Glenn Steele

Resection of Hepatic Metastases from Colorectal Cancer Biologic Perspectives

During the past decade the results of slightly fewer than 1000 resections of liver metastases from colorectal carcinoma have been analyzed, retrospectively reanalyzed, and reviewed. The following are confirmed conclusions: major liver resection can be performed safely (less than a 5% operative mortality rate); 20% to 25% of these patients are cured; no other regional therapy options have any curative potential. The following caveats are also obvious: most patients who are operated on are not cured; although predictors have been proposed to select patients most likely to benefit from surgery, none is discriminating in and of itself; most therapy questions in this group of patients have not been addressed in any formal way; surgery for isolated regionally recurrent colon and rectum carcinoma remains an important stopgap only until effective systemic therapy is discovered. This review of our own and other single and multi-institutional prospective and retrospective data will be framed by the following questions. (1) Does resection of liver metastases cure patients or simply select those who would have survived in the long-term without any therapy? (2) In the absence of any formalized, properly designed trial, how can one judge the benefit of resection? (3) Why do metastases recur only in the liver? (4) What new therapies should focus on the predominant secondary failure sites in the majority of patients who do not benefit from hepatic metastasis resection?

Surgical margin in hepatic resection for colorectal metastasis: a critical and improvable determinant of outcome.

OBJECTIVE To update the analysis of technical and biologic factors related to hepatic resection for colorectal metastasis in a large single-institution series to identify important prognostic indicators and patterns of failure. SUMMARY BACKGROUND DATA Surgical therapy for colorectal carcinoma metastatic to the liver is the only potentially curable treatment. Careful patient selection of those with resectable liver-only metastatic disease is crucial to the success of surgical therapy. METHODS Two hundred forty-four consecutive patients undergoing curative hepatic resection for metastatic colorectal carcinoma were analyzed retrospectively. Variables examined included sex, stage of primary lesion, size of liver lesion(s), number of lesions, disease-free interval, ploidy, differentiation, preoperative carcinoembryonic antigen level, and operative factors such as resection margin, use of cryotherapy, intraoperative ultrasound, and blood loss. RESULTS Surgical margin, number of lesions, and carcinoembryonic antigen (CEA) levels significantly control prognosis. Patients with only one or two liver lesions, a 1-cm surgical margin, and low CEA levels have a 5-year disease-free survival rate of more than 30%. Disease-free interval, original stage, bilobar involvement, size of metastasis, differentiation, and ploidy were not significant predictors of recurrence. The pattern of failure correlates with surgical margin. Routine use of intraoperative ultrasound resulted in an increased incidence of negative surgical margin during the period examined. CONCLUSIONS Surgical resection or cryotherapy of hepatic metastasis from colorectal cancer is safe and curable in appropriately selected patients. Biologic factors, such as number of lesions and carcinoembryonic antigen levels, determine potential curability, and surgical margin governs the patterns of failure and outcome in potentially curable patients. Optimization of selection criteria and surgical resection margins will improve outcome.

Resection of the liver for colorectal carcinoma metastases. A multi-institutional study of long-term survivors.

In this review of a collected series of patients undergoing hepatic resection for colorectal metastases, 100 patients were found to have survived greater than five years from the time of resection. Of these 100 long-term survivors, 71 remain disease-free through the last follow-up, 19 recurred prior to five years, and ten recurred after five years. Patient characteristics that may have contributed to survival were examined. Procedures performed included five trisegmentectomies, 32 lobectomies, 16 left lateral segmentectomies, and 45 wedge resections. The margin of resection was recorded in 27 patients, one of whom had a positive margin, nine of whom had a less than or equal to 1-cm margin, and 17 of whom had a greater than 1-cm margin. Eighty-one patients had a solitary metastasis to the liver, 11 patients had two metastases, one patient had three metastases, and four patients had four metastases. Thirty patients had Stage C primary carcinoma, 40 had Stage B primary carcinoma, and one had Stage A primarycarcinoma. The disease-free interval from the time of colon resection to the time of liver resection was less than one year in 65 patients, and greater than one year in 34 patients. Three patients had bilobar metastases. Four of the patients had extrahepatic disease resected simultaneously with the liver resection. Though several contraindications to hepatic resection have been proposed in the past, five-year survival has been found in patients with extrahepatic disease resected simultaneously, patients with bilobar metastases, patients with multiple metastases, and patients with positive margins. Five-year disease-free survivors are also present in each of these subsets. It is concluded that five-year survival is possible in the presence of reported contraindications to resection, and therefore that the decision to resect the liver must be individualized.

The DCC protein and prognosis in colorectal cancer

BACKGROUND Allelic loss of chromosome 18q predicts a poor outcome in patients with stage II colorectal cancer. Although the specific gene inactivated by this allelic loss has not been elucidated, the DCC (deleted in colorectal cancer) gene is a candidate. We investigated whether the expression of the DCC protein in tumor cells is a prognostic marker in colorectal carcinoma. METHODS The expression of DCC was evaluated immunohistochemically in 132 paraffin-embedded samples from patients with curatively resected stage II and III colorectal carcinomas. The Cox proportional-hazards model was used to adjust for covariates including age, sex, tumor site, degree of tumor differentiation, and use of adjuvant therapy. RESULTS The expression of DCC was a strong positive predictive factor for survival in both stage II and stage III colorectal carcinomas. In patients with stage II disease whose tumors expressed DCC, the five-year survival rate was 94.3 percent, whereas in patients with DCC-negative tumors, the survival rate was 61.6 percent (P<0.001). In patients with stage III disease, the respective survival rates were 59.3 percent and 33.2 percent (P=0.03). CONCLUSIONS DCC is a prognostic marker in patients with stage II or stage III colorectal cancer. In stage II colorectal carcinomas, the absence of DCC identifies a subgroup of patients with lesions that behave like stage III cancers. These findings may thus have therapeutic implications in this group of patients.

Continuous Innovation In Health Care: Implications Of The Geisinger Experience

To achieve the diverse health care goals of the United States, health care value must increase. The capacity to create value through innovation is facilitated by an integrated delivery system focused on creating value, measuring innovation returns, and receiving market rewards. This paper describes the Geisinger Health Systems innovation strategy for care model redesign. Geisingers clinical leadership, dedicated innovation team, electronic health information systems, and financial incentive alignment each contribute to its innovation record. Although Geisingers characteristics raise serious questions about broad applicability to nonintegrated health care organizations, its experience can provide useful insights for health system reform.

The National Cancer Data Base report on colon cancer

BACKGROUND Commission on Cancer data from the National Cancer Data Base (NCDB) report time trends in stage of disease, treatment patterns, and survival for patients with selected cancers. The most current data (1993) for patients with colon cancer are described. METHODS Five calls for data yielded 3,700,000 cases of cancer for the years 1985 through 1993 from hospital cancer registeries across the U.S., including 36,937 cases of colon cancer from 1988 and 44,812 from 1993. RESULTS Interesting trends are as follows: (1) the elderly ( > 80 years) present with earlier stage disease than younger patients; (2) the National Cancer Institute recognized cancer centers have more patients with advanced disease than other types of hospitals; (3) all ethnic groups have generally similar stages of disease at presentation, except for African-Americans who have a slightly higher incidence of Stage IV disease; (4) the proximal migration of the primary cancer continues with 54.7% of primary colon cancer arising in the right colon in 1993 compared with 50.9% in 1988; (5) an interaction between grade and stage of cancer seems present; and (6) patients with Stage III colon cancer who received adjuvant chemotherapy had a 5% improvement in 5-year relative survival. CONCLUSIONS The NCDB data are useful for reporting what cancer treatments are being administered and what outcomes are occurring in the U.S. The data suggest an important biologic role for grade of cancer. They also suggest that African-Americans and other ethnic groups have the same outcome as non-Hispanic whites but that access to medical care may still be less. Finally, the utility of adjuvant therapy for Stage III colon cancer may just be beginning to be appreciated.

Clinical highlights from the National Cancer Data Base: 1996

The National Cancer Data Base, a joint project of the American Cancer Society and the American College of Surgeons Commission on Cancer, provides a mechanism for periodic assessment of hospital-based cancer patient care. From its annual summary, health care professionals can evaluate trends in patient care to make more efficient treatment decisions. This article provides a first look at highlights from the 1996 annual summary.

Factors influencing survival in patients with hepatic metastases from adenocarcinoma of the colon or rectum.

The median survival of all patients with hepatic metastases from colorectal cancer referred to the Sidney Farber Cancer Institute during a five-year period was 12.5 months. Two major factors influenced survival. The first was extent of disease at presentation. The second was the histologic grade of the cancer. The median survival of patients presenting with the least disease, characterized by less than four liver nodules visible on liver scan (n=38), normal liver size on physical examination (n=60), normal liver function test results (n=30), and normal performance status (n=91), was between 18 and 24 months, regardless of treatment. The median survival of those few patients (n=13) who had objective responses to a variety of treatments, most of whom also had minimal disease at presentation, was also 24 months. Patients whose tumors were poorly differentiated or who had abnormal performance status or weight loss of greater than 10 per cent at presentation survived only six months (median). Those with four or more liver nodules, hepatomegaly (greater than 16-cm vertical span on physical examination), or abnormal liver function test results, survived ten, eight, and 12 months (median), respectively. It is concluded that a significant group of patients survived longer than would have been predicted by earlier literature surveys after the diagnosis of colorectal cancer metastatic to the liver. It is suggested that future therapeutic trials, using survival as a measure of response of patients with liver metastases from colorectal cancer, must be prospectively controlled before selection factors can be differentiated from significant therapy effect.

ProvenCareSM: a provider-driven pay-for-performance program for acute episodic cardiac surgical care.

Objective:To test whether an integrated delivery system could successfully implement an evidence-based pay-for-performance program for coronary artery bypass graft (CABG) surgery. Methods:The program consisted of 3 components: (1) establishing implementable best practices; (2) developing risk-based pricing; (3) establishing a mechanism for patient engagement. Surgeons reviewed all class I and IIa “2004 American Heart Association/American College of Cardiology Guidelines for CABG Surgery” and translated them into 40 verifiable behaviors. These were imbedded within a new ProvenCareSM program and “hardwired” within the electronic health record system, including order sets, templates, and “time outs”. Concurrently preoperative, inpatient, and postoperative care within 90 days was packaged into a fixed price. A Patient Compact was developed to highlight the importance of patient activation. All elective CABG patients treated between February 2, 2006 and February 2, 2007 were included (ProvenCareSM Group) and compared with 137 patients treated in 2005 (Conventional Care Group). Results:Initially, only 59% of patients received all 40 best practice components. At 3 months, program compliance reached 100%, but fell transiently to 86% over the next 3 months. Reliability subsequently increased to 100% and was sustained for the remainder of the study period. The overall trend in reliability was significant at P = 0.001. Thirty-day clinical outcomes showed improved trends (Table 1) but only the likelihood of discharge to home reached statistical significance. Length of stay decreased by 16% and mean hospital charges fell 5.2%. TABLE 1. Thirty-day Clinical Outcomes Conclusion:A provider-driven pay-for-performance process for CABG, enabled by an electronic health record system, can reliably deliver evidence-based care, fundamentally alter reimbursement incentives, and may ultimately improve outcomes and reduce resource use.

The Use of Preoperative Plasma CEA Levels for the Stratification of Patients After Curative Resection of Colorectal Cancers

One hundred forty-five patients with colorectal cancer were analyzed in order to correlate the preoperative plasma carcinoembryonic antigen (CEA) levels with the sites and times of disease recurrence. The median follow-up periods of these patients was 50 months (range 36–72 months). Twenty-one patients were found to have metastases at the time of their operation. None of the seven patients whose primary tumors were classified as Dukes/Kirklin A have had tumor recurrence. Seventeen per cent of the patients with Dukes/Kirklin B tumors have had tumor recurrences, and 63% of the patients with Dukes/Kirklin C colorectal primary tumors have had tumor recurrence. No correlation was found between preoperative CEA values and subsequent risk of tumor recurrence or times to recurrence among the patients with Dukes/Kirklin B colorectal primary cancers. In Dukes/Kirklin C patients, however, elevated preoperative CEA values predicted a higher risk of tumor recurrence. Ninety per cent of the patients (19/21) with preoperative CEA levels greater than 5.0 ng/ml have had relapses, with a median time of 17 months before disease recurrence. Only 39% (9/23) of the patients with Dukes/Kirklin C lesions and CEA levels less than 5 ng/ml have had relapses and there is insufficient follow-up data as yet to determine the median survival time. If those patients whose Dukes/Kirklin C primary tumors were poorly differentiated on histologic examination are excluded, the contrast between patients having CEA levels greater than 5.0 ng/ml and those having CEA levels less than 5 ng/ml is even more marked. Sixteen of the 18 remaining patients whose CEA levels were greater than 5.0 ng/ml prior to curative resection have had relapses as compared with only three of 15 patients whose preoperative CEA values were less than 5. We conclude, therefore, that CEA is an important factor in stratifying patients after curative resection of their Dukes/Kirklin C colorectal tumors.