Usefulness of FDG-PET scan in the assessment of suspected metastatic or recurrent adenocarcinoma of the colon and rectum.

PURPOSE: The purpose of this study was to evaluate the clinical efficacy of positron emission tomography with 2-[18F] fluoro-2-deoxy-D-glucose compared with computed tomography plus other conventional diagnostic studies in patients suspected of having metastatic or recurrent colorectal adenocarcinoma. METHODS: The records of 105 patients who underwent 101 computed tomography and 109 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography scans for suspected metastatic or recurrent colorectal adenocarcinoma were reviewed. Clinical correlation was confirmed at time of operation, histopathologically, or by clinical course. RESULTS: The overall sensitivity and specificity of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography in detection of clinically relevant tumor were higher (87 and 68 percent) than for computed tomography plus other conventional diagnostic studies (66 and 59 percent). The sensitivity of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography in detecting mucinous cancer was lower (58 percent; n = 16) than for nonmucinous cancer (92 percent; n = 93). The sensitivity of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography in detecting locoregional recurrence (n = 70) was higher than for computed tomography plus colonoscopy (90 vs. 71 percent, respectively). The sensitivity of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography in detecting hepatic metastasis (n = 101) was higher than for computed tomography (89 vs. 71 percent). The sensitivity of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography in detecting extrahepatic metastases exclusive of locoregional recurrence (n = 101) was higher than for computed tomography plus other conventional diagnostic studies (94 vs. 67 percent). 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography altered clinical management in a beneficial manner in 26 percent of cases (26/101) when compared with evaluation by computed tomography plus other conventional diagnostic studies. CONCLUSION: 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography is more sensitive than computed tomography for the detection of metastatic or recurrent colorectal cancer and may improve clinical management in one-quarter of cases. However, 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography is not as sensitive in detecting mucinous adenocarcinoma, possibly because of the relative hypocellularity of these tumors.

Use of endoanal ultrasound in patients with rectovaginal fistulas.

PURPOSE: The purpose of our study was to define the role of endoanal ultrasound in the evaluation and management of patients with rectovaginal fistula. METHODS: A retrospective review was performed of all patients with rectovaginal fistula who were evaluated by endoanal ultrasound at Barnes-Jewish Hospital at Washington University from 1992 to 1997. RESULTS: Twenty-five females underwent endoanal ultrasound before rectovaginal fistula repair. Mean age was 34 years. Rectovaginal fistulas were caused by obstetric trauma (19 patients; 76 percent), cryptoglandular disease (5 patients; 20 percent), and Crohn's disease (1 patient; 4 percent). Previous rectovaginal fistula repair had been performed in ten patients (40 percent). A history of anal incontinence was present in ten patients (40 percent). Rectovaginal fistula location was above (15 patients), at (7 patients), or below (3 patients) the dentate line. Rectovaginal fistula size was <5 mm (19 patients; 76 percent) or >5 mm (6 patients; 24 percent). Anal manometry revealed decreased sphincter pressures (resting or squeeze) in 12 patients (48 percent). Pudendal nerve latency was abnormal in three patients (9 percent). Endoanal ultrasound identified the rectovaginal fistula in 7 patients (28 percent) and an anterior sphincter defect in 23 patients (92 percent). At surgery sphincter injuries were identified in 23 patients (92 percent). Treatment was either sliding flap repair with anal sphincter reconstruction (22 patients; 88 percent) or sliding flap repair alone (3 patients; 12 percent). Repair of the rectovaginal fistula was successful in 23 patients (92 percent). Complications occurred in 11 patients (44 percent): two recurrent rectovaginal fistulas, five infections, two skin separations, one ectropion, and one hematoma. The two patients with recurrent rectovaginal fistula had prior repairs, and both were subsequently repaired successfully. Of the 11 patients with preoperative anal incontinence, 6 patients (54 percent) were continent and 2 (18 percent) improved after surgery. Cause, size, location, and previous repair of fistula had no effect on final outcome. CONCLUSIONS: Noncontrast endoanal ultrasound was not useful in imaging rectovaginal fistulas and cannot be recommended as a diagnostic or screening tool for the identification of a rectovaginal fistula. However, we recommend that endoanal ultrasound be performed preoperatively in all patients with known rectovaginal fistulas to identify and map occult sphincter defects. Concomitant anal sphincter reconstruction should be considered strongly in patients with rectovaginal fistula and an endoanal ultrasound-documented sphincter defect.

Hepatocyte growth factor stimulates fetal gastric epithelial cell growth in vitro.

BACKGROUND: The growth and development of the fetal gastrointestinal tract is likely mediated, in part, by peptide growth factors. We compared the mitogenic effects of graded doses of hepatocyte growth factor (HGF) to epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), and insulin-like growth factor-1 (IGF-1) on fetal rabbit gastric epithelial cells. MATERIALS AND METHODS: Fetal rabbit gastric epithelial cells were purified by mechanical dissociation and selected culture and grown in short-term (24 h) and long-term (12 days) culture. Stimulation of fetal gastric epithelial cell growth in response to individual peptide growth factors was measured by [3H]thymidine incorporation and cell counting. RESULTS: In short-term culture, HGF stimulated [3H]thymidine incorporation in a dose-dependent manner from a threshold at 10 pM to a maximum at 100 pM. For EGF and TGF-alpha, maximal stimulation occurred at 100 pM. For HGF, maximal [3H]thymidine incorporation was 3.6 +/- 0.7 times basal. For EGF and TGF-alpha, maximal [3H]thymidine incorporation was 4.3 +/- 0.4, and 3.6 +/- 0.4 times basal, respectively. For IGF-1, maximal [3H]thymidine incorporation was only 70% of the maximal effect observed for the other growth factors tested. Rabbit amniotic fluid increased [3H]thymidine uptake in a dose-dependent manner. In long-term culture, purification to greater than 90% epithelial cells was attained after 12 days treatment. For HGF, EGF, TGF-alpha, and 20% rabbit amniotic fluid, significant increases in cell number above control (P < 0.05) were observed at 1 nM concentrations. None of these individual factors, however, increased cell growth as significantly as that of 10% fetal bovine serum. CONCLUSIONS: Our results suggest that: (1) HGF stimulates [3H]thymidine uptake and cell proliferation in fetal rabbit gastric epithelial cells in vitro, and (2) HGF's mitogenic effect on fetal rabbit gastric epithelial cell growth is comparable to that observed for EGF and TGF-alpha, but superior to the effect observed for IGF-1.

Laparoscopic splenectomy. The emerging standard.

BACKGROUND: The purpose of this study was to evaluate the outcome of patients undergoing laparoscopic splenectomy (LS) at the University of California, San Francisco. METHODS: The medical records of the initial 52 unselected patients undergoing LS were reviewed and compared to 28 concurrently treated open splenectomy patients (OS). RESULTS: Patients did not differ with regard to age, gender, body, or splenic weights. The operative time was longer in the LS patients (mean 196 vs 156 min), but the length of stay and duration of ileus were shorter in the LS group. For adult patients admitted exclusively for splenectomy, operative times did not differ between LS and OS and total hospital cost was less in the LS group (mean $8, 939 vs $14,022). Six patients required conversion to OS, four occurring in the first 11 patients treated (overall conversion rate of 11%). Three patients died from complications related to their underlying disease. Two other major complications occurred. Complication rates and transfusion requirements did not differ between OS and LS patients. CONCLUSIONS: Laparoscopic splenectomy is a safe and effective alternative to open splenectomy for treatment of hematologic diseases in patients of all ages.

Roles of gastrin and somatostatin in the regulation of gastric acid secretion in the fetal rabbit.

In adult gastric epithelium, gastrin and somatostatin regulate parietal cell acid secretion; however, their expression and function in the fetus are largely unknown. We defined the developmental expression of gastrin and somatostatin in the fetal rabbit stomach and determined their effects on fetal acid secretion. To define peptide expression, fetuses from 12 time-mated New Zealand white rabbit does were analyzed at successive ages during the third trimester (term is 31 days). Peptides were extracted from fetal gastric tissue by boiling in water and then in acetic acid. Amidated gastrin and somatostatin levels were measured by radioimmunoassay using antisera 1296 for gastrin and 8402 for somatostatin. To determine the effects of gastrin and somatostatin, pentagastrin (64 microg/kg/hr) or octreotide (35 microg/kg/hr) were infused intravenously in conscious pregnant rabbits at 28 days of gestation for 3 hr. Fetuses (n = 45) were harvested and gastric acid was titrated with 0.02 N NaOH. Gastrin and somatostatin tissue content were 12 +/- 3 and 51 +/- 6 pmol/g at gestational day 20, respectively, and increased to 146 +/- 10 and 162 +/- 5 pmole/g by day 30 (P < 0.05). Between days 24 and 26, when gastric acid was first detectable, the molar ratio of somatostatin to gastrin decreased from 5.0 +/- 1.0 to 1.1 +/- 0.1 (P < 0.05). Fetal gastric acid content (micromole) was 28.5 +/- 1.7 in controls, 27.5 +/- 1.9 with pentagastrin treatment, and 15.8 +/- 1.4 micromole with octreotide (P < 0.05). In summary, 1) In fetal gastric tissue, gastrin increased 12-fold and somatostatin increased 3-fold between days 20 and 30 of gestation. 2) The decreased ratio of somatostatin to gastrin between days 24 and 26 of gestation coincides with the onset of fetal gastric acid secretion in the fetal rabbit. 3) Maternal administration of octreotide inhibited fetal gastric acid content; however, pentagastrin had no effect. We conclude that, in the fetal rabbit stomach, the relative expression of gastrin and somatostatin may regulate the onset of parietal cell acid secretion.

Neuroendocrine disorders of the gut.

The regulation of gastrointestinal function is known to involve elements of the enteric nervous system. Processes such as secretion, motility, blood flow, and immune function are all influenced by a complex network of neurons whose cell bodies lie in the gut. These neurons use a wide spectrum of substances as neurotransmitters, although the majority use peptides once thought to function only as gut hormones. It has been increasingly recognized that abnormalities of this neuroendocrine regulatory system underlie many gastrointestinal disorders. The most obvious are states of peptide excess found in patients with gut endocrine tumors such as carcinoid, gastrinoma, and somatostatinoma. Conversely, other disorders appear to be related to deficiency states. Examples include both achalasia and Hirschsprung's disease (congenital megacolon), where the loss of inhibitory neural action leads to abnormalities of peristalsis and sphincter function. Evidence for abnormal neuroendocrine regulation leading to disease states is increasing for many other gastrointestinal disorders.

Extraluminal, transluminal, and observational treatment for vertebral artery injuries.

Injury to the vertebral artery following penetrating trauma is rare and treatment is usually surgical ligation. Recent liberal use of angiography in the evaluation of penetrating neck trauma has identified increasing numbers of patients with this challenging injury. This report describes our recent experience in treating patients with vertebral artery injuries. The purposes of this study were (1) to review the outcome of our patients with vertebral artery injuries, and (2) to develop an approach for managing these patients. Sixteen patients were treated over a 9-year period. Three patients underwent emergent operative exploration for bleeding, three underwent transcatheter embolization alone, and ten were managed conservatively by close clinical observation. No deaths occurred. Ligation was performed for injuries discovered during neck exploration, however, bleeding was sometimes persistent despite proximal control. In our center, where radiological support is readily available, temporary control of bleeding by packing with hemostatic agents allowed subsequent transcatheter embolization of the injured artery. Pseudoaneurysms, arteriovenous fistulae, and extravasations discovered angiographically were usually managed by transcatheter embolization. Patients with vertebral artery narrowings or occlusions were managed by close clinical observation.

Laparoscopic splenectomy. The initial experience at University of California, San Francisco.

OBJECTIVE: To evaluate the outcomes of patients undergoing laparoscopic splenectomy (LS) at a single institution. DESIGN: Case control. SETTING: University teaching hospital. PATIENTS: The medical records of the initial 25 consecutive patients who underwent LS at a single institution were reviewed. For comparison, a control group of 25 patients undergoing open splenectomy (OS) matched for age, diagnosis, and splenic weight were also reviewed. MAIN OUTCOME MEASURES: Data regarding operative time, blood loss, pathologic findings, complications, postoperative hospital stay, ileus duration, preoperative and postoperative hematocrit and platelet counts, blood and platelet transfusions, and hospital costs were collected. RESULTS: Twenty-five patients underwent attempted LS. Four procedures (16%) were converted to OS. Operative time averaged 3.3 +/- 0.2 hours for LS and 2.6 +/- 0.1 hours for OS (P = .001). In the LS group, a regular diet was tolerated 2.1 +/- 0.3 days after surgery (P < .001), and mean postoperative hospital stay was 5.1 +/- 0.6 days (P = .037), compared with 4.3 +/- 0.3 and 6.7 +/- 0.5 days, respectively, in the OS group. No differences were observed in blood loss, complication rate, transfusion requirement, or hospital cost. CONCLUSIONS: Compared with OS, LS requires more operative time, is comparable in blood loss, transfusion requirement, complication rate, and cost, and appears to be superior in terms of return of bowel function and hospital stay.

Mechanisms of gastric acid secretion in the fetal rabbit.

BACKGROUND: The parietal cell specific protein H+/K(+)-adenosine triphosphatase H+/K(+)-ATPase) is responsible for gastric acid secretion in adult mammals; however, its ontogeny and role in fetal acid secretion are unknown. The purpose of this study was twofold: (1) to determine the ontogeny of gastric acid secretion and parietal cell H+/K(+)-ATPase expression in the fetal rabbit and (2) to determine the role of H+K(+)-ATPase in fetal acid secretion. METHODS: For the ontogeny studies 88 fetuses from nine time-mated rabbits were studied at successive gestational ages. Gastric fluid and amniotic fluid pH were measured, and total gastric acid was determined by titration. Gastric microsomal protein was analyzed by Western blot analysis for H+/K(+)-ATPase expression by using a monoclonal antibody to the 94 kd alpha-catalytic subunit. To determine the role of H+/K(+)-ATPase in fetal acid secretion, 37 fetuses at day 26 from four time-mated rabbits were treated with (1) omeprazole (20 mg/kg) injection into the amniotic sac (n = 13), (2) carrier injection (n = 12), or (3) no injection (n = 12). Fetal gastric pH and titratable acid were measured at day 28. RESULTS: Amniotic fluid pH was neutral (7.44 to 7.64) throughout the third trimester. Gastric fluid pH was neutral (7.42 to 7.51) until day 25, when it decreased to 7.16 +/- 0.23 (p < 0.05) and subsequently fell to 5.37 +/- 0.05 by day 30. Titratable gastric acid (micromoles) increased from 0 at day 20 to 54.7 +/- 5.4 by day 30. By use of Western blot analysis and immunohistochemistry, gastric microsomal H+/K(+)-ATPase expression was absent from days 20 through 25 of gestation and first detectable at day 26, with qualitative increases to term. Omeprazole significantly inhibited pH (5.45 +/- 0.13 in controls, 5.56 +/- 0.12 with carrier injection, and 6.01 +/- 0.10 with omeprazole injection; p < 0.05). CONCLUSIONS: These data suggest that (1) gastric acid acid secretion begins at day 25 of gestation and increases to term, (2) gastric microsomal H+/K(+)-ATPase expression is first detectable at day 26 of gestation, and (3) omeprazole inhibits, but does not abolish, gastric acid secretion in the fetal rabbit. We conclude that gastric acid secretion is present before birth in the fetal rabbit and is mediated, in part, by omeprazole-sensitive H+/K(+)-ATPase.

Hepatocyte growth factor induces gastric H+/K(+)-ATPase expression.

The processes regulating the development of the fetal gastrointestinal tract are largely unknown, but are likely dependent, in part, on peptide growth factors. The purpose of this study was to determine the contribution of hepatocyte growth factor (HGF) to the development of the fetal gastric epithelium, with particular reference to the parietal cell. Fifty-six fetal rabbits from 18 time-mated pregnant New Zealand White rabbit does were divided into four groups at Day 23 of gestation (term is 31 days): (1) unoperated control littermates, (2) those prevented from swallowing amniotic fluid by esophageal ligation (EL), (3) those with EL plus intragastric carrier infusion, and (4) those with EL plus intragastric HGF infusion. At Day 28 of gestation, fetal stomachs were harvested and analyzed for gastric weight, DNA content, and H+/K(+)-ATPase expression. In control fetuses, gastric weight was 470 +/- 30 mg, gastric DNA content was 741 +/- 59 micrograms, and gastric H+/K(+)-ATPase expression was 25.4 +/- 2.7 micrograms. EL resulted in a 45% decrease in gastric weight (P = 0.001), a 34% decrease in DNA content (P = 0.04), and a 43% decrease in H+/K(+)-ATPase expression (P = 0.007). These inhibitory effects were not reversed by intragastric carrier infusion. Although intragastric HGF infusion did not significantly restore gastric weight or gastric DNA content, it restored gastric H+/K(+)-ATPase expression to levels no different from those of unoperated controls (23.9 +/- 2.8 micrograms), but significantly greater than those of the EL or carrier infusion groups (P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta-left renal vein fistula syndrome caused by rupture of a juxtarenal abdominal aortic aneurysm: novel pathologic mechanism for a unique clinical entity.

Spontaneous aorta-left renal vein fistula (ALRVF) caused by abdominal aortic aneurysm (AAA) is a rare form of intravascular aneurysm rupture. The literature series of ALRVF, updated here to 19 reported cases, demonstrates that patients with ALRVF present with a unique clinical syndrome characterized by abdominal or left flank pain (84%), a pulsatile abdominal mass (63%), abdominal bruit or murmur (63%), hematuria (100%), and nonfunction of the left kidney on functional imaging studies (100% of patients studied). Operative findings in ALRVF syndrome have included a large AAA (mean diameter 9.2 cm), with frank rupture in only three; in 17 of 19 patients (89%) the ALRVF was associated with a retroaortic left renal vein anomaly. The patient presented here had a large juxtarenal AAA with rupture into the left retroperitoneal space. The wide aneurysm neck and expanding hematoma created an avulsion of the second left lumbar vein from its junction with an anatomically normal (preaortic) left renal vein; the resulting renal vein tear allowed development of an arteriovenous communication that was responsible for the clinical presentation of ALRVF syndrome. The disease found here demonstrates a novel mechanism for the production of ALRVF syndrome in patients with juxtarenal AAA and otherwise normal pararenal venous anatomy.