Laparoscopic retroperitoneal live donor right nephrectomy for purposes of allotransplantation and autotransplantation.

PURPOSE: We report the technique of and initial experience with retroperitoneal laparoscopic live donor right nephrectomy for purposes of renal allotransplantation and autotransplantation. MATERIALS AND METHODS: A total of 5 patients underwent retroperitoneoscopic live donor nephrectomy of the right kidney for autotransplantation in 4 and living related renal donation in 1. Indications for autotransplantation included a large proximal ureteral tumor, a long distal ureteral stricture and 2 cases of the loin pain hematuria syndrome. In all cases a 3-port retroperitoneal laparoscopic approach and a pelvic muscle splitting Gibson incision for kidney extraction were used. In patients undergoing autotransplantation the same incision was used for subsequent transplantation. RESULTS: All procedures were successfully accomplished without technical or surgical complications. Total mean operating time was 5.8 hours and average laparoscopic donor nephrectomy time was 3.1 hours. Mean renal warm ischemia time, including endoscopic cross clamping of the renal artery to ex vivo cold perfusion, was 4 minutes. Average blood loss for the entire procedure was 400 cc. Radionuclide scan on postoperative day 1 confirmed good blood flow and function in all transplanted kidneys. Mean analgesic requirement was 58 mg. fentanyl. Mean hospital stay was 4 days (range 2 to 8), and convalescence was completed in 3 to 4 weeks. CONCLUSIONS: In the occasional patient requiring renal autotransplantation live donor nephrectomy can be performed laparoscopically with renal extraction and subsequent transplantation through a single standard extraperitoneal Gibson incision, thus, minimizing the overall operative morbidity. Furthermore, these data demonstrate that live donor nephrectomy of the right kidney can be performed safely using a retroperitoneal approach with an adequate length of the right renal vein obtained for allotransplantation or autotransplantation.

Constitutive activation of stimulatory guanine nucleotide binding protein (G(S)alphaQL)-mediated signaling increases invasiveness and tumorigenicity of PC-3M prostate cancer cells.

An abnormal stimulation of cAMP signaling cascade has been implicated in various human carcinomas. Since the agents activating G(S)alpha-mediated signaling pathways have been shown to increase in vitro proliferation of prostate cancer cells, present studies examined the G(S)alpha-mediated signaling in tumorigenicity and invasiveness of PC-3M prostate cancer cells. PC-3M cells were stably transfected with plasmids containing either wild type (G(S)alpha-WT) or constitutively active (gsp mutant of G(S)alpha or G(S)alpha-QL) cDNAs. The stable transfectants were then tested for: (1) colony formation in soft agar; (2) cell migration and penetration of basement matrix in an in vitro invasion assay; and (3) the ability to form tumors and metastases in nude mice. PC-3M cells expressing G(S)alpha-QL protein displayed 15-fold increase in their ability to migrate and penetrate the basement membrane as compared to parental PC-3M cells or those expressing G(S)alpha-WT. G(S)alpha-QL transfectants also displayed a dramatically greater rate of growth in soft agar, and greater tumorigenicity and metastasis forming ability when orthotopically implanted in nude mice. All mice receiving PC-3M cells produced primary tumors within 5 weeks after implantation. However, the cells expressing G(S)alpha-QL displayed a significantly faster tumor growth as assessed by prostate weight (greater than 20-fold as compared to PC-3M cells), and produced metastases in kidneys, lymph nodes, blood vessels, bowel mesentery and intestine. Interestingly, expression of G(S)alpha-WT reduced the ability of PC-3M cells to form tumors in nude mice. These results suggest that persistent activation of G(S)alpha-mediated signaling cascade can dramatically accelerate tumorigenesis and metastasizing ability of prostate cancer cells.

Muscarinic cholinergic receptors promote growth of human prostate cancer cells.

BACKGROUND: Recent evidence suggests that muscarinic receptors induce mitogenesis in cells capable of undergoing cell proliferation. Human prostate gland is innervated by the autonomic nervous system and muscarinic receptors have been localized in the prostate gland. METHODS: Effects of carbachol (a stable analog of acetyl choline) on DNA synthesis of LNCaP cells (a human prostate cancer cell line) and primary prostate cells was examined. The DNA synthesis in the cultured cells was assessed using techniques of 3H-thymidine incorporation and bromodeoxyuridine (BrdU) incorporation immunocytochemistry. RESULTS: Carbachol induced a significant increase in BrdU- and 3H-thymidine incorporation of LNCaP cells. The effect of carbachol was completely reversed by atropine, a selective muscarinic antagonist. Subtypes of muscarinic receptors mediating carbachol-induced DNA synthesis were identified using selective receptor subtype antagonists. Pirenzepamine and gallamine did not affect carbachol action on LNCaP cells but diphenylpyralamine, an M3 receptor antagonist, completely blocked carbachol-induced DNA synthesis. Carbachol also stimulated DNA synthesis in primary prostate cells. Prostate carcinoma (PC)-derived primary prostate cells displayed a dramatically greater response to carbachol (a ten-fold increase in DNA synthesis) as compared to benign prostate hypertrophy (BPH)-derived cells (a two-fold increase in DNA synthesis). CONCLUSIONS: M3 receptors stimulate the proliferation of LNCaP cells, BPH-derived and PC-derived primary prostate cells. A dramatically higher response to carbachol by PC-derived prostate cells suggests that M3 receptors may be up-regulated in PC. M3 receptors may play a significant role in PC tumors growth and androgen-independent tumor progression.

Calcitonin stimulates growth of human prostate cancer cells through receptor-mediated increase in cyclic adenosine 3',5'-monophosphates and cytoplasmic Ca2+ transients.

Our recent study has shown that a calcitonin (CT)-like immunoreactive substance(s) is secreted by cultured prostate cells, and secretion of this material is significantly higher in malignant than in benign prostate cells. To test the hypothesis that prostatic CT may serve as a paracrine/neuroendocrine factor, the present study investigated for the presence of CT receptors in the prostate gland. Signal transduction mechanisms activated by CT were examined, and the study also tested its effects on prostate cell proliferation, as assessed by [3H]thymidine incorporation. The results show that high affinity binding sites for [125I]salmon CT were present in plasma membrane fractions of human prostate tissue specimens and the prostate cancer LnCaP cell line. The maximal binding for CT receptors was 564 +/- 163 fmol/mg protein, and the apparent dissociation constant (Kd) was 2.89 +/- 0.58 nM. CT induced a dose-dependent increase in cAMP generation in LnCaP cells. The effect of CT on cytoplasmic Ca2+ transients of LnCaP cells was examined by videofluoromicroscopy. CT (100 nM) induced a rapid and sharp increase in cytoplasmic Ca2+ concentrations in LnCaP cells. The CT-induced increase in cytoplasmic Ca2+ transients appeared to be biphasic (spike and plateau), and this increase was 4- to 10-fold during the initial phase. The profile of this response is characteristic of the activated Ca2+/phospholipid second messenger system. CT also caused a dose-dependent increase in [3H]thymidine incorporation by LnCaP cells. These results suggest that a locally secreted CT-like peptide(s) induces mitogenic responses in prostate cancer cells. This action seems to be mediated through activation of signaling mechanisms, leading to the accumulation of two different second messengers, cAMP and calcium. Activation of dual second messenger systems by CT receptors suggests that the peptide hormone may play an important role in rapidly growing cell populations during the process of tumor formation.

Management of abdominal aortic aneurysm and invasive transitional cell carcinoma of bladder.

Between January 1980 and June 1990 we treated 21 patients with invasive carcinoma of the bladder and abdominal aortic aneurysm. Three distinct groups of patients were identified. Group 1 comprised 8 patients who were initially diagnosed with invasive bladder cancer and during cancer staging a concomitant abdominal aortic aneurysm was found. Group 2 consisted of 10 patients previously treated for invasive bladder cancer who had aneurysmal disease at a later date. Group 3 included 3 patients who underwent a previous aneurysm repair and subsequently had invasive carcinoma of the bladder. Total survival was 9 of 21 patients (43%) with a mean of 84 months of followup after initial diagnosis. This finding is comparable to long-term (greater than 5 years) survival in patients with invasive carcinoma of the bladder alone. In fact, none of the 21 patients studied experienced rupture of the aneurysm and/or died of aneurysmal disease. We found that patients with abdominal aortic aneurysm and invasive bladder cancer have a poor overall prognosis. Although aneurysm repair presents technical challenges, mortality is dependent upon the carcinoma and other vascular or medical diseases, and does not bear direct relationship to abdominal aortic aneurysm.

Combined cholecystectomy and radical genitourinary cancer surgery.

We have routinely performed simultaneous cholecystectomy in patients with cholelithiasis undergoing selected radical genitourinary cancer surgery. A total of 31 patients have undergone cholecystectomy at the time of radical nephrectomy (25), radical cystectomy (5), and radical prostatectomy (1). Operative time was increased twenty-five to forty-five minutes. There was no significant increase in blood loss, postoperative total bilirubin, or number of complications. No complications were directly attributable to the cholecystectomy except for 1 patient who had prolonged drainage from a closed suction drain in the gallbladder fossa. We conclude that concomitant cholecystectomy at the time of radical genitourinary cancer surgery does not significantly increase morbidity and recommend that it be performed in the presence of cholelithiasis.

Initial experience with combined interferon-alpha 2B and carbon dioxide laser for the treatment of condylomata acuminata.

The incidence of condylomata acuminata, a common sexually transmitted disease caused by certain types of human papillomaviruses, is increasing rapidly and treatment regimens presently are not consistently effective. One of the more popular and effective modes of treatment has been laser therapy. Because of the relatively high recurrence rate of condylomata acuminata with laser treatment alone and because laser treatment in some patients with confluent acetowhite lesions would render cosmetically unacceptable results in the entire area were treated, we believed that it was reasonable to use intralesional pretreatment. We present our preliminary data on 14 consecutive patients with the clinical diagnosis of condylomata acuminata who were treated with the combination of carbon dioxide laser and intralesional interferon-alpha 2B. We found the treatment regimen to be effective in decreasing the recurrence rate compared to laser treatment alone and it was well tolerated with only transient side effects in a minority of patients. We are encouraged by our result and have recently begun a randomized double-blind prospective study to provide more conclusive information regarding this treatment combination.

Presence of calcitonin-like immunoreactivity (iCT) in human prostate gland: evidence for iCT secretion by cultured prostate cells.

Immunoreactive calcitonin (iCT) has been detected in human prostate tissue extracts as well as seminal plasma. The present studies were undertaken to examine whether iSCT (immunoreactive salmon CT-like human peptide) co-exists with iHCT (thyroid CT-like substance) in human prostate tissue extracts, and whether these substances are secreted by primary prostate cells in culture. Since the local secretion of these substances seems to increase in some neoplasms, a second objective of the study was to examine whether basal secretion of iCTs from primary prostate cells is increased in carcinoma. The present results have shown that both iHCT and iSCT were present in prostate tissue extracts. The mean iHCT levels in extracts of benign hyperplastic prostates (BPH) were 0.59 ng/g prostate, and these were significantly lower than iHCT concentrations in prostatic carcinoma (PC) (2.53 ng/g). No significant differences in their iSCT contents were observed. However, the results from culture of over 90 individual prostate tissue specimens from BPH or PC indicate that primary prostate cells secreted detectable quantities of iSCT and the basal release of this material from PC prostate cultures was almost four-fold higher than that from BPH prostate cultures. These results suggest that a CT-like immunoreactive material is secreted by primary prostate cells in culture, and the basal secretion of this material is significantly higher in PC cells as compared to BPH cells. Endogenous secretion of prostatic CT, and the elevation of its expression in PC suggest that it may serve as a regulatory factor in the pathophysiology of the prostate gland.

Correlation of ultrasound guided and digitally directed transrectal biopsies of palpable prostatic abnormalities.

The authors evaluated 51 patients with palpable prostatic abnormalities detected during digital rectal examination. These findings consisted of a nodule or an area of induration. Each palpable abnormality was confined to 1 prostatic lobe and there was no suggestion of extracapsular extension of neoplasm or systemic metastatic disease. All patients underwent 7.0 MHz. sagittal ultrasound guided transrectal biopsy followed by digitally directed transrectal biopsy. Biopsies were obtained only from the area of interest. The procedure was performed in the outpatient clinic without use of sedation or anesthesia. Digitally directed biopsies were positive for adenocarcinoma in 9 lesions. Ultrasound guided biopsies detected adenocarcinoma in 23 lesions, including all those detected by the blind digitally directed technique. This study demonstrates greater diagnostic accuracy using 7.0 MHz. ultrasound guided techniques and its routine use is warranted in the evaluation of palpable prostatic abnormalities.

Analysis of bladder carcinoma by subsite. Cystoscopic location may have prognostic value.

Nine hundred fourteen cases of carcinoma of the urinary bladder registered from 1977 to 1988 with the Kansas state tumor registry were evaluated by subsite for differences in grade, histology, sex, age at diagnosis, and survival. Only initial occurrences of carcinoma were included. Carcinoma of the lateral walls accounted for 37.1%; the posterior wall, 17.9%; the trigone, 12.6%; the neck, 11.1%; the ureteric orifices, 9.8%; the dome, 7.7%; and the anterior wall, 3.8%. Malignant neoplasms occurring in the neck of the bladder had a significantly poorer prognosis by survival analysis (P less than 0.05). Malignancies of the dome were found to present as higher grade lesions (P = 0.00003), and carcinoma of the ureteric orifices and lateral walls tended to be of lower grade (P = 0.02 and P = 0.05, respectively). Carcinomas of the anterior wall and dome occurred in a more elderly population (mean ages, 75.6 and 73.9 years, respectively), and carcinomas of the trigone and ureteric orifices occurred in a younger group (mean ages, 68.3 and 67.5 years, respectively). On histologic evaluation the trigone gave rise to more squamous cell carcinoma than expected (P = 0.001, 325% of expected). No distribution difference was noted among subsites with respect to sex. These data show significant differences among subsites of the urinary bladder with regard to survival, grade, histology, and age at diagnosis.

Penetration of topically applied betamethasone sodium phosphate into human aqueous humour.

Gas Chromatography combined with Negative Chemical Ionisation Mass Spectrometry (GCMS) was used to determine the absorption of topically applied beta-methasone sodium phosphate into the aqueous humour of human subjects undergoing routine intraocular surgery. The Betamethasone concentration was greatest in the interval 91-120 minutes following topical administration (mean peak concentration = 7.7 ng/ml). At twelve hours post instillation the mean concentration of Betamethasone was 2.5 ng/ml and detectable levels were recorded in the aqueous humour 24 hours after application (mean concentration 0.4 ng/ml).

Penetration of topically applied dexamethasone alcohol into human aqueous humor.

Gas chromatography combined with mass spectrometry was used to determine the absorption of topically applied dexamethasone alcohol into the aqueous humor of human subjects undergoing routine intraocular surgery. The dexamethasone concentration in aqueous humor was greatest in the interval between 91 and 120 minutes following instillation (mean concentration, 31 ng/mL). Dexamethasone was still detectable in the aqueous 12 hours after instillation.

Precision of cell density estimates and endothelial cell loss with age.

The precision of estimating endothelial cell density of the cornea, using a noncontact method of specular microscopy, was assessed by asking eight individuals with known densities in one operated-on and one unoperated-on eye to have photography on two occasions in the same day. Three photographs of each eye were assessed by two individuals using masking procedures. Interobserver differences were negligible and estimates were similar except for one eye with low density values. The method was applied to a natural history study in which 103 eyes had cell-density estimates at zero and two years, and mean cell loss was found to be 2%. A collateral study using only good photographs that were available at both zero and two years showed a similar loss of 1.86% and reduced the number of counts showing unexpectedly high gains and losses.

A comparison of end versus loop stomas for ileal conduit urinary diversion.

We compared the loop and end stoma techniques for ileal conduit urinary diversion in 54 and 27 adults, respectively, with serious bladder disease during a 3-year interval. Followup by trained enterostomal therapists averaged nearly 2 years for all patients. Stenosis occurred in 12 end stomas (44 per cent) but not in any loop stomas. We believe that this result reflects the inherently better blood supply of the loop stoma, which we recommend over the end ileostomy for patients undergoing ileal diversion.

Treatment of renal cell carcinoma with renal infarction, delayed nephrectomy, medroxyprogesterone, and xenogeneic immune RNA.

The authors have used xenogeneic immune ribonucleic acid (RNA) in the treatment of patients with renal cell carcinoma. This has been used in conjunction with renal artery embolization, delayed nephrectomy, and progestational therapy, using immune RNA derived from sheep cell lymphocytes immunized with patient's tumor. Four of 5 patients with Stage I disease had extremely large primary tumors. This group is alive with no evidence of disease at twelve to twenty-four months. There are no Stage II tumors in this group. One patient with Stage III tumor is alive at twenty-two months without evidence of disease. Three patients with metastases are stable at five to twenty-two months. Two patients have progressive disease at three and six months. This treatment has not been effective in patients with massive tumor burden. The results in the other groups are encouraging.

Inferior vena caval replacement after resection of left renal tumor in canine model.

An animal model simulating the necessity of replacing the inferior vena cava (IVC) with a prosthetic graft is described. Six dogs underwent replacement of the IVC with an expanded polytetrafluoroethylene (E-PTFE) graft using an interrupted-suture technique. Three dogs served as controls, undergoing resection and autograft of the native IVC. Distal side-to-side femoral arteriovenous fistulas were constructed in each case and allowed to remain for six weeks. Subcutaneous heparin and prophylactic antibiotics were administered in the early postoperative period. All grafts were patent at six months, indicating a potentially successful technique for reconstruction of the IVC involved in disease or trauma.

Oral fluorescein and cystoid macular oedema: detection in aphakic and pseudophakic eyes.

The ingestion of oral fluorescein in 38 consecutive cases 6 to 7 weeks after cataract surgery with and without iris clip lens implantation permitted satisfactory fluorography to detect all cases of clinical cystoid macular oedema. There were no adverse reactions from any test subject.