C.A. Jacobi

Laparoscopic resection of colon Cancer: consensus of the European Association of Endoscopic Surgery (EAES).

BackgroundThe European Association of Endoscopic Surgery (EAES) initiated a consensus development conference on the laparoscopic resection of colon cancer during the annual congress in Lisbon, Portugal, in June 2002.MethodsA systematic review of the current literature was combined with the opinions, of experts in the field of colon cancer surgery to formulate evidence-based statements and recommendations on the laparoscopic resection of colon cancer.ResultsAdvanced age, obesity, and previous abdominal operations are not considered absolute contraindications for laparoscopic colon cancer surgery. The most common cause for conversion is the presence of bulky or invasive tumors. Laparoscopic operation takes longer to perform than the open counterpart, but the outcome is similar in terms of specimen size and pathological examination. Immediate postoperative morbidity and mortality are comparable for laparoscopic and open colonic cancer surgery. The laparoscopically operated patients had less postoperative pain, better-preserved pulmonary function, earlier restoration of gastrointestinal function, and an earlier discharge from the hospital. The postoperative stress response is lower after laparoscopic colectomy. The incidence of port site metastases is <1%. Survival after laparoscopic resection of colon cancer appears to be at least equal to survival after open resection. The costs of laparoscopic surgery for colon cancer are higher than those for open surgery.ConclusionLaparoscopic resection of colon cancer is a safe and feasible procedure that improves short-term outcome. Results regarding the long-term survival of patients enrolled in large multicenter trials will determine its role in general surgery.

Inflammatory response after laparoscopic and conventional colorectal resections - results of a prospective randomized trial.

Abstract  Background: Short-term benefits of laparoscopic relative to conventional colorectal resections have been demonstrated in randomized controlled trials. It has been suggested that a diminished cytokine and acute-phase response may be responsible for these advantages. Methods: In a randomized controlled trial, patients underwent laparoscopic (n=30) or conventional (n=30) resection of colorectal tumors. Plasma levels of interleukin-1 receptor antagonist (IL-1RA), interleukin-6 (IL-6), interleukin-10 (IL-10), and C-reactive protein (CRP) were analyzed repeatedly. Postoperative peak levels and area under the curve values were calculated and compared between groups using the Mann-Whitney U-test. Results: Patient characteristics, preoperative cytokine, and CRP plasma levels were not different between each group. Postoperative peak concentrations of IL-6 (P=0.05) and CRP (P<0.001) and the overall postoperative plasma concentrations of IL-6 (P=0.03) and CRP (P=0.002) were lower in the laparoscopic than in the conventional group. Peak and overall IL-1RA (P=0.2; P=0.2) and IL-10 (P=0.4; P=0.6) plasma concentrations, respectively, were not different between groups. Conclusions: IL-6 and CRP plasma levels were lower after laparoscopic than conventional colorectal resections. The less intense inflammatory response may be an indicator of the milder surgical trauma inflicted by laparoscopic than conventional colorectal resection.

New Therapeutic Strategies to Avoid Intra- and Extraperitoneal Metastases during Laparoscopy: Results of a Tumor Model in the Rat

Background: Therapeutic strategies to prevent port site recurrences in laparoscopy surgery of malignancies have not been investigated until now. Methods: The effects of taurolidine, heparin, and povidone iodine on the growth of rat and human colon adenocarcinoma as well as gallbladder carcinoma were investigated in vitro. Furthermore, cytokine release of growth-stimulating IL-1β by peritoneal macrophages was measured after incubation with carbon dioxide and additional incubation with the different agents. In the third experiment, prevention of intra- and extraperitoneal metastases by intraperitoneal instillation of the different agents during laparoscopy was investigated in a colon carcinoma model in the rat. Tumor cells were administered intraperitoneally in 100 rats, and pneumoperitoneum (8 mm Hg) was established over 30 min with carbon dioxide. Rats received either tumor cells, cells + heparin, cells + povidone iodine, cells + taurolidine, or cells + taurolidine + heparin. Results: In vitro, tumor cell growth decreased after incubation with taurolidine, taurolidine/heparin, and povidone iodine. Cytokine release was stimulated by incubation with carbon dioxide and could only be suppressed by incubation with taurolidine in vitro. In vivo, intraperitoneal tumor weight was lower in rats receiving heparin (251 ± 153 mg) and povidone iodine (134 ± 117 mg) compared to the control group (541 ± 291 mg), but even less when taurolidine (79 ± 82 mg) or taurolidine/heparin (18.3 ± 30 mg) were instilled. Conclusion: Heparin slightly inhibits intraperitoneal tumor growth in vivo, while povidone iodine and taurolidine cause a significant decrease in tumor cell growth in vitro as well as intraperitoneal tumor growth in vivo. Cytokine release of peritoneal macrophages is only suppressed by taurolidine. Total tumor take and trocar metastases are only suppressed by taurolidine and taurolidine/heparin.

The Impact of Laparoscopy with Carbon Dioxide versus Helium on Immunologic Function and Tumor Growth in a Rat Model

Background: The pathogenesis of port site recurrences after laparoscopic surgery for malignant disease is still unknown. Whether different gases used to establish pneumoperitoneum have an influence on immunologic function and therefore on promotion of tumor growth has not yet been investigated. Methods: Tumor growth of colon adenocarcinoma DHD/K12/TRb was evaluated in a rat model after insufflation either with CO2 (n = 25) or helium (n = 25) and in a control group (n = 25). Tumor growth was measured subcutaneously and intraperitoneally 5 weeks after insufflation. Beside tumor growth, immunologic changes (peripheral leukocyte subpopulations, plasma levels of TNFα and IL-10) were evaluated during the perioperative course in all animals. Results: Subcutaneous tumor growth was promoted by the CO2 (99 ± 55 mg; p < 0.01) compared to the helium (40 ± 41 mg) and control groups (36 ± 33 mg). Total intraperitoneal tumor weight was 718 ± 690 mg in the CO2 group compared to the helium (549 ± 233 mg) and control groups (521 ± 221 mg). While peripheral leukocyte subpopulations only differed between the laparoscopic groups and the control group during the perioperative course, TNFα plasma levels were significantly decreased and IL-10 plasma levels significantly increased in the CO2 group compared to the helium and control groups in the postoperative course. Conclusion: The insufflation of CO2 promotes tumor growth compared to the helium and control groups in a rat model. In addition, increased tumor growth was associated with a significant increase in IL-10 and a decrease in TNFα plasma levels.

The influence of laparotomy and laparoscopy on tumor growth in a rat model

AbstractBackground: The effects of laparotomy and laparoscopy with different gases on subcutaneous and intraperitoneal tumor growth have not been evaluated yet. Methods: Tumor growth of colon adenocarcinoma DHD/K12/TRb was measured in rats after laparotomy, laparoscopy with CO2 or air, and in control group. Cell kinetics were determined after incubation with carbon dioxide or air in vitro and tumor growth was measured subcutaneously and intraperitoneally after surgery in vivo. Results: In vitro, tumor cell growth increased significantly after incubation with air and CO2. In vivo, intraperitoneal tumor weight was increased after laparotomy (1,203 ± 780 mg) and after laparoscopy with air (1,085 ± 891 mg) and with CO2 (718 ± 690 mg) compared to control group (521 ± 221 mg) (p < 0.05). Subcutaneous tumor growth was promoted after laparotomy (71 ± 35 mg) and even more after laparoscopy with air (82 ± 45 mg) and CO2 (99 ± 55 mg) compared to control group (36 ± 33 mg). Conclusions: Insufflation of air and CO2 promote tumor growth in vitro. In vivo, intraperitoneal tumor growth seems to be promoted primarily by intraperitoneal air and subcutaneous tumor growth by CO2.

Gastrointestinale Lebensqualität nach Duodenopankreatektomie beim Pankreascarcinom Vorläufige Ergebnisse einer prospektiv-randomisierten Studie: PD vs PPPD

BACKGROUND The Whipple operation (PD) is the standard operation in patients with cancer of the head of the pancreas and the periampullary region. However, the pylorus-preserving duodenopancreatectomy (PPPD) is supposed to be superior in gastrointestinal function. METHODS In a prospective randomized trial (October 1994-October 1998) PD and PPPD were compared in terms of global and gastrointestinal quality of life, operation time, duration of hospital stay, transfusions and perioperative morbidity. Quality of life was analyzed under standardized conditions (EORTC-QLQ-30) pre- and postoperatively (weeks 2, 6, 12, 24, 36, 48, and 60). RESULTS A duodenopancreatectomy was performed in 48 patients because of cancer of the head of the pancreas (n = 38) and the periampullary region (n = 10) (PD, n = 24; PPPD, n = 24). The PD and PPPD groups did not differ according to age, gender or UICC stage. Operation time was shorter in the PPPD group (206 +/- 48 vs 306 +/- 54 min) (P < 0.05). Morbidity did not differ between the two groups (PPPD 20% vs PD 30%, P > 0.05). While there was no difference in global quality of life, gastrointestinal quality of life was postoperatively increased in the PPPD group regarding appetite, nausea and diarrhea (P < 0.05). While the preoperative body weight was reached after 6 months in 85% of the PPPD group (n = 20), this was true in only 60% of the PD-group (n = 14) (P < 0.05). CONCLUSION PPPD seems to be associated with a better postoperative gastrointestinal quality of life than PD.Summary.Background: The Whipple operation (PD) is the standard operation in patients with cancer of the head of the pancreas and the periampullary region. However, the pylorus-preserving duodenopancreatectomy (PPPD) is supposed to be superior in gastrointestinal function. Methods: In a prospective randomized trial (October 1994–October 1998) PD and PPPD were compared in terms of global and gastrointestinal quality of life, operation time, duration of hospital stay, transfusions and perioperative morbidity. Quality of life was analyzed under standardized conditions (EORTC-QLQ-30) pre- and postoperatively (weeks 2, 6, 12, 24, 36, 48, and 60). Results: A duodenopancreatectomy was performed in 48 patients because of cancer of the head of the pancreas (n = 38) and the periampullary region (n = 10) (PD, n = 24; PPPD, n = 24). The PD and PPPD groups did not differ according to age, gender or UICC stage. Operation time was shorter in the PPPD group (206 ± 48 vs 306 ± 54 min) (P < 0.05). Morbidity did not differ between the two groups (PPPD 20 % vs PD 30 %, P > 0.05). While there was no difference in global quality of life, gastrointestinal quality of life was postoperatively increased in the PPPD group regarding appetite, nausea and diarrhea (P < 0.05). While the preoperative body weight was reached after 6 months in 85 % of the PPPD group (n = 20), this was true in only 60 % of the PD-group (n = 14) (P < 0.05). Conclusion: PPPD seems to be associated with a better postoperative gastrointestinal quality of life than PD.Zusammenfassung.Hintergrund: Die kephale Pancreaticoduodenektomie nach Kausch-Whipple (PD) gilt als Standardverfahren bei der chirurgischen Therapie des Carcinoms des Pankreaskopfes und der periampullären Region, jedoch soll die pyloruserhaltende Resektion (PPPD) hinsichtlich der gastrointestinalen Funktion Vorteile bieten. Methodik: In einer prospektiv-randomisierten Studie (10/94–10/98) wurden beide Operationsverfahren verglichen. Hauptzielkriterium waren die globale und gastrointestinale Lebensqualität (LQ), Nebenzielkriterien waren die Dauer der Operation und des stationären Aufenthaltes, sowie der Verbrauch von Blutkonserven und die perioperative Morbidität. Die Lebensqualität wurde standardisiert mit Hilfe des EORTC-QLQ-30-Bogens präoperativ und in der 2., 6., 12., 24., 36., 48. und 60. postoperativen Woche erhoben. Ergebnisse: Bei 48 Patienten erfolgte wegen eines Carcinoms des Pankreaskopfes (n = 38) und der periampullären Region (n = 10) eine Duodenopankreatektomie (PD n = 24, PPPD n = 24). Beide Gruppen unterschieden sich nicht hinsichtlich Alter, Geschlecht und Tumorstadium. Die Operationsdauer der PPPD-Gruppe war signifikant kürzer (206 ± 48 vs 306 ± 54 min) (p < 0,05), die Morbiditätsrate beider Operations-Gruppen unterschied sich nicht signifikant (PPPD 20 % vs PD-Gruppe 30 %). Während die globale LQ beider Patientengruppen nahezu identisch war, zeigten sich signifikante Vorteile für die PPPD-Gruppe hinsichtlich der gastrointestinalen Parameter Appetitlosigkeit, Übelkeit und Erbrechen sowie Diarrhoe. In der PD-Gruppe erreichten nur 14 Patienten (60 %) ihr präoperatives Körpergewicht nach 6 Monaten gegenüber 20 Patienten (85 %) der PPPD-Gruppe (p < 0,05). Schlußfolgerung: Diese Ergebnisse deuten auf eine Verbesserung der postoperativen gastrointestinalen Lebensqualität in der PPPD-Gruppe gegenüber der PD-Gruppe hin.

Impact of laparoscopic gases on peritoneal microenvironment and essential parameters of cell function

Several experimental studies confirm the hypotheses that laparoscopic gases influence the development of tumor metastases [12, 14, 23]. The mechanism for this alteration of malignant tumor growth is still unknown. One reason might be an influence of the in sufflation gas on essential cell function regulating parameters. To investigate the changes of the intra- and extracellular milieu, four parameters—extra- and intracellular pH, intracellular free calcium levels, and tissue oxygen partial pressure—were measured during insufflation with carbon dioxide (CO2), helium (He), or a nonhypoxic gas mixture consistent of 80% CO2 and 20% O2. Study design (In vitro experiments) Intracellular calcium and pH levels were measured in DHD/K12/TRb colon adenocarcinoma cells using fluorescence imaging microscopy. (In vivo experiments) Tissue oxygen partial pressure was measured using a flexible micro catheter (Licox CMP) implanted in the abdominal wall of rats. After establishing the pneumoperitoneum an optical system and an aspirator were inserted to control the position of the micro catheter and to aspirate wound exudates for pH measurements of the wound fluid. Results: Creating of pneumoperitoneum with both CO2 and helium caused a decrease in partial pressure of oxygen in the abdominal wall to about 5 mm Hg whereas insufflation with a nonhypoxic gas mixture (80% CO2 and 20% O2) induced no significant changes. The intra- and extra cellular pH values dramatically decreased during CO2 insufflation (7.4 to 6.2) in vitro. Helium caused a pH increase up to 7.6. Free intracellular calcium was enhanced during CO2 insufflation, whereas helium insufflation did not cause any changes in [Ca2+]i. Nevertheless, a significant decrease of [Ca2+]i was observed during reoxygenation following helium-induced hypoxia. Conclusion: Our study demonstrates that insufflation with either CO2 or He causes significant changes of intra- and extracellular parameters regulating essential cell functions such as oxidative phosphorylation to produce ATP, cell proliferation, or onset of apoptosis.

Prognosis Factors in Carcinoma of the Head of the Pancreas

Background: Due to a low survival rate even after a R0 resection of cancer of the head of the pancreas, a strict indication for a pancreaticoduodenectomy seems to be sensible. We have therefore analyzed our patients for possible prognosis factors. Methods: In a retrospective trial the courses of disease of all patients (1981–1996) with resected histologically proven carcinoma of the head of the pancreas were analyzed. The following patient-specific parameters were evaluated and examined in a single or multivariate analysis of prognosis factors: age, gender, tumor size (T status), lymph node involvement (N status), dimension of resection, operation method, time of operation, morbidity, clinic lethality and survival rate. Results: Between 1981 and 1996, 500 patients with ductal adenocarcinoma of the head of the pancreas were treated surgically. The rate of resection increased from 32.1% (1981–1986) to 37.8% (1991–1996) whereas the mortality rate decreased from 13.3 to 7.3%. The 5-year survival rate after resection was 11.8% with a median survival time of 13.8 months. In a multivariate analysis, only small tumors (T1, p < 0.016), the R0 status (p < 0.017) and the resection had a significant influence on the survival rate. Conclusion: Prognosis factors in the treatment of pancreatic cancer were tumor size (T1), tumor resection and R0 status.

Influence of different gases and intraperitoneal instillation of antiadherent or cytotoxic agents on peritoneal tumor cell growth and implantation with laparoscopic surgery in a rat model

AbstractBackground: A generally accepted approach to prevent tumor implantation with laparoscopic surgery does not exist. Alternative gases in combination with intraperitoneal instillation of different antiadherent or cytotoxic agents have not been evaluated. Methods: The effect of taurolidine, heparin, and povidone-iodine on the growth of colon adenocarcinoma DHD/K12/TRb was measured in rats undergoing laparoscopy with carbon dioxide (n= 40), helium (n= 40), or xenon (n= 40). In the procedure, 104 tumor cells were administered intraperitoneally, and pneumoperitoneum was established over 30 min at 8 mmHg with the different gases. The rats additionally received intraperitoneal instillation with one of the following: 1 ml of Ringers solution, 1 ml of 0.5% taurolidine, 1 ml 0.5% taurolidine with heparin (10 U/ml), or 1 ml 0.25% of povidone-iodine. Tumor growth was measured after 4 weeks. Results: Median intraperitoneal tumor weight was lower in rats receiving taurolidine (CO2: 10 mg; helium: 50 mg; xenon: 39.5 mg) or taurolidine with heparin (CO2: 4 mg; helium: 4.5 mg; xenon: 46.5 mg) in all gas groups than in the control groups (CO2: 427 mg; helium: 268 mg; xenon: 345 mg) (p < 0.001). Whereas povidone-iodine caused significantly lower tumor growth in the CO2 group (56.5 mg) (p < 0.01), the combination of helium (145 mg) and xenon (457 mg) with povidone-iodine produced no reduction of tumor growth as compared with the control groups (helium: 268 mg; xenon: 345 mg). Conclusions: Taurolidine and taurolidine with heparin significantly inhibit intraperitoneal tumor growth, with different gases used for pneumoperitoneum. Only povidone-iodine caused significant decrease of tumor growth in combination with CO2. The combination of xenon and povidone-iodine should not be used in patients with cancer because of increased tumor growth.

K-ras mutations in tissue and stool samples from patients with pancreatic cancer and chronic pancreatitis

Background and aim: K-ras oncogene is the most promising molecular marker of pancreatic cancer. However, the incidence of single and combined K-ras mutations in stool and pancreatic tissue is unknown, and it is not clear whether detection of the K-ras oncogene in stool could be employed in screening tests. Patients/methods: Stool and pancreatic tissue of patients with ductal adenocarcinoma (n = 36), cystadenocarcinoma (n = 1), periampullary carcinoma (n = 7), endocrine tumour (n = 2) and chronic pancreatitis (CP, n = 5) were analysed for mutated K-ras sequences prospectively. DNA of stool and pancreatic tissue was amplified by polymerase chain reaction and K-ras status was analysed by hybridisation. Results: K-ras mutations were detected in the pancreatic tissue of 28 patients with ductal adenocarcinoma (78%), in 1 patient with cystadenocarcinoma, in 1 patient with periampullary carcinoma (14%) and in 1 patient with CP (20%). In 1 patient with an endocrine tumour, no K-ras mutations were diagnosed. K-ras mutations were detected in stool in 7 patients with ductal adenocarcinoma (20%), in 1 patient with cystadenocarcinoma and in 2 patients with CP (40%). Sensitivity of K-ras mutations for pancreatic cancer was 78% in tissue and 20% in stool. Conclusion: K-ras mutations lack specificity to discriminate malignant pancreatic disease from chronic inflammation in tissue and stool.