Hepatic resection for metastatic colorectal cancer

One-hundred thirty-one primary hepatic resection for colorectal secondary tumors were performed at Rush-Presbyterian-St. Luke's Medical Center between 1975 and 1993. Perioperative mortality occurred in five patients (3.8%). Twenty-three patients had minor morbidities (18%); major morbidity occurred only in the five patients who died. Curative resections were performed in 107 patients. Overall actuarial survival at 2, 3, and 5 years was 62, 42, and 25 per cent, respectively. Patients with extrahepatic disease (5-year survival, 0% vs 27%; P = 0.049) and positive resection margins (0% vs 30%; P < 0.001) had significantly poorer survival. Among the curative resections, patients who had metachronous hepatic resections did significantly better than those who underwent synchronous colon and hepatic resections (35% vs 13%; P = 0.002). This survival benefit persisted when comparison was restricted to patients with synchronous metastases. Age, sex, race, number of lesions, site of colon primary resection, blood transfusion, disease-free interval, and extent of resection had no effect on survival. All patients who are acceptable surgical risks with potentially resectable metastatic colorectal cancer confined to the liver should undergo exploration. Assessment of resectability should include intraoperative ultrasound in all patients to maximize the probability of tumor clearance.     

Genetic alterations in primary and secondary hyperparathyroidism

OBJECTIVE: To evaluate treatment of patients with primary liver cancer. DESIGN: Prospective protocol including subsets of randomised studies. SETTING: University hospital, Sweden. SUBJECTS: 123 patients with primary liver cancer. INTERVENTIONS: 64 patients underwent hepatic resection, 25 were included in a trial of adjuvant chemotherapy. 24 further patients whose tumours were not resectable were included in a trial of intra-arterial infusion of doxorubicin. MAIN OUTCOME MEASURES: Survival and postoperative morbidity. RESULTS: The median survival time for patients who had had resections was 11 months (range 0-111). Twelve per cent survived more than 5 years. No prognostic factor had any significant effect on outcome. The postoperative mortality was 11% (7/64). The patients allocated to adjuvant chemotherapy survived a median of 10 months (range 1-47) and the controls 29 months (range 8-111) (p=0.04). Patients with unresectable liver cancer treated with intra-arterial doxorubicin lived no longer than untreated controls (median 8 months (range 1-56) compared with 7 months (range 1-28)). CONCLUSIONS: Treatment of patients with primary liver cancer is still an unsolved problem. Adjuvant chemotherapy with doxorubicin had no beneficial effect on survival.     

Combination of systemic acetazolamide and topical dorzolamide in reducing intraocular pressure and aqueous humor formation

BACKGROUND: Neuroendocrine tumors commonly metastasize to the liver. Although surgical resection is considered a treatment option for patients with localized metastases confined to the liver, the longterm survival benefit of liver resection has not been clearly demonstrated. We examined the survival of patients undergoing liver resection for this disease. STUDY DESIGN: Between 1984 and 1995, we evaluated 38 patients with liver-only metastases from neuroendocrine tumors, including 21 carcinoid, 13 islet cell, and 4 atypical neuroendocrine neoplasms. Data from a combined prospective and retrospective database and a tumor registry were analyzed. Of these patients, 15 underwent complete resection of all known disease. The remaining 23 patients, who also had disease confined to the liver, had comparable tumor burden but were believed to be unresectable. The longterm survival rates of these two groups were compared. RESULTS: Patients who underwent liver resection did not differ from those who were unresectable with regard to age, pathology, primary tumor site, serum alkaline phosphatase levels, or percentage of the liver involved. All resections were complete, leaving no residual disease, and consisted of lobectomy (n = 3), segmentectomy (n = 1), and wedge resections (n = 11). There were no operative deaths. Patients who underwent hepatic resection had a significantly longer survival than unresected patients. Although median survival had not been reached in resected patients, the median survival in the unresectable group was 27 months. Patients who underwent liver resection had a higher 5-year actuarial survival (73% versus 29%). CONCLUSIONS: Hepatic resection in selected patients with isolated liver metastases from neuroendocrine tumors may prolong survival. This conclusion was reached by comparing our resected group with an unresectable group with similar tumor burden.     

Determinants of survival following hepatic resection for metastatic colorectal cancer

Hepatic resection remains the only potentially curative treatment for metastatic colorectal cancer. This retrospective review study was undertaken in an attempt to identify factors that influence patient survival following hepatic resection for metastatic colorectal cancer. From January 1978 to December 1993, a total of 301 patients underwent a total of 345 planned hepatic resections for metastatic colorectal cancer. Of those, 245 patients had one resection, 44 had two resections, and 12 had three resections. For all patients the overall median survival was 20.6 months, operative mortality was 1.1%, and overall morbidity was 17.2%. Average hospital stay was 9 days. Statistical analysis included univariate analysis using log rank comparisons, Kaplan-Meier survival curves, and multivariate analysis using Cox proportional hazards regression. The statistically significant factors that influenced survival were distribution of liver metastases, unilobar versus bilobar (p = 0.0001), resected versus nonresected (p < 0.0001), and tumor-free surgical margins versus positive margins (p = 0.001). Surprisingly, the disease-free interval and the original stage of the primary tumor did not predict survival (p = not significant). Other factors that had no influence on survival were type of resection, size and number of liver metastases, ABO blood group, and the number of perioperative blood transfusions. For those patients who underwent resection of unilobar metastases with tumor-free margins, the 5-year survival rate was 29% with a median survival of 35 months and eight survivors > 7 years. In addition, one patient with bilobar disease had survival > 7 years and five patients who had resection of hepatic metastases and extrahepatic cancer simultaneously had survival > 3 years. Our data support the concept that patients with unilobar metastatic disease who undergo surgical resection with tumor-free surgical margins can be afforded a significant opportunity at long-term survival with acceptable morbidity, mortality, and hospital stay. Also, certain patients with bilobar or extrahepatic disease (or both) who undergo complete resection can enjoy a long-term survival. In these subgroups of patients resection should be considered on an individual basis.     

Prognostic significance of lymph node dissection in gastric cancer

The results for 162 patients who underwent curative gastrectomy for gastric cancer from January 1988 to June 1994 were analysed statistically with special reference to the effect of lymph node dissection. Median survival was 69.3 months and the overall cumulative 5-year survival rate was 50.2 (95 per cent confidence interval (c.i.) 41.6-58.1) per cent. By univariate analysis age, histology, depth of tumour invasion, node involvement, number of metastatic lymph nodes and type of lymphadenectomy were found to be significant factors related to survival time. Multivariate analysis with the Cox model and stratified for tumour node metastasis stage revealed that only the number of metastatic nodes (P = 0.04) and the extent of lymphadenectomy (P = 0.003) affected survival independently. With respect to D1 lymphadenectomy, the relative risk associated with D2 and D4 lymphadenectomy was respectively 0.61 (95 per cent c.i. 0.34-1.10) and 0.26 (95 per cent c.i. 0.12-0.60). The 5-year survival rate was 28 per cent for patients who had a D1 dissection, 63 per cent for those who had D2 and 68 per cent for those who had D4. These results suggest that extended lymphadenectomy (D2) and especially superextended lymphadenectomy (D4) can improve survival in patients with gastric cancer.     

Hepatic resection for colorectal liver metastases

The lack of other effective treatment for colorectal liver metastases makes hepatic resection a primary treatment consideration. Between January 1980 and December 1990, 26 selected patients with liver colorectal metastases who underwent hepatic resection were reviewed. The age, sex, site of primary lesion, histological grade, lymph node involvement, location, size, and number of hepatic metastases, type of hepatic resection, and preoperative CEA blood levels were documented. Complete removal with histologically negative resection margins were accomplished in 24 patients. The extent of resection performed was hepatic lobectomy in 12 patients. Segmentectomy in eight patients, and wedge resection in four patients. The 5-year survival rate was 30.5 per cent. Patients with metachronous metastases showed a better survival rate than those with synchronous lesions--46.6% versus 13.6% respectively (P = 0.08). None of the other factors studied showed a significant effect on survival. All patients were followed from the time of hepatic resection to the time of this study or death. During a median follow-up of 30.9 months, 20 patients developed recurrence of their disease (60 per cent in the liver). There was no perioperative mortality. Morbidity arose in 66.6 per cent of patients, with a majority of the complications being minor. We conclude that hepatic resection can be performed safely enough to be recommended in selected patients.     

A pilot study of preoperative chemoradiation for patients with localized adenocarcinoma of the pancreas

BACKGROUND: We hypothesized that delivering adjuvant radiotherapy (RT) preoperatively with chemotherapy might enhance local control of the cancer and patient tolerance for the intervention. METHODS: Thirty-four patients with localized pancreatic cancer (24 head, 8 head and body, 2 body and tail) were treated during the past 6 years with an intramural protocol consisting of 5-fluorouracil (1,000 mg/m2 on days 2 to 5 and 29 to 32) and mitomycin-C (10 mg/m2 on day 2) given with preoperative external beam RT (median 5,040 cGy). Nine patients did not have surgery: 1 refused, 1 died of cholangitis, and 7 were noted to have distant (5) or unresectable local cancer (2) after RT. Of the 25 patients who underwent celiotomy, 11 had liver (8) or peritoneal (3) metastases and 3 had palliative pancreatectomies (2 with liver metastasectomy and 1 with hepatic artery and portal vein replacement). The remaining 11 patients (44% of the cohort with surgery, 32% of all patients) had potentially curative (PC) resections (5 total pancreatectomy, 5 Whipple, 1 distal pancreatectomy). Median tumor diameter by computed tomographic scan was 3.75 cm (range 3 to 5) for the 11 patients who received PC resections and 4.5 cm (range 3 to 7.5) for all patients. Of the 11 patients with PC resections, 8 had evidence of superior mesenteric, portal or splenic venous involvement and 4 had been deemed unresectable at previous celiotomies. RESULTS: One patient developed respiratory failure and one died postoperatively, yielding a 9% rate of major morbidity and mortality. Median follow-up of the surviving patients with curative resection is 33 months (range 14 to 70). Their median survival from the time of tissue diagnosis is 45 months with a median disease-free survival of 27 months. The product limit estimate of 5-year survival is 40% (95% confidence bounds +29%, -30%). One patient had a microscopically positive resection margin, which was a falsely negative frozen section margin at the pancreatic neck. Two patients had positive regional lymph nodes. Five patients have been diagnosed with recurrent cancer. Only 1 has had a local/regional component to the recurrence. CONCLUSIONS: Preoperative RT and chemotherapy followed by resection is well tolerated and safe for patients with locally advanced pancreatic cancer. This approach provides tumor free resection margins and offers prolonged survival to patients with truly localized pancreatic cancer.     

Free revascularized jejunal loop repair following total pharyngolaryngectomy for carcinoma of the hypopharynx: report of 90 patients

Ninety patients with carcinoma of the hypopharynx underwent pharyngolaryngectomy and reconstruction with a jejunal free autograft. Fifty-five patients had primary surgery and 35 salvage surgery for recurrence after radiotherapy. Following primary surgery 28 patients had postoperative radiotherapy and 27 did not. Complications occurred in 51 per cent of patients, the most common being necrosis of the jejunal graft (19 per cent); 12 per cent developed significant stenosis and 4 per cent died in the perioperative period. Eleven per cent of patients developed a fistula. The total number of complications diminished as the experience of the unit increased. Median follow-up was 4.9 years. Of patients treated with primary surgery, 48 per cent developed primary site recurrence (at 3 years) and 53 per cent neck node recurrence (at 5 years). The tumour-specific 5-year survival rate for all patients was 42 per cent. Following primary surgery 28 per cent survived for 5 years and after salvage surgery the rate was 59 per cent. Positive resection margins and extensive neck disease adversely affected survival (P = 0.02 and P = 0.001 respectively). The free revascularized jejunal graft is a safe and predictable method of repair following total pharyngolaryngectomy.     

Cancer resection on the residual lung after pneumonectomy for bronchogenic carcinoma

BACKGROUND: After pneumonectomy for bronchogenic carcinoma, the residual lung may be the site of a new lung cancer or metastatic spread. METHODS: From 1989 to 1995, 13 patients with carcinoma on the residual lung after pneumonectomy for lung cancer were operated on. Three segmentectomies and 7 simple wedge resections were performed, 2 patients had multiple wedge resections, and 1 patient had an exploratory thoracotomy. Nine patients had a primary metachronous bronchogenic carcinoma, 3 had metastases from bronchogenic carcinoma, and no definite conclusion was reached in 1 case. RESULTS: No postoperative mortality was observed. Four patients had postoperative complications. The mean postoperative hospital stay was 14 days. Seven patients are alive, including 5 patients without evidence of disease. Six patients died of their disease, all with pulmonary recurrences. The overall median survival was 19 months, with a probability of survival at 3 years (Kaplan-Meier) of 46% (95% confidence interval, 22% to 73%). CONCLUSIONS: Limited pulmonary resection for lung cancer after pneumonectomy for bronchogenic carcinoma is feasible with very low morbidity. In highly selected patients, surgical resection might prolong survival.     

Inadequate documentation and resection for gastric cancer in the United States: a preliminary report

Patients entered into Southwest Oncology Group gastric adjuvant protocol INT 0016 (SWOG 9008) after a "curative" gastric resection were assessed to determine practice patterns of more than 300 surgeons nationwide who performed "curative" gastric resections for 453 gastric cancer patients. The most common gastric resection performed was distal in 256 patients, proximal in 118, and total in 79. Extragastric organs resected were omentum (285), spleen (59), pancreas (18), and bowel (17). The extent of lymphadenectomy as staged by Japanese rules was 246 (54.2%) D0 resections, 173 (38.1%) D1 resections, 28 (6.2%) D2 resections, and 7 (1.5%) D3 resections. Staging of the cancer was poorly documented, with no statement made regarding the status of the primary cancer in 6 per cent, liver in 10 per cent, lymph nodes in 17 per cent, and omentum in 17 per cent. The greater the lymph node clearance, the greater the chance of resecting to a level of negative lymphatics, given that 45 per cent of nodes were involved when 10 or less were removed, whereas only 17 per cent were positive when more than 40 were cleared. The lack of adequate clearance of lymph nodes and poor documentation of tumor stage suggests that a more regimented surgical approach to this uncommon cancer is required.     

Surgical treatment and outcome in patients with a hepatocellular carcinoma greater than 10 cm in diameter

BACKGROUND: Hepatocellular carcinoma (HCC) over 10 cm in diameter at the time of diagnosis continues to account for a number of patients undergoing hepatic resection. This study evaluated the clinicopathological features and outcome following surgery for large HCC. METHODS: Forty patients with a large HCC (greater than 10 cm) (group 1) resected between 1991 and 1996 were studied retrospectively. They were compared with 245 patients who had smaller HCCs (10 cm or less) (group 2). RESULTS: No patient in group 1 had hepatitis C infection compared with 22.9 per cent in group 2 (P=0.001). Patients in group 1 were significantly younger, had higher alpha-fetoprotein levels (16750 versus 1864 ng/ml; P < 0.001), better liver function, a higher incidence of multiple tumours (27 of 40 versus 42.0 per cent; P=0.003) and venous invasion (35 of 40 versus 52.2 per cent; P < 0.001), and underwent more major resections (37 of 40 versus 26.5 per cent; P < 0.001) than those in group 2. Morbidity and mortality rates and hospital stay were comparable in the two groups. For group 1, the 1-, 3- and 5-year disease-free survival rates were 42, 30 and 28 per cent respectively. Multiple tumours, venous invasion and impaired liver function were factors associated with recurrence. CONCLUSION: Large HCC had specific clinicopathological features. In selected patients, resection is safe and offers the chance of long-term disease-free survival.     

Intensive weekly chemotherapy for advanced gastric cancer using fluorouracil, cisplatin, epi-doxorubicin, 6S-leucovorin, glutathione, and filgrastim: a report from the Italian Group for the Study of Digestive Tract Cancer

PURPOSE: A multiinstitutional trial was performed to confirm the clinical activity, in terms of response rate and toxicity (primary objectives) and duration of responses and survival (secondary objectives), of an intensive weekly regimen in advanced gastric cancer. PATIENTS AND METHODS: Patients with measurable unresectable and/or metastatic gastric carcinoma received 1-day per week administration of cisplatin (CDDP) 40 mg/m2, fluorouracil (5FU) 500 mg/m2, epi-doxorubicin (epi-ADR) 35 mg/m2, 6S-stereoisomer of leucovorin 250 mg/m2, and glutathione 1.5 g/m2. On the other days, filgrastim was administered by subcutaneous injection at a dose of 5 mg/kg. One cycle of therapy consisted of eight 1-week treatments. Patients who showed a response or stable disease received a further 6 weeks of therapy. RESULTS: Of 105 enrolled patients, 11 had locally advanced unresectable disease only; 33 had primary nonresected and metastatic disease; 48 had metastatic disease and primary tumor resected; 10 had locoregional recurrence and metastatic disease; and three had locoregional recurrence only. After one cycle, 18 complete responses (CRs) and 47 partial responses (PRs) were achieved, for an overall response rate of 62% (95% confidence interval [CI], 53% to 71%). Twenty patients had stable disease and 20 progressed on therapy. The median survival duration of all 105 patients was 11 months, with 1- and 2-year survival rates of 42% and 5%, respectively. World Health Organization (WHO) grade III to IV toxicity, in terms of anemia, neutropenia, thrombocytopenia, and mucositis, was experienced by 40 patients (38%). There were no treatment-related deaths. CONCLUSION: These data support the results of the pilot study and confirmed the high activity of the regimen, with acceptable toxicity. This schedule deserves evaluation in the adjuvant setting.     

Primary nonampullary/periampullary adenocarcinoma of the duodenum

Primary duodenal adenocarcinoma not involving the ampullary region is rare. Our aim was to review the outcome of these patients and determine the factors that affect survival. We performed a retrospective review of all patients with primary, nonampullary duodenal adenocarcinoma at the Cleveland Clinic Foundation from January 1986 through December 1996. Twenty-six patients with primary, nonampullary duodenal malignancies were identified. There were 16 adenocarcinomas, 3 gastrinomas, 3 stromal tumors, 3 leiomyosarcomas, and 1 carcinoid tumor. Patients with adenocarcinoma had symptoms present an average of 6.1 months. Tumors were identified by upper gastrointestinal contrast study and esophagogastroduodenoscopy in 90 per cent and 87 per cent of patients, respectively. Twelve of 13 (93%) cancers found in the third or fourth portion of the duodenum were adenocarcinomas. Seven of the 16 adenocarcinomas were resectable on exploration. Those that were contained within the serosa have not recurred (mean, 6 years); one of the two patients with locally invasive adenocarcinoma remains disease free. The average survival for patients with unresectable disease was 6.7 months. The 5-year survival rates were: all adenocarcinoma, 38 per cent; resectable, 86 per cent; and unresectable, 0 per cent. All patients presenting with weight loss or obstructive symptoms died of disease; those with melena survived long term. Patients with tumors other than adenocarcinoma had a 90 per cent 5-year survival. We conclude that patients typically present with a long history of symptoms. Distal duodenal malignancies are most frequently adenocarcinomas. Upper gastrointestinal contrast study or endoscopy is often diagnostic. Patients with weight loss and/or obstructive symptoms had invasive disease and a morbid prognosis. Aggressive surgery is warranted, and most with resectable disease (86%) had long-term survival.     

Synchronous and metachronous primary malignancies in organs other than the stomach in patients with early gastric cancer

BACKGROUND/AIMS: We investigated the outcomes of patients with early gastric cancer, with special reference to the prognosis of patients with synchronous or metachronous primary malignancies in organs other than the stomach. PATIENTS AND METHODS: Among 890 patients with early gastric cancer, 97 (10.9%) had synchronous or metachronous primary malignancies in organs other than the stomach. Ten-year survival rates were compared between patients who had additional malignancies and patients who had early gastric cancer but no other malignant disease (control group). RESULTS: Synchronous primary malignancies were detected in 32 patients and metachronous primary malignancies were detected in 65 patients (17 had developed before gastrectomy and 48 developed after gastrectomy). Hepatic cell carcinoma, lung cancer and colorectal cancer were frequently detected between 2 and 24 years after gastrectomy. The 10-year survival rate was 80.8% for 769 patients in the control group but it was only 49.7% for the 92 patients with additional malignancies. Moreover, metachronous malignant disease was found more over 10 years after gastrectomy in 30 of the 48 cases (62.5%). CONCLUSIONS: These results suggest the importance of long-term follow-up for detection of metachronous carcinomas at sites other than the stomach for patients with early gastric cancer.     

Resection of hepatic metastases from colorectal cancer

BACKGROUND/AIMS: Long term results of hepatic resection for metastases from colorectal cancer depend upon several factors which are related to both features of primary cancer and of metastases. The aim of this study was to evaluate prognostic factors that best correlate with long-term results. MATERIALS AND METHODS: Fifty-eight hepatic resections were performed for colorectal cancer metastases. Long-term results were evaluated in relation to age of patients, features of primary tumor, features of metastases, section margin, number of intra-operative blood transfusions and execution of adjuvant chemotherapy. RESULTS: Overall 5-year survival rate was 17%. 5-year survival rate in patients with stage B primary tumor was 63%, in patients with late metachronous metastases it was 28%, in patients with section margin > 1 cm it was 33% and in patients who did not receive intra-operative transfusions it was 45%. Patients with a solitary metastasis or with metastases sized less than 4 cm and those who received adjuvant chemotherapy also showed a better survival than the others. CONCLUSIONS: Better results were observed in patients without nodal involvement of the primary tumor. Patients with a small solitary metachronous metastasis that appeared more than one year after the colorectal resection and resected with a section margin of more than 1 cm, also showed good results.     

Oesophagogastrectomy for carcinoma of the oesophagus and cardia

A retrospective review was undertaken of all oesophagectomies performed within a single unit over a 12-year period. In all, 298 patients with primary oesophageal cancer underwent resection between March 1979 and December 1991. Four patients had a three-stage oesophagogastrectomy, 27 a thoracoabdominal oesophagogastrectomy and 267 a Lewis procedure. Dysphagia was the predominant presenting symptom. The duration of symptoms was not related to the stage of disease. Before diagnosis, 52 per cent of patients tolerated symptoms for 2-4 months. Adenocarcinoma was found in 180 tumours and squamous cell carcinoma in 103. Half of the patients had evidence of metastatic spread at the time of laparotomy or thoracotomy. The 30-day mortality rate was 10 per cent and the overall actuarial 5-year survival rate of all patients 23 per cent. The actuarial 5-year survival rate of patients without lymph node involvement was 39 per cent compared with 17 per cent for those with positive nodes (P < 0.05). Five of eight patients who had anastomotic leakage died. The almost unselected nature of this series, coupled with the favourable results of oesophagectomy, support the contention that resection remains the preferred mode of treatment for carcinoma of the oesophagus of all histological types.     

Should the presence of coiled blood flow in the left heart ventricle and aorta be taken into consideration when constructing artificial heart valves?]

This study presented the outcome of 92 EOC patients treated by platinum or platinum analogue with cyclophosphamide from January 1, 1993 to December 31, 1995. There were 77 evaluable patients. The follow-up ranged from 4-42 months (median 14 months). The over all 3-year survival was 64 per cent and the median progression-free interval was 16 months for the whole group. There was no significant difference in survival between patients who received cisplatin and those who received carboplatin (P = 0.093). Patients who underwent optimal debulking surgery had significantly longer progression-free interval (P = 0.001) than those who had sub-optimal surgery. Fifty four per cent of patients with clear cell carcinoma died of the disease. Patients who received cisplatin had a drop out rate while on therapy more often (24% vs 5.3%) than that of carboplatin. Toxicities from chemotherapy were moderate but manageable.     

Is resection of pulmonary and hepatic metastases warranted in patients with colorectal cancer?

BACKGROUND: Conventional management of stage IV colorectal carcinoma is palliative. The value of resecting both liver and lung colorectal metastases that occur in isolation of other sites of metastasis is undetermined. OBJECTIVES: Our objectives were to (1) assess the efficacy of resecting both hepatic and pulmonary metastases, (2) investigate the influence of the sequence and timing of metastases, and (3) identify the profile of patients likely to benefit from both hepatic and pulmonary metastasectomy. Patients and methods: Of 48 patients identified with resection of colorectal cancer and, at some point in time, both liver and lung metastases, 25 patients underwent metastasectomy (resection group). The remaining 23 patients comprised the nonresection group. Risk factors for death were identified by multivariable analyses. RESULTS: Median survival was longer after the last metastatic appearance in the resection group (16 months) than in the nonresection group (6 months; P <.001). The pattern of risk also differed; it peaked at 2 years and then declined in the resection group but was constant in the nonresection group. In the resection group, patients with metachronous resections survived longer after colorectal resection (median, 70 months) than patients with synchronous (median, 22 months) or mixed resections (median, 31 months; P <.001). Risk factors for death included older age, multiple liver metastases, and a short disease-free interval. CONCLUSIONS: Younger patients with solitary metachronous metastases to the liver, then the lung, and long disease-free intervals are more likely to benefit from resection of both liver and lung metastases. Patients with risk factors also had better survival with resection than without resection.     

Differential activation of pp60(c-src) and pp62(c-yes) in human colorectal carcinoma liver metastases

pp60(c-src) and pp62(c-yes) are protein tyrosine kinases whose specific activities are increased in primary colorectal carcinomas. Activity of pp60(c-src) is further increased in colorectal liver metastases. This study was undertaken to compare pp60(c-src) and pp62(c-yes) expression and activity in human colorectal carcinoma liver metastases and to determine the potential prognostic significance of differences in activation of these two kinases. The pp60(c-src) and pp62(c-yes) tyrosine kinase activities and protein levels relative to those in normal colonic mucosa were determined using an immune complex kinase assay and immunoblot analysis in tissue specimens from 22 patients with primary colorectal carcinoma and synchronous metastatic liver disease and from 9 patients with metachronous colorectal carcinoma liver metastases. Of the primary colon tumors, 64% of the tumors contained elevated activities of both pp60(c-src) and pp62(c-yes). For liver metastases, however, only 10% had activation of both tyrosine kinases, 61% had elevated pp60(c-src) activity only, and 23% had elevated pp62(c-yes) activity only. Analysis of synchronous metastases from primary tumors with elevated activities in both kinases demonstrated that in 71% of these patients, the activity of either pp60(c-src) or pp62(c-yes) decreases relative to the primary tumor. Protein levels of pp60(c-src) and pp62(c-yes) in primary carcinomas and metastases remained unchanged from levels in normal colonic mucosa. These results demonstrate that differential regulation of the activities of pp60(c-src) and pp62(c-yes) occurs during tumor progression. Patients with either synchronous or metachronous liver metastases and elevated pp62(c-yes) kinase activity have biologically more aggressive disease and a worse prognosis than patients without elevated pp62(c-yes) activity in their liver metastases (median survival, 13 months versus 30 months, P < 0.005, Wilcoxon signed rank test). Analysis of patients with synchronous liver metastases also demonstrated a worse prognosis for those with elevated pp62(c-yes) kinase activity (P < 0.05, Wilcoxon signed rank test).     

Androgen and oestrogen receptors in hepatocellular carcinoma and surrounding liver parenchyma: impact on intrahepatic recurrence after hepatic resection

Seventy-eight patients in whom androgen or oestrogen receptors, or both, were assayed in hepatocellular carcinoma (HCC) and the surrounding liver were discharged from hospital after curative resection of the tumour. Intrahepatic recurrence was evaluated retrospectively after 28-128 months follow-up to determine the association with receptor status. Androgen and oestrogen receptors in HCC significantly influenced the intrahepatic recurrence rate. The recurrence-free 5-year survival rate was 55 per cent for patients who had androgen receptor-negative tumours, 24 per cent for oestrogen receptor-negative, 10 per cent for oestrogen receptor-positive and 0 for androgen receptor-positive (P = 0.0322). Recurrence-free 5-year survival in 57 patients who had both receptor assays was 75 per cent for patients who had androgen receptor-negative, oestrogen receptor-negative tumours, 50 per cent for androgen receptor-negative, oestrogen receptor-positive, but 0 for androgen receptor-positive, oestrogen receptor-positive and androgen receptor-positive, oestrogen receptor-negative (P = 0.0104). The presence or absence of androgen or oestrogen receptor in the liver, however, was not associated with intrahepatic recurrence (P = 0.7534). Thus, androgen receptors are strongly associated with intrahepatic recurrence of HCC, while oestrogen receptors are weakly associated. Receptor status in the normal liver was not related to intrahepatic recurrence.