Serum vascular endothelial growth factor concentrations and postsurgical outcome in dogs with osteosarcoma.

Vascular endothelial growth factor (VEGF) is a key angiogenic growth factor, playing putative roles in both tumour growth and metastasis. The purpose of this study was to correlate pretreatment serum concentrations of VEGF in dogs with osteosarcoma (OSA) with disease-free interval (DFI) and overall survival (OS). Additionally, the effect of serum from dogs with OSA on ex vivo canine endothelial cell (EC) growth was determined. Pretreatment platelet-corrected serum VEGF levels correlated significantly with DFI. No other examined variable predicted outcome. The ability of sera from dogs with OSA to stimulate canine EC proliferation did not correlate with VEGF concentration or outcome. These data support a role for VEGF in the development or progression of metastatic disease in dogs with OSA. The VEGF concentration in tested sera was not a major determinant of ex vivo canine EC proliferation in this study.

Oral immune tolerance to tumor specific antigens may confer growth advantage to esophageal and gastric cancers.

Oral administration of antigens induces antigen-specific systemic immune tolerance (Oral Tolerance). We postulate that the poorer prognosis of foregut cancers might, in part be explained by the systemic immune tolerizing effect of tumor specific antigens shed into and processed by the gut immune system thus conferring a growth advantage specific to individual cancers. Immunocompetent Balb/c mice were fed by gavage, either tumor tissue (JBS/CarB) in phosphate buffered saline (PBS) or PBS alone, daily for 14 days. On day 15 either subcutaneous tumors were induced or animals were immunized with cells in adjuvant. JBS tumors appeared earlier and grew faster in the JBS tumor fed mice than in either the PBS (P = 0.025) or CarB (P = 0.168) fed animals. The delayed type hypersensitivity response in tolerized mice was significantly abrogated (P < 0.01) compared to controls. These experiments demonstrate antigen specific oral immune tolerance for tumors, which is reflected in a faster growth rate and impaired delayed type hypersensitivity response. Similar mechanisms may be operational in human esophagogastric malignancy and may in part explain their poorer outcome.

Principles of oncologic abdominal surgery.

The principles of abdominal oncologic surgery parallel the general principles of all types of oncologic surgery with some variations peculiar to the abdomen. Due to the presence of multiple organ systems within the abdominal cavity, many types of cancer can develop. The surgeon must be prepared to perform several different abdominal procedures depending on the organ system involved and the extent of the cancer. The surgeon as oncologist must be aware of the tumor type, its expected behavior, and current treatment options. This article describes the principles of performing cancer surgery, including preparation for abdominal exploration, methods to facilitate tumor removal, and ways of avoiding tumor recurrence.

Innate resistance to Listeria monocytogenes in tumor-bearing mice.

We have previously described the isolation, cloning, and characterization of a tumorigenic murine fibrosarcoma, designated JBS. Growth of JBS tumors in syngeneic mice initiates an anti-tumor immune response that initially manifests as progressive splenic hyperplasia and an increased proliferative ability in cultured splenocytes. In animals with tumors progressing beyond the 2 cm stage there is a reduction in spleen size and a gradual decrease in splenocyte proliferative abilities, leading to anergy at heavy tumor burdens (>3.5 cm). During the phase of immune hyperresponsiveness in tumor-bearing mice clearance of Listeria monocytogenes by components of the innate immune system is increased. This heightened resistance to infection is most likely macrophage-mediated because these mice demonstrate an increased ability to recruit macrophages to the peritoneal cavity during Listeria infection. In addition, these macrophages are highly activated in vivo as evidenced by an elevated capacity to express class II MHC (Ia) molecules. This increase in macrophage activation status is coincident with an increased capacity of splenocytes from tumor-bearing mice to secrete IFN-gamma. In mice with much heavier tumor burdens (>3.5 cm), down-regulation of the immune response leads to a reduction in peritoneal macrophage numbers, decreased macrophage Ia expression, and diminished splenic clearance of L. monocytogenes. Our data demonstrate that activation of macrophages distal to the tumor site occurs as an initial consequence of tumor growth. It is only in mice with very heavy tumor burdens that functionality of macrophages is sufficiently suppressed to allow increased splenic growth of L. monocytogenes.

Laparoscopic appendicectomy--a successful operation in adults and children.

Laparoscopic appendicectomy has been the subject of several encouraging reports, but has not as yet gained widespread acceptance. We present a series of 159 consecutive laparoscopic appendicectomies performed, over a 4 yr period, in both adults and children. We find the procedure as safe as its open counterpart, with patients fit to leave hospital within the same time period. Perforated appendices were amenable to this procedure, and the location of the appendix did not alter the outcome. Children responded as well as adults post-operatively. Obesity may be an indication for this form of treatment. Removal of displaced faecoliths associated with perforated appendicitis is a difficult technical problem in less than 5 per cent of patients.

Total and partial orbitectomy for the treatment of periorbital tumors in 24 dogs and 6 cats: a retrospective study.

Total or partial orbitectomy were used to treat 24 dogs and six cats with invasive periorbital tumors. The surgical procedure and clinical results were evaluated in this retrospective study. The most common types of tumors treated in this series of patients were multilobular osteochondrosarcoma and squamous cell carcinoma. Two patients died of cardiopulmonary arrest within 24 hours after surgery. One patient developed neurological signs after total orbitectomy that resolved with conservative therapy. Minor complications, which included infection, strabismus, and conjunctivitis, occurred in seven patients. Regrowth of tumor in the periorbital region occurred in 11 patients (36.7%). Tumor resection by orbitectomy provided local disease-free interval of more than 1 year in more than 50% of patients. Survival rate for the first year was 70.4% in this series of patients as determined by life table analysis. Orbitectomy requires detailed knowledge of regional anatomy and experience with performing a combination of surgical procedures. Preoperative diagnostic tests should include imaging techniques to define the extent of the disease. When performed properly, orbitectomy is a valuable procedure that can be used to effectively treat invasive tumors of the orbit.

Laparoscopic management of generalized peritonitis due to perforated colonic diverticula.

PURPOSE: The use of laparoscopic peritoneal lavage in conjunction with parenteral fluids and antibiotic therapy in the management of generalized peritonitis secondary to perforated diverticular disease of the colon was assessed. PATIENTS AND METHODS: This cohort comprised 8 patients with generalized peritonitis secondary to perforated diverticular disease of the left colon that was diagnosed laparoscopically. All the patients had purulent peritonitis, but no fecal contamination. They were treated with laparoscopic peritoneal lavage and intravenous fluids and antibiotics. RESULTS: All patients made a complete recovery, with resumption of normal diet within 5 to 8 days. No patient has required surgical intervention during a 12- to 48-month follow-up. This approach merits further assessment as an alternative to the traditional open surgical management.

A prospective comparison of laparoscopy and imaging in the staging of esophagogastric cancer before surgery.

OBJECTIVE: To carry out a prospective comparison of laparoscopy and combined imaging (CT and ultrasound) in the preoperative staging of distal esophageal and gastric cancer in patients who were selected for surgery. METHODS: Patients with clinically overt metastases or a contraindication to major surgery were excluded. One hundred and forty-five patients underwent chest radiography, CT of mediastinum and abdomen, and ultrasonography of abdomen and laparoscopy. The primary diagnoses were adenocarcinoma of the esophagogastric region in 110 cases, squamous cell carcinoma of the distal esophagus in 30 patients, and five miscellaneous. RESULTS: Thirty nine (27%) patients had metastatic disease outside the potential field of resection. Metastases were detected preoperatively by laparoscopy in 30 patients (sensitivity 77%) and by combined imaging in 15 (sensitivity 38%) (p < 0.01). Twenty four patients with adenocarcinoma had metastases to the peritoneal cavity, which were detected preoperatively by laparoscopy in 23 (sensitivity 96%) and by combined imaging in five (sensitivity 21%) (p < 0.01). Peritoneal metastases were not seen in patients with squamous cell carcinoma. Fifteen patients had hepatic metastases, which were detected preoperatively by laparoscopy in nine (sensitivity 60%) and by combined imaging in seven (sensitivity 47%). Laparoscopy was more sensitive than combined imaging in detecting metastases in patients with adenocarcinoma [laparoscopy 28, combined imaging 10 (p < 0.01)]. CONCLUSION: Addition of laparoscopy to the staging protocol prevented unbeneficial thoraco-abdominal exploration in 20 patients with adenocarcinoma. Thus, laparoscopy should be used in the assessment of patients with adenocarcinoma of the esophagogastric region before performing excisional surgery.

Resection of pulmonary metastases in canine osteosarcoma: 36 cases (1983-1992).

Thirty-six dogs underwent pulmonary metastatectomy for osteosarcoma. All patients had been treated for histologically confirmed osteosarcoma of the appendicular skeleton. Treatment for the primary tumor consisted of amputation or a limb sparing procedure in conjunction with adjuvant chemotherapy, local radiation therapy, or both. Significant factors in determining prognosis included the disease-free interval (DFI) between treatment of the primary tumor and development of pulmonary metastases and the number of metastatic nodules present at surgery. Dogs that developed pulmonary metastases 300 days or more after diagnosis of the primary tumor had a median DFI of 128 days after metastatectomy. Dogs that developed pulmonary metastases fewer than 300 days after diagnosis had a median DFI of 58 days. Dogs with one or two metastatic nodules removed had a median DFI of 95 days, whereas dogs with three or more nodules removed had a median DFI of 53 days. The results of this study indicate that prognostic variables exist for dogs with metastatic pulmonary osteosarcoma and can help predict survival after metastatectomy. These variables are similar to the prognostic variables that have been determined for human patients undergoing pulmonary metastatectomy because of osteosarcoma. Though a controversial procedure, pulmonary metastatectomy seems to be a valid treatment option for selected dogs with metastatic pulmonary osteosarcoma.

Traumatic luxation of the cubital joint (elbow) in dogs: 44 cases (1978-1988).

The medical records from 44 dogs with traumatic luxation of the cubital joint were reviewed. Closed reduction was performed in 35 dogs, and open reduction in 9 dogs. Excellent or good results were achieved in 31 of 35 dogs (88.6%) treated by closed reduction and in 5 of 9 dogs (55.6%) treated by open reduction. Collateral ligament repair, performed in 5 dogs, did not appear to affect the prognosis. Factors such as body weight and type and duration of external coaptation also did not appear to influence the outcome. Increased dysfunction associated with open reduction most likely was caused by the chronic nature of the dislocation, iatrogenic damage to the articular cartilage during reduction, or both. A good prognosis for return to normal function with minimal gait abnormality can be expected in most cases of traumatic luxation of the cubital joint treated by early closed reduction.

Treatment by digital amputation of subungual squamous cell carcinoma in dogs: 21 cases (1987-1988)

Malignant digital tumors were diagnosed in 62 dogs during a 1-year period. Twenty-one (33.9%) of the dogs had subungual squamous cell carcinoma. Each of these dogs had involvement of single digits. Sixteen (76.2%) of the dogs with squamous cell carcinoma were large-breed dogs, and 15 (71.4%) had predominantly black coats. Labrador Retrievers (n = 5, 23.8%) and Standard Poodles (n = 3, 14.3%) were the most commonly represented purebreeds. None of the dogs had evidence of metastases prior to treatment. All 21 tumors were treated by amputation of the involved digit. Histologic evidence of neoplastic bone invasion was found in 15 of the 21 amputated digits (71.4%). Local tumor recurrences were not observed. Only 1 dog developed documented metastatic disease; this dog was euthanatized because of pulmonary metastases 5 months after surgery. At the time of this report, 9 dogs (42.9%) were alive with no evidence of disease (median, 26 months after surgery), and 11 dogs (52.4%) had died or were euthanatized (median, 20 months after surgery). The cause of death in 7 dogs was known to be unrelated to squamous cell carcinoma, and the cause of death in 4 dogs was unknown. The 1-year and 2-year survival rates were 76.2% and 42.9%, respectively.

Effects of olfactory bulbectomy, melatonin, and/or pinealectomy on three sublines of the Dunning R3327 rat prostatic adenocarcinoma.

Conventional antiandrogen therapy for prostatic cancer generally results in the death of androgen-dependent cells, resulting in shrinkage of the tumor, followed by regrowth of the tumor as androgen-insensitive cells take over. Because of reported antigonadotropic and antineoplastic effects of the pineal hormone melatonin (MEL), we hypothesized that this indole might provide an effective therapy for prostate cancer, as it would be effective against both populations of tumor cells. We used three sublines of the Dunning R3327 rat prostatic adenocarcinoma to determine whether MEL could suppress the growth of these tumors and, if so, by what mechanisms this occurs. In one experiments, we compared the growth of a well-differentiated slow-growing Dunning tumor in rats given MEL combined with the potentiating procedure olfactory bulbectomy (BULBX), with that in rats pinealectomized (PINX) or untreated. Tumor growth in BULBX-MEL rats was significantly suppressed over that in the other two groups, as were the weights of the gonads and accessory sex glands. Tumor morphology, DNA concentration, and androgen receptor concentration and distribution were identical in untreated controls and in BULBX-MEL rats, suggesting that the treatment affected all populations of tumor cells equally. With another strain of well-differentiated slow-growing Dunning tumor, we examined the effects of MEL in rats with and without BULBX. Reproductive parameters were not suppressed in BULBX-MEL rats and, while there was a trend toward slower tumor growth in this group, this was not significant. Intact rats given MEL grew larger tumors than did control rats but, again, differences were not significant. In a third experiment, we examined a fast-growing androgen-insensitive anaplastic Dunning tumor. PINX was without effect on this tumor, but BULBX-MEL resulted in a significant suppression of one of the constants in the logistic equation fitted to the growth curves. This indicates that there were some direct antitumor effects of BULBX-MEL on this tumor strain. We conclude that MEL suppresses growth of some Dunning tumor strains.

Effects of short-day photoperiods and of castration on the structural integrity of the ventral and dorsal prostates of the Syrian hamster (Mesocricetus auratus).

Short-day photoperiods and castration both cause reductions in the weights of male accessory sex glands. In the Syrian hamster, we have found that the ventral prostate loses less weight following these treatments than does the dorsal prostate. In this paper, we report on the effects of the pineal and of castration on the structural integrity of these glands, as assessed by stereological techniques. Short days result in little alteration to the ventral prostate or its acinar composition. The typical acinus is narrower following 10 weeks in short days. The ventral prostate also responds to castration with a narrower acinus, and, in addition, it shows a decrease in the epithelial volume fraction and increases in those of the lumen and muscular stroma. In neither case is there a change in the proportion of the gland consisting of acinar or interacinar components. Short-day photoperiods and castration generally show similar effects in the dorsal prostate. In both cases, there are increases in the proportion of the gland made up of interacinar tissue. Within the acini, there are decreases in the volume fractions of lumen and large increases in those of lamina propria and muscular stroma. Following both treatments, typical acini are narrower and show reduction in the thickness of the epithelium and increases in the thickness of the lamina propria and muscular stroma.Thus, in the ventral prostate, both short days and castration lead to subtle changes which are different with each treatment and which differ from those that occur in the dorsal prostate. In the dorsal prostate, there are relative increases in the proportions of nonepithelial elements following both of these treatments. These results are discussed in relation to the mode of action of the pineal in causing accessory sex gland regression.