Parenchyma-Sparing Hepatectomy with Vascular Reconstruction Techniques for Resection of Colorectal Liver Metastases with Major Vascular Invasion.

BACKGROUND: Resectability of colorectal liver metastasis (CRLM) depends on major vascular involvement and is affected by chemotherapy-induced liver injury. Parenchyma-sparing with combined resection and reconstruction of involved vessels may expand the indications and safety of hepatectomy. METHODS: Of 92 patients who underwent hepatectomy for CRLM, 15 underwent major vascular resection and reconstruction. The reconstructed vessels were the portal vein (PV) in five cases, the major hepatic vein (HV) in nine cases, and the inferior vena cava in six cases. RESULTS: All PV reconstructions were direct anastomoses. The HV was reconstructed with an autologous inferior mesenteric venous patch or an external iliac vein interposition graft. Total hepatic vascular exclusion was performed for six patients. Of nine patients with HV reconstruction, three had tumors involving all three major HVs, in whom the left HV was reconstructed as an only vein after extended right hepatectomy. In another six patients, multiple bilobar tumors or tumors in the liver that had chemotherapy-induced injury involved one or two HVs. Parenchyma-sparing by reconstruction of the HV was performed to secure the residual liver function. The patients with vascular reconstruction had an operative time of 462 ± 111 min and a blood loss of 1278 ± 528 mL. No complication classified as Clavien-Dindo 3 or more developed. The median hospital stay was 17 days (range 8-26 days). The cumulative 5-year survival rate for all the patients was 54.6 %, with no significant difference according to vascular reconstruction. CONCLUSION: Parenchyma-sparing hepatectomy combined with vascular reconstruction is a useful option to avoid major hepatectomy among various procedures for resection of CRLM with major vascular invasion.

Retrocaval liver lifting maneuver and modifications of total hepatic vascular exclusion for liver tumor resection.

AIM: To evaluate the efficacy of technical modifications of total hepatic vascular exclusion (THVE) for hepatectomy involving inferior vena cava (IVC). METHODS: Of 301 patients who underwent hepatectomy during the immediate previous 5-year period, 8 (2.7%) required THVE or modified methods of IVC cross-clamping for resection of liver tumors with massive involvement of the IVC. Seven of the patients had diagnosis of colorectal liver metastases and 1 had diagnosis of hepatocellular carcinoma. All tumors involved the IVC, and THVE was unavoidable for combined resection of the IVC in all 8 of the patients. Technical modifications of THVE were applied to minimize the extent and duration of vascular occlusion, thereby reducing the risk of damage. RESULTS: Broad dissection of the space behind the IVC coupled with lifting up of the liver from the retrocaval space was effective for controlling bleeding around the IVC before and during THVE. The procedures facilitate modification of the positioning of the cranial IVC cross-clamp. Switching the cranial IVC cross-clamp from supra- to retrohepatic IVC or to the confluence of hepatic vein decreased duration of the THVE while restoring hepatic blood flow or systemic circulation via the IVC. Oblique cranial IVC cross-clamping avoided ischemia of the remnant hemi-liver. With these technical modifications, the mean duration of THVE was 13.4 ± 8.4 min, which was extremely shorter than that previously reported in the literature. Recovery of liver function was smooth and uneventful for all 8 patients. There was no case of mortality, re-operation, or severe complication (i.e., Clavien-Dindo grade of III or more). CONCLUSION: The retrocaval liver lifting maneuver and modifications of cranial cross-clamping were useful for minimizing duration of THVE.

Kugel patch method prevents the development of a femoral hernia after inguinal herniorrhaphy.

PURPOSE: A femoral hernia is a relatively rare condition, and no standard surgical methods have so far been established. In this study, we investigated the development of a femoral hernia after inguinal herniorrhaphy. METHODS: A total of 1,969 patients who underwent surgery for an inguinal hernia from April 1992 to March 2012 were enrolled in this study. The patients were composed of 1,934 (98.2 %) inguinal hernia and 35 (1.8 %) femoral hernia patients. Of these, we retrospectively studied the femoral hernia cases with reference to the use of inguinal herniorrhaphy. RESULTS: Of all 35 femoral hernia cases, six cases (17.1 %) were femoral type recurrences after inguinal herniorrhaphy performed by the conventional or mesh plug methods. The surgical methods used for the 35 cases were mesh plug repair in 15 cases (42.9 %), the Kugel patch method in seven (20.0 %) and conventional repair in 13 patients (37.2 %). Inguinal type recurrences developed in three cases (8.6 %) that were re-repaired by mesh plug repair or sac resection. There were no femoral or inguinal type recurrences after Kugel patch repair for a femoral hernia. CONCLUSIONS: The results of this study suggested the importance of repairing all hernia orifices when repairing a groin hernia. The Kugel patch repair method is available for all inguinal region hernias by the same approach, and it seems to be useful for preventing the development of recurrence after surgery.

Comparison between percutaneous radiofrequency ablation and surgical hepatectomy focusing on local disease control rate for colorectal liver metastases.

BACKGROUND/AIMS: Therapeutic efficacy of radiofrequency ablation (RFA) for colorectal liver metastases (CRLM) was compared with hepatic resection (HR), focusing on local disease control rate as well as risk factors of recurrence and patients survival. METHODOLOGY: From April 2002 to March 2012, 32 patients underwent RFA and 60 patients underwent HR for CRLM. The rate of local recurrence along the ablated or resected margin was evaluated in these patients. RESULTS: The local recurrence was seen in 8 patients (13.3%) after HR, and 15 (46.9%) after RFA. Multivariate analysis of all patients revealed that RFA as an initial therapy (P < 0.001), venous invasion liver metastases (P = 0.049) were independent risk factors for local recurrence. Subgroup analysis showed that local recurrence rate after RFA was significantly higher than that after HR in patients with tumors 20 mm or larger (P < 0.001), while there was no significant difference in local recurrence rate between RFA and HR in patients with tumors less than 20 mm (P = 0.676). CONCLUSIONS: RFA showed a high risk of local recurrence in comparison to HR especially in patients with tumors larger than 20 mm. Indication of RFA should be restricted drastically considering the limitation of efficacy.

[A case of AFP-producing gastric cancer with peritoneal metastasis treated effectively with chemotherapy, mainly using S-1 and trastuzumab].

A 71-year-old man, diagnosed with advanced gastric cancer and severe pyloric stenosis, was introducted to our hospital. Para-aortic lymph nodes metastasis and pancreas invasion were seen with enhanced CT scan. Serum AFP showed a high price (1,465.3 ng/mL). Because significant peritoneal metastases were seen in the abdominal cavity, gastrojejunostomy was performed. Overexpression of the HER2 gene was seen by immunostaining for peritoneal dissemination of the omentum. After starting S-1 + CDDP + trastuzumab, the AFP was normalized immediately (7. 6 ng/mL). We then performed colostomy for a sigmoid colon stenosis. S-1 + DOC + trastuzumab was administered afterward, and we performed closure of the colostomy because the stenosis was improved. Macroscopic peritoneal dissemination in the abdomen disappeared. AFP-producing gastric cancer with peritoneal metastasis has a poor prognosis, but chemotherapy, mainly with S-1 and trastuzumab, was effective for it.

[Roles of hepatectomy for colorectal liver metastases with necrotic foci caused by prior anti-cancer therapies].

Recent advances in chemotherapy for colorectal cancer prolonged survival. Tumor necrosis may develop as a side effect of chemotherapeutic agents. Recently, radiofrequency ablation sometimes indicated to patients with colorectal liver metastasis, when hepatectomy cannot be performed due to impaired hepatic functional reserve or general condition. We experienced hepatectomy for colorectal liver metastasis containing necrotic foci which was induced by anti-cancer drugs and radiofrequency ablation. Massive liver necrosis and abscess developed in a patient with initially unresectable large liver metastasis 6 months after induction of mFOLFOX6 and bevacizumab. Chemotherapy was discontinued due to systemic inflammatory responses. Extended right hepatectomy resulted in both resection of the tumor and significant improvement of septic condition. Chemotherapy was re-started after the operation. Bevacizumab targeted to tumor-related vascular endotherial cells might be responsible for the massive tumor necrosis. Another patient with chronic renal dysfunction underwent radiofrequency ablation for colorectal liver metastasis 2 cm in diameter in the segment 7. Three months after ablation, the tumor grew very rapidly to 6 cm in diameter. After extended posterior sectorectomy of the liver, blood CEA levels were normalized. Resected specimen showed a massive tumor growth around the necrotic foci of radiofrequency ablation. Hepatectomy played significant roles in these patients with necrotic foci of the liver. Decision and timing of hepatectomy are very important to save the patient.

Prognostic value of immunohistochemical analysis of tumor budding in colorectal carcinoma.

BACKGROUND: Tumor 'budding' of colorectal carcinoma along the invasive margin has been associated with increased malignant potential. This study investigated the possible prognostic significance of budding in invasive colorectal carcinoma. PATIENTS AND METHODS: Specimens resected from 149 patients who underwent potentially curative surgery for invasive colorectal carcinoma were studied. Budding was defined according to Ueno's criteria; budding intensity was assessed by examination of hematoxylin-eosin (HE)-stained specimens and immunohistochemical (IHC)-stained specimens using anti-cytokeratin antibody and anti-lymphatic vessel antibody. RESULTS: Immunohistochemical analysis identified many more budding foci that were not detectable by examination of HE-stained specimens. Multivariate analyses revealed that budding identified using immunohistochemical staining was a significant prognostic marker for disease-free survival and there was significant correlation between budding and microlymphatic vessel infiltration at the invasive tumor front. CONCLUSION: Budding, particularly as assessed with immunohistochemical staining, is a useful predictor of poor prognosis in patients with invasive colorectal carcinoma.

The membrane-anchored matrix metalloproteinase (MMP) regulator RECK in combination with MMP-9 serves as an informative prognostic indicator for colorectal cancer.

PURPOSE: RECK, a membrane-anchored regulator of matrix metalloproteinases (MMPs), is widely expressed in healthy tissue, whereas it is expressed at lower levels in many tumor-derived cell lines. Studies in mice and cultured cells have shown that restoration of RECK expression inhibits tumor invasion, metastasis, and angiogenesis. However, the clinical relevance of these findings remains to be fully documented. Here we examined the expression of RECK and one of its targets, MMP-9, in colorectal cancer tissue. EXPERIMENTAL DESIGN: The RECK and MMP-9 expression levels in colorectal cancer samples from 53 patients were determined by immunohistochemical techniques. The expression level of each protein was scored, and the patients were divided into two groups based on these scores. In 33 cases, we performed gelatin zymography to estimate the degree of MMP-2 and MMP-9 activation. Microvessel density and vascular endothelial growth factor (VEGF) expression were also evaluated histologically. RESULTS: RECK protein was detected in 30 of 53 (56.6%) specimens. Importantly, patients with tumors expressing relatively high levels of RECK (high-RECK group) had a significantly lower risk of recurrence than did patients with tumors expressing relatively low levels of RECK (low-RECK group; P = 0.011). Moreover, RECK-dominant (RECK score > or = MMP-9 score) patients showed a significantly lower incidence of recurrence than did MMP-9-dominant patients (P = 0.0003). Multivariate analysis revealed that the RECK/MMP-9 balance was an independent prognostic factor (P = 0.0122). The expression of VEGF and microvessel density were inversely correlated with the level of RECK expression. CONCLUSIONS: RECK/MMP-9-balance is an informative prognostic indicator for colorectal cancer. Our data also suggest that RECK suppresses tumor angiogenesis, probably by limiting the availability of VEGF in tumor tissues.

Long-term results of high-dose extracorporeal and endocavitary radiation therapy followed by abdominoperineal resection for distal rectal cancer.

PURPOSE: To examine the complications, local effects, survival, and prognostic factors of preoperative high-dose radiation therapy in patients with advanced carcinomas of the distal rectum. METHODS: Forty-one patients with tethered or fixed rectal cancer located a median distance of 3.0 cm from the anal verge were treated with extracorporeal and endocavitary radiation therapy (70 Gy), followed 2 weeks later by abdominoperineal resection (APR). RESULTS: This combined radiotherapy achieved acceptable results. Postoperative complications developed in 18 patients (43.9%), 10 (24.3%) of which involved perineal dehiscence. Two patients (4.8%) suffered more than grade 3 toxicity. Destructive changes were histologically confirmed in all specimens, and there were four (9.8%) sterile specimens. Recurrence developed in 11 patients and there were 6 cancer-related deaths. Among six cases of local recurrence, three were found just outside of the radiation field. The 5-year survival and disease-free survival rates were 82.9% and 71.8%, respectively. Multivariate analysis revealed that nodal involvement was the sole independent prognostic factor for survival. Sexual function was maintained in the most recent patients who underwent APR with autonomic nerve-preserving surgery. CONCLUSION: Although the original aim of our treatment focused on curability, this combination therapy may be an option for selected patients, because of potential prevention of local recurrence, relatively low morbidity, and promising autonomic nerve function.

Adenovirus-mediated gene transduction of truncated I kappa B alpha enhances radiosensitivity in human colon cancer cells.

Nuclear factor kappa B (NF-kappa B) is a transcription factor that is known to regulate apoptosis when cells are exposed to DNA-damaging agents such as ionizing radiation and cytotoxic drugs. We sought to determine if inhibition of NF-kappa B could enhance radiosensitivity in human colon cancer cells in vitro and in vivo. To inhibit NF-kappa B activation specifically, we constructed a recombinant adenovirus vector expressing a truncated form of the inhibitor protein I kappa B alpha (I kappa B alpha Delta N) that lacks the phosphorylation sites essential for activation of NF-kappa B, and transfected two human colon cancer cell lines (HT29 and HCT15) with this vector. In vitro colony-forming assays revealed that the overexpression of the stable I kappa B alpha by AxI kappa B alpha Delta N infection significantly suppressed cell growth after irradiation in both cell lines as compared to infection with a control vector, AxLacZ. Treatment with AxI kappa B alpha Delta N and irradiation successfully inhibited the growth of HT29 xenografted subcutaneous tumors in nude mice with an 83.8% volume reduction on day 38 as compared to the untreated tumors. Furthermore, it was demonstrated that apoptosis was increased by adenovirus-mediated gene transduction of I kappa B alpha Delta N in vitro and in vivo. These results indicated that inhibition of NF-kappa B could enhance radiosensitivity through an increase in radiation-induced apoptosis. We believe that radio-gene therapy using adenovirus-mediated gene transduction of I kappa B alpha Delta N could be an attractive candidate as a treatment strategy for colorectal cancer.

Chemo-radio-gene therapy for colorectal cancer cells using Escherichia coli uracil phosphoribosyltransferase gene.

5-Fluorouracil (5-FU) is one of the most widely used chemotherapeutic agents, and is known to be a radiosensitizer. Previously, we reported that adenoviral transduction of the Escherichia coli (E. coli) uracil phosphoribosyltransferase (UPRT) gene induced marked sensitivity in human colon cancer cells to 5-FU. The aim of the current study was to investigate the efficacy of virally-directed UPRT and 5-FU to enhance the radiosensitivity of HT29 human colon cancer cells. Cytotoxicity as a result of radiation treatment following AdCA-UPRT infection and 5-FU exposure was confirmed by radiation dose-response analysis with colony formation assay. In vivo chemoradio-gene therapy using the UPRT/5-FU/radiation system showed tumor regressive effects even against large HT29-established subcutaneous tumors in nude mice. Our results suggested that adenovirus-mediated UPRT gene transduction combined with 5-FU administration and radiation may be an effective new chemo-radio-gene therapy for colorectal cancer.

Prognostic significance of death-associated protein-kinase expression in hepatocellular carcinomas.

BACKGROUND: Disorder of programmed cell death (PCD) contributes to the pathogenesis and the progression of various cancers. Death-associated protein-kinase(DAP-kinase) was isolated as a positive mediator of apoptosis induced by IFN-gamma. It has been reported that the loss or reduction of DAP-kinase expression was detected in various human tumor cell lines and resulted from methylation of the DAP-kinase gene. MATERIALS AND METHODS: We investigated the expression of DAP-kinase protein by immunohistochemistry and Western-blotting in 43 patients with hepatocellular carcinoma (HCC). Additionally, we examined the methylation status of the DAP-kinase promoter region by methylation-specific polymerase chain reaction. RESULTS: In DAP-kinase-positive HCC cases(n = 16), serum AFP levels were lower (p = 0.009), tumor differentiation was higher (p = 0.048), histological portal invasion and metastatic foci were less (p = 0.004 and 0.016, respectively), apoptosis of tumor cells was more (p = 0.0009), and the disease-free survival rate and the overall survival rate were higher (p = 0.0057 and 0.0246, respectively), compared with DAP-kinase-negative cases. The status of DAP-kinase protein expression closely correlated with IFN-gamma-receptor and Fas expression (p = 0.038 and p < 0.0001, respectively), but not the methylation of promoter region. CONCLUSION: Hepatoma cells may escape from apoptosis through the loss or reduction of DAP-kinase expression, while the block of IFN-gamma signal transduction as well as the methylation of promoter region may reduce the expression of DAP-kinase protein.