The impact of fluid optimisation before induction of anaesthesia on hypotension after induction.

Intra-operative hypotension is a known predictor of adverse events and poor outcomes following major surgery. Hypotension often occurs on induction of anaesthesia, typically attributed to hypovolaemia and the haemodynamic effects of anaesthetic agents. We assessed the efficacy of fluid optimisation for reducing the incidence of hypotension on induction of anaesthesia. This prospective trial enrolled 283 patients undergoing radical cystectomy and randomly allocated them to goal-directed fluid therapy (n = 142) or standard fluid therapy (n = 141). Goal-directed fluid therapy patients received fluid optimisation based on stroke volume response to passive leg raise before induction; those with positive passive leg raise received intravenous crystalloid fluid boluses until stroke volume was optimised. Baseline mean arterial pressure was measured on the morning of surgery and on arriving in the operating theatre. This post-hoc analysis defined haemodynamic instability as either a > 30% relative drop in mean arterial pressure compared with baseline or absolute mean arterial pressure < 55 mmHg, within 15 min of induction. Forty-two (30%) goal-directed fluid therapy patients underwent fluid optimisation after finding an intravascular fluid deficit via passive leg raise testing; 106 (75%) goal-directed fluid therapy and 112 (79%) standard fluid therapy patients met criteria for haemodynamic instability. There was no significant difference in the incidence of haemodynamic instability between the goal-directed fluid therapy and standard fluid therapy groups using absolute mean arterial pressure drop below 55 mmHg (p = 0.58) or using pre-surgical testing or pre-surgical mean arterial pressure values as baseline (p = 0.21, p = 0.89, respectively); however, the difference in the incidence of haemodynamic instability was significant using the operating theatre baseline mean arterial pressure (p = 0.004). We conclude that fluid optimisation before induction of general anaesthesia did not significantly impact haemodynamic instability.

Results of high dose rate brachytherapy, anterior pelvic exenteration and external beam radiotherapy for carcinoma of the female urethra.

PURPOSE: We evaluated a multimodality approach to locally advanced urethral carcinoma in women. MATERIALS AND METHODS: Between August 1996 and July 1999, 6 women were treated for locally advanced carcinoma of the urethra with anterior pelvic exenteration followed by high dose 192iridium intraoperative radiation therapy. Four of the 6 patients were also treated with neoadjuvant or concomitant platinum based chemotherapy. RESULTS: Two patients had no evidence of disease, 3 had distant metastasis and 2 had local recurrence at a mean followup of 21 months (range 12 to 47). Radiation was relatively well tolerated with no major adverse events. CONCLUSIONS: High dose intraoperative brachytherapy followed by external beam radiation is relatively well tolerated. Local control seems to have improved. We must evaluate a larger cohort of patients to determine this impact of the combined modality on local control and patient survival.

The efficacy of transurethral biopsy for predicting the long-term clinical impact of prostatic invasive bladder cancer.

PURPOSE: Involvement of the prostate by bladder cancer directly impacts survival, the risk of urethral recurrence, and treatment decisions concerning the timing of cystectomy and type of urinary diversion. Transurethral lateromontanal loop biopsies are proposed as the most accurate method for evaluating the prostatic urethra. Due to the potential clinical impact on individuals we assessed its accuracy in a large cohort. MATERIALS AND METHODS: Transurethral lateromontanal loop biopsies were performed in 246 of 416 male patients at our institution between 1989 and 1997. The predictive value and sensitivity of transurethral biopsy, patterns of recurrence, survival and clinical impact were assessed in a cohort with 10 years of followup. RESULTS: The sensitivity of transurethral biopsy for prostatic stromal invasion was 53%, specificity was 77%, positive predictive value was 45% and negative predictive value was 82%. At the 10-year followup 129 patients (52.4%) were dead, 85 (32%) had no evidence of disease, 16 (6.5%) had disease and 16 (6.5%) were lost to followup. Mean followup in patients at risk for urethral recurrence was 61.7 months (range 0.56 to 134.1, median 56.8). Delayed urethrectomy was performed in 15 of 235 cases (6.4%) at a mean of 15.2 months. Of the 246 patients 99 had prostatic disease at transurethral biopsy and/or cystectomy, including 11 (11%) with urethral recurrence. No patient required continent diversion takedown or died of urethral recurrence. CONCLUSIONS: Transurethral biopsy did not accurately determine prostatic involvement. Prostatic involvement at biopsy or cystectomy translated into a higher risk of urethral recurrence. However, it did not have significant clinical impact or affect survival and should not be an absolute contraindication to urethral diversion.

MRI of vaginal leiomyomas.

The MR appearances of two cases of vaginal leiomyoma are described. Both patients presented with a periurethral mass; one patient presented during pregnancy. MRI allowed precise anatomic localization of the masses and confident preoperative characterization in both cases.

Mechanisms of prostatic stromal invasion in patients with bladder cancer: clinical significance.

PURPOSE: We assess the pathological mechanisms of silent prostatic stromal invasion in patients with bladder cancer for early detection and treatment. MATERIALS AND METHODS: Between August 1998 and January 1999, 10 patients with clinically organ confined transitional cell carcinoma of the bladder and known prostatic stromal invasion on transurethral biopsy or who were high risk for prostatic involvement due to tumor location near the bladder neck were studied for histological patterns of prostatic invasion. There were 5 cystectomy specimens distended for 24 hours with formalin via a Foley catheter, then step sectioned longitudinally at 3 mm. intervals through the bladder neck and prostate. Standard hematoxylin and eosin staining methods were used and sections were analyzed by 2 pathologists. RESULTS: There were 3 separate patterns of prostatic stromal invasion elucidated, including 2 previously described methods of extravesical or intraurethral invasion into the prostatic stroma and a third one through the bladder neck directly into the prostatic stroma. The third pattern was not grossly evident on endoscopy or urethral biopsy before cystectomy. CONCLUSIONS: Longitudinal sectioning of the bladder neck and prostate of cystectomy specimens suggests tumors at the bladder neck may directly invade the prostatic stroma without histological evidence of extravesical or intraurethral spread. Such direct silent tumor invasion of the prostate by superficial or endoscopically inapparent tumor is difficult to detect clinically by current biopsy methods. New methods of detection are necessary.

Post-chemotherapy surgery in patients with unresectable or regionally metastatic bladder cancer.

PURPOSE: We update our experience with post-chemotherapy surgery in patients with unresectable or lymph node positive bladder cancer. METHODS: Of 207 patients with unresectable or regionally metastatic bladder cancer 80 (39%) underwent post-chemotherapy surgery after treatment with a cisplatin based chemotherapy regimen. We assessed the impact of surgery on achieving a complete response to chemotherapy and on relapse-free survival. RESULTS: No viable cancer was present at post-chemotherapy surgery in 24 of the 80 cases (30%), pathologically confirming a complete response to chemotherapy. Of the 24 patients 14 (58%) survived 9 months to 5 years. Residual viable cancer was completely resected in 49 patients (61%), resulting in a complete response to chemotherapy plus surgery, and 20 (41%) survived. Post-chemotherapy surgery did not benefit those who failed to achieve a major complete or partial response to chemotherapy. Only 1 of the 12 patients (8%) who refused surgery remains alive. CONCLUSIONS: Post-chemotherapy surgical resection of residual cancer may result in disease-free survival in some patients who would otherwise die of disease. Optimal candidates include those in whom the pre-chemotherapy sites of disease are restricted to the bladder and pelvis or regional lymph nodes, and who have a major response to chemotherapy.

Outcome of patients with grossly node positive bladder cancer after pelvic lymph node dissection and radical cystectomy.

PURPOSE: Should the surgeon proceed with surgery when grossly positive nodes are found at cystectomy? To answer this question, we determine the outcome of patients after radical surgery alone for grossly node positive bladder cancer. MATERIALS AND METHODS: A total of 84 patients with grossly node positive (N2-3) bladder cancer found at cystectomy underwent extended pelvic lymph node dissection and have been followed for up to 10 years. The end point of study was disease specific survival. RESULTS: Of the 84 patients 20 (24%) survived and 64 (76%) died of disease. Median survival time was 19 months for all patients and 10 years for surviving patients. Of 53 patients with clinical stage T2 (organ confined) tumors 17 (32%) survived versus 3 of 31 (9.7%) with stage T3 (extravesical) tumors. CONCLUSIONS: A proportion of patients with grossly node positive bladder cancer can be cured with radical cystectomy and thorough pelvic lymph node dissection.

Magnetic resonance imaging and magnetic resonance angiography before postchemotherapy retroperitoneal lymph node dissection.

OBJECTIVES: Retroperitoneal lymph node dissection (RPLND) after primary chemotherapy is an accepted therapeutic approach for metastatic nonseminomatous germ cell testicular cancer. Because of the intense desmoplastic reaction and adherence to venous and arterial walls, accurate imaging of the retroperitoneal vasculature and its relation to residual tumor is essential. We report our experience with magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), including the recently developed technique of bolus-contrast MRA, in patients undergoing postchemotherapy RPLND. METHODS: Eighteen patients underwent MRI of the retroperitoneal region before RPLND. In addition to routine sequences, MRA was performed in 10 patients, including 8 with a three-dimensional technique using bolus intravenous MR contrast. Results were compared with intraoperative and pathologic findings. RESULTS: MRI and MRA provided detailed information on retroperitoneal vasculature and its relation to tumor, including multiple renal vessels (n = 5), duplex inferior vena cava (n = 1), left retroaortic renal vein (n = 2), and common iliac vein thrombus (n = 1). In all cases, bolus-contrast MRA provided unique information on the location and number of renal and lumbar arteries, in addition to information on the aorta and the mesenteric and iliac vessels. The origin and number of renal arteries were accurately identified in all patients by bolus-contrast MRA; 2 patients had supernumerary renal arteries discovered at RPLND that had not been identified on non-bolus-contrast MRI. CONCLUSIONS: Bolus-contrast three-dimensional MRA provides unique information on renal and lumbar vessels. The potential benefit of avoiding vascular injury during dissection should be prospectively evaluated.

Peri-operative care in patients treated for testicular cancer.

The success of combination chemotherapy in treating advanced metastatic germ cell tumors has led to new challenges for the genitourinary oncologic surgeon in the peri-operative care of patients. Surgery remains an integral part of the management of patients with advanced germ cell tumors. Retroperitoneal node dissections following chemotherapy or radiation, or both, are technically more demanding and subject to higher rates of peri-operative complications. Overall post-therapy surgical complication rates range from 33% to 75%, with the highest rates among patients who receive both radiation and chemotherapy. Although most patients with testicular cancer are young and healthy, residual pulmonary, renal, vascular, and neurologic toxicities from chemotherapy can increase the risk of peri-operative complications. In addition, the volume and location of tumor can increase the technical demands, especially when there is a tremendous soft tissue reaction to the chemotherapy. Identification of pre-operative risk factors for peri-operative complications is imperative and the first step in pre-operative planning. Pulmonary toxicity and vascular (cardiac or peripheral) events are the two most immediately life-threatening complications that can occur in the peri-operative period. Due to the high incidence of subclinical pulmonary toxicity, one must consider all patients who have received bleomycin pre-operatively at risk to develop postoperative pulmonary problems. Pre-operative evaluation and judicious fluid management have been shown to reduce the risk of life-threatening respiratory complications in the postoperative period.

Early nasogastric tube removal combined with metoclopramide after radical cystectomy and urinary diversion.

PURPOSE: Prolonged nasogastric decompression increases pulmonary complications by inhibiting clearance of respiratory secretions. The literature supports early nasogastric tube removal following bowel resection. Metoclopramide stimulates bowel activity, promoting return of function. We examined combining early nasogastric tube removal with metoclopramide after radical cystectomy. MATERIALS AND METHODS: From 1994 to 1996, 27 prospective cystectomy patients received intravenous metoclopramide (metoclopramide group) combined with early nasogastric tube removal (less than 24 hours). A total of 54 concurrent cystectomy controls received no metoclopramide and nasogastric tubes remained until return of normal bowel function. RESULTS: Preoperative and perioperative factors were comparable between the 2 groups. Nasogastric tubes were removed from 78% of the metoclopramide group in less than 24 hours, 11% on day 2 and 11% on day 3 compared to none on day 1, 50% on day 2 and 50% on day 3 or greater in controls. The metoclopramide group had a more rapid return of normal bowel sounds (2.9 versus 4.0 days, p = 0.0002) and earlier tolerance of solid food (6.7 versus 7.9 days, p = 0.04). Nasogastric tube replacement was required in 3 of 27 metoclopramide cases versus 5 of 54 controls. Atelectasis occurred more often in the control group (33 versus 15%). There were no bowel related complications in the metoclopramide group but partial small bowel obstruction in 2 controls was treated conservatively. CONCLUSIONS: This preliminary study suggests that combining intravenous metoclopramide with early nasogastric tube removal after cystectomy and urinary diversion may reduce postoperative atelectasis and speed return of bowel function while posing no danger to the small bowel anastomosis. This regimen may result in fewer complications and shorter hospitalizations, translating into lower costs without compromising quality of care.

Prostatic tumor relapse in patients with superficial bladder tumors: 15-year outcome.

PURPOSE: We assessed the outcome of patients with superficial bladder tumors with relapse in the prostate and defined prognostic variables of survival. MATERIALS AND METHODS: A cohort of 186 men with superficial bladder tumors was followed for 15 years. Tumor relapse in the prostate was classified as noninvasive (prostatic urethra and ducts) or invasive (stroma) with intraurethral or direct prostatic invasion. Bladder tumor stage at the time of prostatic relapse was defined as confined or not confined to the bladder. The end point of the study was disease specific survival. The effects of covariates on survival were estimated on multivariate analysis. RESULTS: Of the 186 patients 72 (39%) had relapse in the prostate after a median followup of 28 months (range 3 to 216), including 45 (62%) with noninvasive prostatic tumor and 27 (38%) with stromal invasion. The survival rate was 82% in patients with prostatic urethra or duct involvement compared to 48% with stromal invasion. Intraurethral stromal invasion was associated with a 75% 15-year survival rate versus 9% for extravesical prostatic stromal invasion. Bladder tumor stage and prostatic stromal invasion were independent prognostic variables of survival. CONCLUSIONS: The prostate is a frequent site of tumor relapse in patients with superficial bladder tumors followed for 15 years. Prostatic relapse may portend tumor invasion in the bladder and stromal invasion in the prostate, which significantly reduce survival.

Bleomycin associated pulmonary toxicity: is perioperative oxygen restriction necessary?

PURPOSE: We delineate predictive factors of pulmonary morbidity in patients who receive combination chemotherapy with bleomycin and undergo surgical resection of residual disease, and establish updated guidelines for perioperative management. MATERIALS AND METHODS: A total of 77 patients with high volume stage II to IV nonseminomatous germ cell tumors underwent 97 major surgical procedures a mean of 6.4 months following high dose combination chemotherapy, including bleomycin (mean 437.5 units per 8.2 courses), between 1988 and 1995 at the University of Texas M. D. Anderson Cancer Center. The importance of preoperative pulmonary status, anesthesia time, fraction of inspired oxygen, fluid balance, bleomycin dose, number of acute toxicity episodes, oxygen saturation problems and pulmonary symptoms was examined. Cases were divided into groups according to whether there were postoperative oxygen saturation problems (19) or not (58). RESULTS: There were no significant differences in age, weight, bleomycin dose, number of acute toxicity episodes, cardiac ejection fraction or preoperative pulmonary symptoms between the 2 groups. Restrictive spirometry patterns were seen in 26 of 74 patients (35%), only 9 of whom had postoperative oxygen saturation problems. Mean induction fractional inspired oxygen was 87% (median 100%) for an average of 56 minutes. Intraoperative fractional inspired oxygen averaged 40% for a mean duration of 8.1 hours. Postoperative oxygen saturation problems, consisting of prolonged intubation, pulmonary edema, dyspnea, tachypnea or desaturation requiring diuresis, occurred in 19 patients (25%). Surgery/anesthesia time, amount of blood transfused, estimated blood loss, fluid balance, type of fluid given (all p < 0.0001) and preoperative forced vital capacity (p = 0.012) were significant predictors of postoperative oxygen saturation problems on univariate analysis. On multivariate analysis only the amount of blood transfused, preoperative forced vital capacity and surgical time in descending order remained significant. Maintained intraoperative fractional inspired oxygen was not significant on either analysis. There were no deaths. CONCLUSIONS: Perioperative oxygen restriction in patients treated with bleomycin is not necessary. Intravenous fluid management, including transfusion, appears to be the most significant factor affecting postoperative pulmonary morbidity and overall clinical outcome. In addition, post-chemotherapy forced vital capacity and operative time are significant predictive factors of procedure related pulmonary morbidity.

Methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy and cystectomy for unresectable bladder cancer.

PURPOSE: We combined chemotherapy and surgery to improve local control and survival of patients with unresectable bladder cancer. MATERIALS AND METHODS: A total of 41 patients with unresectable bladder cancer (T4bNX/N + M0) received methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) chemotherapy followed by radical cystectomy when possible. End points were response to M-VAC, local control and survival. RESULTS: Minimum followup was 4 years (range 4 to 7). Of the 41 patients 14 (34%) achieved a complete (T0) and 27 (66%) achieved an incomplete (T+) clinical response to M-VAC, including 29 who underwent exploration and 24 who underwent cystectomy. Definitive surgery was not done in 17 patients due to lack of response to M-VAC with local or systemic tumor progression, or refusal. Nine patients (22%) are alive, including all but 1 after cystectomy for T0 disease, and 2 had T+ tumor confined to the bladder for longer than 5 years. None of the patients with no response or tumor progression on M-VAC survived. Resection of extravesical disease after M-VAC in 16 patients did not prolong survival or improve local tumor control. Six patients required laparotomy for palliation of tumor related complications. CONCLUSIONS: Our results suggest that patients who present with unresectable bladder cancer may benefit from M-VAC and definitive surgery, especially when disease is T0 and P0 status. Surgery may salvage select cases of advanced pelvic tumor down staged by chemotherapy to tumors pathologically confined to the bladder. Alternative treatment strategies are needed for the majority of patients with locally advanced bladder cancer.

Ureteral decompression in advanced nonurologic malignancies.

BACKGROUND: The purpose of this study was to assess the morbidity and determine survival after ureteral decompression in patients with advanced nonurologic malignancies. METHODS: Between June 1988 and June 1993 78 patients were referred to a single surgeon for ureteral decompression. Records were analyzed in relation to primary diagnosis, early and late complications, number of hospitalizations, and survival after decompression. RESULTS: Seventy-two percent of patients initially underwent decompression endoscopically, and 28% required percutaneous nephrostomy placement at initial decompression. Complications occurred in 50% of patients and most commonly included infection (29%), stent obstruction and encrustation (28%), and gross hematuria (9%). The median survival for all patients after the first decompression procedure was 6.8 months (range 0.5-46.1), with an actuarial survival rate at 1 year of 55% and at 3 years of 30%. The eight patients with gastric/pancreatic cancer survived a median of just 1.4 months after decompression (range 0.77-11.8), with a 1-year actuarial survival rate of 12.5% and 3-year actuarial survival of 0%, which was significantly worse when compared with all other groups taken together or individually (p < 0.03). CONCLUSIONS: Ureteral decompression procedures in patients with advanced cancer can be an important component of palliative care but are associated with significant morbidity (50%) in patients whose median survival is < 7 months. The role of ureteral decompression in patients with advanced gastric and pancreatic cancer is limited.

Bladder preservation and continent urinary diversion in T3b transitional cell carcinoma of the bladder.

The patient with T3b transitional cell carcinoma (TCC) of the bladder has traditionally been treated with radical cystectomy and urinary diversion, but initial success with systemic chemotherapy and renewed interest in quality-of-life issues has increased interest in bladder preservation treatments. Unfortunately, despite multiple trials using limited surgical procedures and neoadjuvant or adjuvant chemotherapy, no combined modality has consistently improved survival over the achieved with radical cystectomy alone in patients with T3b disease. Additionally, continent stomal diversions and orthotopic neobladders allow almost normal continence and voiding in both male and female patients, which calls into question the need for bladder preservation. Although no single treatment modality or urinary diversion is right for all patients, a radical cystectomy with continent diversion provides the best chance for survival and allows the best postoperative quality of life. If bladder preservation treatments are used, inclusion in a clinical trial is recommended.

Salvage radical prostatectomy in the management of locally recurrent prostate cancer after 125I implantation.

OBJECTIVE: To define the role of salvage prostatectomy in patients who have locally recurrent prostate cancer following pelvic lymph node dissection and 125I implantation. PATIENTS AND METHODS: Over 1000 patients underwent 125I implantation for localized prostate cancer at the Memorial Sloan Kettering Cancer Center between 1970 and 1986. Salvage radical prostatectomy was performed in a highly selected group of 10 patients with locally recurrent disease. RESULTS: Three of the 10 patients had organ-confined residual prostate cancer following salvage radical prostatectomy. The remaining seven patients had extra-prostatic disease including four patients with positive surgical margins. Two patients with organ-confined disease and one with extracapsular tumour had no evidence of locally recurrent or metastatic disease and continue to have undetectable prostate-specific antigen (PSA) levels at 50, 44, and 31 months following salvage radical prostatectomy. After a mean follow-up of 30 months, the remaining seven patients had a rising PSA level consistent with locally persistent and/or metastatic disease (median 5 ng/mL; range 1.0-144). This PSA elevation occurred within 20 months of salvage radical prostatectomy (median 6 months). Two of these patients developed clinically evident bone metastases. CONCLUSION: Salvage radical prostatectomy, although technically feasible in highly selected patients, should not be widely advocated as an effective treatment option for patients with locally recurrent prostate cancer after 125I implantation.

Reversal by transferrin of growth-inhibitory effect of suramin on hormone-refractory human prostate cancer cells.

BACKGROUND: The second leading cause of cancer-related deaths in American men is metastatic hormone-refractory adenocarcinoma of the prostate, for which there is currently no effective treatment. Transferrin is abundant in bone stroma and has been found to stimulate models of hormone-refractory metastatic prostate cancer. Suramin, a compound that has been used to treat metastatic prostate cancer, has been demonstrated to antagonize the binding of transferrin to the transferrin receptor and to suppress uptake of iron by hematopoietic cells. PURPOSE: The purpose of our study was to determine whether transferrin may reverse the inhibitory action of suramin on metastatic prostate-derived cell lines. METHODS: Five human prostate cell lines (PC-3, PC-3M, DU-145, TSU-Pr1, and LNCaP) derived from metastatic deposits were examined for response to growth stimulation by apotransferrin, for the presence of transferrin receptors by binding of 125I-labeled transferrin, and for relative transferrin receptor messenger RNA (mRNA) content by ribonuclease protection assays. We measured the amount of growth inhibition by suramin in low serum assays to demonstrate maximal inhibition over the apotransferrin to reverse the inhibition of suramin in these tumors. RESULTS: The results clearly demonstrate that the androgen-insensitive metastatic cell lines (PC-3, PC-3M, DU-145, and TSU-Pr1) demonstrate increased cell numbers when exposed to holotransferrin or apotransferrin, while the androgen-sensitive cell line (LNCaP) did not show any increase. All cell lines demonstrated a similar number of transferrin receptors and transferrin receptor mRNA. We used these maximally inhibitory, but clinically relevant, concentrations of suramin to determine whether transferrin could reverse the inhibition, and it did, but only in the androgen-insensitive metastatic lines. Indeed, in the PC-3 cells, inhibition turned to stimulation with the addition of transferrin, and even at the highest concentration of suramin tested, 400 microM, a concentration that would be toxic to patients, the amount of inhibition by suramin was still reduced by more than 50% by transferrin in TSU-Pr1 cells. In the androgen-sensitive LNCaP cells, however, transferrin had limited ability to block the inhibitory activity of suramin. CONCLUSIONS: Concentrations of tumor-stimulating factors, such as transferrin, in the metastatic microenvironment need to be taken into consideration in the use of suramin and suramin-like derivatives. Novel strategies need to be identified that will negate the action of transferrin on androgen-insensitive cells.

Intrathoracic kidney: a case report with a review of the world literature.

We report a case of a right intrathoracic kidney and review the literature. The possible etiologies of intrathoracic kidneys are discussed.