To determine whether the expression of transforming growth factor ␣ (TGF-␣), its receptor (epidermal growth factor receptor [EGFr]), p53 nuclear protein, and proliferation influences prognosis of patients with liver metastases, a study was performed in 45 liver metastases and 33 corresponding primary colorectal carcinomas in patients referred for liver surgery. The expression of TGF-␣, EGFr, p53 nuclear protein, and proliferation rate was correlated with clinicopathological characteristics and survival after partial liver resection. In liver metastases, TGF-␣ expression was low in 42%, intermediate in 35%, and high in 23%. TGF-␣ expression was higher in liver metastases derived from lymph node-positive primary carcinomas, in synchronous and in irresectable liver metastases compared with those derived from lymph node-negative primary carcinomas, metachronous, and resectable liver metastases. Nuclear p53 expression was found in 83% of primary tumors and 71% of liver metastases. p53 expression did not correlate with the various clinicopathological characteristics. Ki67 expression was not associated with clinicopathological characteristics in primary and metastatic tumors. In the 38 patients in whom a partial liver resection was performed, median survival was 25 months in patients with a higher TGF-␣ expression in the metastasis than in the primary tumor and 60 months in patients with comparable or lower TGF-␣ expression in the metastasis than in the primary tumor (P ‫؍‬ .036). Median survival after liver resection was 21 months in patients with p53-negative liver metastases and 58 months in patients with p53-positive metastases (P ‫؍‬ .043). By multivariate analysis, p53 and EGFr expression on liver metastases were the best predictors of diseasefree survival after partial liver resection, with relative risks of 2.38 and 3.33, respectively. In patients with colorectal liver metastases, referred for liver surgery, a higher TGF-␣ expression is associated with unfavorable tumor characteristics, whereas p53 and absence of EGFr expression is associated with a better survival after partial liver resection. (HEPATOLOGY 1998;28:971-979.)Colorectal carcinoma is the second-leading cause of cancer deaths in the Western community. Of all colorectal cancer patients, about 50% will die within 5 years after diagnosis. 1 At the time of initial diagnosis, 15% to 25% of patients present with synchronous liver metastases. 1 It is estimated that overall, only 5% of patients who develop liver metastases of colorectal carcinomas are amenable to partial liver resection. 2 Despite intentionally curative liver resections, only 20% to 30% of these patients have a disease-free 5-year survival. [3][4][5] Furthermore, in patients with recurrences after liver resection, these recurrences often appear early after liver surgery, with the liver being a frequent site of initial failure. 5,6 In the animal model, tumor growth can be influenced by growth factors produced by the tumor cells and by growth factors generated by the organ that harbors the m...

Autosomal dominant polycystic kidney disease (ADPKD) patients can suffer from chronic pain that can be refractory to conventional treatment, resulting in a wish for nephrectomy. This study aimed to evaluate the effect of a multidisciplinary treatment protocol with sequential nerve blocks on pain relief in ADPKD patients with refractory chronic pain. As a first step a diagnostic, temporary celiac plexus block with local anesthetics was performed. If substantial pain relief was obtained, the assumption was that pain was relayed via the celiac plexus and major splanchnic nerves. When pain recurred, patients were then scheduled for a major splanchnic nerve block with radiofrequency ablation. In cases with no pain relief, it was assumed that pain was relayed via the aortico-renal plexus, and catheter-based renal denervation was performed. Sixty patients were referred, of which 44 were eligible. In 36 patients the diagnostic celiac plexus block resulted in substantial pain relief with a change in the median visual analogue scale (VAS) score pre-post intervention of 50/100. Of these patients, 23 received a major splanchnic nerve block because pain recurred, with a change in median VAS pre-post block of 53/100. In 8 patients without pain relief after the diagnostic block, renal denervation was performed in 5, with a borderline significant change in the median VAS pre-post intervention of 20/100. After a median follow-up of 12 months, 81.8% of the patients experienced a sustained improvement in pain intensity, indicating that our treatment protocol is effective in obtaining pain relief in ADPKD patients with refractory chronic pain.

Background chronic pain is often difficult to manage in ADPKD patients and sometimes even leads to nephrectomy. We analyzed long-term efficacy of our innovative multidisciplinary protocol to treat chronic refractory pain, and that aims to preserve kidney function by applying among other sequential nerve blocks. Methods patients were eligible if pain was present ≥ 3 months with a score on a visual analogue scale (VAS) of ≥ 50 out of 100, was negatively affecting quality of life, and if there had been insufficient response to previous therapies, including opioid treatment. Treatment options were in respective order analgesics, cyst aspiration and fenestration, nerve blocks and nephrectomy. Results 101 patients were assessed in our clinic, mean age 50 ± 11 years and 65.3% were females. Eight patients were treated with medication, 6 by cyst aspiration or fenestration, 63 by nerve blocks, whereas 6 received surgery as first treatment option. Overall, 76.9% experienced a positive effect on pain complaints shortly after treatment. VAS score was reduced from 60/100 to 20/100 (p < 0.001) and patients lowered their number of non-opioid and opioid analgesics significantly (p < 0.001, p = 0.006 respectively). A substantial part of the patients (32.6%) needed additional treatment. At the end of follow-up only in 13 patients (12.9%) surgical intervention was necessary: 11 nephrectomies (of which 10 in patients already on kidney function replacement treatment), 1 liver transplantation, 1 partial hepatectomy. After a median follow-up of 4.5 [2.5–5.3] years, 69.0% of the patients still had less pain complaints. Conclusions these data indicate that our multidisciplinary treatment protocol appears effective in reducing pain in the majority of patients with chronic refractory pain, while postponing or even avoiding in most patients surgical interventions as nephrectomy.