Gernot Feifel

Preoperative staging of rectal cancer by intrarectal ultrasound

Digital examination and computed tomography are the current modalities employed to assess the depth of invasion of rectal cancer. Each technique has limitations in that high rectal tumors cannot be examined digitally and CT is unable to detect small tumors. However, preoperative diagnostic capability can be improved with the use of intrarectal ultrasound. We have examined 25 patients with rectal cancer preoperatively with digital examination and intrarectal ultrasound. In order to determine the accuracy of the ultrasonic method, we compared the results to the histopathologic findings of the excised specimen. Digital examination was essentially impossible in eight of the 25 rectal tumors because the tumors were either unreachable or could not be palpated in their full longitudinal extent. Of the remaining 17, digital examination corresponded with pathologic findings in 15, while tumor spread was overestimated in two patients. Sonography corresponded with pathologic findings in 23 of the 25 tumors. Two had been overstaged. Analogous to the TNM classification for postoperative pathologic tumor staging, we propose a preoperative tumor staging based on ultrasonic determination of the infiltrative depth of tumor, which we call u TNM.

Endorectal ultrasound: instrumentation and clinical aspects

During the period 1983 to April 1986, 129 patients with rectal cancer were treated. In 76 of these depth of penetration of the rectal wall by tumour was assessed by ultrasound. T stage determined by ultrasound (uT) corresponded with the pathological stages (pT) in 67 patients. In the remaining 9 cases, ultrasound overstaged the tumour and in only one patient was the growth understaged. Lymph nodes could be visualised in 12 out of 27 patients in whom nodes were looked for but only six cases were found to be positive on histological examination. Of 22 recurrences detected or proven by ultrasound there was a group of 6 patients who had no other sign of recurrence.

Endosonography of pararectal lymph nodes

One hundred thirteen patients with carcinoma of the rectum were evaluated for lymph node metastases by endorectal ultrasound. With the use of 7.5 MHz and based on different echo patterns, two main groups of lymph nodes can be differentiated: hypoechoic and hyperechoic lymph nodes. Compared with pathologic findings, hypoechoic lymph nodes represent metastases, whereas hyperechoic lymph nodes are visualized due to unspecific inflammation. Lymph node metastases can be predicted with a sensitivity of 72 percent and inflammatory lymph nodes with a specificity of 83 percent. The physical basis of the differentiation of lymph nodes was assessedin vitroby the determination of ultrasound parameters (speed of sound, acoustic impedance, attenuation, and backscattered amplitude). The attenuation coefficient of benign lymph nodes [2.5 dB/(MHz×cm)] is significantly higher than the mean value of lymph node metastases [1.3 db/(MHz×cm)]. The results demonstrate that involved nodes can principally be differentiated from not involved nodes. Micrometastases, mixed lymph nodes, and changing echo patterns within inflammatory nodes explain the accuracy rate of 78 percent.

Granulocyte elastase and systemic cytokine response after laparoscopic-assisted and open resections in Crohn's disease

PURPOSE: The aim of this study was to assess whether systemic proinflammatory cytokines (IL-6), anti-inflammatory cytokines (IL-4, IL-10), acute phase proteins (C-reactive protein), or granulocyte elastase are valuable indicators for determining the degree of surgical trauma after openvs. laparoscopic-assisted resections in Crohns disease. METHOD: Eleven patients in each group (open and laparoscopic-assisted surgery) were matched for indication, surgical procedure, and Crohns disease activity index. Serum IL-4, IL-6, and IL-10 were measured using enzyme-linked immunosorbent assay. Serum C-reactive protein was determined by immunoturbidimetric assay. Plasma granulocyte elastase was determined by immunoactivation immunoassay. Blood was sampled preoperatively, six hours after the operation, and at postoperative Days 1 to 5. RESULTS: IL-4 was not detectable in any sample analyzed. Serum IL-6 and IL-10 levels peaked postoperatively in both groups without significant differences between laparoscopic-assisted (185.6±54.1 pg/ml and 112.1±19.4 pg/ml, respectively; mean ± standard error of the mean) and open surgery (431.1±240.4 pg/ml and 196.7±56.5pg/ml, respectively). Serum C-reactive protein levels also rose postoperatively, with a peak on the second day, but showed similar values after laparoscopic-assisted (107.1±12.1 mg/l) and open (128.3±17.5 mg/l) surgery. Plasma granulocyte elastase levels peaked on the first and second postoperative day and were found elevated almost throughout the five-day observation period. Comparison between the groups revealed significantly (P<0.02) lower values after laparoscopic-assisted (Day 1, 46.5±8.9 µg/l; Day 2, 41.9±5.9 µg/l) when compared with open surgery (Day 1, 89.7±13.8 µg/l; Day 2, 91.4±14). CONCLUSIONS: Serum IL-6 and IL-10 may not be ideal measures for evaluation of the degree of tissue trauma in laparoscopic-assisted and open resections in Crohns disease, probably because of interference with disease-specific cytokine interactions. In contrast, granulocyte elastase has to be considered a strong marker discriminating the different severity of surgical trauma induced by laparoscopic-assistedvs. open resection in Crohns disease.

Increased matrix metalloproteinase 2 concentration and transcript expression in advanced colorectal carcinomas

Abstract. Colorectal cancer is one of the most common malignant tumors and entails a relatively poor prognosis. Clinical outcome depends on the extent of local and metastatic tumor spread. Results of in vivo and in vitro studies suggest that the balance between matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases TIMPs) is altered in neoplasia, contributing to the invasive and metastatic properties of malignant tumors. We quantified tissue concentrations of MMP-2 and TIMP-2 in 65 malignant colorectal lesions and corresponding normal mucosa by enzyme-linked immunosorbent assay, western blotting, and in situ hybridization. In situ hybridization and western blot analyses demonstrated a clear increase in both stromal expression of MMP-2 transcripts and protein in primary carcinomas. The protein concentration of MMP-2 was higher in all tumor stages, except stage I tumors, than in normal mucosa and adenomas. MMP-2 concentrations were not related to tumor differentiation or to colonic versus rectal location. Surprisingly, the MMP-2 concentration was not increased in metastases. Interestingly, tissue concentrations and epithelial mRNA expression of TIMP-2 decreased significantly in primary colorectal cancer (UICC stages III and IV) but increased in metastases. Therefore an increased ratio of MMP-2 to TIMP-2 is strongly associated with advanced tumor stages, but a decreased ratio was observed in metastases. These findings suggest that the MMP-2:TIMP-2 ratio may prove useful as a marker of local invasion but not of metastasis in colorectal cancer.

Pattern of mucosal adaptation in acute and chronic pouchitis

PURPOSE: Variant pathological changes have been observed in ileoanal pouches, including inflammation, villous atrophy, and crypt hyperplasia. Therefore, we investigated the type and degree of mucosal adaptation in patients with ulcerative colitis and familial adenomatous polyposis. METHODS: Forty-two patients with ulcerative colitis and 14 patients with familial adenomatous polyposis with ileoanal pouches were assessed. Samples were taken from three months to eight years after creation of an ileoanal pouch. Mucosal architecture was examined by morphometry after microdissection. RESULTS: Structural changes of the mucosa can be categorized into three groups. Compared with preoperative values, patients without pouchitis (73 percent) has only minor decrease of villous length (402µmvs. 540µm) and increase in crypt depth (274.5µmvs. 177µm). In patients with acute pouchitis (20 percent), a slight increase in villous length (477µmvs. 402µm) and pronounced crypt hyperplasia (376µmvs. 274.5µm) was observed compared with noninflamed ileoanal pouches. In contrast, in patients with chronic pouchitis (7 percent), severe villous atrophy (62.5µm) and crypt hyperplasia (543µm) was found. CONCLUSIONS: Minor structural changes of ileoanal pouch mucosa develop early as an adaptive response to a new environment. Only in a small group of patients with chronic pouchitis does severe villous atrophy and crypt hyperplasia of the ileoanal pouch mucosa develop, most likely as a consequence of mucosal inflammation.

Differential Effects of ET-1, ET-2, and ET-3 on Pancreatic Microcirculation, Tissue Integrity, and Inflammation

The differential effects of endothelin-1, -2, and -3 (ET-1, ET-2, and ET-3) on pancreatic microcirculation, pancreatic tissue integrity, and an initial inflammatory response, which are three distinct characteristics of acute necrotizing pancreatitis, were investigated in a dose-dependent manner in rats using in vivo microscopy. Red blood cell (RBC) velocity and functional capillary density (FCD) were estimated after topical superfusion of the pancreas with ET-1, ET-2, and ET-3 (100, 10, 1 pmol), revealing that ET-1 (100, 10, 1 pmol) or high ET-2 (100 pmol) and ET-3 (100 pmol) cause a dose-related deterioration of exocrine nutritive pancreatic blood flow. Analysis of pancreatic exocrine tissue damage employing the Spormann score displayed that the ET-mediated microcirculatory impairment was paralleled by dose-dependent tissue damage, which was significant compared to the control group (topical superfusion with 1 ml, saline solution 0.9%). Estimation of pancreatic postcapillary leukocyte accumulation by histomorphologically counting choracetate esterase (CAE) stained leukocytes in 50 high-power fields per animal demonstrated a significant increase in postcapillary accumulation of white blood cells, after topical administration of ET-1, ET-2, and ET-3 compared to controls. In contrast to ET-caused effects on microcirculation and tissue impairment, quantitative analysis of postcapillary leukocyte accumulation revealed the most pronounced effect after ET-2 administration but not after ET-1 administration. This demonstrates that ET-1, ET-2, and ET-3 are all able to mediate microcirculatory impairment, tissue damage, and inflammation. However, ET-3-induced damaging effects are less pronounced, while ET-1 most severely alters microcirculation and ET-2 preferentially induces leukocyte-dependent inflammation.

Conversion of the failing ileoanal pouch to reservoir-ileostomy rather than to ileostomy alone

PURPOSE: We report the indications, technique, and results of conversion of the ileoanal pouch to the Kocks pouch in five patients. The indication was functional disturbance that could not be corrected by operation. Aim of the conversion operation was re-establishment of fecal control and complete preservation of existing ileal surface. METHODS: The ileal pouch was used again, and in one case an augmentation was made. The continence valve was made three times from the afferent loop and in two cases from a higher ileal segment. RESULTS: Following conversion, function was excellent in three patients with ulcerative colitis and in one patient with familial adenomatous polyposis. One woman who underwent proctocolectomy for slow-transit constipation needed a Brooke ileostomy for continuous abdominal distention pain. CONCLUSION: We conclude that conversion to a continent ileostomy is a rewarding method of safely eliminating dysfunction of the ileoanal pouch that cannot be corrected by operation. Presumption is, however, that the surgeon is familiar with both methods and that the primary disease is suitable for pouch surgery.

Optimization of isolated hyperthermic limb perfusion

During isolated limb perfusion, we studied the impact of limb temperature on the concentration of cytostatic drugs in the tissue to identify a possible selective absorption of cytostatic agents by the various tissues. Ten consecutive patients with malignant melanoma were randomly divided into two different groups and perfused with 1 mg cisplatin per kg body weight. In one group the cytostatic agents were injected under hyperthermic conditions (39.5 degrees C) and in the other group under normothermic conditions (37 degrees C). The platinum concentration in the melanoma was twice as high in the hyperthermic group as in the group under normothermic conditions. In the tumor-free tissue the platinum concentration decreased with temperature while it remained constant in the musculature. This selective concentration of cisplatin in the tumor under hyperthermic conditions is accompanied by fewer side effects. Follow-up will show whether the oncological results will be improved in the hyperthermic conditions as one might expect.

Somatostatin attenuates microcirculatory impairment in acute sodium taurocholate-induced pancreatitis.

Using in vivo microscopy, red blood cell (RBC)velocities, functional capillary density (FCD), andoverall changes in capillary blood flow (PI) wereestimated following intraductal infusion of sodiumtaurocholate (0.8 ml; 4%) alone or in combination withsystemic administration of somstostatin (single bolusSMS 100 μg/100 g body wt). Sodium taurocholatemediated a significant transient decrease in RBCvelocities and a sustained decrease in FCD, which wereparalleled by dramatic flow heterogeneity. Therefore, asignificant reduction in overall capillary blood flowwas calculated. Additional SMS treatment reduced microcirculatory impairment as expressed byreduction of blood flow heterogeneity, a less rarifiedfunctional capillary density, and a recovery of RBCvelocities and acinar capillary overall perfusion to control values. As a result of thismicrocirculatory improvement, pancreas histologyrevealed slightly less severe tissue damage compared tothe non-SMS-treated pancreatitis group. These findingsdemonstrate that exogenous SMS infusion can improvemicrocirculatory failure in acute biliary pancreatitis,which should have a beneficial effect on the course ofthe disease.