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Biomedical subjects

A Mittelman

Publications and source records attributed to A Mittelman.

At least 145 records · Page 8Linked to original sources

The prognostic value of preoperative alkaline phosphatase for resection of solitary liver metastasis from colorectal carcinoma.

A retrospective review was undertaken to determine the influence of preoperative alkaline phosphatase levels on the prognosis of patients who had undergone resection of liver metastasis from colorectal adenocarcinoma at Roswell Park Memorial Institute. From March 1967 to March 1985, 26 patients underwent laparotomy who were thought to have solitary liver metastasis. Twenty of these patients were divided into two groups: group A consisted of seven patients who survived at least 24 months without any evidence of disease and were free of disease at the time of this report. Group B consisted of 13 patients who recurred or died from metastases following liver resection. The preoperative levels of alkaline phosphatase clearly showed that an elevated level before surgery was associated with a poor prognosis in the majority of cases. In group A only one of seven patients had an elevated level where seven of 13 patients in group B had elevated preoperative alkaline phosphatase levels. In conclusion, preoperative alkaline phosphatase levels may be helpful in determining the prognosis of patients considered for curative resection of solitary liver metastasis from colorectal carcinoma.

Adenocarcinoma↗

Thymidylate synthase gene amplification in a colon tumor resistant to fluoropyrimidine chemotherapy.

We have identified amplification of the thymidylate synthase gene in a colonic tumor that had developed resistance to 5-fluorouracil/leucovorin combination chemotherapy. The tumor had previously undergone a partial response to this combination but began to progress following a prolonged period of continuous therapy and relative disease stabilization. Since thymidylate synthase is a target enzyme for 5-fluorouracil, it is likely that the observed gene amplification is responsible for the resistance. Thus, gene amplification may be a relevant mechanism of acquired resistance to fluoropyrimidine chemotherapy in the clinic.

Colonic Neoplasms↗

Toxicity associated with adjuvant postoperative therapy for adenocarcinoma of the rectum.

The Gastrointestinal Tumor Study Group's (GITSG) adjuvant rectal carcinoma study compared four postoperative treatment regimens: (1) control (no adjuvant therapy); (2) chemotherapy alone consisting of pulses of 5-fluorouracil and methyl CCNU for 18 months; (3) pelvic and perineal radiotherapy using parallel opposed fields with 4000 rad in 4.5 to 5 weeks or 4800 rad in 5 to 5.5 weeks; and (4) a combination of both modalities. The results of this study are published elsewhere and show a significantly reduced recurrence rate and prolonged disease-free survival time for the combined modality arm compared with the no therapy arm. Severe toxicity in the combined therapy arm was significantly worse (P less than 0.001) than in either single modality arm. Most of the differences in toxicity experienced between the three regimens involved diarrhea, thrombocytopenia, and leukopenia. Analysis of all parameters of radiotherapy quality assurance data was not significantly associated with toxicity. Radiation enteritis was noted in 5 patients of 96 (5.2%) in the two arms containing irradiation. All five required laparotomy. The two enteritis fatalities occurred late at 605 and 1000 days after start of combined modality treatment, respectively. One other patient on the chemotherapy arm died of acute nonlymphocytic leukemia. The authors conclude that combined radiotherapy and chemotherapy, although significantly more effective in reducing recurrence than no therapy, is significantly more toxic than single-modality therapy in many parameters, although most of the toxicity is transient and therefore not limiting. Late complications, which are less reversible and therefore much more important than early reactions, and radiation enteritis in this study were relatively uncommon. This schedule of combined modality therapy is not only effective but appears to have tolerable toxicity, because of the relative lack of late effects.

Adenocarcinoma↗

A comparison of the 25-cm rigid proctosigmoidoscope with the 65-cm flexible endoscope in the screening of patients for colorectal carcinoma.

A comparison of the rigid with the flexible sigmoidoscope was evaluated in 293 patients as part of a screening project for colorectal cancer at Roswell Park Memorial Institute. Patients with either a positive family history for colorectal cancer, a positive stool guaiac test result, a history of hematochezia, or a change in bowel habits were randomly assigned to either rigid or flexible sigmoidoscopy. The median distance of colon examined with the flexible instrument was significantly greater than with the rigid scope (55 versus 17 cm, respectively). A significantly greater number of malignant and premalignant lesions were found with the flexible instrument than with the rigid scope. It was concluded that the flexible sigmoidoscope is superior to the rigid scope in the process of screening for colorectal lesions.

Adolescent↗

Photodynamic therapy in patients with colorectal cancer.

A pilot study was conducted, in which photodynamic therapy (PDT), a technique in which malignant cells are destroyed by light after being previously photosensitized by a chemical compound, was tried in a group of 14 patients with recurrent or residual colorectal cancer in the pelvis. Three of the six patients with unresectable pelvic recurrences experienced a significant relief of pain after PDT. In two of the five patients who had an incomplete resection of their pelvic recurrences, there was also a substantial relief of pelvic pain after surgery and PDT. In one of these patients subsequent biopsies proved the disappearance of the residual pelvic microscopic disease after several sessions of PDT. Three patients had a recurrence from a squamous cell carcinoma primary of the anal canal. All recurrences were amenable to surgical resection. In one of the patients, PDT was used in an attempt to sterilize an area of residual tumor that was located over the left ischial tuberosity. The patient experienced good relief of pain, but died of her disease 7 months after PDT. In the other two patients, PDT was used as an "adjunct" after resection of their recurrences. One of these patients was free of disease and died of an unrelated cause 12 months after PDT. The other is alive and well. This study demonstrated that PDT can be safe and tolerable in patients with pelvic malignancies. PDT is capable of tumor destruction, can be used repeatedly in areas previously exposed to ionizing radiation, and may have a role in the prevention and management of pelvic-perineal recurrences from colorectal cancer.

Adult↗

Epidermoid carcinoma of the anal canal.

The charts of 67 patients treated for epidermoid carcinoma of the surgical anal canal were reviewed. The clinical presentation, type of surgical procedure performed, lymph node status of the pararectal and inguinal nodes, time of recurrence, site of recurrence, and median survival from the date of primary surgery and from the date of recurrence were determined. There were 55 patients (82%) who had a minimum of 5 years' follow-up since initial treatment. Optimal surgical treatment requires an abdominoperineal resection with wide dissection of the ischiorectal fossa and perineum in all patients, as well as an en bloc excision of the posterior vaginal wall in women. Although excision of the posterior vaginal wall improves the disease-free interval, median survival is not altered, compared with the group without vaginectomy. The predominant sites of local recurrence in men are the pelvis and perineum, and in women, the pelvis and posterior vaginal wall. The status of the pararectal lymph nodes from the operative specimen can give accurate information about the relative risk of recurrence. The presence of inguinal lymph node metastases represents a poor prognosis because of a close association with systemic metastases.

Adult↗

Anastomotic recurrence of adenocarcinoma of the colon.

The cases of 158 patients with locally recurrent colorectal carcinoma were retrospectively studied. Eighteen patients (11.4%) had a recurrent lesion at the site of anastomosis. Sixteen patients who underwent a primary curative resection had a median disease-free interval of 13 months, while two patients with a palliative resection had a disease-free interval of two months. All recurrences occurred within 27 months of the primary surgery. Abdominal pain was the most frequent presenting symptom, followed by melena and a change in bowel habits. Eighty-nine percent of the recurrences occurred in the context of metachronous or synchronous metastases equally distributed between local-regional and distant diseases. Thirteen patients underwent resection of recurrent disease, of which eight resections were curative. The median survival following curative resection was 23 months, with 14 months for palliative resection and five months for no resection.

Adenocarcinoma↗

The morbidity of perineal wounds following abdominoperineal resection for rectal carcinoma.

The clinical charts of 44 patients who underwent an abdominoperineal resection for adenocarcinoma of the rectum at Roswell Park Memorial Institute were retrospectively reviewed. The morbidity of an open perineal wound versus the closed perineal wound were evaluated. All of the patients received a Nichol's bowel preparation and following the abdominal portion of the dissection reperitonealization of the pelvic floor was performed. The overall morbidity for the open perineal wounds was 21% compared to a morbidity of 63% for the perineal wounds that were closed primarily. The mean length of hospitalization from the time of abdominoperineal resection was 21 days for the open perineal group and 22 days for the closed perineal group. The inclusion of wound sinus tracts in our morbidity assessment may explain the higher complication rate of the closed wound group than previously reported in the literature. This retrospective review emphasizes that the morbidity of the open perineal wound following abdominoperineal resection has been overemphasized. One is trading a potentially increased incidence of septic wound complications in the closed perineum for a protracted wound closure in the open perineum.

Abdomen↗

Aminocaproic acid (AMICAR) in advanced colorectal carcinoma.

We treated 20 patients with measurable histologically confirmed colorectal adenocarcinoma with aminocaproic acid (AMICAR). There were 11 males and 9 females with a median age of 63 years. All 20 patients had received prior chemotherapy. The majority of monitoring lesions were distributed between lung and liver. We evaluated 12 patients in this series for response. Three patients had stable disease and nine patients had progressive disease. All patients were evaluable for toxic effects, the most common being nausea and vomiting. AMICAR given orally at 210 mg/kg of actual body weight/day is not an effective single agent in the treatment of metastatic colorectal carcinoma. In view of previously published animal data the role of AMICAR in the adjuvant setting for colorectal carcinoma still needs to be determined.

Adenocarcinoma↗

Common peroneal nerve palsy associated with pelvic surgery for cancer. An analysis of 11 cases.

Eleven occurrences of common peroneal palsies following pelvic surgery for malignant conditions are reported. The patients' clinical course and possible mechanisms of nerve injury were reviewed. It was concluded that the current belief that all peripheral neuropathies occurring under general anesthesia are preventable may not be applicable to patients with pelvic cancer who must undergo tedious, lengthy, meticulous, extirpative surgery in the dorsal lithotomy position. In patients with tumors that are seemingly isolated to the pelvis, amenable for surgical resection, the possible risk of a peripheral nerve injury is superseded if beneficial effects are obtained by controlling the local manifestations of the tumor.

Adenocarcinoma↗

Osseous metastases from colorectal carcinoma.

In a 10 year (1970 to 1980) retrospective study of 66 patients with primary colorectal adenocarcinoma and osseous metastases, there were 47 patients who had bone and other distant metastases whereas 19 patients had osseous metastases only. The median disease-free interval was 21 months. The overall median survival time from diagnosis of osseous metastases was 7 months. Bone scanning is probably more sensitive for diagnosing bone metastases that radiography. Radiotherapy seems to be the most effective treatment for symptomatic osseous metastases.

Adult↗

Perineal effects of postoperative treatment for adenocarcinoma of the rectum.

Nine (4%) first recurrences that involved the perineum were identified in a randomized study of 202 patients treated by no further therapy, chemotherapy only, radiotherapy only, combined radiotherapy and chemotherapy, following complete surgical excision of adenocarcinoma of the rectum. Six of these were in unirradiated patients and in two of the three irradiated patients the perineum was included in the treatment volume. Eight of the nine patients were male and all nine had received abdominoperineal resection (APR). Our quality assurance procedures identified 22 of 96 irradiated patients in whom the perineum was grossly outside the fields. Sixteen of these had undergone APR. As only one of these 16 relapsed in the perineum no definite effect of the surgical procedure on the likelihood of perineal recurrence could be demonstrated. Examination of the pathology reports revealed that 28 patients undergoing APR had tumors within 2 cm of the anorectal junction (pectinate line). Five (17.8%) developed perineal recurrence compared with 4 (3.6%) of 110 patients whose tumors were more than 2 cm from the anus (p less than 0.02-Fisher exact test). No survival differences could be demonstrated between those receiving perineal irradiation and those not but perineal irradiation was associated with toxicity with at least nine (12.2%) out of 74 developing severe complications directly related to the perineum. The routine inclusion of the perineum in postoperative pelvic irradiation fields for all cases of adenocarcinoma of the rectum is questioned. Our current policy following APR includes optional coverage of the perineum for those tumors more than 5 cm from the anorectal junction.

Adult↗

Treatment of colorectal hepatic metastases by intrahepatic chemotherapy alone or as an adjuvant to complete or partial removal of metastatic disease.

Because of the wide variation in reported benefits from the use of intrahepatic chemotherapy for colorectal hepatic metastases, the authors performed their own phase II studies comparing the use of intrahepatic chemotherapy alone and intrahepatic chemotherapy as an adjuvant to complete or partial removal of metastatic colorectal cancer to the liver. Techniques for partial removal included unilateral and bilateral wedge resection, peripheral presinusoidal embolization of the liver, and portal vein branch ligation. Patients were staged using the per cent hepatic replacement method of Pettavel and Taylor, and patients with bilateral metastases were included in the study. Twenty-seven patients, mean age 60.3 years, were examined. There were 19 males, mean age 60.4 years, and eight females, mean age 60 years. The patients were divided into four groups. Group A had an implantable pump only; Group B had an implantable pump and resection; Group C had an implantable pump and arterial embolization and portal vein branch ligation; and Group D had an implantable pump, partial resection, arterial embolization, and portal vein branch ligation. Kaplan-Meyer survival curves were calculated for all of these groups. A separate analysis was carried out for each of the stages, and a comparison was made. The study indicated that the overall median survival time was 18 months and that the more radical the treatment in addition to chemotherapy, the better the results. Such results were not totally dependent on the staging of the tumor volume but were dependent on the degree of extirpation of the tumor. In Group C, consisting primarily of Stage IIa, IIIa, and IV patients (i.e., unresectable patients), a doubling of expected median survival to 12 months could be achieved, compared to those in Group A, which achieved a median survival of only 6 months.

Adult↗

Surface immunoglobulin light chain expression in pre-B cell leukemias.

Cytofluorographic analysis of surface immunoglobulin (sIg) light chain clonal excess (CE), defined as (%kappa+ - %lambda+)/(%kappa+ + %lambda+) cells per discrete level of fluorescence intensity, was carried out on mononuclear cells of 32 leukemic patients. Eight demonstrated sIg light chain CE, including four blastic chronic myeloid leukemias (BL-CML), three "null" acute lymphoblastic leukemias (ALL), and one leukemic lymphoblastic lymphoma. Six of the leukemias demonstrated a kappa CE and two had a lambda CE. Sorted kappa+ PB cells from a BL-CML patient were shown to have a diploid DNA stem line and to bear the "common" ALL antigen. To provide further support for our finding of the expression of sIg light chains in ALL, we studied the REH cell line, derived from a "common" ALL patient and found cytoplasmic mu heavy chain and surface Ig lambda CE. Nucleic acid blotting experiments on REH revealed that both kappa genes had been deleted and that lambda genes had been rearranged, as expected in B cells expressing lambda light chains. Moreover, REH cells contained mu and lambda RNA. When REH cells were treated with TPA the amount of mu chain RNA increased by approximately fivefold and the amount of lambda chain RNA increased by approximately twofold. The finding of sIg light chain in pre-B cell leukemias and in the REH cell line, suggests that these leukemic cells are further differentiated along the B-cell lineage than was previously believed.

Antigens, Neoplasm↗

Comparative analysis of surface membrane immunoglobulin determination by flow cytometry and fluorescence microscopy.

The analysis of membrane surface immunoglobulin (SmIg) on B lymphocytes was carried out in 59 normal individuals and nine patients with B-cell non-Hodgkin's lymphomas by conventional immunofluorescence microscopy and flow cytometry. Five channel settings of a cytofluorograph were evaluated (100, 150, 200, 250, 300) and the mean and standard deviation of the percent positive cells were calculated and compared to the mean and standard deviation of the microscope reading. On the basis of the relative fluorescence reactivity, we were able to determine a fluorescence intensity at which the results of flow cytometry and fluorescence microscopy were comparable. In normal individuals, for cells expressing surface Ia, the channel giving similar results to that of fluorescence microscopy was 150; for kappa and lambda chains, channel 200; for Fab'PV, channel 200; and for IgM, channel 250. In patients with B-cell non-Hodgkin's lymphomas, for cells expressing surface Ia the channel giving similar results to that of fluorescence microscopy was 100; for kappa, channel 100; for lambda, channel 200; for Fab'FV, channel 150; and for IgM, channel 150. Flow cytometric analysis of SmIg appears to be superior to fluorescence microscopy in efficiency, and has the added advantages of being a rapid, sensitive, and objectively quantitative methodology.

B-Lymphocytes↗