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Laparoscopic port-site metastasis of an early stage adenocarcinoma of the cervix with negative lymph nodes.

BACKGROUND: Port-site metastasis (PSM) following laparoscopic surgery for cancer is being increasingly recognized as a potential problem; the majority of cases appear following laparoscopy for a pelvic mass that subsequently proved to be malignant or in the case of a disseminated intraperitoneal disease. The rare cases of PSM following laparoscopy for endometrial and cervical cancer have all been associated with the presence of regional lymph node metastasis or disseminated disease in the peritoneal cavity. We present here a case report of PSM in the absence of spread beyond the primary tumor. CASE: A 48-year-old woman with stage IA1 adenocarcinoma of the cervix was treated with laparoscopically assisted vaginal hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic node dissection. The pathologic study revealed an endocervical adenocarcinoma confined to the cervix with negative lymph nodes. Nine months postoperatively, a cutaneous metastasis at the port-site was diagnosed. This was treated with wide local excision of the recurrence and the port-site track. Explorative laparotomy and para-aortic node sampling showed no evidence of recurrence elsewhere. CONCLUSION: This case emphasizes the risk for PSM in laparoscopic surgery performed for early stage disease.

Adenocarcinoma↗

Laparoscopic port-site recurrence following surgery for a stage IB squamous cell carcinoma of the cervix with negative lymph nodes.

BACKGROUND: Port-site metastases are commonly reported after laparoscopic surgery for ovarian cancer, but have also been reported in patients with cervical or endometrial cancer with positive lymph nodes. Recently, a case of port-site recurrence after laparoscopic surgery for a patient with node-negative early-stage adenocarcinoma of the cervix was reported. We report the first case of port-site metastasis in a patient with stage IB squamous cell carcinoma of the cervix with negative lymph nodes. CASE: A 31-year-old woman had a laparoscopy for pelvic pain. Under anesthesia, she was noted to have a grossly abnormal-looking cervix and a biopsy revealed squamous cell carcinoma. She was referred to a gynecological oncologist and underwent radical hysterectomy and pelvic lymph node dissection through a transverse lower abdominal incision 6 weeks later. Nineteen months postoperatively, she presented with a soft tissue mass in a suprapubic laparoscopic trocar site. CONCLUSION: It is postulated that cells dislodged at the time of cervical manipulation and biopsy may have passed through the fallopian tubes and implanted in the laparoscopic port site due to the "chimney effect" caused by the pneumoperitoneum.

Abdominal Neoplasms↗

Are endometrial carcinoma cells disseminated at hysteroscopy functionally viable?

OBJECTIVE: The aim of this study was to evaluate the rate of transtubal dissemination of endometrial carcinoma cells by hysteroscopy and the functional viability of disseminated tumor cells by assessing cell adhesion in an in vitro model. METHODS: We studied 24 uteri obtained at TAH+BSO in patients with endometrial carcinoma. Further inclusion criteria were negative peritoneal cytology, no involvement of the uterine serosa or extrauterine disease, and endometrial surface involvement >1 cm in diameter. In vitro fluid hysteroscopy was performed with a 5-mm single-flow rigid hysteroscope. A maximum of 150 ml saline was infused at a maximum pressure of 100 mm Hg for a maximum of 3 min. Fluid running off through the tubes was collected. The cell suspension was enriched by a density gradient centrifugation. The isolated cells had a mean viability of 90% as judged by trypan blue exclusion. Viable cells (5 x 10(4) per 2-cm(2) polyvinyl chloride well plate) were cultured with equal parts of Dulbecco's modified Eagle's minimal essential medium and Ham's F-12 for 24 h. The endpoint of the analysis was the adherence of tumor cells to the polyvinyl chloride well plate, which was taken as a proxy for functional cell viability. Cytological evaluation was performed separately by two cytologists blinded to the source and date of the smears. RESULTS: Transtubal fluid dissemination was seen in 20 of 24 (83%) uteri. Tumor cells were found in 17 specimens (71%). In 10 (42%) specimens the disseminated tumor cells were functionally viable. CONCLUSIONS: Our model suggests that hysteroscopy can cause dissemination of malignant cells into the abdominal cavity from uteri containing endometrial carcinoma and that these cells can be functionally viable and adhere to a matrix.

Adenocarcinoma↗

Peritoneal implantation of squamous cell carcinoma following rupture of a dermoid cyst during laparoscopic removal.

BACKGROUND: In recent years, there has been a move toward using laparoscopy in the management of presumed benign ovarian masses. This paper discusses the use of laparoscopy for ovarian masses (particularly dermoid cysts). The focus is on the implications for unexpected malignancies. CASE: We report here a case involving a dermoid cyst that was removed at laparoscopy and was subsequently found to contain a squamous cell carcinoma. Spillage of the cyst's contents occurred at the time of removal. At staging laparotomy, peritoneal implants of the tumor were found, upgrading the tumor from FIGO stage Ia to IIc. CONCLUSION: Spillage rates of dermoid cyst content with laparoscopic removal are inevitably higher than with excision at laparotomy. It remains controversial whether upstaging from FIGO stage Ia to IIc affects prognosis; however, in this case it led to aggressive adjuvant therapy which imposed significant additional morbidity, including loss of fertility, on the patient. One should be aware of the possibility of unexpected malignancy when the decision to manage an ovarian mass laparoscopically is made.

Adult↗

Extraneural metastases in ependymoma.

Ependymomas, glial neoplasms usually arising in the posterior fossa or spinal cord, rarely metastasize outside the central nervous system. We have reviewed all 81 ependymomas evaluated at MSKCC between 1956-1989. Five (6.2%) had extraneural metastases (ENM). The primary tumor was in spinal cord in 3 patients and the cerebral hemisphere in 2. Two tumors were histologically anaplastic; 3 were histologically benign. The 5 patients were 3, 3, 3.5, 16 and 37 years old. Time from initial diagnosis to development of ENM was 0, 15, 35, 40, and 288 months. At the time of ENM the primary tumor was progressing in 4/5 patients. Prior therapy had included resection plus radiation therapy (RT) (1), RT plus chemotherapy (1), resection plus RT plus chemotherapy (2). One patient had not received prior therapy because ENM were present at diagnosis. The sites of ENM included lung and thoracic lymph nodes (2), pleura and peritoneum (2), and liver (1). Both patients with peritoneal ENM had had ventriculoperitoneal shunts. ENM did not correlate with histologic grade, age, or degree of surgical resection. When patients with ependymoma develop signs or symptoms of systemic disease such as abdominal pain, cough, or adenopathy, ENM should be considered.

Adolescent↗

[Tumor cell dissemination in bone marrow and peritoneal cavity. An immunocytochemical study of patients with stomach or colorectal carcinoma].

The tumor spread and the radicality of surgical resection are the most important facts in a patient's prognosis. In spite of curative tumor resection many patients die from metastases or local tumor recurrence. One possible reason is early dissemination of tumor cells which cannot be detected with clinical methods of examination. For this reason the aim of our study was to examine both bone marrow and peritoneal lavage for disseminated tumor cells with an immunocytochemical technique in patients with a gastrointestinal carcinoma. We also wanted to find out whether there was any correlation between the incidence of tumor cell detection and the TNM classification, staging and tumor grading and whether disseminated tumor cells have any prognostic significance. Our study included 54 patients who underwent surgery in our clinic for a carcinoma of the stomach (20 patients) or the colorectum (34 patients) from November 1993 to December 1994. At the beginning of the operation bone marrow had been taken from the iliac spine, and the abdomen was irrigated with 1000 ml saline solution immediately after laparotomy or laparoscopy. After cell separation with Ficoll density centrifugation 5 x 10(5) cells were applied per slide by a cytospin technique. For detection of the tumor cells we used the APAAP technique and the following monoclonal antibodies: KL1, CK2, anti-CEA, 17-1A (bone marrow) and Ber-EP4, B72.3, anti-CEA and 17-1A (peritoneal lavage). Altogether 77% of all patients had tumor cells in the bone marrow and 69% in peritoneal lavage fluid. It was possible to detect tumor cells in bone marrow (67%) and peritoneal lavage fluid (25%) even of patients with T1 tumors. The percentage increased with depth of wall infiltration. There was a marked difference in bone marrow aspirates between patients with lymph-node-negative tumors (N0) and those with lymph-node-positive tumors (N+): 65% had tumor cells in N0 and 85% in N+ stages. This trend was also seen in patients with (M1) and without (M0) metastases, in both bone marrow aspirates and peritoneal lavage fluid. In bone marrow there was a good correlation of tumor cells with staging, but in peritoneal lavage fluid this was not so. Finally, we detected tumor cells more often in bone marrow and peritoneal lavage fluid of patients with poorly differentiated tumors (G3) or diffuse Lauren type than in patients with moderately differentiated tumors (G2) or intestinal Lauren type. After a median follow-up period of 12.5 months patients with disseminated tumor cells had a lower survival rate than patients without tumor cells.

Adult↗

The influence of intramedullary nailing upon the development of metastases in the treatment of an impending pathological fracture: an experimental study.

An experimental model has been developed in which the effects of a pathological fracture and intramedullary nailing on metastatic spread have been investigated. The endpoint used was the production of lung metastases in rats inoculated intracortically with a rhabdomyosarcoma. We have found that a pathological fracture markedly increases the incidence of lung metastases and that intramedullary nailing, by decreasing the incidence of fractures, decreases the incidence of lung metastases. The surgical procedure itself does not increase the incidence significantly. It is concluded that in metastatic disease prophylactic nailing of an impending pathological fracture is the treatment of choice.

Animals↗

Abdominal wall recurrence after laparoscopic-assisted colectomy for adenocarcinoma of the colon. Report of a case.

PURPOSE: To report an unusual mode of colorectal carcinoma recurrence after laparoscopic-assisted right hemicolectomy. METHODS: Retrospective case review. RESULTS: Laparoscopic-assisted colectomy has been shown in a variety of settings to be safe and technically feasible. The question of its efficacy in treating colorectal carcinoma remains uncertain. We report a case of a 71-year-old male who presented with a trocar site abdominal wall recurrence 10 months after a laparoscopic-assisted right hemicolectomy. To our knowledge, this represents the first such reported case in the literature. CONCLUSION: Questions surrounding the efficacy of laparoscopic colectomy in eradicating colorectal carcinoma support the need for rigorous prospective study of this new technique.

Abdominal Muscles↗

Impact of pneumoperitoneum on trocar site implantation of colon cancer in hamster model.

BACKGROUND: Numerous anecdotal reports have documented the spread of colon cancer to trocar sites after laparoscopic-assisted colectomy. We hypothesized that the pneumoperitoneum of laparoscopy potentiated tumor adherence to trocar sites. PURPOSE: This study was designed to determine the effect of CO2 pneumoperitoneum on the rate of tumor implantation at trocar sites. METHODS: Viable GW-39 human colon cancer cells were injected into the abdominal cavity of hamsters (2 x 10(6) cells/hamster). A midline laparotomy, insertion of four 5-mm trocars, injection of viable cells into the mesentery of the cecum, and free peritoneal cavity was performed in two groups: one control group (41) who did not receive a pneumoperitoneum and a comparison group (50) who underwent pneumoperitoneum for ten minutes at an insufflation pressure of 10 mmHg. Animals were killed at six weeks, and hematoxylin and eosin-stained sections of trocar wounds, midline wound, small intestine, cecum, liver, and lung were examined by a veterinary pathologist, who was blinded to operation. RESULTS: Pneumoperitoneum increased tumor implantation in the cecal mesentery and the midline incision (P < 0.05) but did not effect recurrence in the liver, lung, or jejunum. Trocar site implantation tripled with the addition of pneumoperitoneum increased implantation of pneumoperitoneum (26 vs. 75 percent) (P < 0.0001). CONCLUSION: Pneumoperitoneum increased implantation of free intra-abdominal cancer cells at wound sites on the abdominal wall or within the abdominal cavity in this animal model. The use of pneumoperitoneum during laparoscopy in patients with colon cancer should only be performed in a protocol setting to evaluate the effect of pneumoperitoneum on the treatment of cancer.

Animals↗

Intraoperative spillage of tumor cells in surgery for rectal cancer.

Inadvertent perforation or incision into rectal carcinoma during surgery may lead to massive dissemination of tumor cells in the operative area. It was observed in 8.7 percent of 1360 radical resections for cure. In time, the incidence could be reduced from 11.0 to 5.2 percent. Intraoperative spillage of tumor cells influences the incidence of local recurrence. In the last period (1982 to 1985) in cases of spillage of tumor cells, local recurrence was seen in 39 percent as opposed to 12.9 percent in perforation or incision of the tumor. Intraoperative tumor-cell spillage has a negative effect on survival rates, reducing the relative five-year survival rate after resection for cure from 70 to 44 percent. It should be recorded in the surgical and pathologic reports and considered in the analysis of treatment results and in selection of patients for adjuvant radiotherapy.

Humans↗

Possible effect of pneumoperitoneum on the spreading of colon cancer tumor cells.

PURPOSE: By using a murine hepatic metastatic model, we tried to investigate the possible influence of gas insufflation in colon cancer cells spreading from the portal system to the liver. METHODS: After transducing the human placental ALP gene into murine colon cancer cell line CT26, we successfully selected a clone of CT26/DAP that would yield a specific color following histochemical staining. Fifty mice were assigned into two groups, receiving either an intrasplenic injection of 10(6) CT26/DAP cells alone or the cells followed by intra-abdominal helium insufflation with the pressure of 15 cm H2O for ten minutes. Five mice in each group were used to observe their survival and the other mice were killed at four different time periods: 10 minutes, 24 hours, 48 hours, and 72 hours following cell injection. The livers and spleens were removed for histochemical staining. By counting the numbers of specific dark reddish spots of CT26/DAP cells, we could estimate the number of tumor cells on the hepatic surface. RESULTS: At the very beginning following tumor cell injection, we found a significantly greater number of tumor cells on the hepatic surface in mice with gas insufflation (6354 +/- 1072 vs. 2133 +/- 223, respectively; P = 0.012). But the difference of these two groups became smaller and smaller as time went by. The number of tumor cells on the hepatic surface would reach the lowest level at postoperative 48 hours, and the tumor foci then began to grow both in size and number. The above patterns of dynamic change in tumor cell distribution were similar in mice both with and without gas insufflation. Average survival was slightly shorter in mice with gas insufflation, but the difference was not statistically significant. CONCLUSION: Pneumoperitoneum caused by gas insufflation may increase tumor cell spread from the portal system to the liver at the very beginning stage; however, there was no significant difference in long-term survival between mice with and without gas insufflation in this murine animal model.

Adenocarcinoma↗

Sodium hyaluronate carboxymethylcellulose-based bioresorbable membrane (Seprafilm)--does it affect tumor implantation at abdominal wound sites?

PURPOSE: This study examines the effects of a sodium hyaluronate-based bioresorbable membrane (Seprafilm) on tumor implantation at surgical wound and laparoscopic trocar sites. METHODS: GW-39, an established human colon cancer line carried in immunocompetent golden Syrian hamsters was used as the experimental model. Under general anesthesia, a 2-cm midline incision was made to allow placement of four 5-mm abdominal trocars. Hamsters were then randomly assigned to preSeprafilm, postSeprafilm, and control (no Seprafilm) groups. In the preSeprafilm group 0.5 ml of a 5 percent (vol/vol) suspension of the GW-39 tumor cells (approximately 1.675 x 10(6) cells) was injected into the abdomen of each hamster via midline incision. Trocars were removed, the wounds were closed, and 1 cm2 of Seprafilm was placed on the peritoneal surface of each trocar site. In the postSeprafilm group the membrane was placed at each site before injection of tumor cells. The control group did not receive Seprafilm. The animals were killed after seven weeks, and the abdominal wound sites were excised. Sites without gross tumor underwent histologic evaluation. RESULTS: One hundred thirty-two animals were randomly assigned to the three groups. The preSeprafilm group had an 87 percent tumor implantation rate. The postSeprafilm group had a 90 percent tumor implantation rate. The control group had an 88 percent tumor implantation rate. Chi squared analysis demonstrated that these total tumor implant rates and mean tumor mass were similar at all wound sites and between groups. No toxicity was observed in any of the experimental groups. CONCLUSIONS: Sodium hyaluronate-based bioresorbable membrane (Seprafilm) does not influence GW-39 human colon cancer implantation at abdominal wound sites in this hamster model.

Abdomen↗

Influence of cytotoxic agents on intraperitoneal tumor implantation after laparoscopy.

PURPOSE: Recent experimental studies suggest that laparoscopic surgery for abdominal malignancy may be associated with increased tumor implantation. This study investigated the influence of cytotoxic agents (administered intraperitoneally or intramuscularly) on implantation of a tumor cell suspension after laparoscopic surgery in an experimental model. METHODS: Thirty-three Dark Agouti rats underwent laparoscopy with CO2 insufflation and instillation of a tumor cell suspension into the abdominal cavity. Rats were randomly allocated to one of the following study groups (9 rats in the control group, 6 rats in all other groups): 1) control (no intraperitoneal instillation); 2) intraperitoneal normal saline (0.9 percent); 3) intraperitoneal povidone-iodine (Betadine to normal saline 1:10 dilution); 4) intraperitoneal methotrexate (2 doses of 0.125 mg/kg body weight in normal saline administered 24 hours apart); 5) intramuscular injection of 2 doses of 0.125 mg/kg body weight administered 24 hours apart (no intraperitoneal agent). Rats were killed 7 days after the procedure, and the peritoneal cavity and port sites were examined for the presence of tumor. RESULTS: A significant reduction in tumor implantation and port-site metastases was observed in all treatment groups (povidone-iodine and intramuscular and intraperitoneal methotrexate). CONCLUSIONS: This study suggests that tumor implantation after laparoscopic surgery and port-site metastases might be prevented by the intraperitoneal or systemic administration of cytotoxic agents. Further studies are needed to determine whether these findings can be applied to clinical practice.

Animals↗

Laparoscopic surgery for the cure of colorectal cancer: results of a German five-center study.

PURPOSE: The aim of this study was to assess the feasibility and safety of laparoscopic surgery for the cure of colorectal cancer with emphasis on oncologic follow-up in particular. METHODS: A study was performed of patients with colorectal cancer treated by laparoscopy in five German centers between May 1991 and September 1997. Surgical and pathologic data were recorded in an anonymous registry database and analyzed by type of resection. Standard procedures were sigmoid or left colectomy, anterior resection, abdominoperineal resection, and right hemicolectomy. Follow-up information included incidence of local, distant, and port site recurrence and cancer-related death. RESULTS: A total of 399 patients (212 females) with a mean age of 66.6 years underwent laparoscopic curative resections (sigmoid resection, 89; left colectomy, 11; anterior resection, 157; abdominoperineal resection, 102; right hemicolectomy, 40). Conversion was necessary in 6.3 percent (n = 25). Complications requiring reoperation occurred in 9 percent (n = 35). Complications that were treated conservatively occurred in 27.6 percent (n = 110). Thirty-day mortality was 1.8 percent (n = 7). First bowel movements resumed on the third postoperative day; patients did not use analgesics after a mean of five days. Mean postoperative hospitalization was two weeks. According to International Union Against Cancer classification, 147 patients had Stage I cancer, 35 had Stage II cancer, and 217 underwent curative resection for Stage III cancer. Mean number of lymph nodes resected was 12.1. At a mean follow-up of 30 months, one port site recurrence was documented. No local recurrence was observed after curative resection of Stage I colorectal cancer. Of 399 patients, local recurrence occurred in 6 patients (Stage II, 2; Stage III, 4), and distant metastases were documented in 25 patients (Stage I, 3; Stage II, 3; Stage III, 19). The highest incidence of cancer-related death occurred after abdominoperineal resection (4.9 percent). CONCLUSION: To assess the role of laparoscopic colorectal surgery for the cure of cancer objectively, prospective randomized trials are necessary.

Abdomen↗

Model of implantation of tumor cells simulating recurrence in colonic anastomosis in mice.

PURPOSE: Local recurrence after colorectal cancer surgery is usually perianastomotic. An experiment was designed to investigate whether free intraluminal cells can penetrate through a colonic anastomosis and thereby cause local recurrence. METHODS: BALB/c and C57/BL mice underwent ascending colotomy followed by watertight anastomosis. Thereafter, CT-26 murine colon carcinoma cells were injected into the cecal lumen 2 cm proximal to the anastomosis of syngeneic BALB/c mice, whereas B-16 murine melanoma cells were injected in the same fashion into C57/BL mice. Control animals without anastomosis received similar injections. Animals were killed 24 hours, 72 hours, and 30 days after surgery and were checked for tumorigenesis. RESULTS: Results of peritoneal fluid cytology were negative after 24 hours, whereas after 72 hours cancer cells were identified in the peritoneal fluid of 80 percent of mice with colotomy and anastomosis compared with 20 percent of control mice. Thirty days after surgery, 11.1 percent of the control BALB/c mice developed pericecal tumor growth, similar to the overall rate of murine melanoma in C57/BL. In mice with anastomoses, perianastomotic tumor growth was observed in 47.5 percent of BALB/c mice (P < 0.001) and was correlated with the number of injected cells. Tumor growth reached approximately 75 percent tumor take with high cell densities, whereas in C57/BL mice no difference was found between the experimental and control groups. CONCLUSIONS: The findings suggest that free intraluminal cancer cells of colonic origin may penetrate through watertight anastomoses and implant on the anastomotic or peritoneal surface and initiate tumor growth. This anastomotic penetration is cell-mass dependent. The reported experimental model is simple, reproducible, and advantageous for studies of colonic anastomosis.

Adenocarcinoma↗

Effects of pneumoperitoneum on tumor implantation with decreasing tumor inoculum.

INTRODUCTION: The aim of this study was to determine the effect of pneumoperitoneum on the rate of trocar-site implantation with decreasing inoculum of cancer cells. METHODS: A total of 0.5 ml of GW-39 human colon cancer cell suspensions at 1 percent (approximately 3.2 x 10(5) cells) and at 0.5 percent (approximately 1.6 x 10(5) cells; v/v) were injected into the abdomen of hamsters through a midline incision. Animals in each group were randomized to receive either pneumoperitoneum (1 percent = 33; 0.5 percent = 43) or not (1 percent = 32; 0.5 percent = 39). Gross and microscopic tumor implants were documented seven weeks later at four trocar sites. RESULTS: In the 1 percent group, pneumoperitoneum significantly increased trocar-site tumor implants from 50 to 71 percent (P < 0.001). Pneumoperitoneum also resulted in the following: 1) more frequent involvement of all four concurrent sites (38 vs. 10 percent; P < 0.02); 2) more frequent palpable tumors (13 vs. 5 percent; P < 0.01); 3) larger tumor mass (2.1 +/- 0.6 g vs. 0.2 +/- 0.1 g; P < 0.02). In the 0.5 percent group, pneumoperitoneum did not significantly increase trocar-site tumor implants, and it did not result in a larger tumor mass. The percent increase in trocar-site implants owing to pneumoperitoneum was influenced by the amount of tumor inoculum (21 percent in the 1 percent group; 10 percent in the 0.5 percent group). The mass of palpable tumor implants after pneumoperitoneum decreased with decreased inoculum: 1 percent = 2.1 +/- 0.6 g; 0.5 percent = 0.3 +/- 0.1 g (P < 0.0001). CONCLUSIONS: Pneumoperitoneum significantly increased both tumor implantation rate and mass when approximately 3.2 x 10(5) colon cancer cells were injected into the peritoneal cavity. These effects of pneumoperitoneum diminished with one-half as many tumor cells injected in the peritoneal cavity.

Animals↗