Prognostic index for the development of liver metastases in patients with colorectal cancer

The incidence of synchronous and metachronous liver metastases in patients with colorectal cancer is extremely high. Approximately 25 per cent of patients will have overt liver metastases at the time of presentation, and in the remainder up to 40 per cent will eventually develop liver metastases. In an attempt to obtain a prognostic index for the prediction of those patients most likely to develop liver metastases, 134 patients with primary colorectal cancer but without overt liver metastases at initial presentation were followed up for between 5-10 years. Regular liver scans were performed and the presence of liver metastases observed. A total of 47 patients developed liver metastases. Those preoperative variables related to the subsequent development of liver metastases were sex, log10 serum alkaline phosphatase level and Dukes' classification. A prognostic index using these parameters has been calculated.     

Pelvic lymphadenectomy for staging prostatic carcinoma: is it always necessary?

There were 100 patients with clinically localized prostatic carcinoma staged surgically for the evaluation of lymph node metastases. By correlating the incidence of lymph node metastasis with the level of serum acid phosphatase, and the stage and grade of the primary tumor, it was possible to identify 1 group of patients with less than 8 per cent incidence of lymph node metastases and another group with more than 92 per cent incidence of nodal involvement. It is in these 2 groups of patients that pelvic lymphadenectomy for the staging of prostatic carcinoma may not be necessary.     

Dormant liver metastases: an experimental study.

Experimental work was undertaken to evaluate whether intrahepatic recurrences, observed after resection of colorectal liver metastases in humans, could be due to the activation of dormant cancer cells already present within the liver at liver resection. About 250 cell aggregates (DHDK12 colon carcinoma cell line) were injected into the portal vein of 70 BD IX rats. Eight weeks later, 43 rats with no apparent liver metastases were divided randomly into three groups: group 1 (n = 15) served as control; group 2 (n = 15) were given cyclosporin A (10 mg kg body-weight-1 day-1) for 28 days; and group 3 (n = 13) underwent a 70 per cent hepatectomy. Twelve weeks after the injection of cells, when the animals were killed, 20 per cent of rats in group 1 had liver metastases, 80 per cent in group 2 (P less than 0.01) and 62 per cent in group 3 (P less than 0.05). Undetectable liver micrometastases may have been present at 8 weeks and had not developed until stimulation by cyclosporin A-induced immunosuppression or by liver regeneration after hepatectomy. A similar mechanism may occur clinically and explain some of the recurrences observed after resection of liver metastases.     

The use of FDG-positron emission tomography for the evaluation of colorectal metastases of the liver

Each year at least 130,000 people in the United States are diagnosed with colorectal carcinoma. Approximately 14,000 of these patients will have liver metastases, and 20 per cent of these patients will die from these metastases. Surgical resection is the only possible chance for cure in patients with only intrahepatic metastases, and extrahepatic disease is a contraindication to glucose metabolism. Positron emission tomography (PET) allows the in vivo study of the uptake and use of glucose in human cells. Here, we review our experience with the use of PET imaging for the diagnosis and management of colorectal metastases of the liver. We conducted a retrospective chart review of 14 patients undergoing PET imaging for known or suspected hepatic metastases from colorectal carcinoma. Results of CT, magnetic resonance imaging, and PET images were compared with pathological specimens. CT scan identified 7 lesions, and PET identified 31 intrahepatic lesions. Of the 6 patients who underwent surgery, CT identified 4 (20%) and PET identified 17 (85%) of the 20 intrahepatic metastases histologically confirmed. The accuracy (number of lesions) of CT and PET was 20 per cent and 85 per cent, respectively. CT scans had a sensitivity (number of patients) of 50 per cent, and PET had a sensitivity of 100 per cent in patients undergoing surgical resection. PET imaging altered the management in 49 per cent of patients. Twenty-one per cent of patients had their surgery cancelled due to previously undiagnosed extrahepatic metastases. Twenty-one per cent of patients had negative CT scans and underwent surgery on the basis of their PET images, and all had histologically proven disease. One patient avoided a second-look laparotomy when PET revealed a lesion seen on CT to be false positive. PET is an ideal imaging modality to detect intra- and extrahepatic metastases from colorectal carcinomas and would aid in the surgical management of these patients.     

Prospective comparison between serum monoclonal prostate specific antigen and acid phosphatase measurements in metastatic prostatic cancer

Prostate specific antigen, prostatic acid phosphatase antigen and acid phosphatase activity were measured on 175 serum samples serially collected from 80 patients with metastatic stage D adenocarcinoma of the prostate. Prostate specific antigen and prostatic acid phosphatase antigen concentrations were measured with a monoclonal radioimmunometric assay, and acid phosphatase activity was measured enzymatically. The over-all frequency of abnormal levels of prostate specific antigen (76 per cent) was significantly greater than abnormal prostatic acid phosphatase antigen (60 per cent) and acid phosphatase activity (49 per cent) results (p less than 0.001). These differences were greater among the subset of patients in clinical remission. Levels greater than 10 times normal were observed in 68 per cent of prostate specific antigen, 43 per cent of prostatic acid phosphatase antigen and 31 per cent of acid phosphatase activity measurements (p less than 0.001). Three or more serial prostate specific antigen measurements in 17 patients demonstrated excellent correlation with independently assessed clinical disease activity. These results suggest that prostate specific antigen is a more sensitive and potentially more useful tumor marker than acid phosphatase measurements in patients with metastatic prostatic carcinoma.     

Distal bypass for limb salvage in very elderly patients

During the last 3 1/2 years, 40 bypasses to a tibial or peroneal artery (distal bypass) were performed for severe leg ischemia in 34 patients who were 80 years of age or older (range, 80-91; mean, 85). The operative mortality rate was 5 per cent. Cumulative life-table limb salvage rates for the 40 extremities were 91 per cent at 1 year and 81 per cent at 3 years. Graft patency rates at 1 and 3 years were 88 per cent and 56 per cent, respectively. Survival rates for the 36 patients were 91 per cent and 58 per cent at 1 and 3 years, respectively. Among 134 patients younger than 80 years who underwent 142 distal bypasses during the same 3 1/2-year period, no operative deaths occurred. In this younger group, cumulative life-table rates at 1 and 3 years were 89 per cent and 89 per cent, respectively, for limb salvage, 86 per cent and 85 per cent, respectively, for graft patency, and 93 per cent and 78 per cent, respectively, for survival. There were no statistically significant differences in these figures for the younger group when compared with corresponding figures for the older group. Among the 36 very elderly patients who underwent distal bypass for limb salvage, 24 patients (67%) with 25 revascularized limbs are alive and have a salvaged, functional extremity after follow-up as long as 41 months (mean, 21 months). These results suggest that an aggressive approach using distal bypass is warranted for limb salvage in very elderly patients.     

Resectability rate of hepatocellular carcinoma in rural southern Africans

The purpose of this analysis was to ascertain the resectability rate of symptomatic hepatocellular carcinoma in rural southern African black males. All 224 such patients proven to have hepatocellular carcinoma in a single hospital were included in the study. Of 205 patients undergoing a complete diagnostic work-up, 134 [65.3 per cent) were judged on clinical criteria to be inoperable, 23 (11.2 per cent) had pulmonary or osseous metastases, and 38 (18.5 per cent) proved on hepatic imaging and 5 (2.4 per cent) on hepatic arteriography to have an irresectable tumour. Thus, only five (2.4 per cent) of these patients proceeded to laparotomy. Another 7 patients who did not have an arteriogram, 9 with surgical emergencies, and 2 mistakenly believed to have an amoebic hepatic abscess also underwent laparotomy. Only 2 patients (0.9 per cent of 223) proved to have a resectable tumour. The extremely low resectability rate reinforces the urgent need for a surveillance programme to detect early tumours in high-risk members of this population.     

Outcome of colorectal cancer

The outcome of 454 patients who presented with colorectal carcinoma during a 16 year period is reviewed: 54 per cent were males, 58 per cent were aged more than 60 and 10 per cent had an emergency admission, 42 per cent of tumours occurred in the rectum. A curative resection was possible in 68 per cent. Postoperative mortality was 7 per cent. The overall crude 5-year survival was 41 per cent. The mortality from local recurrence was significantly higher in rectal (11.7 per cent) than in colonic cancer (8.8 per cent; P less than 0.01). The rate of recurrence and metastases was higher in patients with low rectal cancer than in patients with cancer of the middle and the upper rectum (P less than 0.01). Distant metastases were the cause of death in 94 per cent of the patients who had a Miles' operation for cancer of the middle rectum, whereas local recurrence was responsible for late mortality in 80 per cent of patients who underwent an anterior resection. No difference in 5-year survival was found in the restorative and in the excisional group.     

Implications of peritoneal washing cytology in patients with potentially resectable pancreatic cancer

BACKGROUND: The aim of this study was to assess the implications of positive peritoneal washing cytology for management of patients with potentially resectable pancreatic cancer.METHODS: Cytological examination of peritoneal washings was performed in 134 patients who underwent surgical resection for pancreatic adenocarcinoma. The clinicopathological findings and the relationship between cytology results (including cytomorphology) and survival were investigated.RESULTS: One hundred and fourteen patients (85 per cent) had negative cytology results (group 1). Excluding one patient with atypical cells, positive cytology results were obtained in 19 patients (14 per cent): 16 patients without macroscopic peritoneal metastases (group 2) and three patients with minimal macroscopic peritoneal metastases (group 3). The patients in group 2 had significantly larger (P < 0.001) and more advanced (P = 0.022) tumours than those in group 1. However, there were no significant differences in postoperative cumulative survival rates between groups 1 and 2 (P = 0.347). Two patients in group 2 are long-term survivors (40 and 58 months). In cytomorphological analyses, the presence of clusters with ragged edges and isolated carcinoma cells can be considered to indicate a high risk of peritoneal recurrence.CONCLUSION: Positive cytology does not directly predict peritoneal carcinomatosis and, while associated with advanced disease, does not contraindicate radical surgery.     

Early stage prostatic cancer investigated by pelvic lymph node biopsy and bone marrow acid phosphatase

A prospective study was done to evaluate 47 patients with early stage prostatic cancer. Pelvic lymphadenectomy was combined with bone marrow acid phosphatase determination to evaluate early metastatic disease. Thirteen patients (28 per cent) had tumor in the pelvic lymph nodes. In no instance was the bone marrow acid phosphatase elevated to more than the normal value for serum by the substrate used. Combined high grade and stage tumors seemed to have an increased incidence of metastases to pelvic lymph nodes. A surprisingly high incidence of B1 lesions (5 of 21 patients or 24 per cent) had positive lymph nodes. Generally, the nodes were moderately well or well differentiated lesions. The metastases were unilateral, frequently microscopic only and involved 1 or only a few nodes. Pelvic lymphadenectomy seems to have a well defined role in the diagnostic study of early stage prostatic cancer, while bone marrow acid phosphatase determinations were of no value.     

Frozen section detection of lymph node metastases in prostatic carcinoma: accuracy in grossly uninvolved pelvic lymphadenectomy specimens

We reviewed our frozen section experience with 310 pelvic lymphadenectomy specimens during the last 5 years. A total of 40 patients (12.9 per cent) had positive lymph nodes on permanent section. In 6 of these patients the lymph nodes were involved grossly and in 34 there were only microscopic metastases. Intraoperative assessment of lymph node involvement classified correctly 299 patients (96.5 per cent of the total number). Whereas previous studies have demonstrated a failure on frozen section to detect all but a few microscopic metastases, we were able by frozen section to identify metastases in 23 of 34 patients (67.6 per cent) with grossly uninvolved lymph nodes. Of the positive frozen sections 16 were in patients with unilateral metastases only, and in 13 of these cases frozen section identified the only positive node present. The average diameter of the metastases found on frozen section was 2.4 mm. In 11 of the 34 patients frozen section did not disclose any of the metastases present on permanent sections (average 1.4 mm.) (false negative rate 3.5 per cent of all patients, 27.5 per cent of those with positive nodes and 32.3 per cent of those with microscopic involvement of lymph nodes only). Ten patients had unilateral metastases and 1 had bilateral involvement. The ability to identify the majority of microscopic metastases, given their adverse effect on prognosis, supports the usefulness of routine frozen section on grossly uninvolved pelvic lymph nodes as a staging procedure before radical prostatectomy.     

Total bone uptake in management of metastatic carcinoma of the prostate

The status of patients with skeletal metastases from prostatic carcinoma was determined from a quantitative uptake and retention measurement of the bone scanning radiopharmaceutical 99mtechnetium-methylene diphosphonate. Whole body counts were performed 5 minutes and 24 hours after intravenous administration of 99mtechnetium-methylene diphosphonate, and were expressed as the percentage uptake by the skeleton at 24 hours. Skeletal uptake determinations were done in 29 patients with prostatic cancer (17 with osseous metastases) who were evaluated at 3 to 6-month intervals. Group 1 consisted of patients who responded to therapy and achieved remission, group 2 included patients with relapse or progressive disease, group 3 consisted of those with metastases who were in remission for longer than 6 months and group 4 included those without evidence of any bony metastases. The baseline mean +/- standard deviation 24-hour skeletal uptake values were 46.1 +/- 12.0 per cent in group 1, 34.3 +/- 13.9 per cent in group 2, 27.0 +/- 5.9 per cent in group 3 and 28.9 +/- 5.5 per cent in group 4. At 3 to 6 months the values in group 1 (responders) decreased by 18 per cent, while those in group 2 (relapse or progression) increased by 19 per cent and those in group 3 (remission) increased by 1.5 per cent. The quantitative 24-hour skeletal uptake test was performed easily, reproducible and at least as useful as concurrent chemical blood tests and subjective bone scan interpretations.     

Serum 5'-nucleotide phosphodiesterase as a predictor of hepatic metastases in gastrointestinal cancer.

Isoenzyme V of 5'-nucleotide phosphodiesterase (5'-NPD-V) is present in the peripheral sera of patients with hepatic metastases. A total of 122 patients underwent prospective serologic analysis followed by operation for primary tumors of the gastrointestinal tract and careful evaluation of the liver. A positive 5'-NPD-V assay was found in fifty-nine of sixty patients with liver metastases. A negative 5'-NPD-V assay was found in forty-three of sixty-two patients with no evidence of hepatic metastases. The accuracy of the test was 84 per cent, and the predictive value was 75 per cent. Serum 5'-NPD-V was abnormal significantly more frequently in patients with metastatic liver disease than were liver scans or carcinoembryonic antigen (CEA), alpha fetoprotein, serum glutamic oxalacetic transaminase (SGOT), and total serum bilirubin or serum alkaline phosphatase levels.     

Pre-treatment testosterone levels: significance in androgen deprivation therapy

From June 1982 to February 1985, 53 patients with stage D2 carcinoma of the prostate confirmed by tissue biopsy, elevated prostatic acid phosphatase and a positive bone scan were initiated on androgen deprivation therapy. Before commencement of treatment all patients underwent determination of serum testosterone levels at 8 a.m. Of the patients 23 received 200 mcg. buserelin per day, 17 received 1 mg. diethylstilbestrol 3 times daily, 6 received 40 mg. megestrol acetate 4 times daily, 2 received 1 mg. leuprolide per day and 5 underwent bilateral orchiectomy. Evaluation of the best response in each patient revealed 3 (6 per cent) complete and 17 (32 per cent) partial responses, while 22 patients (41 per cent) remained stable and 11 (21 per cent) had progression. Pre-treatment serum testosterone levels ranged from 150 to 879 ng. per dl. The mean serum testosterone level in patients having a complete response was 524 +/- 18.04 ng. per dl. The mean in the progression group was 279.4 +/- 110.1 ng. per dl. This difference was not statistically significant owing to the large standard deviation in the progression group. However, of the 15 patients who had a pre-treatment serum testosterone level of more than 500 ng. per dl. only 1 (7 per cent) had progression. None of the patients whose pre-treatment testosterone level was less than 200 ng. per dl. had objective tumor regression. Our study suggests that pre-treatment serum testosterone levels may predict the probability of a satisfactory response to androgen deprivation therapy.     

Lymphangiography and computerized tomography in testicular carcinoma: how accurate in early stage disease?

The usefulness of lymphangiography and computerized tomography was evaluated in 167 consecutive patients with pathological stages I and II testicular carcinoma and metastases of less than 5 cm. Lymphangiography demonstrated 74.4 per cent sensitivity, 77.6 per cent specificity and 76.0 per cent over-all accuracy. Computerized tomography revealed comparable results, with 74.3 per cent over-all accuracy, 73.7 per cent sensitivity and 75.0 per cent specificity. The combination of lymphangiography and computerized tomography performed in 35 patients consistently improved the diagnostic possibilities of either technique alone in patients with positive nodes, reducing the false negative rate from 27 to 10 per cent. On the other hand, this combination increased the false positive rate from 25 to 37 per cent in patients with negative nodes. In patients with clinical stage I disease for whom a wait-and-see policy after orchiectomy is adopted at our institute both methods must be considered mandatory. In all other situations computerized tomography alone should be the preferred procedure in the diagnosis of retroperitoneal lymph node metastases from testicular carcinoma.     

Monoclonal antibody 486 P 3/12: a valuable bladder carcinoma marker for immunocytology

Monoclonal antibodies directed against tumor-associated antigens of bladder carcinoma were used to identify tumor cells in bladder washout specimens of 40 patients with bladder carcinoma (group 1), 41 with no bladder disease or with urinary tract infections (group 2), 41 who received long-term mitomycin C instillation therapy after excision of the tumors (group 3) and 39 who received no prophylaxis after excision of the tumors (group 4). In all groups the same bladder washout specimen was used for standard urinary cytological and immunocytological tests. True positive results were obtained in 90 per cent of the patients in group 1 according to our immunocytological criteria and in 43 per cent according to standard cytology studies. No urine specimens in group 2 (controls) were immunocytologically positive, while 16 of 41 in group 3 and 17 of 39 in group 4 were positive immunocytologically but only 4 and 5, respectively, were positive according to standard cytology studies. Further followup of these patients will show whether cells positive for monoclonal antibody 486 P 3/12 will permit early detection of recurrent bladder cancer and whether one can identify patients who require prophylaxis after removal of the superficial bladder tumors.     

Randomized study of Corynebacterium parvum adjuvant therapy following surgery for (stage II) malignant melanoma

One hundred and fifteen patients with histologically proven primary cutaneous melanoma were entered into a randomized prospective study following surgical removal of clinically obvious regional metastases. The study started in 1977 and was completed in June 1982. Fifty-eight patients (10 with regional skin metastases and 48 with regional node metastases) were in the control group and 57 (15 regional skin, and 42 regional node metastases) received adjuvant C. parvum. Other clinical features were well balanced for each group. C. parvum, 2 mg/m2 IV was repeated eight times at three weekly intervals. The schedule was based on previous work which indicated significant increase in killer cell activity. There was no serious toxicity and 22 patients exhibited tachyphylaxis. Seventeen patients in the control group (11 tumour free) are alive at 24-80 months, and 20 patients in the C. parvum group (12 tumour free) are alive 24-76 months from randomization. No statistically significant difference (P greater than 0.05) was observed between the two patient groups for overall survival (median 26 months) or relapse free survival (median 8 months) from the date of randomization. Nor was the overall survival from the date of primary surgery (median 52 months, range 4-237) or the relapse free survival, median 28 months, range 2-225, significantly different between the two groups of patients. The relapse pattern in the two groups, and survival after relapse were no different though the response rate to actinomycin D and DTIC chemotherapy was significantly higher in the control (48 per cent) than in the C. parvum (23 per cent) group. Toxicity to chemotherapy was not significantly affected by previous C. parvum treatment. Although there were trends for better survival, in the C. parvum patient group, statistically significant activity has not been noted in this study.     

Positive random iliac bone biopsy in advanced prostatic cancer

Forty-one patients with biopsy proved prostatic cancer and with biopsy proved bone metastases were retrospectively evaluated. In 16 per cent of the patients, bone biopsy was positive in spite of negative skeletal survey. Positive skeletal survey and increased serum acid phosphatase levels were found in 78 per cent of the patients, although bone marrow acid phosphatase was elevated in all patients. The determination of bone marrow acid phosphatase was found to be the most sensitive parameter in detection of bone metastases in patients with advanced prostatic cancer.     

Biopsy of resectable colorectal liver metastases causes tumour dissemination and adversely affects survival after liver resection

BACKGROUND: Liver resection is increasingly being performed for metastatic colorectal cancer. This study assessed the need for preoperative biopsy of suspected metastases and whether biopsy has any effect on long-term survival. METHODS: Prospectively collected data on patients who underwent liver resection for colorectal metastases between 1986 and 2003 were reviewed retrospectively. The endpoints of morbidity, operative mortality and long-term survival were compared between patients who had biopsy before referral (group 1) and those who did not (group 2). RESULTS: Patient demographics and disease distribution were similar for 90 patients in group 1 and 508 in group 2. Seventeen patients (19 per cent) who had undergone biopsy either at the time of colorectal resection or radiologically had evidence of needle-track deposits. Operative mortality and morbidity rates in the two groups were similar. The 4-year survival rate after liver resection was 32.5 (s.e. 5.5) per cent in group 1, compared with 46.7 (2.8) per cent in group 2 (P = 0.008). CONCLUSION: Needle-track deposits are common after biopsy of suspected colorectal liver metastases. Biopsy of metastases confers poorer long-term survival on patients after liver resection and cannot be justified in patients with potentially resectable disease.     

Adverse implications of acid phosphatase levels in the upper range of normal

A retrospective review of 102 consecutive patients with surgically staged, clinically localized prostatic carcinoma was performed to determine the relationship between pre-treatment enzymatic acid phosphatase values and histopathological extent of the tumor. Of 96 patients with normal pretreatment acid phosphatase titers (thymolphthalein monophosphate substrate) 77 (80 per cent) had values in the lower and 19 (20 per cent) had values in the upper half of the normal range. Of the latter 19 patients 16 (84 per cent) had histological evidence of extraprostatic tumor extension. Similarly, 5 of 6 patients (83 per cent) with elevated pre-treatment acid phosphatase titers had extraprostatic extension and 1 had a persistent postoperative acid phosphatase elevation that normalized with megestrol acetate therapy. Thus, 22 of 25 patients (88 per cent) with acid phosphatase values in or above the upper half of the normal range had either histological or clinical evidence of extracapsular tumor extension. By contrast, 41 of the 77 patients (53 per cent) with acid phosphatase titers in the lower half of the normal range had extracapsular extension. The predictive value for extraprostatic tumor extension of an acid phosphatase level in the upper half of the normal range was 84 per cent. Furthermore, in the 96 patients with normal acid phosphatase titers the incidence of extraprostatic tumor extension was significantly greater (p less than 0.01, chi-square) in those with values in the upper rather than the lower half of the normal range. Acid phosphatase titers in the upper half of the normal range were proportionately more common among patients with high grade and high clinical stage tumors. However, among patients with low grade and low stage tumors an acid phosphatase value in the upper half of the normal range was an independent variable that correlated with the presence of extracapsular tumor extension. These results confirm previously reported adverse prognostic implications of enzymatic acid phosphatase titers in or above the upper half of the normal range.