Significance of total vascular exclusion for hepatic cryotherapy: an experimental study.

BACKGROUND: In the liver, efficacy of cryosurgical ablation of tumors located near the retrohepatic vena cava is impaired by the heat-sink effect. This could be overcome by total vascular exclusion (TVE) of the liver. In this study, the effect of TVE on cryosurgical ablation of liver tissue close to the retrohepatic vena cava was investigated with regard to the extent of the cryolesion and complications arising from necrosis of the caval wall. METHODS: Of a total of 28 pigs, 14 underwent cryotherapy with TVE compared to 14 without TVE, both involving the vena cava. 7 animals in each group were subjected to one freeze cycle and 7 in each group to two freeze cycles. Temperatures in the cryolesion were monitored and cryolesions were documented sonographically. Laboratory parameters were determined pre- and postoperatively. Follow-up was 14 days. Morphology, extent of the cryolesion, damage to the vena cava and complications were assessed after autopsy. RESULTS: With TVE, freezing rates were increased and cryolesions were significantly larger than without TVE. Transmural necroses of the vena cava with complete necrosis of the intima occurred significantly more frequently after TVE. Macro- and microscopically, the damage to the caval wall was considerably more marked after cryotherapy under TVE but in all cases the continuity of the vessel wall remained intact. There were no ruptures, thrombosis, or strictures of the vena cava. CONCLUSIONS: The combination of cryotherapy and TVE increases the effectiveness of cryoablation in the liver involving the retrohepatic vena cava without any severe vascular complications occurring in the pig.

Hepatic cryotherapy involving the vena cava. Experimental study in a pig liver model.

Liver tumors located near the retrohepatic vena cava are often considered nonresectable. For these patients cryoablation could be a therapeutic option. In this study the safety and efficacy of hepatic cryosurgery involving the retrohepatic vena cava were investigated. Cryolesions involving the vena cava were created in 26 pigs. Follow-up was 24 h and 14 days. The extent of the cryolesion, damage to the vena cava and complications were assessed after autopsy. The cyronecrosis extended into the wall of the vena cava in 81% of the animals. All animals had an uneventful recovery without any complications such as ruptures of the vessel, thrombosis or pulmonary embolism. Microscopically elastic and collagenous fibers of the cava wall remained intact. The continuity of the vessel wall was conserved. In conclusion, the safety and efficacy of cryosurgical treatment involving the retrohepatic vena cava were shown in a pig model.

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.

[Brain concussion: risk factors]. / Die Commotio Cerebri: Risikofaktoren.

AIM: Identification of risk factors for intracranial bleeding after minor traumatic brain injury. METHOD: The charts of 464 patients treated between January 1976 and December 1997 with the initial diagnosis of minor traumatic brain injury were reviewed. They were analyzed for clinical and diagnostic signs putting the patients at risk for intracranial bleeding. RESULTS: About two thirds of the patients (67.5%) were males, the average age being 36.1 years. Leading causes of accident were sudden falls (27.4%) and bike/autocycle crashes (24.8%). 30.4% of the patients were under the influence of alcohol. At the time of admission to the hospital 17.2% of the patients showed impaired consciousness and 12.5% presented neurologic signs. In ten patients an intracranial bleeding was found. All these bleedings were diagnosed at the primary investigation. DISCUSSION/CONCLUSIONS: Following groups of patients with traumatic brain injury have an increased risk for intracranial bleeding: Age > 60 and < 16 years, sudden falls, tachycardia, Glasgow-Coma-Scale < 15, impairment of consciousness, neurologic signs, fracture of the skull and patients suffering from coagulopathy. Drunk patients are difficult to judge; therefore, they should be handled as being at risk. Patients at increased risk should be observed on an intensive care unit whereas patients without those risk factors can be observed on a normal ward or, alternatively, discharged after reexamination and uneventful course after some hours.

Pericentral hepatocytes translocate hydrophilic bile acids more rapidly than hydrophobic ones.

The aim of this study was to analyze whether velocity of periportal and pericentral translocation is different for bile acids differing in their physicochemical properties. Isolated livers of male Sprague-Dawley rats were perfused antegradely or retrogradely, in single pass arrangement with labeled taurodehydrocholate, cholate, taurocholate, glycocholate, or taurodeoxycholate (inflow rate: 32 nmol/min/g liver). Bile was collected at 2-min intervals; aliquots were counted in a liquid scintillation spectrophotometer to trace uptake rate and biliary excretion profile. Biliary excretion patterns of all bile acids tested were almost identical in periportal cells; in contrast, it differed greatly in pericentral cells. Pericentral cells excreted taurodehydrocholate as fast as periportal cells, while periportal cells eliminated taurodeoxycholate about four times as fast and cholate, taurocholate and cholate about two times as fast as pericentral cells. It is concluded that, in contrast to periportal translocation, the velocity of pericentral translocation depends upon the hydrophilicity of the respective bile acid. Therefore, different or additional translocation pathways for bile acids may be involved in periportal versus pericentral cells.

Colchicine inhibits taurodeoxycholate transport in pericentral but not in periportal hepatocytes.

Indirect evidence for a microtubule-dependent vesicular hepatocellular transport of bile acids has accumulated. Since inhibition of this transport by colchicine can be achieved only at high but not at low bile acid infusion rates we were wondering whether this transport pathway shows a hepatic zonation or not. To answer this question we perfused isolated rat livers antegradely or retrogradely, respectively, with unlabeled and labeled taurocholate or taurodeoxycholate. Inhibition of microtubule-dependent bile acid transport was aimed at co-infusion of colchicine. Periportal cells eliminated the likewise hydrophobic taurodeoxycholate as fast as the more hydrophilic taurocholate. In contrast, pericentral cells excreted taurodeoxycholate much slower than taurocholate. Colchicine did not change the biliary taurocholate excretion profile in periportal and pericentral cells. However, colchicine reduced significantly taurodeoxycholate excretion in pericentral but not in periportal cells. It is concluded that a microtubule-dependent vesicular, colchicine-sensitive transport pathway seems to be involved in the translocation of taurodeoxycholate in pericentral but not in periportal cells. Since such a vesicular bile acid transport is regarded to be much slower than transcellular transport by diffusion, this observation may explain the much slower excretion of hydrophobic bile acids like taurodeoxycholate in pericentral than in periportal cells under physiological conditions.

Ergonomics: requirements for adjusting the height of laparoscopic operating tables.

BACKGROUND AND OBJECTIVES: In the last few years many new instruments and devices have been developed and introduced into the operating room (OR). A debate has been ongoing about the optimal ergonomic posture for the operating staff. From practical experience, we have learned that the operating tables cannot be adjusted adequately to allow surgeons of different stature to maintain a comfortable posture. The goal of this study was to establish the most ergonomic table height for the particular physique of the surgeon and the different types of laparoscopic instrument handles that he or she uses. METHODS: In a simulated model, two probands of different stature (50th [BS 50] and 95th [BS 95] percentile) used laparoscopic instruments with four different handle designs (shank, pistol, axial, and rod). The instruments were inserted into a board in three different angles ([IA] = 20 degrees, 30 degrees, 40 degrees). Additionally the elbow angles (EA) of the volunteers were fixed to either 90 degrees or 120 degrees. For every variable (size of surgeon and his or her elbow angle, design of handle, insertion angle of the instrument) the height of the board, as a parameter for the level of the abdominal wall of a patient with pneumoperitioneum, was measured from the floor. RESULTS: All parameters had an effect on the optimal operating table height. The lowest required operating table level was 30 cm, the highest was 60.5 cm. In laparoscopic surgery-long shafted instruments and patients with pneumoperitoneum-the tabletops are too high for over 95% of all surgeons. As skin incision and wound suture are performed the conventional way, the operating tabletop must be adjustable up to the common height of 122 cm. The maximal difference between the optimal heights of the OR-table for one volunteer using two different handles with different insertion angles of the instruments (BS 95, EA 90 degrees, IA 20 degrees, rod handle to BS 50, EA 120 degrees, IA 40 degrees, axial handle) was about 27 cm. CONCLUSION: New operating tables with a much lower adjustability are necessary to fulfill ergonomic requirements. The use of differently designed handles can hinder the ergonomic posture of the surgeon, because each handle requires a different working height.

[Surgically relevant comorbidity: ability to cooperate]. / Chirurgisch relevante Komorbiditäten: Kooperationsfähigkeit.

The ability to cooperate represents an important prognostic factor for the result of any surgical therapy. Cooperation relies on a trustful relationship between physician and patient and requires active participation of the patient. Surgical procedures requiring long-term follow-up depend on a high degree of cooperation. Cooperation is the result of numerous psycho-social factors. The degree of potential cooperation influences to a large extent the decision process for indication and choice of method. The ability to cooperate does not depend on the patient only but it is result of a therapeutic alliance between patient and physician.

Inflammatory consequences of the translocation of bacteria and endotoxin to mesenteric lymph nodes.

BACKGROUND: Translocation of intestinal bacteria to mesenteric lymph nodes (MLNs) has been documented in humans under a variety of circumstances, yet its clinical significance remains to be established. The aim of this study was to correlate detectable translocation to MLNs of bacteria and endotoxin with local and systemic signs of inflammation. METHODS: From each of 10 patients with carcinoma of the cecal region two MLNs were harvested prior to resection. The presence of bacteria and endotoxin in the lymphatic tissue and blood was determined by culture methods and DNA preparation (PCR) and by a Limulus assay, respectively. Inflammatory mediators were determined in plasma and in MLN homogenates. RESULTS: Viable bacteria were detected in MLNs of 7 patients and in 9 of 20 lymph nodes. PCR revealed traces of bacteria in 4 patients and in 6 of their MLNs. Combining both modalities, the translocation rate was 80% and 55% for patients and MLNs, respectively. There was no detectable bacteremia. Endotoxin was found in the plasma of 7 patients and in 9 MLNs from 5 patients. There was no correlation between culture findings and endotoxin concentrations. Moreover, bacteriological data did not correspond to local or systemic inflammation. The group of MLN with detectable endotoxin differed significantly from LPS-negative nodes with respect to interleukin-6, interleukin-10, and sCD14. Systemic concentrations of endotoxin and inflammatory parameters did not correspond to levels within MLNs. CONCLUSION: Translocation to MLNs occurs in patients with cecal carcinoma. This, however, seems not to be of major clinical significance if no additional physiologic insults are encountered. Irrespective of the presence of bacteria, there are variations in inflammatory reactions between lymph nodes from one and the same patient, probably reflecting fluctuating response mechanisms to low-grade translocation.

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.

[Working posture of laparoscopy-practicing surgeons: ideal and reality]. / Die Arbeitshaltung des laparoskopisch tätigen Chirurgen: Ideal und Wirklichkeit.

Since laparoscopic surgery has been established the advantages for the patients of minimal invasive surgery have been discussed extensively. But this method holds considerable disadvantages, due to the non-ergonomic surgeons working position. This is mainly caused by the false positioning of the monitor and operating table as well by the use of foot switches and differing instrument handles. The common working position of the laparoscopically working surgeon leads to serious risks for the patient. The industry and hospital administrations do not know anything about this and only few surgeons are aware of these dangers. The authors want to draw attention to the insufficiencies of the laparoscopic working place. Due to missing resources until now no general concept has been developed that meets current standards.

Impact of 18F-FDG-positron emission tomography for decision making in colorectal cancer recurrences.

Diagnostic imaging for suspected tumour recurrence of primary colorectal cancer frequently lacks specificity and sensitivity. The impact of whole body 18F-FDG-positron-emission tomography (PET) on detection of local recurrences and hepatic or pulmonary metastases was evaluated in a prospective study. Results were compared with computed tomography (CT), ultrasonography, magnetic resonance imaging and conventional chest X-ray. The study included 71 patients (77 investigations) with suspected local recurrence, hepatic metastases or unexplained raised level of the tumour marker carcinoembryonic antigen (CEA). The results demonstrate that 18F-FDG-PET was clearly superior to CT with regard to detection of hepatic metastases. Sensitivity was 1.0 and specificity 0.98 compared with 0.87 and 0.91 for CT. In four cases, 18F-FDG-PET clarified otherwise unclear local recurrences. In five patients, 18F-FDG-PET showed pulmonary metastases that had previously been unknown. In a total of 16 patients (20.8%), 18F-FDG-PET provided additional information leading to a change of the treatment strategy. 18F-FDG-PET clearly has the ability to detect colorectal tumour recurrence and its metastases in a whole body format. Therefore, it may be applied in the follow-up of patients with primary colorectal cancer. Despite the costs, it is certainly recommended for patients with an otherwise unclear increase of CEA level or with unproven local recurrence.

Evidence-based surgery: diverticulitis--a surgical disease?

Sigmoid diverticulitis is an increasingly common disorder. While there is no gender difference, the incidence increases with age. Many reports have been published on the topic, but there is no consensus on certain aspects of treatment. We conducted a literature search covering the past 30 years and report our own data. Two major areas of controversy exist. One concerns indications for elective surgery for symptomatic diverticulitis. The consensus is that there is no indication for prophylactic surgery. The first attack should be treated conservatively; elective surgery is considered following a second attack, but in immunocompromised patients earlier. The second controversy concerns surgical strategy in peritonitis from perforation. Three-stage operations have generally been abandoned. The question is whether to perform a sigmoid resection with primary anastomosis. One end of the spectrum is recent perforation which can be treated safely by resection and anastomosis. The other end is advanced feculent peritonitis in high-risk patients. In this situation a Hartmann procedure is recommended. Although data from prospective randomized studies are lacking, there seem to be indicators in the individual situation that allow a rational selection of the appropriate procedure. Diverticulitis can thus be treated surgically for a broad range of its forms of presentation.

Local inflammatory peritoneal response to operative trauma: studies on cell activity, cytokine expression, and adhesion molecules.

OBJECTIVE: To test the hypothesis that different surgical procedures may lead to different degrees of activation of the human peritoneal response. DESIGN: Clinical laboratory study. SETTING: University Hospital, Germany. MATERIAL: Peritoneal specimens taken from the incision or parietal resection margins at the beginning and end of laparoscopic or open cholecystectomy, or other conventional open operations (n = 5 in each group). MAIN OUTCOME MEASURES: Detection of indicators of the inflammatory response: interleukin 1 (IL-1), interleukin 6 (IL-6), intercellular adhesion molecule- (ICAM-1), antibacterial protein (defensin 3 that reflects the activation of granulocytes), the antibody clone HAM 56 (for detection of local macrophages), and antibodies against macrophage inhibiting factor (MIF)-related proteins 8 and 14 (MRP 8 and 14). RESULTS: The rise between preoperative and postoperative evaluations was significant for each variable (p < 0.05). With one single exception (IL-6 between laparoscopic cholecystectomy and other operations), the one way analysis of variance (ANOVA) showed no significant differences among the three groups in the detectable increases in staining. Linear regression analysis showed no correlation between length of operation and increases in immunohistochemically detected inflammatory variables. CONCLUSION: Minimally invasive surgery does not necessarily mean minimal peritoneal damage. The immunohistochemical evaluation of the local cellular response may provide additional objective criteria for the grading of operative trauma.

Expression and activity of mitogen activated protein kinases in human colorectal carcinoma.

BACKGROUND: Mitogen activated protein kinases (MAPKs) play a central role in the regulation of both cell growth and differentiation. They are involved in signal transduction of oncogenes and growth factors. The role of MAPK in colonic carcinoma is unknown. AIMS: To establish whether the expression and activity of p42/44 MAPKs are altered in colorectal tumours as compared with normal mucosa. METHODS: The expression and activity of p42/p44 MAPK were investigated in 22 colorectal carcinomas, four adenomas, and the corresponding normal colorectal mucosa by the use of western blotting, immunoprecipitation, and in vitro kinase assays. RESULTS: After immunoprecipitation with an antibody specific for p42 MAPK, we found significant inactivation of p42 MAPK in colonic carcinomas as well as in adenomas, whereas most sample pairs showed only minor differences in p42 MAPK expression. Investigation of MAPK with an antibody capable of detecting both p42 and p44 MAPK showed a slight but significant decrease in p44 MAPK content in malignant tissues. With this antibody, only minor alterations in MAPK activity and no correlation with p42 MAPK activity were found. CONCLUSIONS: Inactivation of p42 MAPK could be associated with colonic carcinogenesis.

Evaluation of positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose for the differentiation of chronic pancreatitis and pancreatic cancer.

BACKGROUND: The clinical presentation of patients with pancreatic cancer may resemble the clinical picture of chronic pancreatitis. A definitive preoperative diagnosis is not always obtained in patients with a history of chronic pancreatitis despite the use of modern imaging techniques. Operative strategy therefore remains unclear before operation in these patients. METHODS: Positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) was introduced recently into clinical oncology because of its ability to demonstrate metabolic changes associated with various disease processes. The impact of FDG-PET on the differentiation of chronic pancreatitis and pancreatic cancer was investigated. FDG-PET was performed in 48 patients with chronic pancreatitis (n = 12), acute pancreatitis (n = 3) and pancreatic cancer (n = 27), and in controls (n = 6). Histological examination was undertaken in all cases except controls. The FDG-PET results were obtained without knowledge of results of other imaging procedures. The results were then compared with those of computed tomography, ultrasonography, endoscopic retrograde cholangiopancreaticography, operative findings and histology. PET images were analysed semiquantitatively by calculating a standard uptake value (SUV) 90-120 min after application of the tracer. RESULTS: Cut-off values were validated as follows: SUV greater than 4.0 for pancreatic cancer, SUV of 3.0-4.0 for chronic pancreatitis, and SUV of less than 3.0 for controls. Sensitivity and specificity of PET imaging were 0.96 and 1.0 for pancreatic cancer, and 1.0 and 0.97 for chronic pancreatitis. In five cases only FDG-PET led to the correct preoperative diagnosis. CONCLUSION: The results give further evidence that FDG-PET is an important non-invasive method for the differentiation of chronic pancreatitis and pancreatic cancer. Delayed image acquisition in the glycolysis plateau phase permits improved diagnostic performance. This imaging technique is extremely helpful before operation in patients with an otherwise unclear pancreatic mass, despite its costs.