Australian experience with total pancreatectomy with islet autotransplantation to treat chronic pancreatitis.

BACKGROUND: This study aimed to describe the clinical outcomes of total pancreatectomy with islet autotransplantation (TP-IAT) in Australia. METHODS: Individuals selected for TP-IAT surgery according to the Minnesota Criteria (Appendix) without evidence of diabetes were evaluated including time to transplantation from pancreatectomy, islet numbers infused and post-transplantation HbA1c, C-peptide, total daily insulin and analgesic requirement. RESULTS: Sixteen individuals underwent TP-IAT from Australia and New Zealand between 2010 and 2020. Two recipients are deceased. The median islet equivalents/kg infused was 4244 (interquartile range (IQR) 2290-7300). The median C-peptide 1 month post-TP-IAT was 384 (IQR 210-579) pmol/L and at median 29.5 (IQR 14.5-46.5) months from transplant was 395 (IQR 139-862) pmol/L. Insulin independence was achieved in eight of 15 (53.3%) surviving recipients. A higher islet equivalents transplanted was most strongly associated with the likelihood of insulin independence (P < 0.05). Of the 15 surviving recipients, 14 demonstrated substantial reduction in analgesic requirement. CONCLUSION: The TP-IAT programme in Australia has been a successful new therapy for the management of individuals with chronic pancreatitis including hereditary forms refractory to medical treatment to improve pain management with 50% insulin independence rates.

Phase I trial of the murine monoclonal anti-GD2 antibody 14G2a in metastatic melanoma.

In a phase I trial, 12 patients with GD2 antigen-positive metastatic melanoma received the murine anti-GD2 monoclonal antibody 14G2a. The monoclonal antibody was administered in four doses over an 8-day period with total dose ranging from 10 to 120 mg. All patients receiving greater than 10 mg of 14G2a experienced transient abdominal/pelvic pain during the antibody infusion. Five patients had a delayed extremity pain syndrome following the third and fourth antibody infusion. Four of the five patients developed neurological toxicity, including two patients with significant although reversible motor neuropathy. Two of the patients developed hyponatremia secondary to a syndrome of inappropriate antidiuretic hormone. All 12 patients developed high levels of human anti-14G2a antibody. The plasma half-life of 14G2a was 42 +/- 6 (SD) h. One patient each had a partial response, mixed response, and stable disease, respectively. The very modest antitumor activity accompanied by dose-limiting neurological toxicity at total doses greater than 80 mg may restrict the clinical utility of murine 14G2a.

In-111 labeled monoclonal anti-carcinoembryonic antigen antibody (ZCE025) in the immunoscintigraphic imaging of metastatic antigen-producing adenocarcinomas.

The carcinoembryonic antigen (CEA) is a clinically useful marker since it is expressed by adenocarcinomas of diverse origin. Detection and quantitation of circulating CEA levels is used to follow the clinical course of metastatic adenocarcinoma. In this phase I study, the toxicity, pharmacokinetics, and optimal imaging dose of an In-111 labeled monoclonal anti-CEA antibody (ZCE025) was studied in patients with colorectal carcinoma or any CEA-producing tumor. Twenty-four of 26 evaluable patients (92%) demonstrated at least one site of tumor-specific antibody uptake. Sixty-seven sites of metastatic cancer were identified by conventional diagnostic studies. Twenty-nine (43%) of these sites were demonstrable by radioimmune imaging using ZCE025. Twenty-five additional sites of antibody uptake were observed but could not be associated with metastatic deposits. Lymph node and visceral metastases were visualized more frequently than bone, subcutaneous, lung, or liver metastases. Neither tumor size nor antibody dose (2.5-40 mg) appeared to influence the frequency of tumor imaging. The pharmacokinetics of the In-111 labeled antibody fitted a two-compartment model, and patients receiving less than 10 mg of antibody showed a faster clearance of the antibody than those who received greater than 10 mg.