Martin A. Adson

The natural history of hepatic metastases from colorectal cancer. A comparison with resective treatment.

Five-year survival after resection of hepatic metastases from colorectal cancer is 25%. Although resection palliates some patients who do not live that long, 50% of patients so treated are not helped at all. Until ignorance of a cancers real stage is resolved by improved techniques, the evaluation and choice of therapy can be based only upon knowledge of the natural history of untreated metastases and determinants of prognosis derived from treated patients. Analysis of the survival rates of 252 patients who had biopsy proven, unresected hepatic metastases that were the only evidence of residual disease shows the extent to which natural history, rather than resection, may determine length of survival—and indicates the need for critical analysis of 2− and 3-year survival rates reported after any therapy. Study of 141 patients who had hepatic metastases resected shows that the stage of the primary lesion, being female, and the absence of extrahepatic metastases are significant determinants of favorable prognosis after resection of hepatic metastases.

Perioperative blood transfusion and determinants of survival after liver resection for metastatic colorectal carcinoma.

The authors reviewed their institutional experience with liver resection for metastatic colorectal carcinoma to (1) determine whether perioperative blood transfusion affects survival; (2) identify prognostic determinants; and (3) estimate the patient requirement for a prospective randomized trial designed to demonstrate efficacy of liver resection. Two hundred eighty consecutive patients treated by potentially curative liver resection between 1960 and 1987 were included. Data were obtained for all but 10 patients for at least 5 years after operation or through 1990. Actuarial survival curves related to potential prognostic determinants were analyzed with the log-rank test. Overall, survival was 47 ± 3% at 3 years and 25 ± 3% at 5 years, including 4% 60-day operative mortality rate. Eighty-one patients who did not receive blood 7 days before to 14 days after operation had 60 ± 6% 3-year and 32 ± 6% 5-year survival compared with 40 ± 4% and 21 ± 3% survival rates for 183 patients who received at least one unit (p = 0.03, operative deaths excluded). Extra-hepatic disease (p = 0.015), extrahepatic lymph node involvement (p = 0.002), satellite configuration of multiple metastases (p = 0.0052), and initial detection by abnormal liver enzymes (p = 0.0005) were associated with poor survival rates. Synchronous presentation of metastatic and stage B primary disease was associated with a favorable prognosis (p = 0.003). The requirement for a prospective randomized trial estimated by an exponential survival model would be 36, 74, 168, or 428 patients if 5-year survival without resection were 1, 5, 10, or 15%. We conclude that (1) perioperative blood transfusion may be adversely associated with survival; (2) extrahepatic disease, extrahepatic lymph node involvement, satellite configuration, and initial detection by clinical examination or a liver enzyme abnormality portend a poor prognosis; and (3) a prospective randomized trial of liver resection is impractical because of the large patient requirement, at least by a single institution.

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.

Major hepatic resections for metastatic colorectal cancer.

In 1973, our study of patients with resectable hepatic metastases from colorectal cancer compared survival of 60 patients who had metastases removed with survival of 60 patients with similar lesions that had been biopsied only. We concluded that excision of small, apparently solitary metastatic lesions could be justified on the basis of the low operative risk and prolonged survival. However, the risks and benefits of resection of larger metastatic lesions could not be determined by that earlier study, because only seven of those patients had lesions so large as to require major hepatic resection. Therefore, to evaluate size as a determinant of prognosis after resection, we added to those 7 patients 27 others who were managed since 1973 by major hepatic resection of larger metastases. There were two hospital deaths. Of the 32 surviving patients, 82% lived one year or more, 77% 18 months or more, 58% two years or more, and 41% three years or more postoperatively. Three patients are living 10–22 years after resection. We conclude from a critical analysis of the duration and quality of life of surviving patients that at least 20% and perhaps 30% of these patients were benefited by major hepatic resection of their large hepatic metastasis.

Trends in morbidity and mortality of hepatic resection for malignancy. A matched comparative analysis.

ObjectiveThe authors define more clearly the trends in morbidity and mortality after hepatic resection for malignant disease in matched patient groups during two discrete time periods. Summary Background DataRecent reports have shown improvement in operative morbidity and mortality associated with hepatic resection; however, results often included resections for benign disease and trauma. Furthermore, specific factors contributing to the improvement in operative risks between the last two decades have not been defined. MethodsA retrospective matched comparative analysis was conducted of patients with primary and metastatic hepatic malignancy resected with curative intent between two periods (1976 to 1980 and 1986 to 1990). Eighty-one patients met our inclusion criteria in the early period; this group was matched with 81 patients from the latter period by the following four parameters: age, gender, type of malignant disease, and extent of resection. Records of these two patient groups were abstracted for clinical presentation, co-morbid factors, operative techniques, and perioperative morbidity and mortality. ResultsThe authors found a significant decrease in operative morbidity, median perioperative transfusion, and length of hospital stay in the latter period (1986 to 1990). The incidence of postoperative subphrenic abscess and intra-abdominal hemorrhage was significantly lower during this period. Operative mortality rate was similar for both periods, 4.9% and 1.2%, respectively (p > 0.05). ConclusionHepatic resection for malignant disease currently can be performed with a low morbidity and mortality in the hands of trained and experienced hepatic surgeons; operative risks of hepatic resection should not deter its application in the treatment of primary and metastatic malignant diseases of the liver.

Sigmoid diverticulitis with perforation and generalized peritonitis

Sigmoid diverticulitis with perforation and generalized peritonitis is a grave complication of diverticular disease. To compare accurately the results of two operative approaches—proximal colostomy with drainage and proximal colostomy with resection or exteriorization—the authors assessed the clinical and pathologic features of 121 consecutive patients with perforating sigmoid diverticulitis. There were no differences between treatment groups in age, sex, mean duration of symptoms, clinical presentation, number of coexistent diseases, type of peritonitis or chronic corticosteroid use. Overall mortality for emergency operation was 12 percent. Mortality was significantly greater (P<0.05) among the 31 patients treated by colostomy and drainage (26 percent) than among the 90 patients treated by colostomy and resection or exteriorization (7 percent). Seven of the nine patients who died from persistent sepsis had undergone colostomy and drainage. Four clinical factors were found to be predictive of mortality (P<0.05): persistent postoperative sepsis, fecal peritonitis, preoperative hypotension, and prolonged duration of symptoms. These factors identified a subgroup of patients who, because of an increased risk of death, would be likely to benefit from the more complete eradication of the septic focus that is achieved by colostomy and resection.

Cavernous hemangiomas of the liver: Resect or observe?

Surgical decisions regarding cavernous hemangioma of the liver require consideration of the natural history of the lesion. To provide background, we retrospectively evaluated 49 cases of such hemangiomas exceeding 4 cm in diameter. There were 36 female patients (including 4 infants) and 13 males. Their ages ranged from 1 month to 68 years and averaged 44 years. Surgical procedures that ranged from simple excision to hepatic lobectomy were performed on 13 patients. Four had postoperative complications. There were no surgical deaths or any late deaths attributable to hemangioma. The other 36 patients have been observed for up to 15 years (mean 5.5 years) without the need for surgery. None of the patients in this group died, and none has experienced intraperitoneal hemorrhage or intensification of symptoms, although the size of four lesions increased. The benign course should be considered when deciding on management of lesions that are asymptomatic or so large as to pose significant operative risk.

Hepatoma in the noncirrhotic liver.

The pathologic features, clinical presentation and natural history of hepatocellular carcinoma (HCC) developing in the noncirrhotic liver were studied in 61 patients against a background of 63 patients seen concurrently with HCC complicating cirrhosis. Noncirrhotic HCC had a bimodal age distribution, with females predominating the first age‐clustering (10–50 years) and males predominating the second age‐clustering (50–90 years). Cirrhotic HCC had a unimodal age distribution (40–90 years) with male dominance throughout. Estrogen exposure was noted in 57% of the noncirrhotic HCC women overall and in 80% of those in the younger age‐clustering. The majority of noncirrhotic HCC presented with a single hepatic mass or a dominant primary with satellite lesions in contrast to the usual multinodular or diffuse disease seen with cirrhosis. Twenty‐nine noncirrhotic patients survived complete resection of disease limited to the liver and exhibited a median survival of 2.7 years with a 5‐year survival of 25%. Low histologic grade, minimal necrosis, and the absence of hemoperitoneum, hepatomegaly, and adjacent organ involvement were all favorable prognostic variables. Patients with metastatic or locally unresectable noncirrhotic HCC had a median survival of 9 months, and 24% survived in excess of 2 years. This survival experience is significantly more favorable than cirrhotic HCC patients, who had only a 1.2‐month median and a 3% 2‐year survival. Low histologic grade, mild mitotic activity and the presence of some fibrosis within the specimen were associated with a favorable outcome in advanced noncirrhotic HCC. The favorable prognosis and heterogeneous composition of the noncirrhotic, when compared to the cirrhotic HCC cohort, may be important considerations in the design and evaluation of future clinical trials.

Carcinoma of the Gallbladder

Because primary carcinoma of the gallbladder is asymptomatic in its early, potentially curable stages, three-fourths of patients have unresectable disease at the time of surgical evaluation; for the others, the lesion is found most often incidentally during operations for calculus disease. Thus, reported 5-year survival rates of less than 5 per cent chiefly reflect the results of surgical experience with two groups of patients – the untreated and the undertreated.

Analysis of failure following curative irradiation of gallbladder and extrahepatic bile duct carcinoma

Twenty patients with carcinoma of the gallbladder (GB-4 patients) or extrahepatic bile ducts (EHBD-16 patients) received radiation therapy with curative intent between January, 1980 and December, 1982. All 20 received 4500-5000 rad in 180-200 rad fractions to the tumor and regional lymph nodes. A 1000 to 1500 rad external beam boost was delivered in 180-200 rad fractions in 10 patients who received external beam alone or concomitant 5-Fluorouracil (5-FU). Three of the four GB and 5 of the 16 EHBD patients received a transcatheter boost with 192-Iridium (192Ir) to a dose of 2000-2500 rad calculated at a 0.5-0.1 cm radius. An additional 2 patients with EHBD lesions received an intraoperative electron (IORT) boost of 1500-2000 rad in one fraction calculated to the 90% isodose. Survival and patterns of failure were analyzed by site and treatment method. All four patients with GB carcinoma are dead of disease at 5 1/2, 6, 9 and 10 months from the date of diagnosis respectively. Three of the four developed diffuse peritoneal carcinomatosis. Five of the 16 patients with EHBD carcinoma are alive with a median follow-up of 18 months (range 6-23 months). Four of the 5 patients received a transcatheter 192Ir or IORT boost and all are without evidence of disease. Four of 9 patients who had a subtotal resection with transection of tumor, dilatation of the bile ducts with probes or curettement of the bile ducts developed either diffuse peritoneal carcinomatosis (3 patients) or a recurrence in the surgical scar (2 patients). Local failure was documented in 3 of the nine patients treated with external beam alone +/- 5-FU, and has been documented in one of the seven patients who received an IORT or transcatheter 192Ir boost. Further experience is necessary to determine whether this aggressive treatment will result in long-term disease-free survival in these patients.