Sexual potency following interactive ultrasound-guided brachytherapy for prostate cancer.

PURPOSE: The effect of a therapeutic modality on sexual potency is often an important consideration for patients choosing a treatment for prostate cancer. We prospectively assessed patients' penile erectile function before and following interactive ultrasound-guided transperineal permanent radioactive seed implantation to determine its effect on sexual function. METHODS AND MATERIALS: Eighty-nine patients underwent permanent radioactive seed implantation from June 1990 to April 1994 for localized prostate cancer (T1-T2) and were followed for a median of 15 months (1.5-52 months). 125I seeds were implanted in 73 patients with a combined Gleason grade of 2-6, and 103Pd seeds were implanted in 16 patients with higher grade lesions. The sexual potency of these patients was assessed prior to, at 3 and 6 months, and every 6 months after implantation. Erectile function was graded using a numerical score of 0 to 3 (0 = impotent (no erections), 1 = ability to have erections but insufficient for vaginal penetration, 2 = erectile function sufficient for vaginal penetration but suboptimal, 3 = normal erectile function). The pretreatment potency scores were as follows: 0 in 24 patients, 1 in 6 patients, 2 in 22 patients, and 3 in 37 patients. RESULTS: The actuarial impotency rates (score = 0) following implantation for those patients possessing some degree of erectile function prior to implantation (65 patients) were 2.5% at 1 year and 6% at 2 years. The actuarial decrease in sexual function rates (a drop in score of at least one point) were 29% at 1 year and 39% at 2 years. Only two patients became impotent following treatment and this occurred at 1 year and 16 months. The time period for a decrease in erectile function to occur ranged from 1.8 months to 32.7 months, with a median of 6.8 months. Patients with higher grade tumors showed a greater decrease in potency score compared to patients with lower grade tumors. CONCLUSION: Interactive ultrasound-guided transperineal brachytherapy for the treatment of localized prostate cancer is associated with preservation of erectile function in the vast majority of patients, although a minor decrease in potency is not uncommon.

A dose-response study for I-125 prostate implants.

PURPOSE: No dose-response study has ever been performed for I-125 prostate implants using modern techniques of implant evaluation and modern treatment outcome end points. The amount of activity per volume implanted was increased over time based on review of postimplant dosimetry. This resulted in different delivered dose levels. This study explores the relationship between dose, biochemical failure, and biopsy results. MATERIALS AND METHODS: 134 patients with T1-T2 prostate cancer were implanted with I-125 radioactive seeds and followed from 12 to 74 months (median: 32) postimplant. No patient received external beam irradiation or hormonal therapy. All patients implanted with I-125 had Gleason scores < or =6. One month postimplant, a CT-based three-dimensional dosimetric evaluation was performed on all patients. Using TG43 guidelines, dose-volume histograms were calculated. The dose delivered to the gland was defined as the D90 (dose delivered to 90% of prostate tissue as defined by CT). The D90s ranged from 26.8 to 256.3 Gy (median: 140.8 Gy). Biochemical failure was defined as two consecutive rises in prostate specific antigen (PSA) or a nadir level above 1.0 ng/ml. Posttreatment prostate biopsies (six to eight core samples) were routinely performed at 2 years postimplant. RESULTS: Improvements in freedom from biochemical failure (FFBF) rates were seen with increasing D90 levels. The 4-year FFBF rates for patients with D90 values < 100 Gy, 100-119.9 Gy, 120-13.9 Gy, 140-159.9 Gy, and > or =160 Gy were 53, 82, 80, 95, and 89%, respectively (p = 0.02). Patients receiving a D90 < 140 Gy (65 patients) were similar with respect to presenting disease prognostic factors to those receiving a D90 > or =140 Gy (69 patients). Patients receiving a D90 < 140 Gy had a 4-year FFBF rate of 68% compared to a rate of 92% for those receiving a D90 > or =140 Gy (p = 0.02). Two-year posttreatment biopsies were negative in 70% (33 of 47) of patients with a D90 < 140 Gy compared to a rate of 83% (24 of 29) in patients with a D90 > or =140 Gy (p = 0.2). A multivariate analysis using dose, PSA, score, and stage revealed that dose was the most significant predictor of biochemical failure (p = 0.001). This dose response was more pronounced in patients presenting with PSA levels > 10 ng/ml. In these patients, the 4-year FFBF rates were 51 and 100% for the low and high dose groups, respectively (p = 0.009) and the negative biopsy rates were 64% (14 of 22) and 100% (8 of 8), respectively (p = 0.05). In patients with presenting PSA <10 ng/ml, the 4-year FFBF rates were 82 and 88% for the low and high dose groups, respectively (p = 0.29). CONCLUSION: A dose response was observed at a level of 140 Gy. Adequate I-125 implants should deliver a dose of 140-160 Gy using TG43 guidelines.

Cholangitis associated with cholecystitis in patients with acquired immunodeficiency syndrome.

Four patients with acquired immunodeficiency syndrome developed severe abdominal pain and fever due to acute acalculous cholecystitis. In all patients, preoperative laboratory data showed elevation of alkaline phosphatase and gamma-glutamyltransferase levels. Endoscopic or intraoperative cholangiography showed signs of intrahepatic and extrahepatic cholangitis. Cholecystectomy was performed and prompt relief of symptoms was achieved in all patients; no postoperative complication was observed. One patient did not develop any recurrence during an 18-month period of follow-up; two patients died 2 and 3 months after the operation. One patient developed recurrent abdominal pain and cholestasis 4 months after the operation, with dilatation of the common bile duct and papillary stenosis due to progression of cholangitis. These observations suggest that cholangitis is frequently associated with cholecystitis in patients with the acquired immunodeficiency syndrome. Its pathogenesis is not known.

Screening breast cancer patients for ATM mutations and polymorphisms by using denaturing high-performance liquid chromatography.

All 62 coding exons of the ATM gene, along with 10-20 bases of the intronic region flanking each exon, were screened for DNA base sequence alterations by using denaturing high-performance liquid chromatography (DHPLC) in a series of 52 breast cancer patients. Six (12%) of these patients exhibited a total of eight different novel germ-line mutations that do not represent common polymorphisms. Of these, three patients possessed four nonconservative missense mutations while two conservative missense and two synonymous mutations were detected in the other three patients. In addition, 43 patients were found to have a total of 141 DNA sequence variations representing 21 different common polymorphisms and rare variants. An analysis of the relationship between the presence of a novel ATM mutation and either patient demographics or tumor properties demonstrated a significant difference between African Americans (3/7 = 43%) and other ethnic groups (3/45 = 7%, P = 0.026). None of the other characteristics examined was found to be related to mutation status.

Elective cholecystectomy in selected cirrhotic patients.

Of the 53 cirrhotic patients with cholelithiasis observed at our Institution from 1978 to 1991, 31 were operated on. Twenty-eight Child-Pugh class A, two class B and one class C patients underwent elective cholecystectomy with (5 cases) or without (26 cases) common bile duct exploration. Among the symptomatic patients, nine (18.7%) were refused for surgery because the risk was estimated to be too high. Symptoms ranged from mild-moderate abdominal pain to typical biliary colic. Acute biliary inflammatory complications as cholecystitis or cholangitis could be detected in the clinical history of 5 patients (16%). Although a common clinical feature, jaundice was directly related to gallbladder or common bile duct stones only in one half of the cases. A total of 18 postoperative non-lethal complications occurred in ten patients (32.2%), with haemorrhage from the gallbladder bed being the most frequent event. Bleeding was associated with increased prothrombin time more than 1.5 seconds above the control (p < 0.01) but severe haemorrhage occurred only when the platelet count was less than 100.000/ml (p < 0.05). Common bile duct explorations increased the risk of bleeding. Two of the 3 class B or C patients developed ascites (p < 0.05). It is concluded that elective cholecystectomy can be performed without mortality in selected and symptomatic patients with adequate hepatic functional reserve.

Information systems for the management services organization.

The growth of the management of services organization has been accompanied by the need for better information technology systems to track both patient and physician utilization. The author describes some possible benefits of customizing an information system to meet the needs of these specialized organizations.

[Evaluation of prognostic factors in general surgery; methodological aspects of a multicenter prospective study of 1182 patients]. / Valutazione dei fattori prognostici in chirurgia generale: aspetti methodologici di uno studio prospettico multicentrico su 1182 pazienti.

Surgical risk is defined as the probability of occurrence of early or late complications. For each patient, knowledge of factors affecting surgical risk in a basic step when evaluating prognosis after surgery and determining therapeutic decision. A greater and more effective information may be obtained studying variables within the context of the other ones that more or less condition them. Such a "multivariate" approach allows simultaneously investigating all characteristics by taking account of their correlations. Specification of the problem, choice of the relevant variables, data collection and statistical data processing were considered. Pros and cos of multiple logistic regression model in the assessment of surgical risk were reviewed. The index could be used to identify the most important factors in determining surgical risk and quantify their respective importance. In this way surgical patients could be classified according to risk level. This approach also allow for the concurrent investigation of various potential risk factors and their interactions. For this reason it is termed multifactorial.

[Evaluation of the surgical risk in general surgery: usefulness of a predictive system based on statistical analysis]. / La valutazione del rischio operatorio in chirurgia generale: utilità di un sistema predittivo basato sull'analisi statistica.

1182 patients were prospectively studied in order to evaluate the surgical risk factors. Stepwise regression logistic procedure was employed for statistical analysis. Postoperative complications included death, cardiac, respiratory, hepatic and renal failure, wound infection and sepsis. Various preoperative conditions were associated with postoperative complications but some of them, as malnutrition or operations prolonged over two hours, occurred more frequently. Age did not appear as a major risk factor. The determination of surgical risk is a major problem in general surgical practice and many attempts have been realized in order to predict postoperative outcome. Clinical judgment is still nowadays fundamental but predictive scores based on statistical analysis have proved to be valid and useful tools. The authors underline the importance of surgical risk prediction in therapeutic programming, especially in the aged and in cancer patient. The surgical or non surgical option and the type of operation to be performed result from a careful evaluation of operative risk and expectancy and quality of life.

[Identification of the patient at risk of postoperative infectious complications: risk factors and their evaluation]. / Identificazione del paziente a rischio di complicanze settiche post-operatorie: fattori di rischio e loro valutazione.

The authors report their results of a prospective study on 1182 patients who underwent surgical operation relatively on postoperative infections. Studied variables were: structural and anamnestic: sex, age, smoking, drinking; clinical: evidence of functional changes in various organs, as assessed upon clinical basis and laboratory results; pertinent to surgical intervention: entity, duration, anaesthesia; during and early-after-surgery complications (until discharge or within 30 days since intervention). Stepwise logistic regression model was applied to this set of preoperative and operative factors, four of which were found significantly correlate with postoperative infections: bacterial contamination during surgery, duration surgical intervention greater than 120', cholestasis, serum albumin.

[Multifactorial surgical risk index of the development of respiratory complications]. / Indice di rischio chirurgico multifattoriale per lo sviluppo di complicanze respiratoire.

Respiratory events are between the most frequent postoperative complications. The preoperative conditions associated with postoperative respiratory failure were evaluated in a prospective study of 1182 patients from six Italian Surgical Units. Multiple regression logistic analysis was employed for statistical evaluation and a predictive prognostic score was derived. Only the presence of the following conditions was significant in affecting postoperative respiratory outcomes: preoperative respiratory and cardiac failure, hypotransferrinemia, prolonged surgical procedures (above the 2 hours) and peroperative bacterial contamination. Advanced age did not appear as a major risk factor. Studies on the predetermination of the pulmonary complications have been widely published. Historical risk factors include the presence of respiratory disease, smoking habits, obesity and thoracic or upper abdominal surgical procedures. Although the results of the present study need a prospective confirmation, the predictive scoring system proves to be a usefull tool that can be employed in most of the General Surgery Units.

[Heart complications in general surgery: results of a multicenter study]. / Analisi delle complicanze cardiache in chirurgia generale: risultati di uno studio multicentrico.

Cardiac events are the most dangerous postoperative complications since they may be easily followed by the death of the patient. The related risk factors were prospectively evaluated in a study of 1182 patients. Stepwise regression logistic model was employed for statistical analysis. Preoperative cardiac and respiratory failure, ventricular arrhytmias, compromission of the nutritional status, presence of neoplastic disease and prolonged anesthesia over two hours were the only significative factors related to postoperative cardiac complications. Advanced age was not a major risk factor. The results of the study require a prospective validation. They are however comparable to those observed in the literature Preoperative cardiac evaluation is of utmost importance for cardiac prognosis and various instrumental, sometimes invasive diagnostic procedures have been proposed. The Authors provide a usefull, simple and widely employable system of general and cardiac assessment for the determination of cardiac risk.

[The risk factors for liver and kidney complications in general surgery: the results of a prospective multicenter study]. / Fattori di rischio per le complicanze epatiche e renali in chirurgia generale: risultati di uno studio prospettico multicentrico.

A method for preoperative assessment of surgical risk, in function of several risk factors, was developed using the multiple logistic function, as a model of multivariate statistical analysis. This model has the advantage to express the two considered outcomes (perioperative complications and death) in numerical terms of probability. The data were obtained from 1182 consecutive patients, 14 yrs or more, admitted to six centres in various regions of Italy. Stepwise logistic regression model was applied to a set of preoperative and operative factors, three of which were found to significantly correlate with postoperative hepatic failure: compromission hepatic function time of surgical operation > 120' and nutritional status. The factors significantly correlate with postoperative renal failure were: compromission renal function, bacterial contamination during surgery, time of surgical operation > 120'.

[Analysis of mortality and relative prognostic factors in general surgery: use of the multiple logistic regression model]. / Analisi della mortalità e dei relativi fattori prognostici in chirurgica generale: utilizzazione del modello di regressione logistica multipla.

Surgical risk is defined as the occurrence of complications arising in the individual as a result of surgical stress. The ability to forecast these consequences is an important factor in determining decision taken by surgeon. Several attempts have been made to quantify postsurgical prospects but up till now no overall solution has been found. This paper attempts to define a multifactorial risk index for adults subjected to surgery, with respect to immediate and early per- and post-surgical complications. 1182 adult patients, 14 yrs or more, surgically treated not for urgency during 1985 in six Italian centres, were prospectively studied in order to derive a multivariate prognostic index of after surgery mortality. Stepwise logistic regression model was applied to a set of preoperative and operative factors, five of which were found significantly correlate with death: nutritional status, renal failure, reintervention, bacterial contamination during surgery, age greater than 70 years. Thus, from regression coefficients, scores were derived for modalities of significant variables, allowing to build four classes of risk patients: low (less than 1%), medium (between 1% and 10%), high (between 10% and 50%), extremely high risk (greater than 50%).

[Mortality and clinico-prognostic significance of risk factors in geriatric surgery]. / Mortalità e valenza clinico-prognostica di alcuni fattori di rischio in chirurgia geriatrica.

A prospective study for assessment of operative risk in elderly patients was carried in 1182 adult patients, 14 yrs or more, surgically treated not for urgency during 1985 in six Italian centres. Looking for meaningful relations among prognostic factors and outcome of disease is a relevant topic in biomedical of surgical risk was the use of multiple logistic function. Anamnestic, clinical and surgical variables were "explicative" variables, while occurrence of death and postoperative complications were "response" variables. Multipathology (myocardiosclerosis, respiratory failure) frequently associated with advanced age (greater than 70 yrs) contribute to determine the prognosis in surgery of elderly patient. Stepwise logistic regression model was applied to a set of preoperative and operative factors, five of which were found to significantly correlate with death: nutritional status, renal failure, reintervention, bacterial contamination during surgery, age greater than 70 years. From our data some conclusion may be drown: it is emphasized the major role of surgical factors in affecting the postoperative risk; among clinical variables, renal failure furnishes the most relevant contribution to prognosis; advanced age itself does not substantially affect the surgical risk, its role being confounded by association with other pathologies.

Duodeno-jejunal tumors. Report of 9 cases and literature review.

Nine patients with tumors of the duodenum and the jejunum are described herein and the Literature is reviewed. Of the six patients with a duodenal tumor, five had an adenocarcinoma and one a Brunner's gland adenoma. A predominance of inframpullary tumors was observed within the duodenum. Jaundice and abdominal pain were, respectively, the most common presenting symptoms of the tumors localized in the periampullary and inframpullary region. Treatment was curative in four and palliative in two cases. Duodenopancreatectomy was the treatment of choice for periampullary tumors whereas segmental resection was performed in the only resectable distal duodenal tumor. Of the three patients with jejunal neoplasms, one had an adenocarcinoma arising in the efferent loop of a Billroth II gastrojejunostomy performed 40 years before and two had an high malignant lymphoma. All three the tumors could be resected. According to the Literature, our results show that: 1. The diagnosis of duodeno-jejunal tumors is usually late: 2. Although of critical importance in the improvement of the overall diagnostic accuracy, endoscopy may be inconclusive or even misleading if the entire duodenum is not explored; 3. If duodenopancreatectomy is mandatory for periampullary tumors, segmental resection seems to be an adequate procedure for tumors of the distal duodenum since it does not ignore lymphatic nodes, can be easily performed and has a low postoperative complication rate.

[Cystadenoma of the pancreas: the clinical and preoperative diagnostic problems]. / Il cistoadenoma del pancreas: problemi di clinica e diagnosi preoperatoria.

Pancreatic cystadenomas must be considered in the differential diagnosis of all cystic neoplasms of the pancreas. On the basis of a clinical observation, the authors discuss the most important clinical and diagnostic findings of pancreatic cystadenomas with special regard for what concerns the mucinous type. The authors underline the extreme difficulty of a correct preoperative diagnosis and discuss, after a wide literature review, the utility and the validity of the various imaging, cytological and immunohistochemical preoperative diagnostic procedures. In most cases the final diagnostic confirmation comes from the histology on the resected specimen; therefore all cystic neoplasms, no matter their location within the gland, which are not clearly identified pre or intraoperatively, should be surgically treated and removed.

[Alternative methods of the pancreatico-jejunal anastomosis in resective pancreatic surgery]. / Metodiche alternative alle anastomosi pancreatico-digiunali nella chirurgia resettiva pancreatica.

Pancreaticojejunostomy is still followed by an unacceptable mortality and it warns the necessity to find and to verify more safe alternative methods in the management of pancreatic stump. In this work we analyze the results concerning 14 cases of pancreatic resections in which a pancreaticojejunostomy was not performed but the stump was closed with a mechanical stapler. Distal pancreatectomy with stapler was characterized by a low morbidity (11%) without mortality; this technique is therefore certainly reliable and it may be preferred for its facility and its rapidity. Pancreaticoduodenectomy with stapler has not appeared sufficiently sure, however, some technical improvements, as additional ligation of the pancreatic duct, the pharmacological inhibition of the exocrine secretion and a more extensive resection, seem to be able to make this technique as much reliable.

PSA kinetics following I-125 radioactive seed implantation in the treatment of T1-T2 prostate cancer.

Although there is renewed interest in prostate brachytherapy, little information is available on the effect of the procedure on prostate-specific antigen (PSA) changes over time. This study describes PSA kinetics after iodine-125 (I-125) transrectal ultrasound-guided transperineal implantation of the prostate. From February 1991-September 1997, 207 patients were treated with an I-125 prostate implant alone for T1-T2 prostate cancer. PSA values were obtained prior to treatment and at 1-73 months (median, 24 months). The change in PSA after implantation of the prostate was measured as a fraction of the pretreatment PSA (PSA at follow-up/pretreatment PSA). PSA failure was defined as two elevations in PSA or PSA > 1 ng/ml. One hundred fifty-five patients had PSA values recorded at the 1-month time period. A PSA value greater than the pretreatment PSA at 1 month was found in 27% (42/155). This had no significant effect on future PSA failure. The median percentage change in PSA after implantation for all patients were as follows: 1 month, 0.73; 3 months, 0.30; 6 months, 0.18; 12 months, 0.12; 18 months, 0.12; 24 months, 0.08; 30 months, 0.07; 36 months, 0.08; 42 months, 0.08; and 48 months, 0.05. The most significant decline occurred in the first 12 months. This was followed by a more gradual decline between 12-24 months. There was little change in PSA values after 24 months. The 1-year PSA value had a significant effect on PSA failure. Patients with a 1-year PSA <1 ng/ml (66) had an actuarial 4-year freedom-from-failure rate of 90%, compared to a rate of 62% for those with values >1 ng/ml (69) (P = 0.002). Twenty-seven patients developed PSA failure. The time to PSA failure ranged from 12-48 months (median, 24 months), but most (20/27) failures occurred after 18 months. We conclude that the greatest decline in PSA after I-125 implantation of the prostate occurs during the first year, and little change occurs after 2 years. A 1-year PSA value > 1 ng/ml is highly predictive of eventual PSA failure, which occurs in most patients after 18 months posttreatment.

Acute urinary morbidity following I-125 interstitial implantation of the prostate gland.

The objective of this paper was to evaluate the acute urinary morbidity associated with I-125 interstitial implantation of the prostate gland. From 1991-1995, 117 patients underwent ultrasound (U/S)-guided implantation of the prostate gland. Median dose to 90% of the gland (d90) was 14.68 Gy (range = 1.65-21.75 Gy). The patients' urinary symptoms were recorded pre-implantation and at regular intervals after implantation using the International Prostate Symptom Score (IPSS), a self-assessment questionnaire in which patients scored 7 symptoms: incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia. Median follow-up was 12 months. The natural history of implant-related urinary symptoms was assessed in this manner. In addition, dosimetric factors including U/S prostate volume, total activity, activity per seed, dose volume histogram (DVH) values for dose to gland, and dose area histogram (DAH) values for dose to urethra and bladder were examined for correlation to the severity of each symptom as well as to total IPSS (sum of the individual symptom scores). Total IPSS peaked at 1 month post-implant and gradually returned to approximately baseline at 24 months. Total IPSS directly correlated with total activity and DVH for the prostate. Total IPSS, however, did not correlate with bladder or urethral DAH. With the exception of frequency, individual symptoms did not correlate with dose to gland, bladder, or urethra. Frequency scores did, however, correlate not only with dose to prostate gland but also dose to urethra. The acute urinary side effects of I-125 prostate implantation are transient and peak at 1 month post-implant. The severity of the urinary irritative symptoms developed are closely related to total dose to the gland. Urethral dose appears to affect frequency most significantly. Urinary symptoms, therefore, may be a limiting factor when considering dose escalation with I-125.

The effect of disease and treatment-related factors on biopsy results after prostate brachytherapy: implications for treatment optimization.

BACKGROUND: Posttreatment prostate biopsy is a method of assessing local control after irradiation for prostate carcinoma. An analysis of the effect of disease- and treatment-related factors on biopsy results after prostate brachytherapy was performed to aid in patient selection and treatment optimization. METHODS: Two hundred sixty-eight patients underwent posttreatment prostate biopsy (6-8 cores) 2 years after brachytherapy alone without external beam irradiation. Follow-up ranged from 24 to 111 months (median, 43 months). Implants were performed using a real-time ultrasound guided technique with the isotopes (125)I in 186 and (103)Pd in 82 patients. Ninety-eight patients underwent hormonal therapy (HT) 3 months before and 2-3 months after implant. Implant dose was defined as the D90 (dose delivered to 90% of the gland from the dose volume histogram generated using 1-month computed tomography-based dosimetry). RESULTS: Overall, 89% of patients (238 of 268) had negative biopsies. A positive biopsy was a predictor of biochemical failure. Patients with a positive biopsy had a 5-year freedom from biochemical failure of 40% versus 76% for patients with a negative biopsy (P = 0.0003). Univariate and multivariate analysis found that risk group, HT, and implant dose significantly affected biopsy outcome. Patients with low risk features (prostate specific antigen [PSA] 10 ng/mL or Gleason score >/= 7 or classification T2b or higher) (n = 164) (P = 0.008). Hormonal therapy was associated with a negative biopsy rate of 98% versus 84% for implant alone (P = 0.003). Patients receiving a high implant dose (D90 >/= 140 grays [Gy] for (125)I or >/= 100 Gy for (103)Pd) (n = 174) had a negative biopsy rate of 95% versus 77% for those receiving a low dose (D90 < 140 Gy for (125)I or < 100 Gy for (103)Pd) (n = 87; P < 0.001). CONCLUSIONS: Biopsy results support the use of brachytherapy without external beam irradiation for patients with low risk features and highlight the importance of achieving an adequate implant dose.