Correlative Whole-Body FDG-PET and Intraoperative Gamma Detection of FDG Distribution in Colorectal Cancer

Purpose: 18F-Fluorodeoxyglucose-positron emission tomography (FDG-PET) is the superior imaging modality for detection of primary and recurrent colorectal cancer compared to magnetic resonance imaging (MRI) or computerized tomography (CT). We investigated the feasibility of developing intraoperative procedures for detection of FDG in tumor deposits in order to assist the surgeon in achieving an optimal reduction of tumor burden.Procedures: Fourteen patients (45-83 years of age) were scanned using FDG-PET followed by Gamma Detection Probe evaluation at laparotomy. One patient did not have a pre-operative FDG-PET scan. The collimated detector probe contained a CdZnTe crystal (7mm diameter x 2mm thick). We used a lower window setting of 200 KeV and an open upper window setting. Fasted patients were given an IV bolus of FDG (4.0-5.7 mCi) 15-20 minutes prior to preparation for surgery. Catheterization and the diuretic Lasix were used to remove FDG activity from the bladder. The time from FDG injection to intraoperative GDP data acquisition varied from 58-110 minutes.Results: In all patients, the GDP detected background activity in normal tissues (aorta, colon, liver, kidney, abdominal wall, mesentery, and urinary bladder). The GDP correctly identified single or multiple tumor foci in 13/14 patients as noted by an audible signal from the control unit (3 S.D. above counts obtained from normal tissues). These tumor foci corresponded to regions of high FDG uptake as seen on FDG-PET scans. The one case that the GDP did not localize was a recurrent mucin pseudomyxoma-producing tumor (acellular, mucinous deposits). Ex vivo GDP evaluations demonstrated significant tumor:normal adjacent tissue activity (audible signals in 6/6 tumor samples tested).Conclusions: These data demonstrate that tumors identified from pre-operative whole-body PET scans can be localized during surgery utilizing a gamma probe detector and FDG.     

New intracoronary stent designs: form follows function versus function follows form

Intracoronary stenting improves the acute and long-term safety and efficacy of percutaneous coronary interventions by minimizing the risks of abrupt closure and late restenosis. Enhanced designs of new coronary stents will continue to expand the spectrum of coronary anatomy and clinical settings amenable to nonsurgical revascularization. Improvements in deliverability, application to complex lesions, and durability of results are direct effects of improved design characteristics. Future design features may also include incorporating adjunctive therapies such as antithrombotic or antiproliferative agents with stent-based delivery systems. Results of new stent registries and randomized clinical trials are reviewed.     

Techniques and results in the management of anal and perianal Crohn's disease

We reviewed our experience with 73 patients who had Crohn's disease and underwent local anorectal surgical procedures for perianal suppurative disease during a ten year period. All but one of these patients had intestinal granulomatous disease. The average length of follow-up study was 4.6 years. By using conservative, local anorectal surgical procedures and intensive medical treatment, we were able to establish adequate drainage of abscesses, reduce the inflammatory process and relieve symptoms. Extensive drainage procedures were avoided to preserve the anal sphincter. A sliding endorectal flap repair provided satisfactory results for rectovaginal fistulas and anterior anal fistulas. Proctectomy was eventually necessary in nine patients, the primary indication being severe perianal disease in five. By performing complete excision of the perineal disease at the time of proctectomy, we were able to achieve primary healing of the perineal wound in eight of these patients. Patients were classified according to five categories of results: healed after initial local treatment, eight patients; healed after more than one local treatment, 30 patients; incomplete healing with acceptable condition, 17 patients; healed after fecal diversion, nine patients, and required proctectomy, nine patients. The majority of patients with Crohn's disease and anal and perianal suppurative disease can be managed by meticulous drainage of sepsis and preservation of the anal sphincter.     

Decline in serum calcium, magnesium, and phosphorus values with oral glucose in normal neonates: studies of serum parathyroid hormone and calcitonin

In 10 normal term infants aged 52 +/- 2.5 hours, serum calcium, magnesium, phosphorus, ionized calcium, parathyroid hormone, and calcitonin were studied at 0, 1/2, 1, and 2 hours after administration of 1.77 +/- 0.08 gm/kg glucose orally over 20 minutes. In response to glucose administration, serum glucose concentration rose and serum P, Ca, and Mg concentrations fell. Serum PTH concentration rose significantly, and blood ionized Ca and pH were unaltered. Serum calcitonin was elevated, as compared with adult values, and did not change. We suggest that in neonates, as in adults, oral ingestion of glucose lowers serum Ca, Mg, and P, and a compensatory rise in serum PTH concentration maintains blood ionized Ca concentration.     

Exclusion of breast cancer as an integral tumor of hereditary nonpolyposis colorectal cancer

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant genetic predisposition syndrome that accounts for 2-7% of all colorectal cancers. Diagnosis of HNPCC is based on family history (defined by Amsterdam or Bethesda Criteria), which often includes a history of multiple synchronous or metachronous cancers. The majority of HNPCC results from germ-line mutations in the DNA mismatch repair (MMR) genes hMSH2 and hMLH1 with rare alterations in hMSH6 and hPMS2 in atypical families. Both HNPCC and sporadic MMR-deficient tumors invariably display high microsatellite instability (MSI-H). Two types of HNPCC families can be distinguished: type I (Lynch I) with tumors exclusively located in the colon; and type II (Lynch II) with tumors found in the endometrium, stomach, ovary, and upper urinary tract in addition to the colon. A proposed association of breast cancer with type II HNPCC is controversial. To address this important clinical question, we examined MSI in a series of 27 female patients who presented with synchronous or metachronous breast plus colorectal cancer. Although MSI-H was found in 5 of 27 (18.5%) of the colon cancers, in all cases the matched breast cancer was microsatellite stable. We also examined the breast tumors from three women who were carriers of MMR gene mutations from HNPCC families. None of these three breast tumors displayed MSI nor was the expression of MMR proteins altered in these tumors. We conclude that breast cancer largely arises sporadically in HNPCC patients and is rarely associated with the HNPCC syndrome.     

The contractile potency of adenosine triphosphate and ecto-adenosine triphosphatase activity in guinea pig detrusor and detrusor from patients with a stable,unstable or obstructed bladder

PURPOSE: We compared the potency of adenosine triphosphate (ATP) and its nonhydrolyzable analogue alpha,beta-methylene ATP for generating contractions in human detrusor smooth muscle from patients with a stable, unstable and obstructed bladders. The different ATP potencies were compared with the ecto-adenosine triphosphatase (ATPase) of these samples. MATERIALS AND METHODS: Contractile experiments were done in vitro by superfusing samples with purines and dose-response curves were generated. Ecto-ATPase activity was measured from the rate of ATP hydrolysis sensitive to the ecto-ATPase inhibitor ARL 67156 with a luciferin-luciferase assay. RESULTS: ATP generated contractions with a mean EC50 of 933 microM. in tissue from stable bladders and was significantly more potent in tissue from unstable and obstructed bladders (EC50 141 and 172 microM., respectively). alpha,beta-methylene ATP was more potent in tissue from stable and unstable bladders (mean combined EC50 3 microM.). In guinea pig detrusor the mean EC50 for ATP and alpha,beta-methylene ATP was 138 and 5.5 microM., respectively. Mean total ATPase activity in unstable bladder biopsies plus or minus standard deviation was about 50% of that in stable bladder biopsies (2.54 +/- 1.50 versus 1.37 +/- 0.46 nmol. per second per mg. protein ). The ARL 67156 sensitive fraction was also significantly less in samples from unstable compared with stable bladders (mean 0.94 +/- 0.41 versus 0.36 +/- 0.26 nmol. per second mg. protein ). CONCLUSIONS: The greater potency of ATP for generating contractions in detrusor from unstable bladders may be due to reduced extracellular hydrolysis, allowing purine greater access to detrusor smooth muscle. This finding may explain atropine resistant purine based contractions in detrusor from unstable bladders.