Novel markers of graft outcome in a cohort of kidney transplanted patients: a cohort observational study.

Renal biopsy (RBx) informs about kidney transplantation (KTx) prognosis. In our observational study the prevalence of histological anomalies and the prognostic role of CD45, vimentin (VIM) and periostin (POSTN) in KTx-RBx have been evaluated. One hundred forty-six KTx-RBx (2009-2012) were analysed for general histology and in immunohistochemistry for CD45, VIM and POSTN. Clinical data of the 146-KTx patients were collected at the RBx time (T0), 6 and 12 months before and after RBx. Follow-up time was 21 ± 14 months. Glomerulosclerosis was 20% glomeruli/biopsy. Tubular atrophy (TA), Interstitial infiltrate (I-Inf) and interstitial fibrosis (IF) were slight in 21-18% and 25%, moderate in 22-30% and 26% and severe in 30-18% and 28% of patients. Fifty-eight percent of patients had lesions compatible with IF-TA. CD45, VIM and POSTN correlated to each-other and to TA, I-Inf and IF. VIM and POSTN correlated to GS. CD45 and VIM correlated directly to renal function (RF) and 25(OH)VitD, while POSTN inversely to 25(OH)VitD. Thirty patients restarted dialysis (HD+). HD+ had lower T0-eGFR, and higher CD45, VIM and POSTN than HD-. POSTN resulted the strongest in discriminate for HD+ . CD45, VIM and POSTN correlate to each-other and predict graft outcome. POSTN was the strongest in discriminate for HD+. 25(OH)VitD might influence inflammation and fibrosis in KTx.

Orchiectomy alone in clinical stage I nonseminomatous testis cancer: a critical appraisal.

Sixty-two consecutive patients with clinical stage I nonseminomatous testicular cancer were entered into a prospective study to receive no treatment after orchiectomy until clinical evidence of recurrent disease. Of 59 evaluable cases, 41 (69.5%) remained continuously disease free for a median duration of 30 months (range, 18 to 46 months), and evidence of metastatic disease developed in 18 patients (30.5%) from 2 to 36 months after orchiectomy. The median disease-free interval for relapsing patients was 6 months. Retroperitoneal metastases developed in ten patients; seven patients had pulmonary metastases, and one patient had progressive elevation of the serum alpha-fetoprotein level. Relapses were significantly more frequent in patients with either embryonal carcinoma, infiltrating testicular cancer (pT greater than 1), peritumoral vascular invasion, or in those who underwent transscrotal biopsy. One patient with relapse refused salvage therapy and died. The remaining 17 patients have been rendered disease free with cisplatin combination chemotherapy and/or surgery. However, two patients showed further recurrence, with one in the lung and the other one also in the retroperitoneal nodes. In our opinion, surveillance following orchiectomy will provide useful information in clinical stage I nonseminomatous testicular cancer, but it is a difficult study. For the time being, it should be restricted to specialized centers only. In the meanwhile, retroperitoneal lymphadenectomy remains the standard treatment.

[Description of 5 cases of rhabdomyosarcoma of the testis]. / Descrizione di 5 casi di rabdomiosarcoma del testicolo

The paper reports 5 cases of paratesticular rhabdomyosarcoma in patients of 10 to 18 years of age out of 438 cases of testicular tumours admitted to the Istituto Naxionale per lo Studio e la Cura dei Tumori in Milan (1.14%). Two cases were far advanced and died within a few months despite chemotherapy and radiotherapy. Only one of the three operated patients was cured and is still living 4 years after treatment. This patient had negative nodes and a full course of post-operative chemotherapy. The causes of failure in the other two cases are believed to be: not performing retroperitoneal lymphadenectomy in one and not giving post-operative chemotherapy in both. It is concluded that radical orchiectomy, retroperitoneal lymphadenectomy (followed by radiotherapy in N+ cases) and post-operative chemotherapy are the treatment of choice for operable paratesticular rhabdomyosarcoma.

[The action of chemotherapy on cicatrization processes]. / L'azione della chemioterapia sui processi di cicatrizzazione

The increasing use of chemotherapy in association with surgery has prompted the suggestion that cancer chemotherapeutic drugs may interfer with the healing process. To test this hypothesis 30 Wistar rats were subjected to laparotomy and colonic resection and treated with 5-Fluorouracil or Mitomycin C. The bursting strength of the abdominal scars and the colonic anastomotic bursting pressure revealed some interference in the rats treated with 5-Fluorouracil (Student's t test P less than 0.05) but none in the case of Mitomycin C. This preliminary study deserves to be followed up.

[Study of 12 cases of non-Hodgkin's lymphoma of the testicle (author's transl)]. / Studio di 12 casi di linfoma non-Hodgkin a primitiva manifestazione testicolare

Twelve consecutive cases of non-Hodgkin's lymphomas with initial testicular involvement have been considered in this retrospective evaluation. In 801 cases with referred for treatment to the Istituto Nazionale Tumori of Milan from 1962 to 1974 evidence of initial testicular involvement was observed in 1,4% of cases. Of the whole group of testicular tumors treated in our Institute only 3% were classified as non-Hodgkin's lymphomas. Six out of 12 patients with stage I (2 cases) and II (4 cases) diseases were treated with Cobalt therapy to the retroperitoneal nodes. Only one patient remained free of disease after radiotherapy. Three patients relapsed after primary irradiation and six patients classified as stage IV were treated with chemotherapy. Patients receiving combination chemotherapy had in general a better quality of response and a larger, but not significantly different, survival, compared to patients given simple agent sequential chemotherapy. Since the differential diagnosis between testicular lymphomas and seminomas may cause some difficulties and therapeutic implications are different, clinicians should be alert to this problem: in our case series testicular non-Hodgkin's lymphomas was the most frequent non-germinal tumor of the testicle.

[Long-term results and planning of therapy of seminal tumors of the testis]. / Risultati a distanza e pianificazione terapeutica dei tumori seminali del testicolo

The paper retrospectively reviews the modalities and the long-term results of treatment of 200 consecutive patients with pure seminoma and of 125 patients with testicular carcinomas admitted to the Istituto Nazionale per lo Studio e la Cura dei Tumori of Milan from 1929 to Jan 1973. Radical orchiectomy with high ligation of the spermatic cord at the internal inguinal ring was performed in all previously untreated patients. Those who had had a scrotal operation performed elsewhere were radically reoperated upon. Lymphography and cobalt 60 telecurietherapy were introduced in 1960 and new treatment plans were employed for the irradiation of the deep lymphnodes. Since 1968 all operable carcinomas have undergone bilateral retroperitoneal lymphadenectomy and since 1964 all patients with advanced disease have been treated with chemotherapy (single agent or combination). Survival rates were calculated by the actuarial method. The new treatment modalities proved to be significantly superior to the old ones. In pure seminoma a 92% cure rate was obtained in NO patients after prophylactic irradiation of retroperitoneal nodes (2,500-3,000 rad in 3 weeks). In NI-3 patients the cure rate was as high as 75% after radical irradiation of retroperitoneal nodes (3,500-4,000 rad in 4 weeks) as well as prophylactic irradiation of mediastinum and both supraclavicular fossae. Extended radical radiotherapy (combined with chemotherapy in some patients) cured 2/6 N4 and 3/8 M1 patients. According to the old modalities of treatment, figures were respectively 72% in NO cases, 40% in N1-3 and 0% in N4 and M1 patients. In carcinomas, the cure rate after retroperitoneal lymphadenectomy was 91% in N--patients and 47% in N+ cases. In N+ patients post-operative radiation was also performed (4,000-5,000 rad in 5 weeks). After radiotherapy alone (without lymphadenectomy) the rates were 62% in NO and 28% in N1-2 patients. In primary inoperable patients (N3-4 and M1) chemotherapy, with or without radiation, significantly prolonged the survival rate. It is concluded that radiotherapy is the treatment of choice for pure seminoma and in N4 and M1 cases a full course of chemotherapy must be combined with extensive irradiation. Retroperitoneal lymphadenectomy is mandatory in all operable cases of testicular carcinoma while adjuvant chemotherapy may further improve the prognosis in N+ cases. For inoperable carcinomas chemotherapy (plus radiotherapy) is the treatment of choice. The new multiple drug regimens are providing encouraging results.

Reliability of diagnostic imaging after orchiectomy alone in follow-up of clinical stage I testicular carcinoma: excessive cost with potential risk.

From 1981 to 1984, 86 consecutive patients with previously untreated nonseminomatous testicular carcinoma were classified as clinical radiological stage I and treated with orchiectomy alone. The follow-up program included chest x-ray and lymphangiography (LAG) every month and abdominal computed tomography (CT) bimonthly. All patients were followed for 15 to 63 months after orchiectomy (median 32 mo.). Metastases developed in 23 patients (26.7%) and in 13/23 there was retroperitoneal lymphadenopathy. Time of relapse after orchiectomy ranged from 2 to 36 months (median 7 mo.) with a shorter interval for chest (4 mo.) compared with retroperitoneal metastases (7 mo.). Lung metastases were readily identified at an early stage (less than 2 cm) whereas more than one-third of retroperitoneal nodal metastases were greater than 5 cm at time of diagnosis. LAG detected metastases in 8/11 patients (72.7%), abdominal CT in 8/10 (80%), and both together (LAG and CT) 7/8 (87.5%). In clinical stage I nonseminomatous testicular carcinoma, the high incidence of concomitant but often asymptomatic regional and distant metastases and the relatively high cost and inconvenience of follow-up using abdominal CT imaging, LAG and chest x-ray suggest that orchiectomy is best combined with retroperitoneal node dissection at time of initial presentation to insure more accurate and safe staging of tumor dissemination.

[Surgical treatment of complications in cases with cancer of the colon and rectum]. / Il trattamento chirurgico delle complicanze del cancro del colon-retto

Personal experience and the literature are referred to in an examination of complications arising in the course of cancer of the large intestine. A personal series assembled in about 20 years is presented. It consists of 135 cases of heteroplasia, including 57 emergency admissions for complications. The surgical technique employed is described. The results show that surgical risk and post-operative mortality are lower in patients subjected to major radical surgery, as opposed to those for whom symptomatic management or simple, derivative operations are prescribed.

[Interferon and vinblastine in presumably operable metastases of renal carcinoma]. / Interferone e vinblastina nelle metastasi presumibilmente operabili da carcinoma renale.

From January 1987 to December 1990, 14 consecutive patients with resectable metastases from renal cell carcinoma, underwent 3 cycles of preoperative alpha-2a Interferon (INF), 18 MUI s.c. 3 times a week, and Vinblastine (VLB), 0.15 mg/kg on day 1, every 21, days. Out of the 13 patients who completed the treatment, 4 (30.7%) achieved a clinical response (1 CR and 3 PR). Nine (69.3%) patients were submitted to surgery: all, including the CRer, had residual cancer and only 4 were radically resected. The latter were further submitted to 3 INF and VLB cycles: 2 relapsed after 7 and respectively 30 months, whilst 2 (15.4%) are alive disease-free at 12 and 52 months respectively.

[Therapeutic alternatives in the treatment of class T1N0 squamous cell carcinoma of the penis: indications and limitations]. / Alternative terapeutiche nel trattamento del carcinoma spinocellulare del pene di categoria T1N0: indicazioni e limiti.

At INT of Milan between 1964 and 1990, 204 consecutive native patients suffering from penile cancer have been treated. 101 (59%) patients out of 171 with invasive cancer (23 affected with Tis were excluded) have been classified T1N0M0. 74 patients have been treated with penis conserving methods, such as circumcision, radiotherapy, laser excision and primary chemotherapy + conserving surgery. Overall local failure and/or nodal relapses occurred in 27% (20/74). Relapses are significantly related with grading but there isn't any relationship with macroscopical aspect or size of the tumor. The conservative treatment had been possible in 80% of patients. In our experience T1N0 clinical stage conservative therapy does not worsen the prognosis.

Inhibition of autonomic storm by epidural anesthesia does not influence cardiac inflammatory response after brain death in rats.

BACKGROUND: After brain death (BD) donors usually experience cardiac dysfunction, which is responsible for a considerable number of unused organs. Causes of this cardiac dysfunction are not fully understood. Some authors argue that autonomic storm with severe hemodynamic instability leads to inflammatory activation and myocardial dysfunction. OBJECTIVES: To investigate the hypothesis that thoracic epidural anesthesia blocks autonomic storm and improves graft condition by reducing the inflammatory response. METHODS: Twenty-eight male Wistar rats (250-350 g) allocated to four groups received saline or bupivacaine via an epidural catheter at various times in relation to brain-death induction. Brain death was induced by a sudden increase in intracranial pressure by rapid inflation of a ballon catheter in the extradural space. Blood gases, electrolytes, and lactate analyses were performed at time zero, and 3 and 6 hours. Blood leukocytes were counted at 0 and 6 hours. After 6 hours of BD, we performed euthanasia to measure vascular adhesion molecule (VCAM)-1, intracellular adhesion molecule (ICAM)-1, interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, Bcl-2 and caspase-3 on cardiac tissue. RESULTS: Thoracic epidural anesthesia was effective to block the autonomic storm with a significant difference in mean arterial pressure between the untreated (saline) and the bupivacaine group before BD (P < .05). However, no significant difference was observed for the expressions of VCAM-1, ICAM-1, TNF-α, IL-1ß, Bcl-2, and caspase-3 (P > .05). CONCLUSION: Autonomic storm did not seem to be responsible for the inflammatory changes associated with BD; thoracic epidural anesthesia did not modify the expression of inflammatory mediators although it effectively blocked the autonomic storm.

Unilateral lymphadenectomy in intraoperative stage I nonseminomatous germinal testis cancer.

Bilateral retroperitoneal lymphadenectomy is mainly a staging procedure in patients with stage I nonseminomatous testis cancer, and it causes permanent loss of antegrade ejaculation in approximately two-thirds of the cases. Between May 1978 and August 1981, 61 consecutive patients with no intraoperative evidence of lymph node involvement underwent unilateral retroperitoneal lymph-adenectomy for nonseminomatous germinal testis tumors. Microscopic metastases were found in 1 to 4 retroperitoneal nodes in 6 cases (9.8 per cent). Antegrade ejaculation was absent postoperatively in 11 patients (18 per cent), with no significant difference between patients who underwent lymph node dissection on the left or right side. Ejaculation returned spontaneously in 3 patients, 1 of whom fathered a child. The disease recurred in 10 patients 3 to 35 months after lymphadenectomy (median 6 months). Disease recurred in 8 of 55 patients (14.5 per cent) with negative nodes and 2 of 6 (33.3 per cent) with positive histological findings. No patient suffered retroperitoneal recurrence. The more than 3-year survival rates free of disease were 96.4 and 83.3 per cent in patients with pathological stages I and II disease, respectively. Unilateral retroperitoneal lymphadenectomy in patients with intraoperative stage I nonseminomatous germinal testis cancer preserves antegrade ejaculation in more than 80 per cent of the cases without apparently compromising the long-term survival.

Comparison between clinical and pathological staging in low stage nonseminomatous germ cell testicular tumors.

Between January 1985 and December 1990, 208 consecutive patients with low stage nonseminomatous germ cell testicular tumors underwent retroperitoneal lymphadenectomy. In all of the patients the disease was staged with post-orchiectomy serum alpha-fetoprotein and beta subunit of human chorionic gonadotropin determinations, as well as chest x-rays and computerized tomography or magnetic resonance imaging of the abdomen and pelvis. Bipedal lymphangiography was performed in 139 patients. Of the 208 patients 173 (83%) had clinical stage 1 and 35 (17%) had low clinical stage 2 disease: 21 had tumors on radiographic imaging that were smaller than 2 cm. (clinical stage 2A) and 14 had tumors between 2 and 3 cm. (clinical stage 2B less than 3 cm.). Retroperitoneal metastases were found in 31 of 156 clinical stage 1 cancer patients (19.8%) with negative or normally decreasing serum tumor markers after orchiectomy, 15 of 16 (93.8%) with persistent positive markers, 8 of 14 clinical stage 2A cancer patients (57.1%) with negative or normally decreasing markers, all 7 stage 2A cancer patients with positive markers and all 14 clinical stage 2B cancer patients. Lymphangiography added little to the reliability of clinical staging. We conclude that due to the relatively low accuracy of clinical staging, retroperitoneal lymphadenectomy remains the treatment of choice for clinical stages 1 and 2A nonseminomatous germ cell testicular tumors with normal serum markers after orchiectomy.

Cisplatin combination chemotherapy in advanced seminoma.

Thirty-one patients were treated with cisplatin combination chemotherapy for advanced seminoma (26 Stage III or bulky Stage II testicular, and five disseminated extragonadal). Seventeen (89%) of 19 patients not previously pretreated and four (80%) of five who had received only abdominal irradiation entered continuous complete remission (CR), versus only two (28%) of seven patients who had received extensive infra- and supradiaphragmatic radiotherapy. Results were not significantly influenced by stage, human chorionic gonadotropin (HCG) titers and histologic subgroups, whereas patients with lactic dehydrogenase (LDH) values exceeding 500 mIU/ml did worse (50% continuous CR rate in 12 cases) than those with normal or less elevated titers (89% continuous CR rate in 19 cases). After a median follow-up period of 34 months (range, 12+ to 77+ months), 23 patients (74.5%) remain alive in continuous CR, two (6%) died in CR and another one (3%) entered CR after deferred treatment of residual disease. Five patients (16%) died of cancer. Toxicity was severe in extensively irradiated patients, but it was acceptable in those not pretreated and in those who had received only subdiaphragmatic radiotherapy. Cisplatin combination chemotherapy can be successfully and safely used as the primary treatment of choice in patients with advanced seminoma. It is also an excellent salvage therapy for patients who had received subdiaphragmatic irradiation only. On the contrary, it is very difficult to treat with chemotherapy extensively irradiated patients.

Difficulties of a surveillance study omitting retroperitoneal lymphadenectomy in clinical stage I nonseminomatous germ cell tumors of the testis.

Between August 1981 and December 1984, 85 consecutive patients with clinical stage I nonseminomatous germ cell tumors of the testis who were suitable for close observation entered a surveillance study after orchiectomy alone. All patients had unequivocally negative chest x-ray, bipedal lymph-angiography, and computerized tomography of the abdomen and pelvis, and normal levels of alpha-fetoprotein and human chorionic gonadotropin before entering the study. Patients were followed closely for 24 to 64 months (median 42 months) with regular chest x-rays, plain films of the abdomen for lymphangiography control, and serum determinations of alpha-fetoprotein and human chorionic gonadotropin but it was difficult to obtain computerized tomography scans of the abdomen at scheduled intervals for such a long period. Followup was closed December 31, 1986. At that date 62 patients (73 per cent) were continuously free of disease after orchiectomy alone and 23 (27 per cent) suffered relapse. The over-all occurrence rate of retroperitoneal relapses was 16.5 per cent and they usually were detected late, 4 to 36 months (median 10 months) after orchiectomy. Lung metastases were detected much earlier, 2 to 10 months (median 3 months) after orchiectomy. Alpha-fetoprotein and human chorionic gonadotropin elevations preceded the radiographic demonstration of metastases in 8 patients only (35 per cent) and in 1 they were the only sign of relapse. All but 1 patient with relapse were cured with chemotherapy and/or surgery, with an over-all survival rate free of disease of 98.8 per cent. Invasion of the epididymis, rete testis and spermatic cord, primary scrotal surgery, peritumor vascular invasion and embryonal carcinoma were associated with a higher risk for relapse but it was impossible to find clear-cut indications to select patients for adjuvant chemotherapy, retroperitoneal lymphadenectomy or no treatment. Furthermore, the followup of retroperitoneal nodes proved to be much more difficult than expected. Unilateral or modified retroperitoneal lymphadenectomy facilitates management of clinical stage I nonseminomatous germ cell tumors of the testis: only the chest and markers must be followed, the status of the retroperitoneal nodes is known immediately and antegrade ejaculation is preserved in the majority of cases.

Psychological aspects of testis cancer therapy: a prospective study.

We examined the impact of testis cancer and its curative therapies on the outlook of life, working activity, partner relationship and sexual function in 31 consecutive patients 18 to 51 years old (mean age 29.3 years, median 28 years) who already had undergone orchiectomy. Of the patients 13 subsequently were treated with chemotherapy alone, 6 with retroperitoneal lymph node dissection alone, and 7 with chemotherapy and an operation, while 5 seminoma patients were treated with radiotherapy. The patients were examined 3, 6 and 18 months after orchiectomy. Each patient was required to fill out a questionnaire to gather information relative to their work activities, emotional relationship with the partner and sexual life. The patients also completed an assessment form on the quality of life (Spitzer QL-Index) and a series of horizontal analogues to evaluate anxiety, mood, nausea, weakness and general health status. The statistical analysis of the linear and quadratic components for the variables under study was done with the general linear model for block design. Psychosocial adaptability of these patients, regardless of the treatment they underwent, in time became progressively less problematic and the development of psychosocial problems during the long-term adjustment was low. Only 2 patients reported worsening of the emotional relationship with the partner after treatment: 1 underwent chemotherapy and an operation, and 1 underwent radiotherapy. With regard to sexual life, no serious dysfunction was noted apart from the loss of ejaculation in 11 of 13 patients who underwent retroperitoneal lymph node dissection. Of our sample patients who had lost ejaculation only 2 suffered from a high state of anxiety. The anxiety scores on the last completed linear analogue were 2.6 and 4.1, whereas at the same time the mood scores were 1.9 and 4.4. Therefore, it is important for the clinician to assess the psychogenic aspect of this side effect when this type of operation is proposed.

Combined surgery and chemotherapy for retroperitoneal metastases of testicular carcinomas other than pure seminoma.

The results of treatment in 210 patients with testicular carcinomas other than pure seminoma are analysed. Patients with negative retroperitoneal nodes had a very good prognosis following lymph node dissection alone. Patients with positive nodes did much better after adjunctive chemotherapy than after post-operative irradiation. Patients with advanced disease showed significant improvement with intensive chemotherapy combined with surgery. Presently retroperitoneal lymphadenectomy combined with intensive chemotherapy seems to be the treatment of choice for metastatic testicular carcinomas.

Relapse pattern of pathologic stage I nonseminomatous germ cell tumors of the testis following orchidectomy and lymphadenectomy.

A retrospective analysis of patients with pathologic stage I nonseminomatous germinal testis tumors treated with orchidectomy and retroperitoneal lymphadenectomy was done in an attempt to define the relapse pattern and to eventually identify risk factors predisposing to tumor recurrence. Of 102 patients, 91 (89.2%) remain disease free with a median follow-up of greater than 5 years (range 3-10 years), and 11 (10.8%) suffered relapse 3-35 months after lymphadenectomy (median free interval 6 months). 9 of 11 patients developed primarily intrathoracic recurrences. The tumor was so rapidly progressing at relapse, that it was diagnosed when clinically advanced in 7 of 11 cases. Nevertheless, 8 of 11 patients were salvaged with effective available chemotherapy and resection of residual disease. Only scrotal violation showed a significant increased risk of tumor recurrence (5 of 24 cases, versus 6 of 78 who had inguinal orchidectomy, p less than 0.05). We recommend a very close follow-up for all patients with pathologically assessed stage I nonseminomatous germinal testis tumors during the first 3 years following orchidectomy and retroperitoneal lymphadenectomy. With early recognition of relapse, an approximately 100% cure rate will be achieved with effective available chemotherapy.