Outcome of palliative operations for malignant bowel obstruction in patients with peritoneal carcinomatosis from nongynecological cancer.

BACKGROUND: Malignant bowel obstruction (MBO) secondary to peritoneal carcinomatosis carries a grave prognosis. We evaluated clinicopathologic factors that predict outcomes after palliative operations for MBO. METHODS: Data on patients undergoing laparotomy for palliation of gastrointestinal MBO at City of Hope between 1995 and 2000 were retrospectively collected. Successful palliation was defined as the ability to tolerate solid food (TSF). RESULTS: Sixty-three patients underwent operative treatment. In 20 patients, MBO was the first presentation of disease; for others, the median disease-free interval was 15 months. The complication rate was 44%, and postoperative mortality was 15%. The median length of stay was 12 days. Twenty-nine patients (45%) were discharged from the hospital on a regular diet; 22 (76%) continued to eat until their last follow-up. Median survival was 90 days. Univariate factors for longer survival were TSF on discharge, colorectal primary, and nonmetastatic status at first diagnosis. Patients with ascites and whose cancer first presented with MBO had an inferior survival. Noncolorectal primary remained a multivariate predictor for decreased survival. TSF was predicted by the absence of ascites, an obstruction not involving the small bowel, and a preoperative albumin of >3.0 mg/dl. Multiple logistic regression analysis yielded presence of ascites and small-bowel obstruction as predictors of inability to TSF. CONCLUSIONS: Only one third of patients with MBO from peritoneal carcinomatosis will have prolonged postoperative palliation with significant, but acceptable, treatment-related morbidity. TSF at discharge is a useful predictor of continued palliation for most patients. Patients with colorectal cancer may have superior survival outcome and better palliation; others are at risk for poor outcomes, especially in the presence of ascites and MBO of small bowel. In these patients, highly selective use of laparotomy is recommended.

Surgical palliation at a cancer center: incidence and outcomes.

HYPOTHESIS: Surgical intervention in palliative care is common; however, the indications, risks, and outcomes are not well described. DESIGN: Retrospective review of surgical cases during a 1-year period with a minimum 1-year survival update. SETTING: A National Cancer Institute-designated comprehensive cancer center. PATIENTS: Patients with a cancer diagnosis undergoing operative procedures. MAIN OUTCOME MEASURES: Number of palliative surgeries and analysis of length of stay, morbidity, and mortality. RESULTS: Palliative surgeries comprised 240 (12.5%) of 1915 surgical procedures. There were 170 major and 70 minor procedures. Neurosurgical (46.0%), orthopedic (31.3%), and thoracic (21.5%) surgical procedures were frequently palliative. The most common primary diagnoses were lung, colorectal, breast, and prostate cancers. Length of hospital stay was 12.4 days (range, 0-99 days), with 21.3% of procedures performed on an outpatient basis. The 30-day mortality was 12.2%, with 5 patients dying within 5 days of their procedure. The overall mortality was 23.3% (56/240). Mortality for surgical procedures classified as major was 21.9% (44/170) and 10.0% (7/70) for those classified as minor (Fisher exact test, P<.01). CONCLUSIONS: Significant numbers of palliative procedures are performed at our cancer center. Overall morbidity and mortality were high; however, a significant number of patients had short hospital stays and low morbidity. Palliative surgery should remain an important part of end-of-life care. Patients and their families must be aware of the high risks and understand the clear objectives of these procedures.

A phase I radioimmunotherapy trial evaluating 90yttrium-labeled anti-carcinoembryonic antigen (CEA) chimeric T84.66 in patients with metastatic CEA-producing malignancies.

Chimeric T84.66 (cT84.66) is a genetically engineered human/murine chimeric IgG, with high affinity and specificity to carcinoembryonic antigen (CEA). The purpose of this Phase I dose escalation therapy trial was to evaluate the toxicities, biodistribution, pharmacokinetics, tumor targeting, immunogenicity, and organ and tumor absorbed dose estimates of cT84.66 labeled with 90Y. Patients with metastatic CEA-producing malignancies were first administered 5 mCi 111In-labeled DTPA-cT84.66 (5 mg), followed by administration of the therapy dose of 90Y-labeled DTPA-cT84.66 1 week later. The therapy infusion was immediately followed by a 72-h administration of DTPA at 250 mg/m2/24 h. Dose levels of administered activity ranged from 5 to 22 mCi/m2 with three to six patients per level. Serial nuclear scans, blood samples, and 24-h urine collections were performed out to 5 days after infusion. Human antichimeric antibody response was assayed out to 6 months. Patients were administered up to 3 cycles of therapy every 6 weeks. Radiation absorbed doses to organs were estimated using a five compartment model and MIRDOSE3. Twenty-two patients received at least one cycle of therapy, with one individual receiving two cycles and two receiving three cycles of therapy. All were heavily pretreated and had progressive disease prior to entry in this trial. Reversible leukopenia and thrombocytopenia were the primary dose-limiting toxicities observed. Maximum tolerated dose was reached at 22 mCi/ m2. In general, patients with liver metastases demonstrated more rapid blood clearance of the antibody. Thirteen patients developed an immune response to the antibody. Average radiation doses to marrow, liver, and whole body were 2.6, 29, and 1.9 cGy/mCi 90Y, respectively. Dose estimates to tumor ranged from 66 to 1670 cGy (8.7 to 52.2 cGy/mCi 90Y) for each cycle of therapy delivered. Although no major responses were observed, three patients demonstrated stable disease of 12-28 weeks duration and two demonstrated a mixed response. In addition, a 41-100% reduction in tumor size was observed with five tumor lesions. 90Y-labeled cT84.66 was well tolerated, with reversible thrombocytopenia and leukopenia being dose limiting. Patients with extensive hepatic involvement by tumor demonstrated unfavorable biodistribution for therapy with rapid blood clearance and poor tumor targeting. Average tumor doses when compared with red marrow doses indicated a favorable therapeutic ratio. Stable disease and mixed responses were observed in this heavily pretreated population with progressive disease. This trial represents an important step toward further improving the therapeutic potential of this agent through refinements in the characteristics of the antibody and the treatment strategies used. Future trials will focus on the use of peripheral stem cell support to allow for higher administered activities and the use of combined modality strategies with radiation-enhancing chemotherapy drugs. Further efforts to reduce immunogenicity through humanization of the antibody are also planned. Finally, novel engineered, lower molecular weight, faster clearing constructs derived from cT84.66 continue to be evaluated in preclinical models as potential agents for radioimmunotherapy.

Esthetic reconstruction after mastectomy for inflammatory breast cancer: is it worthwhile?

BACKGROUND: Because inflammatory breast cancer (IBC) has been viewed as a malignancy with a poor likelihood of longterm survival, few women have been offered esthetic reconstruction after mastectomy for IBC. Recent advances in multimodality therapy have improved the outcomes for women with this disease. The purpose of this review was to assess the results of esthetic breast reconstruction in the population with IBC. STUDY DESIGN: Review of medical records at the City of Hope National Medical Center for the 10-year period ending in May 1997, revealed 23 women who underwent elective esthetic breast reconstruction after mastectomy for IBC. The records of these patients were reviewed retrospectively. Patients requiring reconstruction for large surgical chest wall defects were not included in the review. RESULTS: Treatment for IBC included mastectomy in all patients, chemotherapy in 22, and chest wall radiation therapy in 14. Immediate reconstruction was performed at the time of mastectomy (n = 14) or was delayed (n = 9). The types of reconstruction included transverse rectus abdominis musculocutaneous flap (n = 18), latissimus dorsi flap (n = 2), or prosthetic mammary implant reconstruction (n = 3). Seven women chose to undergo additional reconstruction procedures (ie, nipple reconstruction) after their initial reconstruction. With a median followup of 44 months for survivors, 16 patients developed recurrence after reconstruction. Of these, 6 were local recurrences and 10 were distant failures. Seven patients are currently alive with no evidence of disease, 4 are currently alive with disease, and 12 have died as a result of breast cancer. The median disease-free survival after reconstruction was 19 months. The median overall survival after reconstruction for all patients was 22 months. The only negative predictor of survival was a positive surgical margin at mastectomy. CONCLUSIONS: The significant emotional and esthetic benefits of breast reconstruction should be available to women with IBC. In light of the improving prognosis of IBC with current aggressive multimodality treatment, reconstructive procedures should be offered as part of comprehensive therapy.

Contralateral prophylactic mastectomy improves the outcome of selected patients undergoing mastectomy for breast cancer.

BACKGROUND: Risk factors for contralateral breast cancer (CBC) may indicate a benefit for contralateral prophylactic mastectomy (CPM) at the time of unilateral mastectomy for breast cancer. The purpose of this study is to evaluate the efficacy of CPM in preventing CBC. METHODS: sixty-four patients undergoing CPM and a control group of 182 patients not undergoing CPM and matched for age, stage, surgery, chemotherapy, and hormonal therapy were retrospectively compared for CBC rate, disease-free survival, and overall survival. RESULTS: Thirty-six CBCs occurred in the control group. In the CPM group, 3 CBCs were found at the time of prophylactic mastectomy, but none occurred subsequently (P = 0.005). Disease-free survival at 15 years in the CPM group was 55% (95% confidence interval [CI] 38% to 69%) versus 28% (95% CI 19% to 36%) in the control group (P = 0.01). Overall survival at 15 years was 64% (95% CI 45% to 78%) CPM versus 48% (95% CI 39% to 58%) in controls (P = 0.26). CONCLUSION: CPM prevented CBC and significantly prolonged disease-free survival. Future studies will need to address risk assessment and contralateral breast cancer prevention in patients treated for early breast cancer.

Beyond palliative mastectomy in inflammatory breast cancer--a reassessment of margin status.

BACKGROUND: Inflammatory breast cancer is a locally advanced tumor with an aggressive local and systemic course. Treatment of this disease has been evolving over the last several decades. The aim of this study was to assess whether current therapies, both surgical and chemotherapeutic, are providing better local control (LC) and overall survival (OS). We also attempted to identify clinical and pathologic factors that may be associated with improved OS, disease-free survival (DFS), and LC. METHODS: A 25-year retrospective review performed at the City of Hope National Medical Center identified 90 patients with the diagnosis of inflammatory breast cancer. RESULTS: Of the 90 patients identified with inflammatory breast cancer, 33 received neoadjuvant therapy (NEO) consisting of chemotherapy followed by surgery with radiation (n = 26) and without radiation (n = 7). Fifty-seven patients received other therapies (nonNEO). Treatments received by the nonNEO group consisted of chemotherapy, radiation, mastectomy, adrenalectomy, and oophorectomy, alone or in combination. The median follow-up was 28.9 months for the NEO group and 17.6 months for the nonNEO group. Borderline significant differences in the OS distributions between the two groups were found (P = .10), with 3- and 5-year OS for the NEO group of 40.0% and 29.9% and for the nonNEO group of 24.7% and 16.5%, respectively. DFS and LC were comparable in the two groups. Lower stage was associated with an improved OS (P < .05). The 5-year OS for stage IIIB was 30.9%, compared to 7.8% for stage IV. In those patients with stage III disease who were treated with mastectomy and rendered free of disease, margin status was identified by univariate analysis to be a prognostic indicator for OS (P < .05). The 3-year OS, DFS, and LC for patients with negative margins were 47.4%, 37.5%, and 60.3%, respectively, compared to 0%, 16.7%, and 31.3% in patients with positive margins. CONCLUSIONS: This study suggests that in patients with inflammatory breast cancer and nonmetastatic disease, an aggressive surgical approach may be justified with the goal of a negative surgical margin. Achievement of this local control is associated with a better overall outcome for this subset of patients. The ability to obtain negative margins may further identify a group of patients with a less aggressive tumor biology that may be more responsive to other modalities of therapy.

Ethnic differences in the behavior of hepatocellular carcinoma.

BACKGROUND: The purpose of this study was to examine the clinical presentation, prognostic factors, and survival rates of patients with hepatocellular carcinoma (HCC) and to examine differences between Asian and non-Asian patients with HCC. METHODS: A review of the clinical characteristics and laboratory evaluations for 76 patients in two different broad ethnic groups (Asians [Group 1] and non-Asians [Group 2]) who underwent treatment for HCC from 1977-1995 was performed. Chi-square and Cox regression analyses were performed to assess factor interaction and association with survival. RESULTS: A total of 24 patients in Group 1 and 52 patients in Group 2 were reviewed. Of the clinical variables examined, a higher rate of a history of hepatitis B positivity was observed in Group 1 compared with Group 2 (32% vs. 6%; P=0.001). Among the 76 patients with HCC, a 1-year survival estimate of 41.4% was found. There was a borderline significant difference in survival between Group 1 and Group 2 with a 1-year survival estimate of 29.5% versus 46.9%, respectively (P=0.08). Better overall survival was found in patients who had tumors that were resectable (P=0.0001), had an alpha-fetoprotein level <10 ng/mL (P=0.02), or were a younger age at the time of diagnosis (P=0.01). There was a trend for Asian race (P=0.08) to be associated with poorer survival. When these risk factors were entered into a multivariate analysis, tumor resectability and non-Asian race were most predictive of improved survival (model P value = 0.007). When controlling for the multiple variables most often reported to be associated with HCC, Asians had a significantly lower survival than non-Asians (P<0.01). CONCLUSIONS: In this study it appears that the outcome for Asian patients with hepatoma is worse than for non-Asian patients, even when controlling for factors commonly associated with HCC. Biologic or social factors that are not appreciated currently may be involved in Asian patients with HCC, contributing to a poorer clinical outcome.

Resection with external beam and intraoperative radiotherapy for recurrent colon cancer.

OBJECTIVE: To review treatment outcomes for patients with locoregional recurrent colon cancer who underwent resection, intraoperative radiotherapy (IORT), and external beam radiotherapy (EBRT). DESIGN: Retrospective study of patients treated between January 1990 and June 1994. SETTING: Tertiary care cancer center. PATIENTS: Eleven patients with bulky recurrent colon cancer extending to adjacent organs or structures signed informed consent forms to receive IORT. INTERVENTION: Of 10 patients who underwent exploratory laparotomy, 5 had no metastatic disease and underwent resection, IORT, and EBRT. Complete resection was accomplished in 4 patients. Doses of IORT ranged from 13 to 20 Gy depending on residual tumor burden; EBRT was typically delivered postoperatively to a dose of 45 Gy. MAIN OUTCOME MEASURES: Survival and locoregional tumor control. RESULTS: All 4 patients who underwent complete resection, IORT, and EBRT are alive without locoregional recurrence 53 to 77 months after treatment. Of these, only 1 patient developed distant metastases. The fifth patient, who had gross residual tumor, developed local recurrence 5 months after IORT. One patient developed an IORT complication-ureteral fibrosis leading to ipsilateral nephrectomy. CONCLUSION: Long-term disease-free survival can be achieved in selected patients with bulky regional recurrence of colon cancer with complete tumor resection, IORT, and EBRT.

Dose escalation trial of indium-111-labeled anti-carcinoembryonic antigen chimeric monoclonal antibody (chimeric T84.66) in presurgical colorectal cancer patients.

UNLABELLED: Chimeric T84.66 (cT84.66) is a high-affinity (1.16x10(11) M(-1)) IgG1 monoclonal antibody against carcinoembryonic antigen (CEA). The purpose of this pilot trial was to evaluate the tumor-targeting properties, biodistribution, pharmacokinetics and immunogenicity of 111In-labeled cT84.66 as a function of administered antibody protein dose. METHODS: Patients with CEA-producing colorectal cancers with localized disease or limited metastatic disease who were scheduled to undergo definitive surgical resection were each administered a single intravenous dose of 5 mg of isothiocyanatobenzyl diethylenetriaminepentaacetic acid-cT84.66, labeled with 5 mCi of 111In. Before receiving the radiolabeled antibody, patients received unlabeled diethylenetriaminepentaacetic acid-cT84.66. The amount of unlabeled antibody was 0, 20 or 100 mg, with five patients at each level. Serial blood samples, 24-hr urine collections and nuclear images were collected until 7 days postinfusion. Human antichimeric antibody response was assessed up to 6 mo postinfusion. RESULTS: Imaging of at least one known tumor site was performed in all 15 patients. Fifty-two lesions were analyzed, with an imaging sensitivity rate of 50.0% and a positive predictive value of 76.9%. The antibody detected tumors that were not detected by conventional means in three patients, resulting in a modification of surgical management. Interpatient variations in serum clearance rates were observed and were secondary to differences in clearance and metabolic rates of antibody and antibody:antigen complexes by the liver. Antibody uptake in primary tumors, metastatic sites and regional metastatic lymph nodes ranged from 0.4% to 134% injected dose/kg, resulting in estimated 90Y-cT84.66 radiation doses ranging from 0.3 to 193 cGy/mCi. Thirteen patients were evaluated 1-6 mo after infusion for human antichimeric antibody, and none developed a response. No major differences in tumor imaging, tumor uptake, pharmacokinetics or organ biodistribution were observed with increasing protein doses, although a trend toward increasing blood uptake and decreasing liver uptake was observed with increasing protein dose. CONCLUSION: Chimeric T84.66 demonstrated tumor targeting comparable to other radiolabeled intact anti-CEA monoclonal antibodies. Its immunogenicity after single administration was lower than murine monoclonal antibodies. These properties make 111In-cT84.66, or a lower molecular weight derivative, attractive for further evaluation as an imaging agent. Yttrium-90 dosimetry estimates predict potentially cytotoxic radiation doses to select tumor sites, which makes 90Y-cT84.66 also appropriate for further evaluation in Phase I radioimmunotherapy trials. Although clinically important changes in biodistribution, pharmacokinetics and tumor targeting with increasing protein doses of 111In-cT84.66 were not demonstrated, the results do suggest that antibody clearance from the blood is driven by hepatic uptake and metabolism, with more rapid blood clearance seen in patients with liver metastases. These patients with rapid clearance and potentially unfavorable biodistribution for imaging and therapy may, therefore, be a more appropriate subset in which to evaluate the role of administering higher protein doses. This underscores the need to further identify, characterize and understand those factors that influence the biodistribution and clearance of radiolabeled anti-CEA antibodies, to allow for better selection of patients for therapy and rational planning of radioimmunotherapy.

Local recurrence in breast cancer: implications for systemic disease.

BACKGROUND: Recurrence in breast carcinoma follows a pattern of growth marked by local, regional, or widespread dissemination. Local recurrence may be the harbinger of systemic disease or failure of local control. Delineation of these processes may have implications in treatment. METHODS: A retrospective review found 1,171 patients with stages I and II breast cancer from 1978 to 1990 treated at the City of Hope Medical Center. RESULTS: Twenty-seven percent (n = 313) of patients developed recurrences. These were classified as local, including chest wall and regional nodes (n = 40), local and distant (n = 63), and distant (n = 210). Mean follow-up was 60 months. Multivariate analysis demonstrates tumor size was not different between the three groups, but the presence of positive lymph nodes was: local = 51%, local and distant = 78%, and distant = 64%. The disease-free interval was longest in the local group (42 months) versus the local and distant group (23 months) and distant group (39 months). Median survival was calculated from the time of recurrence: local = 90 months, local and distant = 26 months, and distant = 16 months. CONCLUSIONS: A group of patients with local recurrence have improved survival and do not develop distant disease. This group may benefit from aggressive surgical treatment to control local disease. These data suggest that a subset of breast tumors can act locally aggressive without metastatic potential.

Survey of physicians' attitudes relative to the field of surgical oncology.

BACKGROUND: Surgical oncology as a distinct field of expertise is fairly young. The current study was designed to gain a better understanding of the attitude of practicing physicians toward the field of surgical oncology. METHODS: Three hundred twenty-seven physicians in the San Gabriel Valley (a suburban area adjacent to Los Angeles) responded to an anonymous survey of opinions regarding surgical oncology. Responses were placed into a computerized database. RESULTS: Of those responding, 179 were primary care physicians, 52 were general surgeons, 78 were gynecologists, and 18 were medical oncologists. Overall, 89% of physicians were familiar with the field of surgical oncology, but only 47% had ever heard of The Society of Surgical Oncology (SSO). Ninety-four percent of the respondents felt that a surgical oncologist should care for patients with complex cancer, and 63% of respondents felt that surgical oncologists should care only for patients with complex cancer. Familiarity with the field of surgical oncology and with the SSO correlated with the percentage of the physicians practice that was cancer related. Only 22% of physicians felt that the field of surgical oncology is redundant to the general surgical specialties. CONCLUSIONS: Results of the survey indicate that there is considerable recognition of the unique expertise of the surgical oncologist by the medical community. Unfortunately, many physicians are not familiar with the SSO. Educating physicians in the community about the SSO may help to further expand the role of the surgical oncologist in the care of the patient with cancer, standardize the expectations of the skills and training of a surgical oncologist, and set a benchmark for the surgical subspecialty.

Separation and microanalysis of growth factors by Phast system gel electrophoresis and by DNA synthesis in cell culture.

A simple, micro-scale method was established for the characterization of growth factors at picogram levels using Phast system gel electrophoresis followed by monitoring the mitogenic activity by DNA synthesis in cell culture instead of staining methods. The separations and bioassays were carried out with a procedure involving Phast polyacrylamide gel electrophoresis or isoelectric focusing, gel slicing along the template, elution of growth factors through Transwell membranes and measurement of [3H]thymidine incorporation into DNA of normal rat kidney (NRK) fibroblasts. Transwell cell culture chamber inserts separated sliced gel pieces from culture cells and also permitted the direct elution of growth factors into the culture medium. The lower limit of sensitivity for human epidermal growth factor (hEGF) and transforming growth factor type alpha (TGF-alpha) were about 50 and 200 pg, respectively. At these concentrations, they were not detectable by the current most sensitive silver staining technique. Iodinated hEGF and TGF-alpha were also used to demonstrate the feasibility of determining the isoelectric point and molecular weight of peptides at picogram levels. This method is reliable, reproducible and can improve current methods for the characterization of growth factors.

Prognostic significance of carcinoembryonic antigen in colorectal carcinoma. Serum levels before and after resection and before recurrence.

The use of carcinoembryonic antigen was evaluated in 425 patients with a mean follow-up of 48 months. The preoperative and postoperative carcinoembryonic antigen levels were predictive of recurrence and survival independent of the tumor stage. In a multivariate regression analysis of age, location, tumor stage, and preoperative and postoperative carcinoembryonic antigen levels, the latter three factors were significant prognostic variables with respect to the adjusted survival. Recurrent disease was found in 42% of patients, excluding patients with stage IV disease. The carcinoembryonic antigen level at recurrence was greater than 5 ng/mL in 79% of the patients and in 89% of the intra-abdominal recurrences. Carcinoembryonic antigen level at recurrence was not predictive of postrecurrence survival except in the subgroup of locoregional disease. The life span in patients with liver and lung metastases was not influenced by carcinoembryonic antigen level at recurrence. Preoperative and postoperative carcinoembryonic antigen levels can indicate a poorer prognostic group of patients with colorectal cancer who may benefit from adjuvant treatment. The carcinoembryonic antigen at recurrence can be used effectively to diagnose intra-abdominal recurrences and project survival after development of local/regional disease.

When is polypectomy sufficient treatment for colorectal cancer in a polyp?

Eighty-seven patients with a carcinoma in a polyp were reviewed over a 12-year period. Ten histologic criteria were analyzed for an association with the presence of residual carcinoma. Four factors were identified as having prognostic value: size greater than 1.5 cm, sessility, cancer of at least 50% of the adenoma volume, and invasive carcinoma. Polypectomy alone is adequate treatment unless the carcinoma invades deeper to the muscularis mucosa and is associated with one or more of these characteristics.

Aromatic amine acetyltransferase as a marker for colorectal cancer: environmental and demographic associations.

In this pilot, case-controlled investigation of 43 colorectal and 41 control male patients, we compared associations of colorectal cancer with the aromatic amine acetyltransferase polymorphism, nutritional and demographic characteristics, medical histories, industrial and occupational histories, and exposures from home environments and personal habits. Persons with the "fast" acetylator trait were at greater risk of colorectal cancer (odds ratio: 2.48; 95% confidence interval: 1.02, 6.03). Results that differed from previous reports were positive associations of colorectal cancer with agricultural and manufacturing industries and with consumption of meats prepared by smoking, curing, and barbecueing. As expected, exercise frequency, cruciferous vegetables, and dietary fiber served as protective factors.

Tuftsin increases survival in murine peritoneal carcinomatosis.

Tuftsin increases macrophage superoxide anion generation as well as chemotactic, phagocytic, and secretory activities. The antitumor effect of tuftsin is mediated through the increased cytotoxic properties of primed macrophages. Peritoneal carcinomatosis presents a tumor model where the antineoplastic activation of peritoneal macrophages can be studied. Tuftsin given by intraperitoneal injection into Balb/C mice with peritoneal carcinomatosis demonstrated significant improvement in survival rates of treated mice over controls. Superoxide generation by peritoneal macrophages was increased by tuftsin; however, after progressive tumor growth, there was a reduction in the amount of superoxide produced. In the group treated with carrageenan, the survival rate was lower than in controls. The superoxide generation was increased by carrageenan, but to lower levels than by tuftsin. The assay of superoxide generation by macrophages by itself cannot be used as a measure of tumor cytotoxicity induced by tuftsin.

Immunosuppression in patients with metastatic squamous cell carcinoma from the skin.

Sixteen of 70 patients with metastatic squamous cell carcinoma (SCC) from the skin had evidence of clinical immunosuppression. In addition to patients with lymphoproliferative disorders or renal failure, those with cicatricial pemphigoid and those undergoing chronic oral corticosteroid therapy were identified as being at high risk. Host immune surveillance appears to play a major role in determining the metastatic potential of cutaneous SCC.

Necrotizing gas-forming infections in cancer patients.

Necrotizing gas-forming infections in cancer patients present some unique characteristics, such as nontraumatic, spontaneous clostridial gangrene and gangrene involving an ischemic tumor mass. These infections can be rapidly progressive and uniformly fatal without surgical debridement. We review ten cases of gas gangrene seen during an 18-year period. Four were caused by Clostridium species and six by other organisms. Neutropenia was present in seven patients. During the last nine years, Clostridium septicemia occurred in 54 patients; in only two of those patients did gas gangrene ensue.

Arachidonic acid-dependent peroxidative activation of carcinogenic arylamines by extrahepatic human tissue microsomes.

Prostaglandin H synthase (PHS), an arachidonic acid-dependent peroxidase, has been implicated in the peroxidative activation of carcinogenic aromatic amines in extrahepatic carcinogen target tissues of experimental animals. We have examined the arachidonic acid-dependent activation of [3H]benzidine to DNA-bound products by microsomal preparations from 75 normal human tissues obtained during necessary surgical procedures. For several samples of urinary bladder epithelium, prostatic epithelium, colonic mucosa, and peripheral lung tissue, an arachidonic acid-dependent, microsomal-catalyzed activation of benzidine was observed; and the activity could be inhibited appreciably by indomethacin, a known inhibitor of PHS. Little or no arachidonic acid-dependent activity was detected in human placenta, breast, or liver microsomes or the majority of colon microsomes. Substrate specificity was also examined with purified ram PHS and with human bladder and with active colon preparations. Purified PHS catalyzed the activation of benzidine much greater than 2-naphthylamine, 2-amino-6-methyldipyrido[1,2-alpha:3',2'-d]imidazole greater than 4-aminobiphenyl greater than 2-amino-3-methylimidazo[4,5-f]quinoline greater than 3-amino-1-methyl-5H-pyrido[4,3-b] indole. In comparison, human bladder and colon microsomes catalyzed the activation of benzidine greater than 4-aminobiphenyl, 2-amino-6-methyldipyrido[1,2-alpha:3',2'-d]imidazole, 2-naphthylamine greater than 2-amino-3-methylimidazo[4,5-f]quinoline, 3-amino-1-methyl-5H-pyrido[4,3-b]indole. To confirm the occurrence of PHS antigen in human extrahepatic tissues, an avidin/biotin-amplified competitive enzyme-linked immunoabsorbent assay was developed with purified ram PHS and a commercially available monoclonal antibody known to cross-react with human platelet PHS. The avidin/biotin-amplified enzyme-linked immunosorbent assay, which detected ng quantities of ram PHS, clearly established the presence of the PHS protein in human bladder, prostate, and lung microsomes. In contrast, PHS antigen was not detected in the liver or placental microsomes. The interindividual and tissue-dependent variability of PHS and its role in aromatic amine carcinogenesis are discussed.