[Preparation of patients scheduled for inguinal hernia surgery]. / Ihre Aufgaben vor der Leistenbruch-OP. Diagnose sichern, Risiko abschätzen, aufklären.

In principle, hernias should always be managed surgically. In the event of an acute incarceration, the patient must be referred to hospital immediately, since the condition is lifethreatening. The decision as the type of surgical procedure is made on an individual basis, with preference being given to mesh implantation, which has a clearly reduced recurrence rate. Laparoscopic (expensive) repairs require general anesthesia, and usually a stay in hospital. Open procedures are increasingly being done on an outpatient basis under local anesthesia. The implantation of a mesh is associated with a quicker resumption of normal activities by the patient.

[Soft-tissue tumors: primary excision or wait and see?]. / Lipom, Atherom, Fibrom. Wann muss ein Weichteiltumor raus?

Soft tissue tumors are relatively commonly seen lesions in the doctor's office. An initial differentiation between malignant and benign tumors is usually possible on the basis of the case history and a careful physical examination. In adults, primary excision under local anesthesia is the treatment of choice in many cases, while in children and in the case of large tumors suspected of being malignant, a histological diagnosis must always be obtained. A number of procedures are available for biopsy taking. If the definitive histological work-up confirms malignancy, or if the findings are uncertain, the diagnostic investigation should be extended to include such imaging procedures as CT scanning or MRI.

Influence of gastrin, gastrin receptor blockers, epidermal growth factor, and difluoromethylornithine on the growth and the activity of ornithine decarboxylase of colonic carcinoma cells.

Polyamines are essential factors of cell growth and differentiation. Modulation of the cellular polyamine content by 2-difluoromethylornithine (DFMO) inhibiting ornithine decarboxylase (ODC), or by hormones inducing ODC, influences cell growth. Gastrin acts trophically on some colonic carcinomas and their growth is inhibited by gastrin receptor blockers. The mechanism of the trophic action of gastrin on colonic carcinomas is not known. In this study the effect of gastrin, gastrin receptor blockers, epidermal growth factor (EGF) and DFMO on growth and ODC activity of four human colon carcinoma cell lines (SW 403, SW 1116, LS 174 T and Lovo) was investigated. Growth and ODC activity of all cell lines were inhibited by DFMO. Growth of the SW 403 cell line was increased by gastrin and inhibited by the gastrin receptor blocker benzotrypte. The other cell lines did not respond to gastrin and the gastrin receptor blocker. In SW 403 cells ODC activity was increased by gastrin, and was also elevated after treatment with the gastrin receptor blocker. These in vitro results were confirmed by studies on tumours that developed from SW 403 cells in nude mice. Combination of benzotrypte and DFMO did not enhance the antiproliferative effect. EGF increased growth of SW 403 cells, but no induction of ODC activity was measured. LS 174 T cells were not stimulated by EGF. Medium replacement was the strongest stimulus of ODC activity in SW 403 cells already inducing ODC after 3 h. During cell culture ODC activity was high after seeding and decreased continuously with increasing cell density. These data suggest that gastrin induces ODC in gastrin-sensitive colonic carcinoma cells. DFMO appears to be a valuable antiproliferative agent in colonic carcinoma cells.

Growth of colorectal carcinoma cells: regulation in vitro by gastrin, pentagastrin and the gastrin-receptor antagonist proglumide.

The growth-regulating effects of pentagastrin, gastrin and the gastrin-receptor antagonist proglumide were investigated in three established cell lines derived from human colorectal carcinomas in vitro and after transplantation into nude mice. In vitro a significant increase of cell growth in the SW 403 cell line incubated with pentagastrin or gastrin was observed. In the Lovo cell line this effect was only detected after synchronization of cell growth. Pentagastrin and gastrin had no effect on the growth of the Ls 174 T cell line. Proglumide reduced cell proliferation in all three cell lines as well as in the L929S cell line derived from fibroblasts, which served as control. After transplantation into nude mice all tumor cell lines increased, Lovo and Ls 174 T as undifferentiated tumor, SW 403 as differentiated. Pentagastrin increased and proglumide decreased growth in SW 403 tumors, whereas no effect was observed on Ls 174 T and Lovo tumors. We therefore conclude that growth of some colorectal carcinomas is regulated by gastrin, but that the effect of proglumide is unspecific rather than related to blockage of gastrin receptors. The growth-regulating effect of gastrin could be due to tumor differentiation.

Expression of gastrin, gastrin/CCK-B and gastrin/CCK-C receptors in human colorectal carcinomas.

To investigate further the presence of an autocrine proliferative loop involving gastrin in colorectal carcinomas and to clarify the receptor responsible, 102 human colorectal carcinomas and 10 hepatic metastases were investigated for the expression of the genes encoding gastrin, the gastrin/CCK-B receptor and the gastrin/CCK-C receptor. Levels of RNA expression were assayed by RNase protection assay. In addition, gastrin/CCK receptors on crude membranes of tumour tissue were assayed by radioligand binding. High-affinity gastrin/CCK-B receptors were not detected in any of the carcinomas investigated, whereas in 36% low-affinity binding was observed, consistent with the expression of the gastrin/CCK-C receptor. RNase protection assay detected the RNA for the gastrin/CCK-B receptor in 11% of the carcinomas investigated, whereas the RNA for the gastrin/CCK-C receptor was demonstrated in 75% and the RNA for gastrin in 86% of the carcinomas investigated. These results confirm the recent demonstration of progastrin fragments in colorectal carcinomas. One possible explanation for progastrin expression is that such progastrin fragments may participate in an autocrine proliferative loop. The receptor involved in this loop is more likely to be the low-affinity gastrin/CCK-C receptor rather than the gastrin/CCK-B receptor, which is rarely expressed in colorectal carcinomas.

Effects of neoadjuvant radio-chemotherapy on 18F-FDG-PET in esophageal carcinoma.

AIM: To investigate whether results of [F-18]-fluorodeoxy-d-glucose (FDG) positron emission tomography (PET) of esophageal cancer (EC) before and after neoadjuvant radio-chemotherapy correlate with histopathology after esophageal resection. METHODS: Twenty consecutive patients with EC without distant metastases were examined twice with 18F-FDG-PET during primary staging and after neoadjuvant radio-chemotherapy. FDG standardised uptake values (SUV) were correlated with the histopathological findings (percentage of viable tumour cells, tumour regression grade 1-5). RESULTS: Regression analysis revealed a slight (not significant) positive correlation between SUV(pre) (R=0.41, p=0.08) and SUV(post) (R=0.37, p=0.11) and the percentage of viable tumour cells in the resectate. Although all patients showed a significant decrease in SUV after radio-chemotherapy (p < 0.01) the percentual decrease of the SUV after therapy (DeltaSUV%) did not significantly differ between the TRG-groups. In 12 of 20 patients (60%), therapy-induced esophagitis was detected in post-therapeutic PET images. CONCLUSION: In EC, a higher pre-therapeutic SUV might be correlated with a higher fraction of vital tumour cells remaining after radio-chemotherapy. Applying the neoadjuvant therapy protocol and the study design used in this examination, there is no correlation between decrease in SUV and histopathology.

Is MIB-1 proliferation index a predictor for response to neoadjuvant therapy in patients with esophageal cancer?

BACKGROUND: The overall survival rate for patients with an esophageal cancer remains poor. As a consequence, preoperative chemoradiation was introduced for patients with tumor stage T >1 M0 regardless of tumor histology or localization. However, factors predicting response to this therapy pretherapeutically are largely unknown. METHODS: Clinical results of preoperative chemoradiation were investigated. The rates of proliferation and apoptosis were determined in pretherapeutic tumor samples and correlated with tumor response and long-term survival after surgery. RESULTS: A complete tumor response due to chemoradiation (n = 42; cervically localized tumors excluded) was achieved in 11 patients (26%) after resection. Five-year survival rate was significantly improved in these patients compared with those who did not respond to chemoradiation (48% versus 5.5%; P = 0.003). Chemoradiation was performed without benefit in 43%. Perioperative hospital mortality rate was 14.3% in all patients. No correlation of apoptosis with response to chemoradiation or postoperative long-term survival was observed. However, there was a clear correlation between the proliferation rate as determined by MIB-1 immunohistology. Five-year survival rate of patients with a proliferation index (PI) >/=39% was 38% compared with 0% in tumors with a PI <39%. Tumors with a PI >/=39% responded to chemoradiation in 71.4%, but 100% of tumors with a PI <39% did not. Mean survival time of these patients was 33 months and 11 months, respectively (P = 0.015). CONCLUSIONS: The results indicate that the PI may be used for stratification of patients treatment prior surgery. However, these results need further validation in larger patient numbers in the search for factors indicating response pretherapeutically to preoperative chemoradiation in esophageal cancer.

The influence of ischemic bowel wall damage on translocation, inflammatory response, and clinical course.

BACKGROUND: While vascular patency and overall viability of the gut can be evaluated perioperatively, damage to the mucosal barrier can hardly be judged in the perioperative setting and, moreover, will probably determine the clinical course. METHODS: In 19 consecutive cases with intestinal ischemia, the clinical course was correlated to the severity of the disease (APACHE II; Septic Severity Score, SSS), the intraabdominal and systemic inflammatory response, and the translocation of bacteria and endotoxin. RESULTS: The comparison of the 10 survivors with the nonsurviving group revealed no differences as to the length of history, serum lactate levels, white blood cell counts, body temperature, markers of the inflammatory response, or quantity and macroscopic quality of the exudate. Differences were found in intraperitoneal bacteriology (prevalence 0.37, negative predictive value for lethal outcome 0.8), endotoxin concentrations in the exudate (P = 0.02) and in the plasma (P = 0.015), fibrinopeptide A levels (exudate P = 0.036; plasma P = 0.015), PGE2 plasma concentration (P = 0.0357), and APACHE II (P = 0.0034) and SSS (P = 0.0027) values. CONCLUSION: The clinical course of ischemic bowel wall necrosis seems to depend on the severity of the disease at admission and on the integrity of the mucosal barrier rather than on inflammatory response, therapeutic measures, or supportive treatment.

Results in surgery for primary and metastatic chest wall tumors.

OBJECTIVES: Resection of chest wall tumors is often indicated for palliation from pain or chronic ulceration. However, under various conditions, it may lead to lasting tumor control and substantial freedom of disease might be achieved. Therefore, the long-term survival after chest wall resection for primary and metastatic tumors and its relation to the underlying histology was analyzed. METHODS: The medical files of 82 consecutive patients with tumors of the chest wall operated between 1 January 1989 and 31 October 1998 were reviewed. Follow-up data were collected from the outpatient's clinic and house physicians, respectively. Complete excision was accomplished in 71 patients. In 19 patients, partial or complete resection of the sternum was performed. Twenty-eight patients underwent chest wall resection extending to intrathoracic structures (lung, diaphragm, pericardium). The following subgroups were defined according to the histology: (A), sarcoma (n=32); (B), breast cancer (n=22); (C), renal cell cancer (n=9); (D), other metastases (n=7); (E), miscellaneous (n=12). The survival probability was calculated by the Kaplan-Meier method (SAS software system). RESULTS: One of 41 female patients died from postoperative complications on day 30 after resection of ulcerating breast cancer recurrence (hospital mortality, 1.2%). The median survival times in groups A-E were 27, 32, 19, 16 and 22 months, respectively. CONCLUSIONS: Chest wall resection offers immediate relief in the case of severe pain and unpleasant sequelae of ulceration. Moreover, it contributes to substantial long-term survival. This, in particular, applies to local recurrence after breast cancer.

Predictive factors for response to neoadjuvant therapy in patients with oesophageal cancer.

BACKGROUND: Preoperative radio-chemotherapy (RCX) was introduced to improve the outcome of patients with oesophageal cancer (EC), but conflicting results have been released. Some 20-30% of patients show a complete pathological response, however, the perioperative morbidity and mortality is increased. To search for factors indicating response prior to the onset of RCX we investigated the proliferative activity (MIB-1), the expression of vascular endothelial growth factor (VEGF), and the capillary density (CD34) in samples of EC obtained by endoscopy prior to the start of the treatment. METHODS: Forty-six (MIB-1) and 21 (VEGF, CD34) tissue specimens of ECs were available from 56 patients undergoing pretherapeutic endoscopy, RCX and surgery. Perioperative morbidity was divided into surgery and non-surgery related morbidity. MIB-1, VEGF and CD34 expression were investigated immunohistochemically. Multivariate analysis was carried out to prove independence of investigated variables. RESULTS: Postoperative morbidity was noticed in 54 of 56 operated patients. Eight of 56 patients who received RCX died in hospital. Survival was significantly different between the group of complete responders (n=14) and non-responders (n=23; P=0.0026). None of the investigated tumour samples from patients with a complete response (CR) had a proliferation index of less than 45. Tumour samples from patients with a CR showed a VEGF expression of 10.7 compared with 36.58 of tumours with no response (P=0.035). CD34 expression showed a correlation with VEGF expression. The relation of mean indices of VEGF expression and proliferative activity in tumours from patients with complete, partial or no response was 10.7:58.8, 18.3:53.8 and 36.6:43.5, respectively. CONCLUSIONS: According to these results, it may be expected that tumours with a VEGF/MIB-1 ratio of 1:6 or less prior to RCX will respond to this therapy.

Validation of FDG positron emission tomography for differentiation of unknown pulmonary lesions.

OBJECTIVE: The impact of the (2-(fluorine-18)-fluoro-2-2deoxy-D-glucose)-positron emission tomography ((18)F-FDG-PET) for discrimination of pulmonary lesions was evaluated in a single centre prospective study. METHODS: In the study, 109 patients with pulmonary lesions of unknown origin verified by computed tomography were enrolled consecutively (April 1999--May 2000). They were subject to (18)F-FDG-PET diagnostics. (18)F-FDG-PET images were interpreted by two independent nuclear medicine physicians who were blinded to the results of other imaging procedures. In 87 patients, surgery was applied followed by histological investigation, which served as the gold standard. In 22 other patients, extensive tumour load or assumed benign dignity of the lesions prevented surgery. RESULTS: Overall sensitivity of (18)F-FDG-PET in 87 resected patients was 0.86. Differentiation in malignant (n = 69) and benign lesions (n = 18) revealed sensitivities of 0.9 and 0.72, respectively. Sensitivity of (18)F-FDG-PET in inflammatory lesions was markedly lower (0.43) than in benign tumours (0.91). Standard uptake values were significantly increased in malignant tumours compared with benign lesions (9.9 and 1.6, respectively; P = 0.035). There was a clear correlation of sensitivity with tumour size with a failure rate of 27% in lesions < or = 1cm (n = 15), 10% (n = 20) in lesions between 1 and 2 cm and 12% (n = 45) above 2 cm. In primary bronchial carcinoma, a clear correlation of sensitivity was observed with regard to tumour grading (G1, three out of five; G2, 24 out of 27; G3, 26 out of 26; and G4, one out of one). Lymph node involvement was correctly suggested in 10 out of 19 (52.6%) patients. However, false positive lymph node enhancement was indicated in one out of 18 (5.5%) operated patients with benign lesions and eight out of 39 (20.5%) with bronchial carcinoma. CONCLUSION: (18)F-FDG-PET at present does not serve as the gold standard for early detection of small and well-differentiated tumours. However, it contributes efficiently to the detection of malignancy in tumours >1cm, which are moderately or poorly differentiated. Positive lymph node imaging must not preclude surgery but requires histological proof. Discrimination of benign and malignant pulmonary tumours by (18)F-FDG-PET appears to be hampered in inflammatory lesions.

[Insidious and often fatal. Appendicitis with few symptoms in the elderly patient]. / Tückish und oft tödlich. Die symptomarme Appendizitis des älteren Patienten.

The age peak for acute appendicitis is between 10 and 20 years. Although older persons more rarely develop appendicitis, in the group of over-45-year-olds the perforation and mortality rates are appreciably higher. The reason for this is the fact that in the elderly, the symptoms are often veiled, so that the diagnosis is delayed. A particular role in this connection is played by pain killers and non-specific findings. In particular, however, the commonly present co-morbidity in older patients with appendicitis often leads to recalcitrant infections, and not infrequently to sepsis with a potentially fatal outcome. For the establishment of the diagnosis, therefore, a careful physical examination and thorough history-taking, together with a comprehensive laboratory work-up is essential. Imaging procedures such as X-rays of the abdomen, ultrasonography and, where indicated, such further measures as a barium enema or a CT scan may help establish the diagnosis in patients with unclear clinical symptoms, and thus prevent perforation.

[Diverticulosis: the dimensions of a growing problem]. / Von der Entzündung zur Perforation. Wenn aus harmlosen Divertikeln ein Notfall wird.

The etiology of diverticulitis remains unexplained. One hypothesis postulates that a diet low in fiber results in low-volume feces, which in turn leads to a segmental increase in muscle tone with bulging of the mucosa. Diverticulitis then occurs through micro-/macroperforation of the resulting diverticulum. Four grades are distinguished ranging from local mesenteric inflammation (grade I) to fecal peritonitis (grade IV). Asymptomatic diverticulitis requires no treatment. Diverticular bleeding must be carefully distinguished from upper gastrointestinal tract bleeding, carcinoma, and angiodysplasia. In the case of symptomatic diverticulitis ("left-sided appendicitis") a differentiation must be made between the acute and chronic forms. The diagnosis of diverticulitis is based on laboratory findings, x-rays and CT scans. If chronic diverticulitis is suspected, it is important to exclude carcinoma of the colon. Whether treatment should be surgical or conservative will depend on the severity of the condition, and on the complications that may be expected with conservative therapy.