Canine malignant lymphoma and 2,4-dichlorophenoxyacetic acid herbicides.
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2,4-Dichlorophenoxyacetic Acid↗
Biomedical subjects
S S Sternberg
Publications and source records attributed to S S Sternberg.
Fatal thrombocytopenia and liver failure associated with carboplatin therapy.
A patient with fatal severe thrombocytopenia and acute hepatic necrosis complicating carboplatin (JM8, CBDCA, NSC 241240) therapy is described. The patient, an 18-year-old man with acute lymphocytic leukemia, was given high-dose carboplatin as a part of a phase I trial of this agent for the treatment of leukemia. Carboplatin (270 mg/m2/day) was administered as an intravenous infusion on five consecutive days, and the patient died 10 days after his last dose of carboplatin from complications of thrombocytopenia and acute liver necrosis. Autopsy revealed hemorrhage into the substance of the myocardium and hemorrhagic centrilobular liver necrosis. The temporal relationship between the initial rise in this patient's liver function tests and treatment with carboplatin suggests that this patient's liver failure was in part due to carboplatin. The autopsy findings of hemorrhage into the substance of the myocardium and centrolobular liver necrosis suggest that, in addition to its direct effects, carboplatin may have also contributed indirectly to this patient's liver failure through the complications of thrombocytopenia.
Adolescent↗
The National Polyp Study. Patient and polyp characteristics associated with high-grade dysplasia in colorectal adenomas.
The National Polyp Study (NPS), a randomized clinical trial to evaluate effective surveillance of patients discovered to have one or more colorectal adenomas, was the framework for this statistical analysis which used a multiple logistic model to assess the independent risk factors of patient and polyp characteristics associated with high-grade dysplasia in adenomas. The database included 3371 adenomas from 1867 patients. Adenoma size and the extent of the villous component were found to be the major independent polyp risk factors associated with high-grade dysplasia (p less than 0.0001). The adjusted odds ratios were 3.3 for medium-sized adenomas and 7.7 for large adenomas relative to small adenomas and 2.7 for villous A adenomas, 3.4 for villous B adenomas, and 8.1 for villous C and D adenomas relative to tubular adenomas. Increased frequency of high-grade dysplasia in adenomas located distal to the splenic flexure was attributable mainly to increased size and villous component rather than to location per se. The adjusted odds ratio was 1.4 (p less than 0.11) for left-sided location. Multiplicity of adenomas affected the risk for high-grade dysplasia in patients but was dependent on adenoma size and villous component and was not an independent factor. The adjusted odds ratio was 1.3 (p less than 0.17) for multiplicity. Increasing age was associated with risk for high-grade dysplasia in patients, and this effect was independent of the effect of adenoma size and histological type. The adjusted odds ratio was 1.8 (p less than 0.0016) for age greater than or equal to 60 yr. Gender was not associated with high-grade dysplasia. The adjusted odds ratio was 1.0 (p less than 0.95) for men. The size of the patient series, the prospective nature of the data collection, the completeness of information on all patients, the requirements of complete examination of the entire colon and pathological examination of all lesions encountered, and the exclusion of patients with previously diagnosed adenomas are, collectively, features unique to this study. The detailed model provided by the analysis integrates multiple patient and adenoma factors associated with high-grade dysplasia in colorectal adenomas.
Adenoma↗
Conservative treatment of distal rectal cancer by local excision.
From 1954 through 1982, 57 patients with invasive, distal rectal cancer had a full-thickness local excision with curative intent. Prognostic criteria and need for further treatment were based on the histopathologic results of the operative specimen. The overall 5-year survival rate was 83.4%. The rectal cancer-specific mortality rate was 10.5%. None of the 27 patients without adverse prognostic factors died from rectal cancer, and for this group local excision alone was sufficient treatment. The only single factors associated with an adverse outcome were mucinous characteristics and full-thickness invasion. Ulceration alone and penetration into the muscularis propria alone were not adverse factors. In the presence of multiple adverse prognostic factors, mucinous characteristics or full-thickness penetration, local excision was inadequate treatment and an abdominal perineal resection was necessary.
Adenocarcinoma↗
Early gastric cancer.
Thirty-six patients with early gastric cancer were studied. In 15 patients, malignancy was restricted to the mucosa; in 21 patients, submucosal invasion was noted. Lymph node involvement was found in four patients. Kaplan-Meier estimates for 5-year survival were 92 percent for mucosal lesions and 65 percent for submucosal lesions (overall 5-year survival rate 73 percent). Mucosal lesions were significantly larger than were submucosal lesions (3.7 +/- 0.6 cm versus 2.5 +/- 0.4 cm, mean +/- SE; p less than 0.005). Associated malignancy was recorded in 13 of 36 patients. When compared with data from a large Japanese study, early gastric cancer in the United States tends to develop more distally in the stomach and in patients approximately one decade older. Survival was not as favorable as in Japan. This may be related to patient age and the high incidence of associated nongastric malignancy.
Adenocarcinoma↗
The National Polyp Study: overview of program and preliminary report of patient and polyp characteristics.
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Adenoma↗
Toxicity, elimination, and metabolism of 10-ethyl-10-deazaaminopterin in rats and dogs.
10-Ethyl-10-deazaaminopterin (10-EdAM) is an antifolate compound with greater therapeutic activity than methotrexate against transplanted tumors in mice. When given weekly for 3 weeks, the 10% lethal dose in rats was 125 mg/kg (i.p.) and in dogs it was 2.5 mg/kg (i.v.). The major histopathological findings in intoxicated animals were damage to the mucosa of the gastrointestinal tract in rats and dogs and hypocellularity of the marrow in rats. The elimination of 50 mg/kg of 10-EdAM from the plasma of rats was triexponential with a terminal phase t1/2 of 18.5 h but a mean residence time of 0.7 h. The primary route of elimination in rats was biliary secretion of parent compound and eventual excretion of the parent compound and the deglutamate metabolite in the feces; the 7-hydroxy metabolite was also present in plasma, bile, and feces. Biliary elimination was independent of dose over a 5-fold range. The elimination of 10-EdAM from the plasma of dogs was also triexponential with a mean terminal phase t1/2 of 9.1 h and a mean residence time of 2.5 h; nonrenal clearance was the primary route of elimination. The pharmacokinetic parameters were independent of dose over the range of 0.25 to 5.0 mg/kg. High tissue concentrations of 10-EdAM were observed initially in liver, kidney, and small intestine of rats, while concentrations in bone marrow were low. Some polyglutamate formation was observed in these tissues as early as 0.5 h after drug administration but declined over 72 h.
Aminopterin↗
Upper gastrointestinal neoplasia in familial polyposis.
Upper gastrointestinal (UGI) endoscopy was performed in 41 asymptomatic American patients with familial polyposis to assess the prevalence of gastric and duodenal polyps and to characterize their pathological features. Eighteen patients (44%) had UGI endoscopic abnormalities. Six patients had both gastric and duodenal lesions. Eight patients had only gastric polyps, and four had duodenal polyps only. The presence of other extracolonic expressions of polyposis had a suggestive but statistically insignificant correlation with UGI polyps. Patients with familial polyposis and duodenal adenomatous polyps are at high risk for the development of periampullary cancer; screening and identification of these individuals is recommended.
Adenomatous Polyposis Coli↗
Adenocarcinoma of the upper esophagus arising in ectopic gastric mucosa. Two case reports and review of the literature.
Although ectopic gastric mucosa is often mentioned as a source of upper esophageal adenocarcinoma, few such cases have actually been documented. We report two cases and offer a review of the literature. Ectopic gastric mucosa in the upper esophagus is a relatively common congenital condition, but the risk of malignant transformation is extremely low. Ectopic gastric mucosa should be distinguished from Barrett's esophagus, an acquired condition with a well-documented predilection for developing adenocarcinoma.
Adenocarcinoma↗
Improved survival in epidermoid carcinoma of the anus in association with preoperative multidisciplinary therapy.
From 1972 to 1983, we treated 78 patients who had primary epidermoid carcinoma of the anus. Forty-four of these patients were treated by protocol, while 34 patients were not treated according to protocol. Protocol consisted of fluorouracil (750 mg/m for 5 days) and mitomycin (10 to 15 mg/m on day 1), followed sequentially by 3000 rad (30 Gy) over three weeks, followed by surgery. There were 20 local excisions and 29 abdominoperineal resections in the protocol group, and 11 local excisions and 14 abdominoperineal resections in the nonprotocol group. In the protocol group, 26 patients (59%) had no residual cancer in their operative specimens, while only ten (29.9%) of the nonprotocol patients had no remaining cancer. Four (11.7%) of the 34 nonprotocol patients had pathologically positive inguinal nodes, compared with only three (4.5%) of 44 protocol patients. Thirty-four (77%) of 44 protocol patients remained free of disease, while ten patients experienced local or pelvic recurrence. In contrast, only 17 (50%) of 34 patients in the nonprotocol group remained free of disease. Of 17 recurrences, five were at distant sites. The status at this writing of all patients in the protocol group was 32 (75%), with no evidence of disease, four alive with disease, and eight dead of or with disease. Of the untreated patients, only 11 (32%) remained without evidence of disease, two were alive with disease, and 19 were dead of or with disease. Smaller carcinoma size (less than 5 cm, 27 of 32 had no evidence of disease), younger age, female gender, and deep infiltration also predicted a statistically significant survival advantage after protocol treatment. Controlled, prospective, multi-institutional trials should stratify for these factors when comparing new treatment modalities.
Adult↗
Toxic terror: a counterattack.
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Animals↗
Giant kidney worm (Dioctophyma renale) infection mimicking retroperitoneal neoplasm.
A 50-year-old Chinese man was found by ultrasound and computed tomography to have a retroperitoneal mass in the right upper quadrant of the abdomen. At operation, a hemorrhagic cyst was detected at the upper pole of the right kidney adjacent to the adrenal gland. Microscopic examination revealed that the cyst wall was composed of granulomatous tissue loaded with eggs and cross-sections of parasites, identified as Dioctophyma renale. The eggs were characterized by a birefringent striated double wall. The presence of cross sections of adult worms of D. renale in human tissue has not been previously described. Another unique feature of this case was that the right kidney was intact, as examined grossly at laparotomy and by intravenous pyelography. Eggs were not detected in the urine.
Cysts↗
En bloc pelvic lymphadenectomy and sphincter preservation in the surgical management of rectal cancer.
From 1968-1976, 412 patients were operated on for rectal cancers. One hundred fifty-six underwent abdominoperineal resection (APR) and 256 underwent low anterior resection (LAR). One hundred ninety-two underwent en bloc pelvic lymphadenectomy in conjunction with their resection, while 220 patients underwent more conservative or conventional resection. Thirty-day hospital mortality was 1.7%. The cancer-related 5-year survival was 58.8% for all patients. The proportion of patients surviving 5 years after LAR (62.8%) was significantly better than those surviving after APR (52.4%), p = 0.008. Statistically significantly superior survival was observed after extended dissection when compared to conventional resections in Dukes' A, B, and C patients as a whole (63.8 and 54.3%) and in Dukes' C patients in particular. Superiority of en bloc pelvic lymphadenectomy versus conventional resection was observed in all cases of Dukes' Stage C, Astler-Coller Stage C1, Level II (adjacent) lymph nodes, and Level I (proximal) lymph nodes and was most effective in combination with sphincter-preserving operations. Patient groups were compared for bias and/or case selection, using both contingency tables and Cox-based multiple covariant linear regression analysis, and none was found. In the face of current adjuvant therapy, which is of questionable benefit and which carries its own treatment morbidity, en bloc pelvic lymphadenectomy is advocated as an adjunct to the curative operations for rectal cancer. To improve the overall benefit, patients can be selected for pelvic lymphadenectomy as an adjuvant to resection when preoperative examination suggests that the rectal cancer penetrates the bowel wall. Accurate preoperative staging may help to define a more restricted group of patients warranting (pelvic lymphadenectomy) (PLND). A control randomized trial of the effectiveness of PLND is appropriate to further test its value.
Adenocarcinoma↗
Treatment alternatives. Localized rectal cancer.
Cancers that occur in the low or mid rectum, and are superficial and freely movable on the underlying bowel wall, should be considered for local treatment provided they are not anaplastic and are technically accessible to excision. Although a variety of methods have been shown to be effective, we propose that initial local surgical excision as a "total biopsy" is the most rational approach to the management of such lesions. Factors indicating a poor prognosis, including extension through the entire thickness of the bowel wall, incomplete surgical excision, poorly differentiated histologic grading, venous or lymphatic invasion, or colloid type of tumor, can be identified, and more aggressive surgical treatment can be urged. When these factors are absent, the total biopsy then constitutes definitive treatment for this highly selected population.
Adult↗
Patterns of pelvic recurrence following definitive resections of rectal cancer.
Patterns of local and distant recurrences following resections for rectal cancer provide clinical perspective for multidisciplinary prevention and follow-up programs. From 1968 to 1976 at Memorial Hospital, 412 patients with potentially curable rectal cancer were treated by anterior (AR) or abdominoperineal (APR) resections. First sites of recurrences were categorized as pelvis, liver, distant viscera, and intraabdominal/retroperitoneal sites. Pelvic recurrences were further evaluated according to the location of the tumor, type of resection, and stage of disease. Among the 412 cases, 182 (44.2%) patients developed recurrence, of which 105 (57.6%) were pelvic. Pelvic recurrence was the predominating site either alone (55 of 103) or with concomitant extra-pelvic sites (50/79). In instances of single-site first recurrence, pelvic failure was recognized earliest at 19.1 months, which was significantly earlier than single-distant visceral sites at 34.9 months. Pelvic recurrence was selectively related to various categories of the Dukes and modified Dukes staging systems. Dukes stage significantly predicted pelvic recurrence rates for Dukes A verus B. Astler-Coller stages of B2 and C1 were associated with significantly lower rates of pelvic recurrence (29.7% and 22.1%, respectively) than C2 cancers. The incidence of pelvic recurrence was significantly increased for low and mid rectal cancers as compared with cancers at or above 12 cm. The type of resection utilized (APR versus AR) was associated with no difference in the rate of pelvic recurrence, except for the few patients in whom AR was performed for low rectal Dukes C cancers. Patients with pelvic recurrence had an ultimate disease-free survival of only 3.8% as compared with patients with no pelvic recurrence of whom 77% remained alive without disease or went on to die of other causes. The timing and predominance of pelvic failure in rectal cancer with its own treatment-related morbidity and overall dismal survival outcome justifies organized multidisciplinary efforts to prevent such failure and prospective trials of comprehensive follow-up programs to evaluate improved cure rates or palliation.
Female↗
Juvenile nasopharyngeal angiofibroma. A 30 year clinical review.
Thirty-one patients with juvenile nasopharyngeal angiofibroma treated at Memorial Sloan-Kettering Cancer Center from 1949 to 1979 were reviewed. Eighteen of the patients were previously untreated and in the other 13, previous treatment elsewhere had failed. Median follow-up was 54 months. All the patients were male adolescents whose presentations were characterized by epistaxis (73 percent) and nasal obstruction (60 percent). The tumors invariably arose within the nasal cavity or nasopharynx and involved neighboring structures in 58 percent of the patients. Treatment included surgery (30 patients), radiotherapy (13 patients), the administration of androgens (11 patients), sclerotherapy (2 patients), and cryotherapy (1 patient). Of the 18 primary patients, 14 were managed surgically with irradication of disease in 12 (86 percent). Of the four primary patients initially treated nonsurgically, disease recurred in three, all of whom were rendered free of disease by surgical excision. Of the 13 secondary patients, 8 were free of disease after surgery only, and 2 were free of disease after multimodal therapy with surgery being the last treatment employed. There were no deaths. Maxillary radionecrosis (one patient) and facial cellulitis (three patients) constituted the only significant morbidity. This study has demonstrated the clinical characteristics of juvenile nasopharyngeal angiofibroma and supports the primary role of surgical excision in its management.
Adolescent↗
Aspergillosis of the cerebral ventricles in a heroin abuser. Case report and review of the literature.
Aspergillosis of the cerebral ventricles developed in a 36-year-old heroin abuser who died during the sixth week of illness. The diagnosis was not made during life. A review of our case and of four previous cases from the literature indicates that aspergillosis should be considered in parenteral drug abusers with the syndrome of chronic meningitis or ventriculitis. The diagnosis is difficult to establish, but serologic tests may be helpful. This form of CNS aspergillosis can be cured with antifungal drugs.
Adult↗
Fatal pulmonary tumor embolization following peritoneovenous shunting for malignant ascites.
A 44-year-old white male with pseudomyxoma peritonei and intractable malignant ascites is described. This patient underwent three peritoneovenous shunt procedures utilizing first the LeVeen shunt and finally the Denver shunt in a surgical attempt at palliative decompression of his malignant ascites. The peritoneovenous shunts resulted in massive tumor embolization to the pulmonary vasculature, clinically asymptomatic disseminated intravascular coagulation, and partial thrombosis of the superior vena cava. The pulmonary tumor embolization was manifest clinically as moderate pulmonary hypertension with increased pulmonary vascular resistance and persistent hypoxia.
Adenocarcinoma, Mucinous↗