Immunochemotherapy of human colon carcinoma xenografts in nude mice using combinations of idarubicin-monoclonal antibody conjugates.

Tumour cell heterogeneity is probably a principal cause of treatment failure and represents a formidable barrier for effective antibody-targeted chemotherapy. Idarubicin (Ida), a more potent and less cardiotoxic analogue of daunomycin, has been demonstrated to specifically target and eradicate homogeneous, cloned, murine tumour cell populations in vitro and in vivo when coupled to monoclonal antibodies (MoAb); however, the antitumour activity of Ida-MoAb conjugates against human tumour xenografts remains to be established. In this study, the value of cotargeting conjugates to different human tumour-associated antigens within a solid tumour has been assessed by comparing the effects of combinations of Ida-anti-colon carcinoma MoAb conjugates with any one Ida-anti-colon carcinoma MoAb conjugate used alone. Individual Ida-MoAb conjugates have previously been evaluated for their specific binding and cytotoxicity to one of two different human colon carcinoma xenografts (Colo 205 or LIM2210) in vitro, although their efficacy alone or in combination required assessment in vivo. Combinations of the most effective Ida-MoAb conjugates were demonstrated to enable a greater number of complete tumour regressions than the most efficacious Ida-MoAb conjugate administered alone in vivo; some combinations inhibited control tumour growth by up to 95%. This study suggests that Ida-MoAb conjugates can be effective against subcutaneous human tumours in nude mice, although it is unlikely that any single conjugate will eradicate all the tumour cells in a solid tumour, and the value of 'cocktails' of drug-MoAb conjugates against some xenografts (i.e. LIM2210) appears to be limited.

Factors related to the presentation of patients with thick primary melanomas.

OBJECTIVE: To identify any characteristics of patients that are associated with presentation with thick primary melanoma. DESIGN: This was a retrospective survey of the clinical records of 1300 patients attending the Newcastle Melanoma Unit. Characteristics of 131 patients with thick melanomas (defined as 3 mm or greater in thickness) were compared with those of 543 patients with thin melanomas (defined as 0.75 mm or less in thickness). Comparisons were made using contingency table analysis, Wilcoxon rank sum tests, log rank analysis and logistic regression. SETTING: The Newcastle Melanoma Unit is a tertiary referral centre for the treatment of primary melanoma. PATIENTS: We surveyed all 1300 patients attending the Newcastle Melanoma Unit over the years 1981-1990. They represented approximately 90% of the patients in the Hunter region of New South Wales who developed melanoma during this period. Excluded from analysis were 39 patients with occult primary melanomas, 79 with multiple primary melanomas, 51 with primary melanomas of unknown thickness and seven with incomplete records, leaving 1124 patients in the study. MAIN OUTCOME MEASURES: These were selected before the results were known. The hypothesis was generated following analysis of the data. RESULTS: Patients with thick primary melanoma were more likely to be men (68% men and 32% women in the thick melanoma group, compared with 45% and 55% respectively in the thin melanoma group, P less than 0.005) over 60 (75% were over 50 years of age in the thick group versus 33% in the thin melanoma group, P less than 0.001) with nodular melanoma (62%, versus 2% in the thin melanoma group, P less than 0.001) and with melanoma on the head and neck (27%, versus 12% in patients with thin melanoma, P less than 0.005). The time from detection of a change in skin to diagnosis was not longer for those with thick compared to those with thin melanomas. CONCLUSION: The greatest problem of those with thin melanomas. CONCLUSION: The greatest problem of detecting melanoma at an early (surgically curable) stage appears to be in patients over the age of 50 who have nodular melanoma, particularly in the head and neck.

Intravenous but not intracolonic epidermal growth factor maintains colonocyte proliferation in defunctioned rat colorectum.

The role of epidermal growth factor in the proliferation of normal and premalignant colonocytes in vivo is not fully understood. In particular, the relative importance of its possible systemic and intraluminal routes of action has not been fully clarified. Rats with surgically defunctioned distal colorectums were used, and mini osmotic pumps were implanted to study the effects of intraluminal and IV administration of epidermal growth factor on colonocyte proliferation. Within 2 weeks of bypass, colonocyte proliferation in defunctioned colorectum has decreased to about one third the rate in normal colorectum or in colorectum proximal to the defunctioning colostomy. Intraluminal epidermal growth factor, infused from the time of operation did not reverse this hypoplasia, whereas IV epidermal growth factor maintained colonocyte proliferation at approximately the normal rate in bypassed colorectum. This model is suitable for testing other putative colonic mitogens for possible intraluminal and systemic effects.

Changes in the DNA ploidy patterns of human colorectal carcinomas, subsequent to culture or xenografting.

DNA ploidy patterns were measured by flow cytometry in 7 human carcinomas and compared with the DNA histograms of 3 cell lines and 25 xenografts and derived from them. Four of the carcinomas showed DNA ploidy changes on initial xenografting or early passaging, while 2 carcinomas showed stable ploidy patterns over several xenograft passages. One xenograft derived from a cell line showed a marked, but stable, increase in DNA content over the original human carcinoma. Two of the 3 cell lines were DNA aneuploid, and at least 1 line was apparently derived from a minor subpopulation in the original carcinoma. The possible mechanisms and implications of these changes are discussed.

Appendicitis and appendicectomy in a Melanesian population.

A prospective study of patients with appendicitis has been conducted over a 3-year period in the Melanesian population of the North Solomons. Patients presented with suspected appendicitis at an annual rate of 39 per 100,000 population. Appendicitis was confirmed at operation at an annual rate of 22 per 100,000 population. The disease was considerably more frequent in male than in female patients. The annual appendicectomy rate was 29 per 100,000 population. Thirty per cent of patients presented with signs of late or complicated appendicitis, while 37 per cent of patients submitted to operation were found to have advanced appendicitis. The incidence and pattern of appendicitis in the North Solomons are quite different from those seen in the urbanized populations of developed countries.

Skin cancer in the North Solomons.

The Melanesians of the North Solomons are exposed to intense equatorial sunlight and yet have a very low incidence of skin cancer. This study reveals no proven cases of basal cell carcinoma in these people, and demonstrates the rarity of squamous cell carcinoma and melanoma arising in normal pigmented skin. Most, if not all squamous cell carcinomas, arise in skin damaged by tropical ulceration, burns or osteomyelitis. Melanoma arises from the unpigmented skin of the sole of the foot. North Solomon Islanders are very deeply pigmented. Presumably, dense cutaneous melanin in normal undamaged skin provides the highly effective protection against solar carcinogenesis which these people enjoy. Chronic or recurrent skin ulceration with subsequent repair, scarring and loss of pigment is the precursor to almost all non-melanoma skin cancer in these people. Most of these cancers could be prevented by split thickness skin grafting of chronic ulcers, and protection of ulcerated, depigmented and scarred skin from solar radiation.

Haemoperitoneum: an unusual complication of Fitz-Hugh Curtis syndrome.

A case of haemoperitoneum following minor trauma in a patient with Fitz-Hugh Curtis syndrome is presented. This is a rare complication of a condition which is common in Papua New Guinea and many other communities. Laparoscopy is the key to diagnosis of this syndrome which is often overlooked or misdiagnosed.

Laparoscopy ... a useful technique for the general surgeon.

A series of 227 consecutive laparoscopies performed over 3 years at a provincial hospital in the North Solomons Province is presented. There were no deaths due to the procedure and morbidity was 2.4%. Positive findings were revealed in 89% of patients, allowing rapid decisions to be made regarding patient management: a vital consideration in a busy surgical unit with limited resources. Laparoscopy provides an efficient, safe, rapid and direct approach to many abdominal problems encountered in general surgery, particularly liver disease, blunt abdominal trauma, intraperitoneal infection and neoplasia.

Phencyclidine in CSF and serum: a case of attempted filicide by a mother without a history of substance abuse.

A previously healthy 30-year-old black woman with no history of substance abuse was hospitalized after she attempted to drown her 4-year-old son. She had become progressively confused and delusional after a flu-like illness 2 weeks before. Serum and lumbar CSF samples assayed for phencyclidine (PCP) by gas chromatography-mass spectrometry with d5 PCP as an internal standard were positive. The patient recovered rapidly after treatment with haloperidol and acidification of her urine. Suspicion of PCP abuse should remain high among patients with psychosis, even for those with no history of substance abuse.

Fibreoptic endoscopy: does it have a role in the investigation of upper gastrointestinal disease in Papua New Guinea?

The first 150 fibreoptic examinations of the upper gastrointestinal tract performed in the North Solomons are reported. Sixty-one percent of examinations revealed a significant abnormality; this is a more efficient diagnostic yield than can be achieved with contrast radiology. This series confirms that fibreoptic endoscopy is the most efficient method of diagnosing upper gastrointestinal disease available in Papua New Guinea, and its more widespread use is advocated.

Bilateral tubal pregnancy with vaginal delivery.

A 26-year-old woman was admitted with a diagnosis of septic incomplete abortion. Subsequently she was discovered to have bilateral tubal ectopic pregnancies. The right tube was not badly damaged. Its contents were removed by linear salpingotomy and the tube was repaired. Fifteen months later the patient delivered a live infant.