISTs, 4 patients had low-risk GISTs, and 3 patients had very low-risk GISTs. All tumors were c-kit positive. Four patients underwent a radical resection, whereas 7 patients underwent an endoscopic resection (n=3) or a transanal excision (n=4). Two high-risk patients without adjuvant Imatinib mesylate therapy developed metastases, but the other high-risk patients with adjuvant Imatinib mesylate therapy didn't. CONCLUSION: Colorectal GISTs occurred predominantly in the rectum. Because GISTs do not metastasize through the lymphatics, small GISTs that are amenable to local excision or endoscopic resection can be treated by either of these techniques as long as negative microscopic margins are obtained around the primary tumor. Patients with high-risk GISTs should be considered for the use of Imatinib mesylate as adjuvant therapy.

Treatment of Multiple Colorectal Cancers

PURPOSE: The detection of synchronous and metachronous colon cancer is important for the surgical treatment. The aim of this study is to review the clinicopathological characteristics of multiple colon cancers. METHODS: A retrospective analysis was performed with 43 patients with multiple colon cancers who underwent surgical treatment from June 1996 to May 2008. Patients with familial adenomatous polyposis and cancer from inflammatory bowel disease were excluded. RESULTS: There were 43 cases of multiple colon cancers. Synchronous colon cancers were present in 30 patients and metachronous colon cancers were present in 18 patients. The mean age was 61.33+/-11.44, and the male-to-female ratio was 23:20. The index cancer and the second cancers in synchronous colon cancers, as well as the first colon cancer in metachronous colon cancers showed, significantly more distal tumor locations. However, the second cancers in metachronous colon cancers showed no significant differences in tumor location. As for stage, a more advanced stage was noted in the index cancer than in the second cancers in synchronous cancer. However, an early stage was noted for the first colon cancer in metachronous cancers. Seventeen patients with synchronous cancer and 14 patients with metachronous colon cancer underwent a total or a subtotal colectomy. CONCLUSION: Detection of synchronous colon cancer was important for deciding the extent of surgical resection. Patients with colon cancer should be considered for frequent colonoscopy follow-up for early detection of metachronous colon cancer.

Outflow Reconstruction using Cryopreserved Aortic Patch in Right Lobe Living Donor Liver Transplantation

METHODS: Living donor liver transplantation (LDLT) using a right lobe graft has been widely used to compensate for the cadaveric organ shortage. Successful reconstruction of the middle hepatic vein (MHV) is required to provide an adequate functional volume in LDLT with using the right lobe. We describe herein a new technique using a cryo-preserved aortic patch for outflow reconstruction of the right lobe graft with or without MHV. METHODS: From November 2005 through March 2006, 20 adult patients who received a right lobe graft (n=10) or an extended right lobe graft (n=10) for LDLT were included. During the bench procedure of the right lobe graft, we reconstructed the new MHV with using cryopreserved veins just like the MHV of the extended right lobe graft, and we then made a venous pouch to form a common trunk between the MHV (or new MHV) and the RHV of the right lobe graft with using a cryopreserved aortic patch. During graft implantation, anastomosis of an outflow tract was made between the venous pouch of the graft and the common trunk of recipient's RHV-MHV-LHV. One week following the transplantation, measurement of the pressure gradient between the MHV and IVC was done, as well as performing regular follow-up 3D-CT scans and liver function tests. RESULTS: The mean pressure gradient between the reconstructed MHV and the recipient's IVC was 2.3+/-1.2mmHg, and in all cases, the serial liver function tests showed gradual improvement as the days progressed post-operatively. There was no evidence of hepatic venous congestion of the graft and/or obstruction of the reconstructed MHVs according to the serial postoperative follow-up images of the Doppler US and MD-CT. CONCLUSION: We suggest that reconstructing the outflow tract with a cryopreserved aortic patch is a good alternative technique for preventing anterior segment congestion in LDLT with using a right lobe graft with or without MHV.

The Clinical Significance of Routine Screening for the Renal Functional Asymmetry in Potential Live Kidney Donor

PURPOSE: An insufficiently functioning nephron might fail to meet the metabolic demands of a kidney donor, as well as the recipient, and may lead to hyperfiltration. An extreme asymmetry of the functional capacity of donor's bilateral kidneys might result in insufficiency to the recipient or donor. METHODS: Since February 1996, 99mTc-DTPA renal scintigraphy has been routinely included in the evaluation of renal functional asymmetry of a donor. The functional ratio of each kidney, using 99mTc-DTPA, as well as the serum creatinine (Scr) and creatinine clearance (Ccr), were measured and calculated using the 24-hour urine from a hundred donors. RESULTS: A hundred kidney donors were analyzed, including 62 male and 38 female donors. In the healthy donors, the average functional ratios of the left vs. the right kidneys were 52.5 vs. 47.5%. Seventy-three donors donated their left kidney and 27 their right. The Scr of the donors increased from 0.9+/-0.2 to 1.3+/-0.3 mg/dl after the nephrectomy. Both the Ccr in the 24 hour urine and the Ccr obtained using the Cockcroft and Gault formula of the remnant kidney after kidney donation increased from 54.5+/-11.4 to 68.0+/-14.3 ml/min/1.73 m2, and from 40.8+/-9.3 to 53.6+/-11.6 ml/ min/1.73 m2, respectively. CONCLUSION: Attention should be paid to the functional asymmetry of the kidney when choosing a kidney for donation. To protect the remnant kidney of a donor from hyperfiltration damage after donation, it is important to leave an adequate functioning nephron mass to meet the metabolic demands of the donor.