Biomedical subjects
Publications and source records attributed to B D Minsky.
The sixth published case of a leiomyosarcoma of the anus is reported and the previous literature reviewed. Treatment with successful preservation of anal sphincter function is described. Local excision of the tumor was followed by external beam radiation therapy and an Iridium-192 implant. The details and rationale for this mode of therapy for resectable anal tumors are discussed.
The growth and morphology of 4 tumorigenic rat urothelial cell lines grown on collagen-coated nylon discs was characterized and compared to normal cells. In contrast to cells cultured on a plastic substrate with or without a thin "nonporous" collagen coating, tumor cells grown on porous collagen-coated nylon discs: 1) grew to greater protein densities; 2) formed tissue structures characteristic for the type of tumor they developed upon back-transplantation; and 3) could be grown and cultured indefinitely without subculturing. Thus, similarly to normal urothelial stratification and differentiation in vitro, tumorigenic cells apparently require a "porous" collagen substrate to allow differentiation analogous to that observed in vivo.
The flow of membrane between the cytoplasm and the lumenal surface during the expansion-contraction cycle of urinary bladder was estimated by stereological examination of electron micrographs of urothelial cells from guinea pigs, gerbils, hamsters, rabbits, and rats. The quantitative data obtained allowed an approximation of the surface area, volume, and numbers of lumenal membranelike vesicles and infoldings per unit volume of cytoplasm. Depending upon the species, approximately 85 to approximately 94% of the membrane surface area translocated into and out of the cytoplasm was in the form of discoidal vesicles. The remainder was accounted for by infoldings of the lumenal plasma membrane. The density of vesicles involved in transfer of membrane was quite similar in all the species examined, except guinea pigs which yielded lower values. In contrast, the densities of the total cytoplasmic pools of discoidal vesicles potentially available for translocation varied greatly among the different species. In general, species of animals with a highly concentrated urine had a greater density of discoidal vesicles than species with a less concentrated urine. This correlation may indicate an authentic relationship between lumenal membranes and the tonicity of urine, such as increased membrane recycling or turnover with increasingly hypertonic urine; or it may signify the existence of some other, more obscure relationship.
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Combined modality therapy is the standard adjuvant therapy for selected patients with adenocarcinoma of the rectum. In the postoperative setting, the primary goal is to decrease local recurrence and improve overall survival. In the preoperative setting, adjuvant therapy has the additional potential benefit of enhancing sphincter preservation and less acute toxicity as compared with postoperative adjuvant therapy. Investigational trials are in progress to examine new systemic chemotherapeutic agents and altered radiation fractionation schemes.
Twenty-five patients with prostatic cancer were prospectively examined with a prototype endorectal surface coil featuring a birdcage resonator circuit design. The purpose was to determine the safety of an intracavitary probe for magnetic resonance (MR) imaging of the pelvis that incorporates the "inside-out" characteristics of a volume coil design and allows high-resolution MR imaging of the prostate and potentially serves as an alternative to single-loop intracavitary surface coils. Clinically useful images supplementing images obtained with the body or external surface coils were obtained with the prototype probe. It was tolerated by all patients enrolled in the study, and none experienced side effects. The cylindrically symmetric sensitivity profile of the probe allowed identification of prostate tumors and pelvic lymph node and bone metastases. Volume-type coils may improve endopelvic MR imaging when used alone or in combination with external coil systems.
Phospholipid extracts of surgical tissue specimens from 18 patients, consisting of normal esophagus, distal esophageal tumor and normal stomach, were analyzed using 31P NMR. The prominent phospholipids detected in these tissues included cardiolipin (CL), phosphatidylethanolamine plasmalogen, phosphatidylethanolamine (PE), phosphatidylserine (PS), sphingomyelin (SPH), phosphatidylinositol (PI), phosphatidylcholine plasmalogen and phosphatidylcholine (PC). Very small quantities of the phospholipids lysophosphatidylcholine, phosphatidic acid, phosphatidylglycerol, and an uncharacterized phospholipid at -0.13 delta also were detected in some of the 54 tissue specimens analyzed. The mean relative concentrations of these phospholipids, in mole percentages of total detected phosphorus, were determined from the acquired spectra and used to differentiate among the three tissue groups. The relative concentrations of the following phospholipids differed significantly (p < 0.001) among the respective tissue groups: normal esophagus vs esophageal tumor, PS, SPH, PI, PC; normal esophagus vs normal stomach, CL, PE, PS, SPH; esophageal tumor vs normal stomach, CL, PE. Membrane phospholipids implicated in modulating the growth and metastases of tumors of epithelial origin can be profiled to discriminate among normal esophagus, distal esophageal tumor and normal stomach using 31P NMR.
The conventional surgical treatment for patients with potentially curable transmural and/or node positive rectal cancer is a low anterior resection or abdominoperineal resection. Recently, there has been increasing interest in the use of local excision and postoperative radiation therapy as primary therapy for selected rectal cancers. The limited data suggest that the approach of local excision and postoperative radiation therapy should be limited to patients with either T1 tumours with adverse pathological factors or T2 tumours. Transmural tumours, which have a 24% local failure rate, are treated more effectively with standard surgery and pre- or postoperative therapy. The results of local excision and postoperative radiation therapy are encouraging, but more experience is needed to determine if this approach ultimately has similar local control and survival rates as standard surgery.
Adjuvant chemoradiation therapy following resection of T3N0 rectal cancer is recommended in order to reduce the incidence of local recurrence and improve survival. However, recent experience with rectal cancer resection utilizing sharp dissection and total mesorectal excision has resulted in a reduction in local recurrence rates to as low as 5% without adjuvant treatment. The purpose of this study was to determine if rectal cancer resection utilizing sharp mesorectal excision alone is adequate treatment for local control of T3N0 rectal cancer. Between July 1986 and December 1993, 95 patients with T3N0M0 rectal cancer underwent resection with sharp mesorectal excision and did not receive any adjuvant therapy. Various prognostic factors were analyzed for their association with local recurrence and survival. Seventy-nine patients had a low anterior resection, 10 of whom had a coloanal anastomosis, and 16 had an abdominoperineal resection. The median follow-up was 53.3 months. Six patients had local recurrence, 12 had distant recurrence, and three had local and distant recurrences. The overall local recurrence rate was 9% crude and 12% 5-year actuarial. The overall crude recurrence rate was 22%. The 5-year disease-specific survival rate was 86.6% with an overall survival of 75%. Postoperative complications occurred in 18 patients (19%). Five patients (6%) had a documented anastomotic leak. Perioperative mortality was 3%. No technical factors, including type of resection (low anterior vs. abdominoperineal), location of tumor, or extent of resection margin, were significant for determining local recurrence. The only histopathologic marker significant for determining local recurrence was lymphatic invasion (P <0.04). Sharp mesorectal excision with low anterior resection or abdominoperineal resection for T3N0M0 rectal cancer results in a local recurrence rate of less than 10% without the use of adjuvant therapy. Therefore, in select patients with T3N0M0 rectal cancer, the standard use of adjuvant therapy for local control may not be justified.
Combined modality therapy is an effective adjuvant therapy for many patients with clinically resectable rectal cancer. The indications for adjuvant therapy for rectal cancer are based on the pattern of failure after surgery. Despite radical surgery, local-regional failure frequently occurs in patients with transmural or node-positive rectal cancers. The incidence of treatment failure in the pelvis is directly correlated with the extent of transmural penetration (microscopic vs gross) and the additional risk of lymph node metastases. In the post-operative setting its use is dictated by pathologic stage and the type of operation (i.e. conventional surgery or a local excision). The choice of which post-operative adjuvant regimen to recommend in the non-protocol setting remains controversial. If 5-FU alone is used, then it is best administered by continuous infusion. In the preoperative setting, the use of adjuvant therapy depends on the clinical stage and the need for sphincter preservation. Phase I/II trials examining the use of newer chemotherapeutic agents such as Tomudex, UFT/leucovorin, CPT-11, oxaliplatin, eniluracil and capecitabine with preoperative radiation therapy are in progress. This review examines both the selection criteria and results of adjuvant combined modality therapy for patients with clinically resectable rectal cancer.
Following potentially curative surgery for resectable adenocarcinoma of the rectum, the incidence of local failure is 15% to 35% in stages T3N0 and T1N1-2 and 45% to 65% in stages T4N0, T3N1-2, and T4N1-2. In order to determine the impact of pelvic radiation therapy +/- chemotherapy on local failure and survival, we present a prospective analysis of our results of 25 patients treated with this approach. The median follow-up was 30 months (range: 10 to 48 months). For the total patient group the 3-year actuarial survival was 74%. In order to more accurately analyze the patterns of failure, actuarial calculations were performed. The actuarial incidence of local failure as a component of failure was 17%. For patients with node positive disease (T1-4N1-2), the overall survival was 80%, and the actuarial incidence of local failure as a component of failure was 15%. Complications were acceptable and the incidence of small bowel obstruction requiring surgery was 8%.
We report the impact of selected clinicopathologic features on local failure and disease-free survival in 22 patients with localized, mobile, primary resectable rectal cancer treated with local excision and postoperative radiation therapy. Full thickness local excisions with negative margins were performed in 21 patients. One patient had a transanal snare excision of a T1 polyp. Postoperatively patients received 4500-4950 cGy (medial 4680 cGy) whole pelvis, and in 15 this was followed by a conedown of 360-1000 cGy (median 360 cGy). Two received 5-FU. Tumors were evaluated for size, gross appearance, distance from the ana verge, T stage, blood vessel invasion, lymphatic vessel invasion, and DNA content (ploidy, DNA index, and proliferation index). The median follow-up was 37 months (range 5-73). With increasing T stage there was a corresponding increase in local failure (T1: 0%, T2: 17%, and T3: 33%) and a decrease in disease-free survival (T1: 100%, T2: 67%, and T3: 50%). When accounting for the effect of T stage, tumors which were either BVI-or ulcerative were associated with an increase in local failure, and tumors which were < or = 3 cm, ulcerative, or nonaneuploid were associated with a decrease in disease-free survival. However, none of the differences reached statistical significance. Although other clinicopathologic features may have an impact, T stage remains the most reliable clinicopathologic feature by which to predict local failure and disease-free survival in patients with rectal cancer who undergo local excision and postoperative radiation therapy.
PURPOSE: The Patterns of Care Study (PCS) of the American College of Radiology periodically develops a decision tree and current management guidelines for major malignancies where radiation has an important role. The decision tree is a framework which depicts the division of patients into treatment groups. The treatment guidelines are useful in management and also serve as a starting point for quality assessment. For the first time, PCS decided to develop consensus management guidelines for esophageal cancer. MATERIALS AND METHODS: A consensus panel was convened to define the key issues and develop guidelines for esophageal cancer management. A modified Delphi process was used to achieve consensus. RESULTS: The consensus panel developed guidelines for the management of patients with adenocarcinoma or squamous cell carcinoma of the esophagus with a Karnofsky performance status of over 50. Patients with clinical stage I or II esophageal cancer can be treated with curative intent using either a primary surgical or primary chemoradiation approach. For patients with clinical stage III malignancy, where the most common approaches are palliative, surgical resection is generally not recommended and chemoradiation is the preferred treatment. CONCLUSION: The PCS has developed treatment guidelines for esophageal cancer based on consensus committee deliberations. These guidelines can be useful for those who manage esophageal cancer.