Intraperitoneal Dissemination Research Articles

Biochemical Characterization of Primary Peritoneal Carcinoma Cell Adhesion, Migration, and Proteinase Activity

Primary papillary serous carcinoma of the peritoneum (PPC) is clinically and histologically similar to advanced stage epithelial ovarian carcinoma. PPC classically presents with widespread intraperitoneal dissemination, superficial invasion, and minimal ovarian involvement. Surgical cytoreduction and combination chemotherapy utilized for patients with epithelial ovarian carcinoma have produced varying results for patients with PPC. These differences in response may be secondary to the stage of disease or due to biological differences in metastatic behavior between these carcinomas. In this study, short-term primary cultures of PPC and epithelial ovarian carcinoma (OVCA) were compared to enable biochemical comparison with respect to components of the metastatic cascade including adhesion, migration, and proteinase activity. These data demonstrated similar properties in adhesive profiles of PPC and OVCA, with preferential adhesion to type I collagen and vitronectin. Matrix-degrading proteinases including matrix metalloproteinases (MMP)-2, MMP-9, and urinary-type plasminogen activator were produced by both cell types. PPC migration was stimulated by multiple extracellular matrix proteins, whereas OVCA cells demonstrated maximal migration on type I collagen coated surfaces. Together our data suggest biochemical similarities between PPC and OVCA with respect to individual components of the metastatic cascade.

Intraperitoneal Dissemination Probably Caused by Needle Biopsy of Alveolar Echinococcosis of the Liver: Experimental Study

Alveolar echinococcosis of the liver (AEL) is a parasitosis with a potential for malignant tumor-like behavior. The disease is diagnosed by a combination of serologic tests, diagnostic images, and the histology of needle biopsy specimens. It remains unresolved whether the biopsy induces subsequent troubles. We designed this study to investigate critical problems after needle biopsy of AEL lesions using an experimental model. Five samples were prepared from the resected lesions of AEL patients: (A) 10% suspension of trypsin digests of the minced lesion; (B) 10% suspension of mesh-filtered sediment of the minced lesion; (C) 10% sediment suspension after washing the nonminced lesion; (D) supernatant after centrifuging intracystic fluid; (E) 10% sediment suspension after centrifuging intracystic fluid. A 1-ml aliquot of each sample was injected intraperitoneally into jirds (gerbils) or cotton rats, respectively. The animals were sacrificed 12 weeks later, and intraperitoneal metacestodes were observed. All samples except D developed metacestodes, and their histologies were all lesions of typical alveolar echinococcosis. These results suggest that a needle biopsy may cause intraperitoneal dissemination or tracial implantation of the parasites along the track of the needle.

A rat model of non-lethal bacterial infection.

The purpose of the study was to develop a small animal model of intraperitoneal infection without mortality and with a catabolic response to the infection, viz., to mimic the clinical situation in man. Intraperitoneal infection was induced in female Wistar rats by deposition of a gelatin capsule containing a mixture of Escherichia coli and Bacteroides fragilis and adjuvant substances. Seven groups of animals were infected with different bacterial inocula (0.2-4.3 x 10(6) CFU) to establish reproducible and dose-dependent changes in mortality, body weight in relation to food intake, blood cultures, peripheral blood leukocyte counts, and abscess formation on autopsy. No mortality was observed in animals with an inoculum below 2.2 x 10(6) CFU in spite of positive blood cultures. Initial weight loss was followed by weight gain in all animals except the group infected with the low inoculum (0.2 x 10(6) CFU). This group had no mortality, was in a catabolic state for three days, indicated by weight loss in spite of nearly normal food intake, and the infectious state was supported by intraperitoneal dissemination of small abscesses. The low-grade character of the infection was reflected by changes in peripheral blood lymphocyte and neutrophil granulocyte concentrations. In conclusion, this study presents a small animal model with a reproducible dose response to the bacterial challenge, allowing prolonged studies of metabolic changes following infection.

ＤＩＶＥＭＡ‐ＡＤＭ結合体によるマクロファージおよびＮＫ細胞の抗腫よう活性の増強

Divinyl ether and maleic anhydride (DIVEMA) is a synthetic polyanion known to stimulate antitumor activity in macrophages (Mφ) and natural killer cells (NK). This compound is used as a carrier of anticancer drugs because of its efficient covalent binding and release of anti-cancer drugs. Recently, the conjugate of DIVEMA with adriamycin (ADM) was reported to have higher tumor control activity in mice-bearing intraperitoneal dissemination of fibrosarcoma (FSaI) cells than either DIVEMA or ADM alone. We here report on the effects of intraperitoneal (ip) injection of this conjugate on the cytotoxicity of peritoneal Mφ and splenic NK against FSaI cells. The conjugate clearly enhanced Mφ cyotoxicity, the maximum cytotoxicity being obsereved 7 days after ip. This cytotxicity enhancement was similar to the activation by DIVEMA, but it was stronger than that by ADM alone. On the other hand no activation of splenic NK by administration of either the conjugate or ADM was observed, despite remarkable NK activation by DIVEMA. These findings indicate that a part of the immunostimulatory activity of DIVEMA remains in the conjugate when DIVEMA is used as a carrier for ADM. Consequently the data also suggest that the antitumor effects of the conjugate resulted from combined effects of the host-mediated activity and the direct cytotoxicity of ADM itself.

Evidence for preferential adhesion of ovarian epithelial carcinoma cells to type I collagen mediated by the alpha2beta1 integrin.

Epithelial ovarian carcinoma, the leading cause of gynecologic cancer death, is characterized by widespread intra-abdominal metastases mediated primarily by surface shedding of tumor cells and peritoneal implantation. Whereas hematogenous metastasis is known to involve cellular adhesion, extracellular matrix proteolysis and cell migration, the role of these processes in the intraperitoneal dissemination of ovarian cancer remains unclear. To analyze further the role of adhesion and proteolysis in ovarian carcinoma dissemination, we have characterized the adhesive profiles of 4 primary cultures of ovarian carcinoma cells and 5 ovarian carcinoma cell lines. Our data demonstrate preferential adhesion of ovarian carcinoma cells to interstitial type I collagen. Analysis of adhesion molecule expression demonstrated the presence of the alpha2 and beta1 integrin subunits by cell surface ELISA, immunoprecipitation and immunohistochemistry. Furthermore, antibodies directed against the alpha2 and beta1 subunits inhibited adhesion of ovarian carcinoma cells to type I collagen by 56% and 95%, respectively. Plasminogen activator and matrix metalloproteinase production by adherent cells was not altered as a consequence of adhesion to individual extracellular matrix proteins; however, adhesion to an extracellular matrix comprised primarily of interstitial collagen increased plasminogen activator activity in 5 of 5 cell lines. Since the ovarian carcinoma micro-environment is rich in type I collagen, our data suggest that preferential adhesion to type I collagen followed by secretion of serine and metalloproteinases may represent a biochemical mechanism by which the intraperitoneal dissemination of ovarian carcinoma is mediated.

Observations concerning cancer spread within the peritoneal cavity and concepts supporting an ordered pathophysiology.

This chapter considered the observations that concern the spread of cancer emboli within the abdominal cavity. These collected observations begin to construct a pathophysiology that allows one to predict some important aspects of disease progression. The factors that should be considered are enumerated in Table 4. Taken together, these factors support an ordered phenomenon whose complete understanding will help design new and more effective treatment strategies.

Pathobiology of peritoneal carcinomatosis from ovarian malignancy.

A detailed analysis of the patterns of treatment failure of ovarian malignancy may lead to a more comprehensive understanding of the natural history of the disease. A hypothesis was generated that suggests treatment failure was caused by ovarian cancer persistence and by reimplantation of tumor emboli trapped within surgically traumatized tissues. Nine ovarian cancer patients who had previously undergone standard surgical removal of the primary cancer were prospectively studied at a reoperative procedure. The operative findings at the time of primary cancer surgery and reoperative surgery were scored for the presence of tumor in 9 abdominopelvic regions and 17 abdominopelvic sites. These data were then statistically analyzed. In 7 of the 9 patients ovarian cancer recurrence was associated with an increased intraperitoneal dissemination of tumor. A mean of 3.1 regions were involved at the time of the initial surgery and 5.3 were involved at reoperation. The regions most consistently involved were those in close proximity to the primary cancer. The anatomic sites that showed a preponderance of recurrence were the rectosigmoid colon, cul-de-sac of Douglas, left paracolic gutter, vagina, and abdominal incision. Traumatized sites always showed more cancer recurrence than nontraumatized sites. The vaginal cuff and abdominal incision, sites free of cancer after hysterectomy but at high risk for tumor cell entrapment, were disproportionately common sites for cancer found at reoperation. This study shows that in this reoperative setting ovarian cancer recurrence is most common in the pelvis and the left lower part of the abdomen. The cul-de-sac of Douglas and the rectosigmoid colon are anatomic sites at extreme risk for disease progression. These are sites in which ovarian cancer implants not removed by routine hysterectomy and bilateral salpingo-oophorectomy will persist. Also, sites traumatized by surgery were disproportionately involved by cancer at reoperation. These data may be interpreted to suggest that anatomic sites with cancer persistence and with cancer implantation induced by surgical trauma are the most common sites for ovarian cancer recurrence in this select group of patients.

Abdominal wall metastasis and peritoneal carcinomatosis after laparoscopic assisted colectomy for colon cancer

We report a case of a port-site recurrence with diffuse peritoneal carcinomatosis after laparoscopic-assisted right hemicolectomy. The interval between resection of the colonic adenocarcinoma and diagnosis of the recurrence was short (1 month), suggesting that intraperitoneal dissemination and tumour implantation on surgical wounds may represent the principal mechanism of recurrence after laparoscopic surgery. Review of the literature shows an alarming increase in the occurrence of this devastating complication. Although beneficial to the patient in the immediate post-operative period, the adequacy of laparoscopic-assisted colectomy in tumour is increasingly under question.

Significance of peritoneal cytology in patients with potentially resectable adenocarcinoma of the pancreatic head

Recurrence in the peritoneum occurs in up to 50% of patients after a potentially curative pancreaticoduodenectomy. Previous authors have implicated preoperative fine-needle aspiration (FNA) as a cause of intraperitoneal tumor dissemination, although prior studies of peritoneal cytology findings have largely involved patients with locally advanced disease. A consecutive series of patients referred to our institution between 1991 and 1993 with suspected or biopsy-proven adenocarcinoma of the pancreatic head was studied prospectively. All patients fulfilled criteria for resectability as assessed by computed tomography: no metastatic disease, no encasement of the superior mesenteric or hepatic arteries, and a patent superior mesenteric-portal venous confluence. Peritoneal washings were obtained at the time of staging laparoscopy and/or at subsequent laparotomy. Data regarding peritoneal cytology results, previous FNA, preoperative chemoradiation, eventual resection, pattern of disease recurrence, and survival were collected. A total of 80 peritoneal washings from 60 consecutive patients were prospectively examined. Forty-nine (82%) of 60 patients underwent FNA before peritoneal washings were obtained. A total of four patients (7%) had positive peritoneal cytology findings: three (6%) of 49 who underwent prior FNA and one (9%) of 11 with no prior FNA. Similarly, no differences in eventual peritoneal failure or short-term survival were observed for patients who underwent prior FNA compared with patients who did not. All four patients with positive peritoneal cytology findings had metastatic disease (liver, three; peritoneum, one) at a median of 4.8 months after diagnosis; three of the four died of disease at a median of 8 months. Positive peritoneal cytology findings are rare in patients with radiologically resectable adenocarcinoma of the pancreas. When found, positive peritoneal washings are an indicator of advanced disease characterized by unresectability, early metastasis, and short survival. Computed tomographic-guided FNA does not appear to increase the risk for positive peritoneal washings and represents a valid approach to the pretreatment diagnosis of patients with suspected pancreatic malignancy.

Patient selection and treatment of peritoneal carcinomatosis from colorectal and appendiceal cancer.

Colorectal cancer is a disease process that disseminates through lymphatic channels, through hematogenous routes, and by invasion through the bowel wall. These mechanisms result in lymph node metastases, liver metastases, and peritoneal seeding. Although lymphatic and venous dissemination requires an invasive local process, peritoneal seeding may occur with both high grade and low grade malignancies. Cancer dissemination that causes liver and lymphatic metastases occurs prior to surgical resection of the primary colorectal cancer. Peritoneal seeding and seeding of the resection site (local recurrence) may also occur as a result of the surgical trauma that accompanies resection of the primary lesion. Leakage of malignant cells from transected lymphatic channels may be the mechanism of this intraoperative intraperitoneal cancer dissemination. To limit the progression of peritoneal seeding and to treat large volume, low grade intraabdominal tumor deposits, combinations of cytoreductive surgery and intraperitoneal chemotherapy have been successfully employed. Selection factors that correlate with long-term benefit are (1) low grade of malignancy, (2) lack of lymph node or liver metastases, and (3) treatment of low volume disease. For patients with moderate or high grade colorectal cancer, only a low volume of disease can be treated successfully. For patients with low grade cancer, peritonectomy procedures are used to achieve minimal residual disease before initiating the intraperitoneal chemotherapy. In properly selected patients, peritoneal carcinomatosis from colorectal and appendiceal cancer is a treatable condition that may result in long-term disease-free survival.

Disseminierte intraperitoneale Trophoblast-Aussaat nach laparoskopisch behandelter Extrauteringravidität

We report on the atypical course of a 31-year old primigravida, who underwent conservative treatment for a tubal pregnancy. After confirmation of the diagnosis by means of laparoscopy, a linear salpingotomy and removal of the products of gestation were performed through the laparoscope. Routine measurements of the serum HCG levels postoperatively showed, after a short period of decreasing HCG levels, a new rapid increase of HCG values. At relaparoscopy, evidence for an intraperitoneal dissemination of trophoblastic tissue was found and confirmed by histology. After treatment with 20 mg methotrexate q.i.d. per os for 5 days, HCG levels returned to normal within a short time. Apart from a minor degree of an aphthosal stomatitis, the patient did not experience any major side effects from the treatment.

Laparoscopic Observation of Hepatocellular Carcinoma with an Unusual Growth Pattern —Four Case Reports—

Abstract: Usually a laparoscopy is performed for many cases of hepatocellular carcinoma (HCC), but HCC with an unusual growth pattern is not encountered frequently. In this study we report on four cases of HCC which show an unusual growth pattern, who were found out of 96 cases of HCC examined by laparoscopy at our clinic. The first case of HCC considered occurred in a 72–year–old male with intraperitoneal dissemination; the second case, was discovered in a 71–year–old female, and had extrahepatic growth; the third case, in a 56–year–old male, ruptured spontaneously and produced an encapsulated hematoma; the fourth case, present in a 64–year–old male, also ruptured spontaneously. The clinico–pathological and laparoscopic features of HCC with an unusual growth pattern are discussed, placing emphasis on the value of laparoscopy in the diagnosis of HCC with an unusual growth pattern.

A CASE OF MALIGNANT OMENTAL MESOTHELIOM WITH PULMONARY ASBESTOSIS

Malignant peritoneal mesotheliomas lack in clinical manifestations, are difficult to be diagnosed preoperatively, and have no effective treatments with poor prognosis. Etiologically malignant mesotheliomas are often associated with asbestos exposure, however, peritoneal ones are rarely caused by as bestos exposure and only 18 cases have been reported in Japan.The case is a 45-year-old male carpenter who had the past history of exposure to asbestos from 1961 to 1965. The patient had been in good health until 1988, when he first noticed abdominal distention. On admission, abdominal CT scan revealed ascites and a soft tissue density mass just beneath the abdominal wall. The diagnosis of malignant mesothelioma was made as a result of cytological examination of ascites. When laparotomy was performed, a malignant mesothelioma araising in the omentum with multiple intraperitoneal dissemination was found. Though chemotherapy, irradiation, and steroid the rapy were given, he died 4 months after his admission. At autopsy, numerous asbestos bodies were found in the alveolar spaces, and also interstitial fibrosis and pleural thicknings were found, which led to a diagnosis of pulmonary asbestosis. From around 1960 a use of a large quantity of asbestos was started, and in a relation to fact a possible increase in the occurrence of malignant tumors due to asbestos exposure can be inferred. Health care including the abdomen as well as chest is necessary for those experienced asbestos exposure throughout all their lives.

Occult, high-risk endometrial cancer

In a series of 173 consecutive patients with endometrial cancer treated by a fixed protocol 62 tumors (36%) appear “estrogen independent,” i.e., there is no history of estrogen ingestion and no recognized risk factors such as obesity or diabetes mellitus. A high proportion of these tumors are of advanced stage and grade. Prognosis is poorer and mortality higher than for “estrogen-dependent” tumors. Twenty-two tumors were truly occult (no spontaneous vaginal bleeding). Factors which identify this high-risk group are described and the reasons for delay in diagnosis discussed. Spread by intraperitoneal dissemination is considered a major factor in the poorer prognosis. Cytology of peritoneal washings is a useful diagnostic and prognostic aid. An estrogen provocation test is suggested as a means of earlier recognition which could reduce mortality in this group.

Dissemination of carcinoma: Unusual complication of percutaneous nephrostomy

Percutaneous nephrostomy is a safe and highly effective means of urinary diversion. We report a case of unusual complications: severe peritonitis and massive intraperitoneal dissemination of carcinoma.

Two-and-One-Half-Year Survival of Patient With Ruptured Wilms' Tumor

To the Editor.— Rupture of a Wilms' tumor with intraperitoneal dissemination of tumor cel's rarely occurs. Of the few reported cases, all died either from the acute episode or soon afterwards from widespread metastases. 1,2 We recently observed such a case in which there was prolonged survival. Report of a Case.— A 5-year-old white boy was admitted to the Nassau County Medical Center because of severe abdominal pain. On the day prior to admission, after playing football with his father, he started to have continuous pain on the right side of his abdomen which became progressively worse. When examined he showed exquisite tenderness to abdominal palpation and percussion. There was boardlike rigidity, and obvious rebound tenderness. Bowel sounds were decreased and results of rectal examination were normal. The hemoglobin level was 10.4 gm/100 ml, hematocrit value was 33%, and white blood cell count was 17.700/cu mm, with 89% neutrophils, 5%