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S D Goldstein

Publications and source records attributed to S D Goldstein.

11 recordsLinked to original sources

Use of guanylyl cyclase C for detecting micrometastases in lymph nodes of patients with colon cancer.

INTRODUCTION: Guanylyl cyclase C appears to be expressed only in colorectal cancer cells in extraintestinal tissues. Thus, guanylyl cyclase C may be useful as a marker to detect colorectal cancer micrometastases not detectable by histopathology in lymph nodes of patients. METHODS: Twelve patients with colon adenocarcinoma, Dukes Stages A through C2, and one patient with a tubulovillous adenoma were included in this study. Forty-two lymph nodes were collected from fresh surgical specimens, and each was examined by histopathology and reverse transcription followed by polymerase chain reaction using guanylyl cyclase C-specific primers. Histopathology identified colon cancer cells in 6 of 16 lymph nodes from five Dukes Stage C patients but not in lymph nodes from the patient with a tubulovillous adenoma, the Dukes Stage A patient, or six Dukes Stage B patients. Reverse transcription followed by polymerase chain reaction using guanylyl cyclase C-specific primers was performed on all 42 lymph nodes. RESULTS: Guanylyl cyclase C messenger RNA was not detected by reverse transcription followed by polymerase chain reaction in lymph nodes from the patient with the tubulovillous adenoma or the patient with Dukes Stage A colon carcinoma. Seven lymph nodes from Dukes Stage C patients revealed guanylyl cyclase C messenger RNA including six lymph nodes containing histopathologically confirmed metastases. Of significance, guanylyl cyclase C messenger RNA was detected in 6 of 21 lymph nodes from Dukes Stage B patients. Indeed, clinical staging of two patients could be upgraded from B to C using reverse transcription followed by polymerase chain reaction and guanylyl cyclase C-specific primers. CONCLUSION: Reverse transcription followed by polymerase chain reaction using guanylyl cyclase C-specific primers might be useful to more accurately assess micrometastases in lymph nodes of colorectal cancer patients undergoing disease staging.

Adenocarcinoma

Guanylyl cyclase C is a selective marker for metastatic colorectal tumors in human extraintestinal tissues.

Guanylyl cyclase C (GCC) has been detected only in intestinal mucosa and colon carcinoma cells of placental mammals. However, this receptor has been identified in several tissues in marsupials, and its expression has been suggested in tissues other than intestine in placental mammals. Selective expression of GCC by colorectal tumor cells in extraintestinal tissues would permit this receptor to be employed as a selective marker for metastatic disease. Thus, expression of GCC was examined in human tissues and tumors, correlating receptor function with detection by PCR. GCC was detected by ligand binding and catalytic activation in normal intestine and primary and metastatic colorectal tumors, but not in extraintestinal tissues or tumors. Similarly, PCR yielded GCC-specific amplification products with specimens from normal intestine and primary and metastatic colorectal tumors, but not from extraintestinal tissues or tumors. Northern blot analysis employing GCC-specific probes revealed an approximately 4-kb transcript, corresponding to recombinant GCC, in normal intestine and primary and metastatic colorectal tumors, but not in extraintestinal tissues. Thus, GCC is selectively expressed in intestine and colorectal tumors in humans and appears to be a relatively specific marker for metastatic cancer cells in normal tissues. Indeed, PCR of GCC detected tumor cells in blood from some patients with Dukes B colorectal cancer and all patients examined with Dukes C and D colorectal cancer, but not in that from normal subjects or patients with Dukes A colon carcinoma or other nonmalignant intestinal pathologies.

Biomarkers, Tumor

Escherichia coli heat-stable enterotoxin receptors. A novel marker for colorectal tumors.

PURPOSE: Receptors for Escherichia coli heat-stable toxin (ST) are selectively expressed in membranes of intestinal mucosa cells and colon carcinoma cells in vitro, suggesting their use as a marker for colorectal tumors in vivo. The present studies examined the expression and function of ST receptors in normal human tissues and primary and metastatic colorectal tumors obtained from patients at surgery. METHODS: Surgical specimens were obtained as follows: from normal colon; from primary adenocarcinomas from all anatomic divisions of the colon and rectum; from gallbladder, kidney, liver, lung, lymph node, ovary, peritoneum, stomach; and from colon carcinomas metastatic to liver, lung, lymph node, ovary, and peritoneum. Membranes prepared from these specimens were assessed for the presence and functional characteristics of ST receptors. RESULTS: ST bound specifically to membranes from each division of normal colon and rectum and all primary and metastatic colorectal tumors examined. The affinity and density of ST receptors were similar in tumors of different grades and from various metastatic sites. ST-receptor interaction was coupled to activation of guanylyl cyclase in all normal samples of colon and rectum and all primary and metastatic colorectal tumors examined. In contrast, neither ST binding nor ST activation of guanylyl cyclase was detected in any extraintestinal tissues examined. CONCLUSIONS: Functional ST receptors are expressed in normal colonic tissue and primary and metastatic colorectal tumors but not by extraintestinal tissues in humans. Expression of ST receptors does not vary as a function of the metastatic site or grade of these tumors. Receptors expressed by colorectal tumors retain their characteristic function, with binding of ST coupled to activation of guanylyl cyclase. These studies support the suggestion that ST receptors represent a specific marker for human colorectal tumors that may have use as a target for directing diagnostics and therapeutics to these tumors in vivo.

Adenocarcinoma

Occluded coloanal anastomosis: transrectal US-guided balloon dilation.

Balloon dilation is a well-described, nonoperative, alternative treatment for postoperative strictures of the colon and rectum. This procedure may not be technically feasible when an occluded lumen prevents passage of a guide wire across the obstruction. The authors describe the use of transrectal ultrasound guidance to initially pass a needle across an occlusive web at the coloanal anastomosis after proctosigmoidectomy. This allowed placement of a guide wire across the occlusion and subsequent successful balloon dilation.

Anal Canal

The double-staple technique in colorectal anastomoses: a critical review.

The widespread availability and use of stapling devices have changed colorectal surgery. In 1980, Knight and Griffen developed the "double-staple" technique, using a circular stapler to transect a linear rectal staple line. This eliminated the need for a hand-sewn, distal purse string, which was sometimes difficult or even impossible to accurately place low in the pelvis. To evaluate this procedure, the authors have reviewed their results with the double-staple technique over the past 5 years. One hundred four patients underwent this procedure between 1985 and 1990 at Thomas Jefferson University Hospital (Philadelphia, PA). There were 60 men and 44 women, with a mean age of 62.4 years. Seventy-two patients underwent operation for carcinoma of the rectum or sigmoid. Thirty-five of these had preoperative radiation therapy. Other diagnoses included 1) diverticular disease, 2) rectal prolapse, 3) villous adenoma, 4) endometrial carcinoma, 5) fistula, 6) stricture, 7) Crohn's disease, 8) colonic endometriosis, 9) lymphoma, 10) ovarian carcinoma, and 11) ulcerative colitis. Incomplete "donuts" were observed in 5 patients. Diverting colostomies were performed in 23 patients, ileostomies in 3. Postoperative complications relating to the double-staple technique itself included a rectovaginal fistula in 1 patient. There were 3 clinical leaks (2.8%), all treated nonoperatively. No strictures were observed. As previously observed, the authors believe the double-staple technique offers certain advantages over traditional, hand-sewn and stapled anastomoses, for instance: 1) there is significantly less contamination, 2) the anastomosis is technically easier, and 3) bowel segments of different diameters can be easily anastomosed.

Adult

Sphincter preservation for cancer of the distal rectum using high dose preoperative radiation.

Sphincter preservation surgery for cancer of the distal rectum is recognized as being associated with a high incidence of local recurrence. High dose preoperative radiation with new surgical techniques is described as an attempt to widen the scope of sphincter preservation in patients who by conventional management would have an abdomino-perineal resection and permanent colostomy and to reduce the incidence of local recurrence. Since 1976, 121 patients with cancers of the rectum have selectively been treated with high dose preoperative radiation (4000 cGy to 6000 cGy) followed by combined abdominotranssacral resection (56); transanal abdominotransanal resection (28); anterior resection (21), or a full thickness wide local excision (16). This report details the results of 43 patients observed for a minimum of 2 years whose tumors were located from 0-6 cm of the dentate line. All patients received the full course of preoperative radiation, a minimum dose of 4000-4500 cGy in approximately 4 1/2 weeks that was delivered using 180-250 cGy per fraction. Patients with tumor fixation were given an additional boost of 1000-1500 cGy preoperatively. Surgery was carried out 4-6 weeks following the completion of radiation. There was no perioperative mortality. Anastomotic failure occurred in 3 patients and was reconstituted in two. Sphincter function was maintained in all but 6 patients (86%), 2 of these had a subsequent abdominoperineal resection, and 3 a diverting colostomy. Seven of 43 (16%) patients with tumors below 6 cm developed a local recurrence, and 6 of the 7 recurrences occurred in patients with fixed tumors, especially those located from 0-3 cm from the dentate line. Eleven patients are dead of disease. The 5-year actuarial survival rate for this group is 72%. Results indicate that high dose preoperative radiation can significantly extend the scope of sphincter preservation to selected cancers of the disal rectum with excellent survival without increasing the risk of pelvic perineal recurrence.

Adult

Anal fissures and fistulas.

Thorough understanding of the pathophysiology of anal fissures and fistulas is essential for the physician treating these conditions. An acute fissure often heals in a month with conservative management; long-standing disease is relieved by lateral internal sphincterotomy. An acute fistulous abscess must be drained by unroofing the abscess rather than by simple incision, which fosters recurrence. Chronic fistula in ano requires fistulotomy, which can be done with a local anesthetic. Fistulas with multiple external orifices should be treated by a specialist in rectal surgery.

Fissure in Ano

Relapsing acute pancreatitis as the presenting manifestation of an ampullary neoplasm in a patient with familial polyposis coli.

The incidence of periampullary carcinoma is increased in patients with familial polyposis coli or the Gardner syndrome. Patients with familial polyposis coli and ampullary tumors usually present with obstructive jaundice or abdominal pain. We report the case of a 41-year-old woman with the Gardner syndrome in whom relapsing acute pancreatitis was the presenting manifestation of an ampullary neoplasm. A diagnosis of ampullary neoplasm should be considered in any patient with familial polyposis coli or the Gardner syndrome and pancreatitis, even in cases of relapsing acute pancreatitis.

Acute Disease