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Intraperitoneal exfoliated cancer cells in patients with colorectal cancer.

PURPOSE: The aims of this study were to evaluate potential predictors of exfoliated free cancer cells in the peritoneal cavity and to assess intraoperative peritoneal lavage cytology as a prognostic indicator in patients with colorectal cancer. METHODS: From 1985 to 1987, intraoperative peritoneal lavage cytology was performed in 140 patients with colorectal cancer. Among them, 88 patients underwent curative resection and 52 patients had noncurative surgery. Cytology was examined twice, i.e., immediately after opening the peritoneal cavity (precytology) and just before closing the abdomen (postcytology). One hundred milliliters of saline was poured into the peritoneal cavity and it was retrieved by suction after irrigation. Cytologic examination was performed after staining with Papanicolaou, Giemsa, periodic acid-Schiff, and Alcian blue stains. RESULTS: Among the 140 patients examined, the incidence of positive cytology in the prelavage was 15 percent, and that in the postlavage was 9 percent, although it was 16 percent in either lavage. Among patients with curative resection, 10 percent had positive cytology. Seven characteristics were identified as features of tumors which are prone to exfoliate cells into the peritoneal cavity: 1) macroscopic peritoneal dissemination, 2) liver metastasis, 3) more than 20 ml of ascites, 4) ulcerated tumors without definite borders, 5) invasion of the serosal surface or beyond, 6) semiannular or annular shape, and 7) moderate or marked lymphatic invasion. In patients undergoing curative surgery, among these features, circumferential involvement was the only one correlated closely with positive cytology (P < 0.02). Positive cytology was associated with a worse outcome. In patients who were resected curatively, the postcytology had a stronger influence on local recurrence than the precytology; the local recurrence rate in patients with positive postcytology was higher than in those with negative postcytology, regardless of the precytology. All patients with cancer cells in the peritoneal cavity at the end of surgery had recurrence. CONCLUSIONS: Seven characteristics were identified as risk factors for exfoliation of cancer cells into the peritoneal cavity in patients with colorectal cancer. These findings may be helpful for the choice of laparoscopic surgery in this era of increasing port-site metastases after laparoscopic procedure. The results of peritoneal lavage cytology at the end of surgery were correlated with the long-term postoperative outcome of colorectal cancer. Thus, meticulous follow-up and possibly adjuvant chemotherapy may be beneficial for patients with free cancer cells in lavage fluid, even after curative surgery.

Adult↗

Resection of peritoneal implantation from hepatocellular carcinoma.

BACKGROUND: Peritoneal implantation is a rare presentation of hepatocellular carcinoma (HCC). This article presents the clinical features and surgical outcomes of 16 patients with HCC in whom isolated peritoneal implantation from HCC was found and who underwent surgical resection. METHODS: From 1988 to 2000, 16 patients with HCC after hepatic resection who underwent resection of peritoneal implantation of HCC were retrospectively reviewed. RESULTS: Four hundred sixty-five of 749 patients (62.1%) had recurrence of HCC after hepatic resection. Sixteen (3.4%) developed isolated peritoneal implantation and underwent resection. During the detection of the peritoneal implantation, the alfa fetoprotein level was increased in 13 of these 16 patients. Five of 15 patients had a peritoneal mass discovered by ultrasonography, and 14 of 15 patients had a mass discovered by computed tomography. The follow-up period ranged from 2.1 to 81.6 months (median, 16 months). The median disease-free and overall survivals of the 16 patients were 7.89 and 15.98 months, respectively. CONCLUSIONS: Peritoneal implantation occurs infrequently in posthepatectomy patients. Increased alfa fetoprotein values after hepatic resection should suggest recurrence of HCC. Computed tomography is superior to ultrasonography in detection of peritoneal implantation from HCC. Surgical resection of peritoneal implantation from HCC might prolong survival in selected patients.

Adolescent↗

Port site metastasis after diagnostic laparoscopy for upper gastrointestinal tract malignancies: an uncommon entity.

BACKGROUND: The role of laparoscopy for diagnosing, staging, and treating intra-abdominal malignancies is increasing. This study was designed to examine the incidence of port site metastasis and open incision site metastasis for upper gastrointestinal tract (GI) malignancies. METHODS: From a prospective database maintained by the Department of Surgery, patients undergoing laparoscopy for upper GI malignancies were identified. Clinical outcomes and recurrences were noted. RESULTS: Between January 1993 and January 2001, 1965 laparoscopic procedures were identified. After those patients lost to follow-up were excluded, 1650 procedures were performed in 1548 patients. Port site implantation for all laparoscopies occurred in 13 (.79%) of 1650, with a median time to recurrence of 8.2 months. After laparotomy, open incision site recurrence occurred in 9 (.86%) of 1040 (not significant). Among the patients resected, there were 5 (.60%) of 830 port site recurrences and 7 (.84%) of 830 open incision site recurrences. At the time of diagnosis of recurrence, all of the patients with port site and five of seven with open site implantation had distant or local disease, or both, as well. CONCLUSIONS: Port site implantation after diagnostic laparoscopy for upper GI malignancy is uncommon, does not seem to be different from open incision site recurrence, and occurs in the setting of advanced disease. Therefore, the risk of port site recurrence cannot be used as an argument against laparoscopy in upper GI malignancy.

Adolescent↗

Tumor cells adhere to intraperitoneal injection sites.

Tumor cells injected intraperitoneally form cell plaques at injection sites in the abdominal wall of mice within a few minutes. Tumor cells appear to be transported passively and chemotactic factors are not involved. Dihydrocortisol blocks cell adherence and silica particles , assumed to destroy macrophages, abolish cell plaque formation.

Animals↗

The facilitation of peritoneal dissemination of a tumor by laparotomy in a rabbit model.

The effects of conventional laparotomy and laparoscopic surgery on the peritoneal dissemination of VX2 tumors were evaluated in a rabbit model. Either 5 x 10(3) or 5 x 10(4) of VX2 tumor cells were inoculated into the peritoneal cavities of rabbits which were divided into three groups according to the procedure performed, namely, a conventional laparotomy group (group 1), a laparoscopy group (group 2), and a control group (group 3). All the animals were killed 2 weeks after the treatment to examine the spread of the VX2 tumor in the omentum. In the experiment in which 5 x 10(3) tumor cells were inoculated, no significant difference was found in the number of metastases among the three groups. Conversely, after inoculating 5 x 10(4) tumor cells, the mean numbers of metastatic colonies greater than 1 mm in diameter in the greater omentum were 14.4+/-4.7 in group 1, 9.9+/-2.4 in group 2, and 3.3+/-1.1 in group 3, with a significant difference between groups 1 and 3, and between groups 2 and 3, but not between groups 1 and 2. In conclusion, conventional laparotomy facilitated the greatest peritoneal dissemination of a VX2 tumor in this animal model when 5 x 10(4) tumor cells were inoculated. Furthermore, laparoscopic surgery influences tumor growth to almost the same degree as conventional laparotomy.

Animals↗

[Peritoneal instillation of taurolidine and heparin for preventing intraperitoneal tumor growth and trocar metastases in laparoscopic operations in the rat model].

BACKGROUND: Although port-site metastases occur after laparoscopic surgery, there is no generally accepted approach to prevent tumor implantation so far. METHODS: In order to prevent tumor metastases, the effect of taurolidine and heparin on the growth of colon adenocarcinoma DHD/K12/TRb was measured in vitro and in a rat model. After incubation of the cells with heparin, taurolidine or both substances, the cell kinetics were determined. In a second experiment, tumor cells were administered intraperitoneally in rats (n = 60) and pneumoperitoneum was established over 30 min. Rats were randomized into four groups (I: tumor cells; II: cells + heparin; III: cells + taurolidine; IV: cells + taurolidine + heparin). RESULTS: While tumor cell growth was not influenced by heparin in vitro, growth decreased significantly after incubation with taurolidine and taurolidine/heparin. In vivo, intraperitoneal tumor weight was lower in rats receiving heparin (298 +/- 155 mg) and taurolidine (149 +/- 247 mg) than in the control group (596 +/- 278 mg). When the two substance were combined, tumor growth was even less (21.5 +/- 36 mg). Trocar metastases were only lower in rats receiving taurolidine or the combination of taurolidine and heparin. CONCLUSION: In vivo, heparin inhibits intraperitoneal tumor growth only slightly, while taurolidine causes a significant decrease in tumor cell growth in vitro as well as intraperitoneal tumor growth and trocar metastases in vivo.

Adenocarcinoma↗

[Port metastases: fact or fiction?].

In the early 1990s, the first reports appeared indicating a disturbingly high incidence (20%) of port site metastases following laparoscopic procedures for visceral and gynecological malignancies. At the same time, animal experiments were performed to investigate the phenomenon of port site metastases. The results were independently and repeatedly verified by different groups. In view of these distressing facts, a controversial, at times emotional discussion arose that evolved at least in part without strict regard to the available data. In the recent past, reports on increased incidence of port site metastases after laparoscopic interventions have completely vanished from the literature. Figures on incidence reported by various authors range between 0.5% and 1.3% and thus are comparable to the rate for surgical wound metastases (0.8-1.6%) as known from open conventional methods. Prospective studies have even shown that the survival rate in comparison to conventional techniques is 20% better, at least for laparoscopically treated stage I-III colorectal carcinomas. At present the discussion on the phenomenon of port site metastases can be considered closed. Port site metastases are thus no longer a fact, but also not fiction, since this phenomenon does occur in a small percentage of patients after laparoscopy just as after open surgery.

Humans↗

Lower extremity compartmental anatomy: clinical relevance to radiologists.

A thorough understanding of compartmental anatomy is necessary for the radiologist participating in the care of a patient with a lower extremity musculoskeletal malignancy. Localization of tumor to compartment of origin and identification of extracompartmental spread preoperatively are needed to correctly stage a tumor and determine the appropriate surgical management. An understanding of the locations of fascial boundaries, extracompartmental tissues, and neurovascular structures of the thigh and lower leg facilitates this diagnostic process. For the radiologist planning to biopsy a suspicious musculoskeletal lesion, consultation with the referring orthopaedic surgeon is recommended in order to jointly select an appropriate percutaneous biopsy approach. Adequate preprocedural planning ensures selection of an approach which prevents iatrogenic tumor spread beyond the compartment of origin, protects neurovascular structures, and allows complete resection of the biopsy tract and scar at the time of surgical resection without jeopardizing a potential limb-sparing procedure. Cross-sectional anatomic review and case examples demonstrate the importance of a detailed understanding of compartmental anatomy when approaching the patient with a lower extremity musculoskeletal tumor.

Adult↗

Is rectal washout necessary in anterior resection for rectal cancer? A prospective clinical study.

BACKGROUND: Implantation of exfoliated malignant cells has been suggested as a possible mechanism of tumor recurrence in colorectal anastomoses that might be prevented by cytocidal washout. The aim of our study was to assess whether malignant cells are likely to be collected by a circular stapler introduced transanally to perform an anastomosis and to observe local recurrences during follow-up, with special attention to the washout status of patients. METHODS: Between May 1999 and March 2004, 96 patients with carcinoma of the rectum and distal sigmoid colon undergoing anterior resection under the care of three surgeons (only one of whom routinely performed rectal washout) were prospectively studied. While 38 patients had rectal washout with 5% povidone-iodine before anastomosis, 58 patients did not. A circular stapler was used for anastomosis, and the stapler was immediately rinsed in 100 ml of saline. The fluid was then classified as "acellular," "malignant cells identified," or "benign cells identified" by pathologists. RESULTS: Malignant cells were collected from the circular stapler after use in 3 patients (8%) on whom rectal washout was performed and in 2 (3%) patients who did not have rectal washout performed (P=0.631). Three patients (8%) in the washout group developed local recurrence, and 2 patients (3.4%) in the no-washout group had local recurrence (one was anastomotic recurrence) (P=0.338). The median follow-up time was 23 (range: 9-70) months. CONCLUSIONS: There were no differences in terms of the number of patients who had malignant cells collected from the circular stapler and local recurrence rates between the two groups. Although this is not a randomized study and size and mean follow-up time of the study were not sufficient, our results did not offer rational arguments in support of intraoperative rectal washout when a circular stapler is used after low anterior resection for carcinoma. Because of the limitations of our study, however, we are unable to arrive at a definite conclusion regarding rectal washout. There is a need for a randomized, controlled, large-scale, multicenter trial to establish the clinical relevance of intraoperative rectal washout.

Aged↗

Influence of gases on intraperitoneal immunity during laparoscopy in tumor-bearing rats.

Laparoscopy has been associated with metastases to abdominal wall wounds. In addition, many recent experimental studies suggest that laparoscopy is associated with increased tumor dissemination. It is possible that immune or metabolic disturbances due to the use of a pneumoperitoneum could contribute to this problem. To investigate this possibility, we studied the effect of two insufflation gases and gasless laparoscopy on in vivo peritoneal macrophage function and intraperitoneal pH in an experimental model. A carcinoma was implanted into the flank of 32 experimental rats that underwent laparoscopic surgery in one of four treatment groups: anesthesia alone, gasless laparoscopy, helium insufflation, and CO2 insufflation. Intraperitoneal pH was monitored during surgery, and peritoneal macrophage function was determined 3 days after surgery by harvesting peritoneal macrophages and then examining their ability to produce tumour necrosis factor-alpha (TNF-alpha). CO2 insufflation was associated with a consistent fall in intraperitoneal pH and a significant reduction in TNFalpha production. These findings did not occur in the other study groups. The results of this study demonstrate that CO2 insufflation results in depressed intraperitoneal macrophage activity. It is possible that it is mediated by pH changes. In addition, it could be a contributing factor to the development of port-site metastases. Further studies are needed to determine whether the factors identified act during clinical surgery.

Animals↗

Endoscopic surgery: fit for malignancy?

Neither experimental nor clinical data confirm the repeatedly published opinion that video-endoscopic surgery promotes tumor growth or the occurrence of implantation metastases in cancer patients. On the contrary, alterations due to pneumoperitoneum by the application of different gases, pressures, and temperatures might provide the basis for a new therapeutic approach to cancer surgery. Oncologically adequate resections defined by such terms as "no touch isolation" and "monobloc resection" can be performed video-endoscopically in a variety of intraabdominally or intrathoracically located cancers if a standardized technique is used. The benefit of video-endoscopic surgery is limited in large tumors, especially if they have reached the organ surface. There is still a major deficit in the clinical evaluation of video-endoscopic interventions in most oncologic diseases. Randomized studies comparing video-endoscopic and conventional surgery have been reported only for the resection of colorectal carcinoma. They show that laparoscopic resections can be performed with a minimum of postoperative complications to the same extent as conventional resections and offer several advantages during the early postoperative period. No reliable data from comparative trials are as yet available on the long-term results.

Endoscopy↗

No incidence of port-site recurrence after endosurgical procedure for pediatric malignancies.

Port-site recurrence (PSR) following laparoscopic procedures has been an unpredictable complication in adult cancer patients; however, no data exist about this phenomenon in the pediatric field. The aim of this study was to determine whether PSR, following endosurgical procedure for malignancies, is a typical complication or a rare event in the pediatric population. Eighty-one questionnaires were mailed to members of The Japanese Society of Pediatric Endosurgeons. They were asked to provide a list of their institutions that had experience with PSR after endosurgical procedures for pediatric malignancies. Among 29 institutions, a total of 129 endosurgical procedures for pediatric malignancies were reported; these included 85 laparoscopic and 44 thoracoscopic procedures, performed on 104 neuroblastomas, 8 hepatoblastomas, 7 nephroblastomas, and 10 other tumors. Of the 104 neuroblastomas, 83 were found by mass screening using high levels of urinary vanillylmandelic acid and homovanillic acid. Sixty-five of the 83 patients had their tumor excised, and 18 had their tumor biopsied by endosurgical procedures. Additionally, 47 of these patients did not require any postoperative chemotherapy. No incidence of PSR was reported in any of the patients that underwent endosurgical procedures. The PSR following endosurgical procedure is a rare phenomenon in the pediatric population. Both, laparoscopic and thoracoscopic procedures, are safe and recommended for treating pediatric malignancies, especially mass-screened neuroblastomas.

Child↗

Peritoneal closure reduces port site metastases: results of an experiment in a rat ovarian cancer model.

BACKGROUND: The arm of this study was to assess the role of peritoneal closure in the prevention of port site metastasis after carbon dioxide (CO2) CO2 pneumoperitoneum. METHODS: We developed a xenograft ovarian cancer model by intraperitoneal injection of 27 106 IGR-OV1 line cells in nude rats Seven days after the inoculation, the animals underwent a CO2 pneumoperitoneum. At the end of the procedure, port sites were randomly closed either with suture of peritoneum (n = 14, group A) or without suture of peritoneum (n = 12, group B). The rats were killed 7 days after surgery and their port site scars were resected. Tumor implantation was assessed by a pathologist who was blinded to the type of wound closure. RESULTS: The animals in group B were significantly more likely to have at least one port site metastasis frequent (seven of 12, or 58.3%) than those in group A (two of 14, or (14.3%) (p = 0.037). Port sites with metastases were seen more frequently in group B (eight of 24, or (33.3%) than in group A (three of 28, or 10.7%) (p = 0.046). CONCLUSIONS: Our results shows that peritoneum closure decreases the risk of port site metastasis.

Animals↗

Combined laparoscopic-assisted right hemicolectomy and low anterior resection for synchronous colorectal carcinomas.

BACKGROUND: Two cases of combined laparoscopic- assisted right hemicolectomy and low anterior resection for malignancy are presented to illustrate the technical aspects of performing two concurrent laparoscopic-assisted bowel resections with sequential anastomosis. Although there are similarities with laparoscopic-assisted total proctocolectomy, the need for complete mesenteric dissection in two areas, removal of two separate specimens containing malignancy, and the need for two anastomoses raise unique technical considerations which include port placement, sequence of dissection, choice of specimen extraction sites, specimen handling, and sites for extracorporeal anastomosis. METHODS: Operative notes, operative videotapes, and hospital inpatient and outpatient records were reviewed for both patients. RESULTS: Laparoscopic-assisted combined resection was completed in both patients. In both cases, laparoscopic total mesorectal excision was performed. Maximum incision length was 6 cm. Both patients were ready for discharge on postoperative day 3. CONCLUSION: Combined laparoscopic assisted right colectomy and low anterior resection can be performed for synchronous colorectal malignancies with curative intent.

Aged↗

Rapid flow carbon dioxide laparoscopy disperses cancer cells into the peritoneal cavity but not the port sites in a new rat model.

BACKGROUND: The role of carbon dioxide (CO2) in the pathogenesis of tumor recurrence after laparoscopy remains controversial. Using a new rat model, we studied the effect of different CO2 flow rates on the dispersal of free cancer cells. METHODS: A novel model of desufflation without trocar was developed, and 55 Fischer rats were randomized into three flow groups: group A (rapid, 0.67 l/min; n = 20), group B (slow, 0.44 l/min; n = 20), and group C (gasless, n = 15). We vented CO2 via a portless surgical valve that filtered cells. After the abdominal wall had been suspended to create space, half of the animals in each group (nonrecovery) received 7.5 x 10(6) immunolabeled rat colon cancer cells (RCC2) intraperitoneally, whereas the other half (recovery) received 7.5 x l0(6) viable RCC2 before insufflation or gasless laparoscopy. Nonrecovery animals were killed after 20 l of insufflation. Parietal peritoneal and port-site specimens were examined for RCC2 by fluorescence microscopy (FM) and flow cytometry (FC). The recovery animals were killed at 4 weeks for evidence of wound recurrence. RESULTS: Nine of 10 nonrecovery animals in A had RCC2 on FM or FC, as compared with 2 animals in each of the nonrecovery groups B and C (p = 0.018, Fisher's exact test). Two of the nine animals in group A also had RCC2 in their portless valves. Two recovery (A) animals developed wound recurrence as compared with none in the other groups (p = 0.315). CONCLUSION: In this model, rapid CO2 flow dispersed free cancer cells into the peritoneal cavity, but not into the port sites, thus supporting a role for CO2 in the intraperitoneal dispersal of free cancer cells, but not in wound recurrence.

Abdominal Neoplasms↗

Excision of laparoscopic port sites increases the likelihood of wound metastases in an experimental model.

BACKGROUND: Case reports of patients developing tumor metastases at port sites following laparoscopic surgery have prompted the development of preventive strategies to address this potential problem, including local excision of the port sites. While it has been suggested that this strategy could be used clinically, its efficacy has not been established. METHODS: Twenty four immune-competent Dark Agouti rats underwent laparoscopy and standardized intraperitoneal laceration of an implanted abdominal flank tumor, using an established laparoscopic cancer model. Rats were randomized to either control (n = 12) or wound excision (n = 12) groups. Both groups underwent laparoscopy using carbon dioxide (CO2) insufflation and two mini-laparoscopy ports. In the wound excision group, one of the port site wounds was excised following desufflation of the abdominal cavity. One week later, the port site wounds were excised for histological examination. RESULTS: Wound involvement with tumor was significantly more common following wound excision than with untreated control wounds (nine of 12 vs two of 12, p = 0.002). In the wound excision group, tumor metastases arose preferentially in the excised port site wound. CONCLUSION: This study suggests that excision of laparoscopy port site wounds following laparoscopic surgery for cancer does not prevent the subsequent development of port site tumors. Furthermore, the excision of port sites may actually increase the risk of tumor metastases arising in port sites, suggesting that the clinical application of this strategy should be avoided pending further evaluation.

Abdominal Neoplasms↗

Distribution of intrasplenically injected colon cancer cells following pneumoperitoneum in mice.

BACKGROUND: Few studies have examined tumor cell distribution following laparoscopic surgery for colorectal cancer. We examined the effect of carbon dioxide pneumoperitoneum on the distribution of intrasplenically injected colon cancer cells in mice. METHODS: Mice were intrasplenically injected with 2 x 10(4) colon 26 cells labeled with 111In-oxine and were randomized to undergo pneumoperitoneum at 10 mmHg for 30 min or to receive no treatment other than anesthesia. Radioactivity of the liver, lungs, and spleen was measured 30, 60, 90, or 150 min following tumor inoculation. RESULTS: The dynamic changes in the hepatic radioactivity were not similar between groups. However, the values were not significantly different at any time point. The radioactivity of lungs was extremely low in both groups throughout the experimental period. CONCLUSIONS: Pneumoperitoneum does not appear to cause the accumulation of intraportally spreading tumor cells in the liver, but it may affect the dynamic changes of tumor cells. Also, tumor cell localization in the lungs is negligible in both pneumoperitoneum and control groups.

Adenocarcinoma↗