Hepatic resection for metastasis from colorectal cancer

Summary Twenty-five patients who had hepatic metastases from carcinomas of the colon and rectum had resection for cure at Memorial Hospital, with a determinate five-year survival rate of 40 per cent, and 10-year survival rate of 28 per cent. Most of the hepatic metastatic lesions were solitary, small, and peripheral, and were treated with simple wedge resection. These favorable results justify an aggressive approach to solitary metastatic lesions in the liver.     

Hepatic resection for colorectal metastases

PURPOSE: Hepatic resection affords the best hope of survival for patients with colorectal carcinoma metastatic to the liver. However, recurrences are observed in about 60 percent of patients after curative hepatic resection. The purpose of this study was to examine the prognostic factors of patients undergoing curative hepatic resection for colorectal metastases. METHODS: Between April 1984 and September 1997, 168 patients underwent curative hepatic resection for colorectal metastases. The clinicopathologic factors studied for prognostic value were gender, age, primary site, nodal status of primary tumor, time of metastases, preoperative serum level of carcinoembryonic antigen, hepatic tumor size and distribution, number of metastases, type of hepatic resection, resection margin, presence of micrometastases in resected specimen and microscopic fibrous pseudocapsule between the hepatic tumor and surrounding hepatic parenchyma, nodal status of hepatoduodenal ligament, adjuvant regional chemotherapy, and perioperative transfusion. RESULTS: The overall survival was 42 percent at three years and 26 percent at five years, including a 3.5 percent 60-day surgical mortality rate. Thirty-one percent of patients had micrometastases located at a median distance of 3 mm from the metastatic tumor edge. Presence of microscopic fibrous pseudocapsule was observed in 28 percent of patients. Univariate and multivariate analyses showed that significant prognostic factors for survival were nodal status of primary tumor, number of metastases, resection margin, microscopic fibrous pseudocapsule, and adjuvant regional chemotherapy. CONCLUSIONS: We conclude that 1) hepatic resection is effective in select patients with colorectal metastases; 2) adequate resection margin and adjuvant regional chemotherapy can improve outcome; and 3) microscopic fibrous pseudocapsule may offer additional postoperative information as an independent prognostic factor.Presented at the 11th Biennial Scientific Meeting of the Asian Pacific Association for the Study of the Liver, Perth, Western Australia, February 16 to 20, 1998.     

Hepatic steatosis is associated with lower incidence of liver metastasis from colorectal cancer

Purpose

Both hepatic steatosis (HS) and colorectal cancer (CRC) are conditions associated with metabolic syndrome. The liver is the most frequent site of distant metastasis of CRC; however, the impact of HS on the incidence of liver metastasis of CRC is not clearly defined. Then, the correlation with the presence or absence of HS was analyzed.

Methods

A total of 604 CRC patients receiving curative surgical resection who had a preoperative non-enhanced computed tomography (CT) were enrolled. The mean attenuation values (in Hounsfield units) of the liver and spleen were obtained on a plain CT slice, and the patients with liver–spleen attenuation ratio lower than 1.1 were objectively defined as HS. The clinicopathological features of these patients were analyzed, and the association between HS and the clinical features of CRC was examined.

Results

Sixty-three (10.4 %) among the 604 patients were diagnosed as HS. Recurrence-free survival (RFS) and hepatic RFS, but not extrahepatic RFS, were significantly higher in the group with HS (p?=?0.04 and p?=?0.006). However, this effect was not evident in the group of patients with obesity, defined as body mass index?>?25.0. Among the stage I~III cases, HS was significantly associated with lower hepatic, but not extrahepatic, RFS. Moreover, absence of HS was an independent risk factor for hepatic RFS (p?=?0.003).

Conclusion

Metastases of CRC are less frequent in fatty liver. Steatosis may be an unfavorable microenvironment for metastatic formation in the liver.     

Pulmonary resection for metastases from colorectal cancer

BACKGROUND: We reviewed our experience in the surgical treatment of 47 patients with colorectal pulmonary metastases and investigated factors affecting their survival. METHOD: From September 1986 to December 1999, 47 patients underwent 59 thoracotomies for pulmonary metastases from colorectal cancer. RESULTS: The median interval between colorectal resection and lung resection (disease-free interval [DFI]) was 33 months. Overall, 5-year survival was 48%. Five-year survival was 51% for patients with solitary metastasis (n = 30), 47% for patients with ipsilateral multiple metastases (n = 11), and 50% for patients with bilateral metastases (n = 6), and there were no significant differences. Five-year survival was 80.8% for 14 patients with DFI of < 2 years and 39.7% for 30 patients with a DFI of > 2 years (p = 0.22). Five-year survival for 11 patients with normal prethoracotomy carcinoembryonic antigen (CEA) levels was 70%, and that for 26 patients with elevated prethoracotomy CEA levels (> 5 ng/mL) was 36% (p < 0.05). Eight patients had extrathoracic disease. The median survival time after pulmonary resection was 18.5 months, and the 5-year survival was 60%. A second resection for recurrent metastases was performed in five patients, and a third resection was done in one patient. All six patients are alive. The median survival of five patients who underwent a second thoracotomy was 22 months (range, 2 to 68 months), and one patient is alive 39 months after the third resection. CONCLUSION: Pulmonary resection for metastases from colorectal cancer may help prolong survival in selected patients, even with bilateral lesions, recurrent metastasectomy, or extrathoracic disease. Prethoracotomy CEA level was found to be a significant prognostic factor.     

Brain metastasis from colorectal cancer

Purpose The mechanism of brain metastasis is not well understood, but the affinity between cancer cells and neural tissues may be involved in the process. The aim of our study is to elucidate the involvement of neural cell adhesion molecule (NCAM) and therapeutic parameters in patients with brain metastasis from colorectal cancer.Methods We retrospectively identified 17 patients with brain metastasis from colorectal cancer. Data were collected with regard to patients characteristics, location, and stage of primary tumor, and extent and location of metastatic disease. NCAM histochemical staining was undertaken using a paraffin block, and compared with 56 Dukes C patients and 13 Dukes D patients.Results Neural cell adhesion molecule expression was significantly higher in the primary tumors of the brain metastasis patients than in the lesions of the Dukes C and Dukes D control groups (p=0.0004). Patients whose tumor was managed by radiosurgery survived longer than patients who had had whole brain radiation or those who had been left untreated.Conclusion The fact that NCAM expression was high in the primary tumors of brain metastasis patients suggests that the affinity of cancer cells to a particular organ is important for circulation-mediated metastasis. Controlling local tumors using radiosurgery is certainly going to play an important role in extending survival and improving the patients quality of life (QOL).     

Ovarian metastasis from colorectal cancer

Controversies exist regarding the surgical treatment of the ovaries in women with primary colorectal cancer. A review of the authors' experience and the surgical literature reveals an incidence of ovarian metastases from colorectal cancer of approximately 6 percent. This problem may occur somewhat more frequently in premenopausal women. Resection of the ovaries at the time of colectomy is unlikely to affect survival. Removal of the ovaries at the time of bowel resection will prevent repeat laparotomy to resect an ovarian mass in approximately 2 percent of women with large bowel cancer. Oophorectomy should be performed in all postmenopausal females at the time of primary resection. Oophorectomy should be performed in premenopausal women if any gross abnormality of the ovary is detected or if peritoneal implants are seen at the time of primary resection.     

Preoperative selection of patients with colorectal cancer liver metastasis for hepatic resection

Surgical resection of colorectal liver metastases(CRLM) has a well-documented improvement in survival. To benefit from this intervention, proper selection of patients who would be adequate surgical candidates becomes vital. A combination of imaging techniques may be utilized in the detection of the lesions. The criteria for resection are continuously evolving; currently, the requirements that need be met to undergo resection of CRLM are: the anticipation of attaining a negative margin(R0 resection), whilst maintaining an adequate functioning future liver remnant. The timing of hepatectomy in regards to resection of the primary remains controversial; before, after, or simultaneously. This depends mainly on the tumor burden and symptoms from the primary tumor. The role of chemotherapy differs according to the resectability of the liver lesion(s); no evidence of improved survival was shown in patients with resectable disease who received preoperative chemotherapy. Presence of extrahepatic disease in itself is no longer considered a reason to preclude patients from resection of their CRLM, providing limited extra-hepatic disease, although this currently is an area of active investigations. In conclusion, we review the indications, the adequate selection of patients and perioperative factors to be considered for resection of colorectal liver metastasis.     

Perioperative chemotherapy with bevacizumab and liver resection for colorectal cancer liver metastasis

Background:

Surgery remains the only curative option for patients with colorectal cancer liver metastases (CRLM). Perioperative chemotherapeutic strategies have become increasingly popular in the treatment of CRLM. Although the role of bevacizumab (Bev) in this setting remains unclear, its widespread use has raised concerns about the use of Bev as part of perioperative chemotherapy.

Methods:

We retrospectively reviewed all patients who received Bev and underwent liver resection between July 2004 and July 2008 at the McGill University Health Center. Chemotherapy-related toxicity, response to chemotherapy, surgical morbidity and mortality, liver function and survival data were assessed.

Results:

A total of 35 patients were identified. Of these, 26 (74.3%) patients received oxaliplatin-based cytotoxic chemotherapy, six (17.1%) received irinotecan-based therapy and the remainder received both agents. A total of 17 patients (48.6%) underwent portal vein embolization prior to resection and 12 (34.3%) underwent staged resection for extensive bilobar disease. A median of six cycles of preoperative Bev were administered. Nine patients (25.7%) experienced grade 3 or higher chemotherapy-related toxicities. Four events were deemed to be related to Bev. The overall response rate was 65.7% (complete and partial response). One patient progressed on therapy, but this did not prevent R0 resection. The incidence of postoperative morbidity was 42.3%. A total of 21.7% of complications were Clavien grade 3 or higher. There were no perioperative mortalities. There were no cases of severe sinusoidal injury or steatohepatitis. The Kaplan–Meier estimate of 4-year survival was 52.5%.

Conclusions:

These data confirm the safety of chemotherapy regimens which include Bev in the perioperative setting and demonstrate that such perioperative chemotherapy in patients with CRLM does not adversely affect patient outcome. There was no increase in perioperative morbidity compared with published rates. The addition of Bev to standard chemotherapy may improve response rates, which may, in turn, impact favourably on patient survival.     

Treatment strategies for hepatic metastasis from colorectal cancer

Hepatic micrometastases of the parenchyma adjacent to a macroscopic lesion were detected in 17 of 31 resected liver metastases. Fifty-nine micrometastatic lesions were detected in total; 26 lesions were situated in the portal vein (PV), 22 in the central vein (CV), 5 in the bile duct (BD), and 6 in the sinusoid (SS). A histological study confirmed the direct invasion of the macrometastatic cancer cells into the adjacent PV, CV, BD, and SS. According to the tumor doubling time, the mean diameter of the macrometastases in 19 remnant livers was calculated to have been 0.57±0.87 cm at the time of the primary resection. The calculated diameter of 3 of these 19 macrometastases was found to be less than 0.01 cm, the minimum implantable size, indicating that the cancer recurrence in these specimens may have developed from macroscopic metastatic lesions as a satellite, and not from the primary tumor. In 13 patients who received doses of 5250 mg or more of 5 fluorouracil (FU) via the hepatic artery, the cumulative disease-free rate 2 years postoperatively was 100%; this value was 47.6% in 11 patients who received less than 5250 mg of 5 FU via the hepatic artery, and 0% in 39 patients who received no chemotherapy (P<0.005). These results suggest that anatomical hepatic resection for satellite lesions, combined with prophylactic hepatic arterial chemotherapy for micrometastases, decreases the recurrence rate of hepatic metastases in the remnant liver.     

Hepatic resection for metastasis from adenoid cystic carcinoma of parotid gland.

Adenoid cystic carcinoma is the commonest malignant tumor of the submandibular and minor salivary glands; the parotid gland constitutes a small share of this neoplasm. We present a 30-year-old woman with solitary liver metastasis from an adenoid cystic carcinoma of the parotid gland, which had been surgically treated 10 years ago. The patient underwent successful resection of this metastasis.     

Hepatic resections for bilobar liver metastases from colorectal cancer

The present study was performed to assess survival benefits in patients who underwent a hepatic resection for isolated bilobar liver metastases from colorectal cancer. Thirty-eight patients underwent a curative hepatic resection for isolated colorectal liver metastasis. Among them, 11 patients had bilobar liver metastases and 19 had a solitary metastasis. The remaining 8 patients had unilobar multiple lesions. We investigated survival in two groups those with bilobar and those with solitary metastatic tumors. Survival and disease-free survival were 36% and 18% at 5 years, respectively, in the patients with bilobar liver metastases, while these survivals were 43% and 34% in the patients with solitary liver metastasis. In the 38 patients, repeated hepatic resections were performed in 15 patients with recurrent liver disease. The 5-year survival and disease-free survival rates for these patients were 38% and 27%, respectively, after the second hepatic resections. Of the 11 patients with bilobar liver metastases, 5 underwent a repeated hepatic resection, and they all survived for over 42 months. Based on our observations, a hepatic resection was thus found to be effective even in selected patients with either bilobar nodules or recurrence in the remnant liver.     

Therapeutic options for peritoneal metastasis arising from colorectal cancer

Peritoneal metastasis is a common sign of advanced tumor stage, tumor progression or tumor recurrence in patients with colorectal cancer. Due to the improvement of systemic chemotherapy, the development of targeted therapy and the introduction of additive treatment options such as cytoreductive surgery(CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC), the therapeutic approach to peritoneal metastatic colorectal cancer(pm CRC) has changed over recent decades, and patient survival has improved. Moreover, in contrast to palliative systemic chemotherapy or best supportive care, the inclusion of CRS and HIPEC as inherent components of a multidisciplinary treatment regimen provides a therapeutic approach with curative intent. Although CRS and HIPEC are increasingly accepted as the standard of care for selected patients and have become part of numerous national and international guidelines, the individual role, optimal timing and ideal sequence of the different systemic, local and surgical treatment options remains a matter of debate. Ongoing and future randomized controlled clinical trials may help clarify the impact of the different components, allow for further improvement of patient selection and support the standar-dization of oncologic treatment regimens for pm CRC. The addition of further therapeutic options such as neo-adjuvant intraperitoneal chemotherapy or pressurized intraperitoneal aerosol chemotherapy, should be investig-ated to optimize therapeutic regimens and further improve the oncological outcome.     

Repeated liver resection for recurrent metastases from colorectal cancer

BACKGROUND/AIMS: Repeat hepatectomy is the most effective treatment for recurrent colorectal liver metastases. We aim to assess how repeated liver resections increase survival, without unacceptable surgical risk. METHODOLOGY: Between December 1992 and December 1998, among 19 patients, 5 underwent secondary resection of recurrent metastatic disease. Following the primary liver surgery, three patients had systemic chemotherapy with 5-fluorouracil and two locoregional chemotherapy via Port-a-cath in the gastroduodenal artery. We evaluated survival and we compared time of surgery, duration of Pringle maneuver, blood losses and postoperative stay in the hospital between first and second liver surgery. RESULTS: Perioperative mortality at second liver resection was nil; morbidity minor; mean duration of surgery 320 vs. 260 min; Pringle maneuver 35 vs. 25 min; blood losses 1300 vs. 650 mL; postoperative stay 12.6 vs. 11.5 days. Mean total survival from time of colon resection was 50 months. As an interesting secondary finding, we observed prolonged inhibition of liver regeneration following treatment with Methotrexate. CONCLUSIONS: Repeated hepatic resection is a safe procedure for selected patients. Surgical risk is slightly increased, but the risk/benefit ratio is definitely in favor of as many repeated resections as needed, whenever there is a chance of curative surgery.