Wound metastases following laparoscopic and open surgery for abdominal cancer in a rat model

The recent application of laparoscopic resection techniques to malignant disease has raised safety concerns due to metastasis to surgical access wounds. The significance and incidence of this problem are controversial. In the present study a rat model, in which an implanted tumour was lacerated, was used to investigate whether application of laparoscopic techniques for malignant abdominal disease leads to an increased risk of tumour dissemination and implantation within the peritoneal cavity, and abdominal wall wounds. Malignant cells were implanted into the abdominal wall of 42 rats, resulting 7 days later in the growth of a tumour measuring 20-25 mm in diameter. There were three control groups: no surgery (n = 6); blunt manipulation of the tumour laparoscopically (n = 6); and blunt manipulation of the tumour at laparotomy (n = 6). Twenty-four rats underwent surgical laceration of the tumour capsule at either laparoscopy (n = 12) or laparotomy (n = 12). All rats were killed 1 week later, and examined for macroscopic evidence of tumour metastasis. The abdominal surgical wounds were excised for independent microscopic examination by a histopathologist. Growth of the primary tumour was greater in rats that had an operation than in unoperated controls, and was greater after laparotomy. However, wound metastases were five times more likely after laparoscopic tumour laceration than after the same procedure through an open incision (ten of 12 rats versus two of 12, P = 0.0033). Wound metastases following laparoscopic tumour manipulation are an important and real problem, with significant implications for the application of laparoscopic techniques to excise malignant disease in humans.     

Effects of carbon dioxide pneumoperitoneum, air pneumoperitoneum, and gasless laparoscopy on body weight and tumor growth

BACKGROUND: The oncologic consequences of intraperitoneal carbon dioxide (CO2) insufflation during the laparoscopic resection of cancer are under debate. The effect of other insufflating gases or gasless laparoscopy on cancer requires study. OBJECTIVE: To study body weight and tumor growth in rats after CO2 pneumoperitoneum, air pneumoperitoneum, and gasless laparoscopy. METHODS: On day 1, an 8-mg bolus of ROS-1 tumor was placed under the renal capsule of both kidneys in rats. In experiment A, rats had either CO2 insufflation (n=10) or a gasless laparoscopic bowel resection (n=10) on day 3 and were humanely killed after 7 days. In experiment B, rats had either a laparoscopic bowel resection with CO2 insufflation (n=11) or insufflation with air (n=11) on day 3 and were killed after 7 days. In both experiments, postoperative weight loss and tumor growth were measured, and the differences were tested with an analysis of covariance. RESULTS: Renal subcapsular tumor growth in the group having gasless laparoscopy was less than that in the group having CO2 pneumoperitoneum (P=.04). Postoperative weight loss in these groups showed no differences (P=.55). No differences in tumor growth or weight loss were found between rats having insufflation with CO2 and those having insufflation with air (P=.61 and P=.68, respectively). CONCLUSIONS: The restoration of body weight after a laparoscopic surgical procedure was similar with CO2, air, or gasless laparoscopy. Gasless laparoscopy was associated with less renal subcapsular tumor growth than was insufflation with CO2. Therefore, the application of gasless techniques in laparoscopic oncologic surgical treatment demands further study.     

Chimeric human epidermal reconstructs to study the role of melanocytes and keratinocytes in pigmentation and photoprotection

OBJECTIVE: To compare the ability of peripheral blood monocytes (PBM) and peritoneal macrophages (PM) to mediate the in vitro cytolysis of endometrial cells from eutopic and ectopic endometrium in women with endometriosis. DESIGN: Prospective study of immune function. SETTING: Institute for the Study and Treatment of Endometriosis and university-based research laboratories. PATIENT(S): Twenty-four women with endometriosis (15 in stage I/II, 9 in stage III/IV) and 4 patients treated with GnRH agonists. INTERVENTION(S): Peritoneal fluid and peripheral blood were sampled and eutopic and ectopic endometrium were biopsied during diagnostic laparoscopy. MAIN OUTCOME MEASURE(S): Lysis of autologous endometrial cells. RESULT(S): Peripheral blood monocytes were significantly more cytolytic than peritoneal macrophages against autologous uterine endometrial cells. However, PBM and PM displayed a similar degree of cytolysis against a hepatoma cell line. Ectopic endometrial cells were significantly more resistant to cytolysis by autologous PBMC than were matched eutopic endometrial cells, and were completely resistant to cytolysis by autologous PM. CONCLUSION(S): The reduced capacity of PM from women with endometriosis to mediate the destruction of endometrial cells coupled with the increased resistance of ectopic endometrial cells to macrophage-mediated cytolysis may facilitate the survival of these cells within the peritoneal cavity of women with endometriosis.     

Growth of transplanted tumours in mice treated with macrophages and their products

The antitumour activity of peritoneal macrophages, added to tumour inocula (Winn test), was determined. Macrophages harvested from mice immunised with tumour, or from tumour-bearing mice, suppressed or inhibited tumour growth when in direct contact with tumour cells. Incubation of macrophages exhibiting antitumour activity with tumour cells yielded supernatant fluids capable of interfering with tumour growth. Consistent induction of antitumor activity required either addition of indomethacin to the incubation mixture, or collection of macrophages from immunised or tumour-bearing donors that had ingested indomethacin in the drinking water. Tumour growth was significantly inhibited when tumour inocula were suspended in supernatant fluid, or when mice were given several subcutaneous injections of supernatant prior to tumour transplantation.     

Laparotomy and laparoscopy differentially accelerate experimental flank tumour growth

BACKGROUND: Surgery depresses host tumoricidal activity and may increase tumour growth. This study compared the effects of laparoscopy with laparotomy on extraperitoneal tumour growth and immune function in a murine model. METHODS: C57BL/6 female mice aged 8-10 weeks had tumours induced in the right flank (n=45) and were randomized to undergo halothane anaesthesia only, laparoscopy or laparotomy. Flank tumour volume was assessed over 10 days. A second group of animals (n=540) were randomized to undergo the same procedures and killed at 24, 48 and 96 h. Splenocytes were harvested for natural killer (NK) cell and lymphokine activated killer (LAK) cell cytotoxicity studies. RESULTS: There was a significant increase in flank tumour growth in the first 48 h after laparotomy and laparoscopy compared with controls (P < 0.01). By 96 h the difference was only significant in the laparotomy group (P< 0.01). Both NK and LAK cell cytotoxicities were suppressed significantly (P < or = 0.03) from 24 h up to 96 h following laparotomy compared with control and laparoscopy groups. There was also a significant suppression in the laparoscopy group compared with controls in the first 48 h after operation (P < or = 0.02). CONCLUSION: Extraperitoneal tumour growth was significantly accelerated after laparotomy and correlated with significantly suppressed NK and LAK cytotoxicity for at least 4 days after operation. Laparoscopy had a shorter, less profound effect on tumour growth and immune function.     

Clinical considerations and therapeutic options in papillomatosis of common bile duct. Clinical case

Gunshot wounds of the abdomen are associated with a 90% or greater incidence of intra-abdominal injury, prompting many trauma centers to routinely explore these patients via laparotomy. Increasingly, diagnostic laparoscopy has been used to evaluated the abdomen to exclude peritoneal violation by the missile. Retrospective analysis of the experience at a Level I Trauma Center with 20 isolated abdominal gunshot wound patients who did not have obvious indications for laparotomy such as peritonitis or shock is detailed. Outcome and cost analysis were compared in patients who had diagnostic laparoscopy or laparotomy. Patients who underwent diagnostic laparoscopy instead of laparotomy had a 42% reduction in operative time, a 33% reduction in hospital charges, and a reduction in hospital length of stay from an average of 3.5 days to less than one day. The only operative complication noted was in a patient who underwent laparotomy. Diagnostic laparoscopy may be used in select patients to exclude significant intra-abdominal injuries following gunshot wounds of the abdomen with reduction in health care costs and morbidity.     

A method of determining peritoneal penetration in gunshot wounds to the abdomen

BACKGROUND: It has previously been shown that 98% of gunshot wounds that penetrate the peritoneal cavity cause injuries that require surgical repair. Many gunshot wounds in the vicinity of the abdomen (GSWA) may actually be tangential and not penetrate the peritoneal cavity at all. Patients with such wounds may not require laparotomy. It is important to determine which patients with a potential tangential GSWA actually have penetration of the peritoneal cavity to minimize negative laparotomies. This study was undertaken to determine the sensitivity, specificity, and accuracy of diagnostic peritoneal lavage (DPL) in the determination of peritoneal penetration for patients who sustain GSWA. METHODS: DPL was performed for all patients who had sustained a GSWA in whom peritoneal penetration was unclear, i.e., patients whose GSWA appeared to be tangential, thoracoabdominal, or transpelvic and for whom a clear indication for laparotomy (shock, peritonitis, etc.) did not exist. Our threshold for a positive DPL was 10,000 red blood cells (RBC)/mm3. A prospective data base was kept with information on the location of the wound, DPL result, findings at laparotomy, and outcome. RESULTS: During a 4-year period, 429 consecutive DPLs were performed for GSWA at our urban Level I trauma center. One hundred fifty DPLs were positive, with more than 10,000 RBC/mm3. Six of these patients were found to have no peritoneal penetration at laparotomy (false-positive). The remaining 144 patients with positive DPLs were found to have operative injuries (true-positive). Of the 279 patients with DPL counts less than 10,000 RBC/mm3, 2 developed indications for laparotomy and were found to have intraperitoneal injuries (false-negative). The remaining 277 patients had no peritoneal injuries (true-negative). This was demonstrated either by laparotomy done for another indication (n = 7) or by uneventful inpatient observation for 24 hours (n = 270). The sensitivity, specificity, and accuracy of DPL in determining peritoneal penetration in GSWA is therefore 99, 98, and 98%, respectively. CONCLUSION: For patients who sustain GSWA for whom peritoneal penetration is unclear, DPL is a sensitive, specific, and accurate test to determine the need for laparotomy. It remains our test of choice when confronted with these patients.     

Abdominal stab wounds: evaluation of sinography

This paper reviews a 30-month experience with 172 patients suffering abdominal stab wounds treated at the Denver General Hospital, during a period when policy included liberal sinography and all penetrating injuries were explored. Laparotomy was performed in 87%. Of the 65 patients undergoing sinography, 62% indicated peritoneal penetration; of these, 30% had no visceral injury. An additional 10%, with minor intraperitoneal injuries, probably would not have required celiotomy. In 25 cases the stab penetrated the peritoneal cavity after first entering the chest. Peritoneal tap and peritoneal lavage were used in 10 patients. It is concluded that the cost/benefit ratio of sinography is so poor that it is rarely indicated. When doubt exists as to significant intraperitoneal pathology following an abdominal stab wound, close observation without sinography is recommended for determining indication for laparotomy.     

In vitro suppression of macrophage spreading caused by supernatants of tumour, thymus, and lymph node cells

Peritoneal macrophages washed out from C3Hf/Bu mice were cultivated in medium 199 supplemented with 35% foetal calf serum. If the pH of the medium was adjusted to 7.2, there were 70% spread macrophages after six hours of incubation at 37 degrees C. We investigated the effect of tumour cells on macrophage spreading. Supernatants from cell cultures of a fibro-sarcoma of C57BL mice and lymphoma of C3Hf/Bu mice were used to determine the number of spread macrophages after 6 hours of culture in these supernatants. Supernatants from cell cultures of the kidney, thymus and lymph nodes of normal C57BL or C3Hf/Bu mice and peritoneal cells of normal C3Hf/Bu mice in medium 199 alone served as control. We observed that supernatants from both allogeneic and syngeneic tumour cell cultures reduced significantly the percentage of spread macrophages in comparison with the percentage of spread macrophages found in the kidney culture supernatants. However, a similar spreading inhibition was caused also by supernatants from the thymus and lymph node cell cultures. In these experiments we confirmed the earlier observations that tumour cells can suppress the activation of macrophages, and we also pointed to the possibility that this effect is not specific only for malignant tissues.     

Presence of the nematode Physaloptera sibirica Petrow and Gorbunow 1931, parasite of carnivores, in the lerot Eliomys quercinus L. in the Alps

Radiolabelled sarcoma cells injected into the tail veins of normal rats were held up almost exclusively in the lung, and were not observed to pass through into the systemic circulation. Intramuscularly injected tumour cells were retained at the site of injection. Radioactivity was lost from both sites though more rapidly from the lung than from muscular tissue and was probably the result of tumour-cell death. Alveolar macrophages did not take part in the destruction of tumour cells in the lung. There was an increased rate of radiolabel loss from the lungs of hyperimmune, post-excision and tumour-bearing rats, as compared with normal rats. The destruction was immunologically specific; it was detected earlier, was more comprehensive in the hyperimmune and post-excision animals than in tumour-bearing animals, and correlated with the ability of the hyperimmune and post-excision animals to reject larger numbers of intravenous unlabelled tumour cells, than the tumour-bearing rats.     

Function of peritoneal exudate cells after abdominal surgery

Peritoneal macrophages and polymorphonuclear neutrophils are key cells in the repair of postoperative injury. Increased numbers of macrophages migrate into the peritoneal cavity after operation and the function of these cells changes over the postoperative interval. Macrophage activities, such as respiratory burst, arachidonic acid metabolism, monokine secretion, and plasminogen activator inhibitory activity, are elevated by peritoneal operation. However, the secretion of plasminogen activator activity is decreased after operation. The kinetics with which each of these functions changes varies with the parameter examined, indicating a complex regulation of the differentiation of leukocytes after operation. In addition, the activity of postoperative macrophages can be modulated in vitro by exposure to cytokines and conditioned media from polymorphonuclear neutrophils and macrophages. Thus, cell-cell interactions and factors secreted within the peritoneal cavity may regulate the contribution of postoperative leukocytes to peritoneal repair after operation.     

Alveolar bone loss and restorative dentistry in the primary molars

Stab wounds to the abdomen can present a diagnostic dilemma to the trauma surgeon, especially in the thoracoabdominal region. Patients with lower chest and upper abdominal stab wounds are at risk for both intraabdominal and cardiac injury. Current options in the evaluation of these patients include mandatory laparotomy, diagnostic peritoneal lavage, thoracoscopy, sonography, and observation. Each has its own inherent advantages and disadvantages, but none of them represents the gold standard. Herein is reported a case of a patient with an epigastric stab wound who underwent diagnostic laparoscopy and laparoscopic transdiaphragmatic pericardial window to rule out both peritoneal penetration and cardiac injury.     

Tumor cell seeding caused by hysteroscopy?

154 patients suffering from endometrial carcinoma who underwent CO2-hysteroscopy pretherapeutically, were examined as to whether hysteroscopy lead to tumour cell spread to the peritoneal cavity and worsened the prognosis of the patients. For that purpose, both fallopian tubes of 118 women were investigated thoroughly by histology for intratubarian spread of tumourous cells. Only in one of the 118 patients a single tumour cell complex was detected inside the ampullar part of a fallopian tube. Comparing the investigated patients with data from the literature in terms of five-year survival rates and frequency of relapses, our collective showed the same outcome as those from the literature. These results prove, that the prognosis of endometrial carcinoma is not worsened by CO2-hysteroscopy.     

Inhibitory effects of candesartan on responses to angiotensin peptides in the hindquarters vascular bed of the cat

Lactobacillus casei strain Shirota (LcS) has been shown to have potent anti-tumour and anti-metastatic effects on transplantable tumour cells and to suppress chemically-induced carcinogenesis in rodents. In particular, intrapleural (i.pl.) administration of LcS into tumour-bearing mice has been shown to effectively inhibit the growth of tumour cells in the thoracic cavity and to significantly prolong survival time. Also, i.pl. administration of LcS has been shown to induce the production of several cytokines, such as IFN-gamma, IL-1beta and TNF-alpha, in the thoracic cavity of mice, resulting in the inhibition of tumour growth and increased survival. On the other hand, oral administration of LcS has been shown to inhibit the growth of implantable tumour cells in rodents, and to restore the decreased mitogenic response of tumour-bearing mice. Administration of LcS has also been shown to inhibit chemically-induced bladder cancer in rodents. These findings suggest that treatment with LcS has the potential to ameliorate or prevent a variety of diseases through modulation of the host's immune system, specifically cellular immune responses.     

Role of activated macrophages in augmentation of endotoxin hepatotoxicity

In this study, to clarify the role of activated macrophages in the augmentation of endotoxin hepatoxicity, rats were pretreated with zymosan, an activator of macrophages, before the induction of endotoxin hepatotoxicity, and some were given pentoxifylline, an inhibitor of tumour necrosis factor production. The intravenous injection of zymosan induced many granulomas composed of macrophages in the lungs and the liver, while the intraperitoneal injection caused granulomas in the greater omentum. Endotoxin hepatotoxicity. as shown by focal and random hepatocellular coagulative necrosis and elevation of serum transaminase activities, was more intense in the rats pretreated with zymosan than in those which were not injected with zymosan. This augmented endotoxin hepatotoxicity was significantly inhibited by pentoxifylline treatment. These findings indicate that endotoxin hepatotoxicity may be augmented in the presence of activated macrophages which produce chemical mediators, particularly tumour necrosis factor.     

Body temperature variations during laparoscopic cholecystectomies

OBJECTIVE: To study changes over time in body temperature related to insufflation of CO2. PATIENTS AND METHOD: Fifty patients were randomly assigned to 2 groups of 25 to undergo cholecystectomy by either laparoscopy or laparotomy. Total intravenous anesthesia with propofol, pancuronium and fentanyl was used in both groups. Ventilation was maintained at 0.5 FiO2. Central temperature was continuously measured by a distal esophageal thermometer and results were recorded every 10 minutes in both groups. All operations lasted approximately 80 min. RESULTS: We found that temperature gradually decreased over time in both groups. In the laparotomy group the decrease reached 0.20 degree C (SD 0.03) at 80 min. During laparoscopy the temperature decrease was 0.43 degree C (SD 0.04) for the same time period. The differences were statistically significant. We observed no pathophysiologic repercussions associated with these results. CONCLUSIONS: Laparoscopic surgery, even when the abdominal cavity is not exposed to room air, induces a loss of temperature that is greater than that of laparotomy, because of insufflation of CO2 at 4 degrees C. The decrease was 0.4 degree C for every 50 l of CO2 insufflated during the study.     

Interferon-gamma (IFN-gamma) and interleukin-6 (IL-6) in peritoneal fluid and macrophage-conditioned media of women with endometriosis

PROBLEM: The presence of the various cytokines in human peritoneal fluid has been incompletely evaluated. Changes in cytokine levels may be related to activation of peritoneal macrophages, development of endometriosis, and infertility. This study assesses peritoneal fluid levels of interferon gamma (IFN-gamma) and interleukin-6 (IL-6), and peritoneal macrophage production of IL-6, in women with and without endometriosis. METHOD: Peritoneal fluid was obtained from 62 women at the time of diagnostic or operative laparoscopic surgery for benign gynecologic disease. Peritoneal macrophages were isolated, cultured for 24 h, and the culture media collected. IFN-gamma and IL-6 levels in peritoneal fluid samples and macrophage conditioned media were determined by commercial ELISA. RESULTS: IL-6 was significantly higher in the macrophage conditioned media of women with endometriosis as compared with controls. IL-6 levels were fourfold higher in early stage endometriosis (P < 0.05) and eightfold higher in advanced endometriosis. There were no significant differences between groups in the peritoneal fluid levels of IL-6 or IFN-gamma. CONCLUSIONS: Peritoneal macrophage IL-6 secretion is increased in women with endometriosis, and appears to correlate with disease stage. IFN-gamma does not appear to be responsible for the activation of macrophages in women with endometriosis.     

Clinical evaluation of 0.5% ferric hyaluronate adhesion prevention gel for the reduction of adhesions following peritoneal cavity surgery: open-label pilot study

The objective of this study was to assess the safety and to make a preliminary assessment of the efficacy of 0.5% ferric hyaluronate adhesion prevention gel in reducing adhesions in patients undergoing peritoneal cavity surgery by laparotomy, with a planned 'second-look' laparoscopy. The study was a randomized, open-label, placebo-controlled, parallel-group design in patients desirous of fertility at the Women's and Children's Hospital, Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, California. Female patients aged 24 to 41 years received 300 ml 0.5% ferric hyaluronate adhesion prevention gel or lactated Ringer's solution as an intraperitoneal instillate at the completion of the laparotomy procedure. At second-look laparoscopy 4-12 weeks after the laparotomy, the presence of adhesions was evaluated. Haematology and serum chemistry were determined throughout the study interval. All patients tolerated the procedures well and did not manifest any serious adverse events. At second-look laparoscopy, patients treated with 0.5% ferric hyaluronate adhesion prevention gel had significantly fewer adhesions than control patients. When adhesions did form, they were significantly less extensive and less severe in patients who received 0.5% ferric hyaluronate adhesion prevention gel. In conclusion, 0.5% ferric hyaluronate adhesion prevention gel was safe and highly efficacious in the reduction of the number, severity and extent of adhesions throughout the entire abdomen following peritoneal cavity surgery.     

Laparoscopy in high-risk cardiac patients

Fifteen patients with severe cardiac disease (American Society of Anesthesiologists III or IV) underwent laparoscopy using radial artery and pulmonary artery catheters to determine intraoperative hemodynamic changes. Cardiac output (CO), mean arterial blood pressure (MAP), central venous pressure, heart rate, systemic vascular resistance (SVR) and mixed venous oxygen saturation (SVO2) were recorded before anesthetic induction, after induction, but before peritoneal insufflation, after insufflation and after release of pneumoperitoneum. Peritoneal insufflation led to significant elevations in MAP and SVR and reduction in CO. For seven patients, a decrease in SVO2 after peritoneal insufflation was predictive of significant worsening of hemodynamic parameters, suggesting inadequate cardiac reserve. In all patients, hemodynamic parameters returned toward baseline once pneumoperitoneum was released. There were no perioperative cardiac complications. While it is evident that laparoscopy presents serious hemodynamic stress, it can be performed safely in high-risk patients, using aggressive intraoperative monitoring.     

Murine peritoneal macrophages activated by the mycobacterial 65-kilodalton heat shock protein express enhanced microbicidal activity in vitro

After an intraperitoneal (i.p.) injection of purified protein derivative, peritoneal macrophages from mice infected with Mycobacterium bovis bacillus Calmette-Guérin (BCG) show an enhanced respiratory burst, inhibit the intracellular proliferation of Toxoplasma gondii, and kill Listeria monocytogenes more efficiently than peritoneal macrophages from normal mice. One of the immunodominant antigens of Mycobacterium spp. is the 65-kDa heat shock protein (Hsp 65), and in the present study, we determined whether injection of this protein into mice leads to activation of their peritoneal macrophages. After an i.p. injection of Hsp 65, peritoneal macrophages from BCG-infected CBA/J mice also released more H2O2, inhibited the proliferation of T. gondii, and killed L. monocytogenes faster than peritoneal macrophages from normal mice, although Hsp 65 was less effective than purified protein derivative. When normal mice were injected with Hsp 65 suspended in saline after a booster injection with Hsp 65, their macrophages did not display enhanced antimicrobial activity, indicating that an adjuvant was required for a cellular immune response against Hsp 65. In the present study, the adjuvant dimethyl dioctadecylammonium bromide (DDA) was preferred because it contains no endotoxin or mycobacterial antigens and because it has been reported that DDA does not induce the production of gamma interferon. Peritoneal macrophages from C57BL/6 and CBA/J mice that had received a subcutaneous injection of Hsp 65 suspended in DDA followed by an i.p. booster injection of Hsp 65 suspended in saline were activated, as indicated by the enhanced production of H2O2, inhibition of the intracellular proliferation of T. gondii, and increased rate of intracellular killing of L. monocytogenes in vitro relative to that by resident peritoneal macrophages and peritoneal macrophages obtained from mice that had received ovalbumin instead of Hsp 65. The rate of phagocytosis of L. monocytogenes was not affected by Hsp 65 treatment. Despite the in vitro expression of enhanced microbicidal activity of peritoneal macrophages, no difference in the growth of L. monocytogenes in the liver and spleen between Hsp 65-treated and control mice was found.