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Purpose: Nonpalpable tumors of the testis are generally incidental findings on ultrasound examination. Most of these tumors are benign but some turn out to be germinal tumors at histology. Therefore, intraoperative histopathologic analysis of nonpalpable testicular lesions is pivotal for guiding a testis-sparing surgical approach., Methods: We report clinical and pathologic characteristics of 3 small nodules of the testis with challenging histologic features at intraoperative frozen section examination and peculiar histology. One was a known testicular mass, undertreated for 5 years, whose enlargement worried the patient, while the other 2 were incidental findings during clinical testicular examination for non-neoplastic diseases., Conclusions: The 3 cases reported are characterized by small size, which limited the accuracy of preoperative ultrasound diagnosis. Intraoperative frozen section examination was able to rule out a diagnosis of germ cell malignancy in all cases, but diagnosis was conclusive only at histology. Knowledge of unexpected rare testicular lesions is of great relevance at the time of frozen section examination in view of conservative surgical strategy.

Aims and Background: Patients treated for Hodgkin's disease with chemotherapy or with the association of chemotherapy and radiotherapy have an increased risk of secondary leukemia. The aim of this study was to evaluate the leukemogenic risk due to these treatment modalities., Methods: We performed a case-control study on a population of 1410 patients treated for Hodgkin's disease from 1970 to 1990 in our Institute. Among these patients, we identified 25 cases of secondary leukemia and 3 cases of myelodysplasia, all occurring more than one year after the diagnosis of Hodgkin's disease. Three cases occurred among the patients treated with radiotherapy alone. When we analyzed the risk in relation to the type of treatment (radiotherapy, chemotherapy, or both), the comparisons were relative to patients treated with radiotherapy alone., Results: We found that chemotherapy alone is associated with a fivefold increased risk (odds ratio = 5.4) compared with radiotherapy alone. When both treatments are used, the risk is not further increased (odds ratio = 4.4). Patients receiving more than 6 courses of chemotherapy have an excess risk (relative risk = 2.5) compared with those treated with 6 courses or less. No increased risk was observed after splenectomy., Conclusions: This study confirms an increased incidence of secondary leukemia occurring in patients treated for Hodgkin's disease. The increased risk seems to be correlated with the number of courses of alkylating agent therapy, whereas it is unaffected by the addition of radiotherapy.

A very simple, low dose, orally administered regime (10 to 15 mg of fluoximesterone + 6 mg of deflazacort daily for periods of 1 to several months) resulting in mild-acceptable toxicity (essentially some weight gain) determined subjective improvement in 2/3 of 34 evaluable patients (out of 36 treated) and an objective measurable tumor reduction in 1/3, although most patients had been previously treated with chemotherapy and hormone treatment and proved primarily or secondarily refractory. The receptor status at the beginning of fluoximesterone+deflazacort treatment was not known, except in one negative-receptor patient, who responded to the combination after becoming resistant to tamoxifen (see photo). In some patients the condition of hormone refractoriness would suggest a no-treatment policy, but a trial with this regime is always convenient as it may improve both duration and quality of life.

A young patient developed Hodgkin's disease 11 years after surgical, chemotherapeutic and radiation treatment for stage IIIA embryonal carcinoma of the testis. The importance is stressed of establishing a tissue diagnosis when there is an unexpected course of the disease.

A total of 21 untreated patients (5 males, 16 females; median age, 55 years; range, 28-72) with advanced measurable colorectal carcinoma were treated with an association of 5-fluorouracil (1000 mg/weekly) and alpha-2 interferon (three times a week s.c.: 6 x 10(6) U in the 1st month, 9 x 10(6) U in the 2nd month, 12 x 10(6) U in the 3rd month and then 18 x 10(6) U) until maximum response or progression of disease. Sites of disease involved liver in 10 patients, lung in 6, supraclavicular lymph nodes in 3, skin in 1, abdomen in 4, and vagina in 1 patient. Nine responses (42.8%) were documented (4 complete and 5 partial) with metastases confined to the liver, lung, nodes and skin. Median duration of response was 11 months (range, 4-17+) and median survival was 10 months (range, 2-17+). Side effects (fever, flu-like syndrome and leukopenia) required a dose reduction of 5-fluorouracil in 8 patients and interferon in 2 patients.

Twenty-eight patients affected with disseminated prostate cancer, which proved hormone resistant (after castration and oestrogen administration), have undergone combined treatment with Testosterone (for 13 days) and 32P (for the last 7 days of the Testosterone treatment). During the initial fase of the treatment (Testosterone only), 14 patients experienced pain exacerbation and/or fever and one experienced immediate improvement. The exacerbation quickly disappeared following 32P administration, and 26 of the patients had distinct improvement at some time during or after treatment, with a mean remission duration of 3 months and mean survival rate of 7 months. No lytic or soft part deposit showed improvement; improvement was noticeable only in the mixed type or osteo-sclerotic metastases. This observation suggests that the androgen stimulates uptake of the isotope not inside the tumor cells but in the bone matrix around the tumoral deposit. The patient who showed very early improvement had a subsequent relapse on oestrogens, but later responded to the androgen alone.

Thirty-four evaluable patients with metastatic colorectal carcinoma (13 rectal primary and 21 colonic primary, 4 pretreated and 30 untreated) received 4'epi-doxorubicin at the dose of 75 mg/m2 i.v. once every 21 days, for a minimum of 2 courses. Symptomatic toxicity (mainly confined to gastrointestinal complaints) was short-lived and easily managed. Hematologic toxicity was mild. Transient electrocardiographic abnormalities were found in 50% of patients, without signs of significant cumulative cardiotoxicity. Three previously untreated patients achieved a partial response (lasting 16, 12 and 12 weeks, respectively) with a response rate of 9% (3%-23%, 95% confidence interval). More interestingly, all responsive patients had rectal cancer: further studies of 4'epi-doxorubicin confined to the rectal localization seem warranted.

Eighteen evaluable patients with advanced malignant lymphoma were treated with a combination of cis-dichlorodiammineplatinum (II) (50 mg/m2 i.v. on day 1), VP 16-213 (100 mg/m2 i.v. on days 1, 3, 5), and prednisone (50 mg/m2 per os on days 1-5), recycling every 2 weeks. All patients were previously pretreated. There were 3 complete remissions (patients with Hodgkin's disease), and 4 partial remission (2 patients with Hodgkin's and 2 with non-Hodgkin's lymphoma), for a median duration of 8 weeks. In addition, 2 minor responses (patients with Hodgkin's disease) were observed. Vomiting and myelosuppression were the most prominent toxic effects. In most heavily pretreated patients, myelosuppression was moderate to severe: in these patients and in patients with bone marrow involvement, a schedule interval of 3 weeks should be more appropriate. Nephrotoxicity was minimal. This combination chemotherapy showed some activity in the management of advanced malignant lymphomas; further studies in this area are justified.

Clinical response to high-dose medroxyprogesterone (MPA), administered following three different routes of administration (i.m., p.o. + i.m., p.o.) and monitoring drug plasma levels, was evaluated in pretreated advanced breast cancer patients. Fifty-eight of 68 eligible patients were considered evaluable for response. Age ranged between 36 years and 82 years. Fifty-six of 58 evaluable patients were postmenopausal. An overall remission rate of 48% was achieved with i.m. MPA, 50% with combined (i.m. + p.o.) modalities; only a 19% remission rate was recorded in the p.o. group. Response rate and MPA plasma concentrations were correlated, and a drug level of 80 ng/ml, by means of a GLC method, seems to identify a subset of patients with high probability of response. Only mild toxic effects were recorded.

Fifteen patients with nonseminomatous testicular cancer underwent multidrug treatment which included cis platinum, Velban and bleomycin. The latter drug was administered in monthly 5 day courses of 100 mg/m2. No impairment of antitumor effect resulted since 12 of 15 patients had remissions (10 complete and 2 partial). Pulmonary toxicity was practically abolished: a median dose of 675 mg per patient (range 450 to 1050) was followed by normal lung X-ray and normal or near normal functional parameters after completing treatment. Median arterial oxygen pressure was 78 mm Hg (range 62 to 89), and median Tiffeneau index was 84 (range 64 to 87). Only 2 of 15 patients had skin marks from bleomycin toxicity at the end of treatment, so that cutaneous toxicity was also very low. Oral mucosa reversible damage was prominent in 2 patients. On the contrary, alopecia was a common finding.

Sixty-five patients with advanced solid tumors were treated with 4'epi-doxorubicin, a new analogue of doxorubicin (DXR). Forty-three of 61 evaluable patients had not received previous chemotherapy and/or hormonal treatment. 4'Epi-doxorubicin has been administered at the dose of 75 mg/m2 i.v. once every 21 days, for a minimum of 2 courses. The pattern of acute toxicity was similar to that of DXR. Transient electrocardiographic abnormalities were found in about 50% of patients. The ratio of pre-ejection period to the left ventricular ejection time (PEP/LVET) increased within 1 h after drug injection and returned to near basal values after 24 h. Three patients received a total dose of more than 550 mg/m2, still maintaining a baseline PEP/LVET ratio near to pretreatment values. Up to now, no patient has developed clinical signs of heart failure. Partial responses were seen in patients with tumors generally sensitive to DXR such as breast carcinoma (6 of 14) and soft tissue sarcomas (2 of 6), and in patients with tumors generally resistant to DXR such as melanoma (1 of 9), colorectal carcinoma (3 of 18) and pancreatic carcinoma (1 of 2). These data suggest that 4'epi-doxorubicin may have a broader spectrum of antitumor activity than DXR.

The antineoplastic activity of vindesine was evaluated in 57 patients with non-small-cell carcinoma of the lung, 53 patients were fully evaluable for response and toxicity. Twenty-seven patients had squamous cell carcinoma (WHO I), 14 had adenocarcinoma (WHO III), and 12 had large cell carcinoma (WHO IV). Forty percent of patients were previously treated. Vindesine was administered at a weekly i.v. dose of 3 mg/m2. Partial remissions were observed in 2 of 12 patients with large cell carcinoma and in 1 of 27 patients with squamous cell carcinoma. Among 14 patients with adenocarcinoma, 3 minor responses were observed. Drug-related toxic effects (mainly leukopenia with manageable and reversible neurotoxicity) required modification of dose in 41% of patients: this finding and previous treatment may have adversely affected the response rate. It is concluded that vindesine as a single agent has some activity in large cell carcinoma. Activity in the other histologic types was minimal but not totally absent and deserves further evaluation, possibly in non-pretreated patients.

Antithrombin III (AT III), the primary inhibitor of plasma protease coagulation proteins, was evaluated in groups of patients with different neoplastic disease. When compared with that of 25 health subjects, the mean value of AT III biologic activity was elevated in all groups, significantly in gastrointestinal (p less than 0.02) and lung (p less than 0.001) tumors, lymphoma (p less than 0.02) and in the group with various primary cancers (p less than 0.05). No difference was found between 46 patients tested under chemoradiotherapy and 216 patients who had not undergone therapy for at least 1 month. Four patients with clinical thrombosis had normal ATIII biologic activity. Of the 262 patients studied, 14 had low AT III biologic activity without clinical thrombosis and normal protein concentration. In 71 patients (27%) an excess of immunoassayable protein of 20% or more over biologic activity was found. Double immunoelectrophoresis performed in 5 of these showed for 3 patients an enlarged second are of precipitation. Moreover, no correlation was observed between the activity and protein AT III concentration (r = 0.05). The likelihood of the presence of circulating AT III-protease complexes is discussed.

Forty-four patients (9 stage II, 15 sage III, 7 stage IV, and 13 in complete remission) with Hodgkin's disease without any clinical coagulation disorder were studied. Fibrinogen behavior was evaluated by measuring fibrinogen level and using 1251-fibrinogen, the half-life, survival and fibrinogen turnover. Platelet count and fibrinogen/fibrin degradation products (FDP) were also assayed. The fibrinogen half-life, survival and turnover were significantly longer and faster, than those found in 10 healthy subjects, in stage II, III and IV subjects (p less than 0.001, p less than 0.001, p less than 0.05 for stage II; p less than 0.001, p less than 0.001, p less than 0.001 for stage III; p less than 0.005, p less than 0.005, p less than 0.001 for stage IV, respectively). In most cases, FDP values were within the normal range, although they were significantly higher than those of control group in stages III and IV. Intravascular coagulation and fibrinolysis were not found in the 13 patients with complete remission. In these patients, the behavior of fibrinogen was normal, suggesting that the parameters studied are related to the presence of the tumor, and can be useful in monitoring the state of remission.

A psychological study of 80 patients undergoing mastectomy showed that the preoperative period is more affected with anxiety, that the patients need communication to remove the anxious state, and that disclosure of the diagnosis should always be accompanied by an understanding interview that includes a clear and moderately optimistic evaluation of the consequences, plans for the future, involvement of the partner and other relatives. Physician and psychologist should share this task to inform the patient and help the patient's psychological reaction towards a constructive cooperation for treatment and rehabilitation.

Forty-four previously untreated patients with advanced inoperable and/or disseminated gastric carcinoma were given an i.v. combination (FAM2) chemotherapy of 5-fluorouracil, 400 mg/m2 on days 1, 2 and 3, and 21, 22 and 23; adriamycin, 40 mg/m2 on days 2 and 22; and mitomycin C, 10 mg/m2 on day 1, with a recycle on day 42 (1 cycle = 41 days). Forty patients have completed 2 cycles and are evaluable (median number of cycles 5; range 3 to 8): 26 of these achieved a partial remission, with a response rate of 65%; 4 (10%) gained a stable situation for 3 to 6 months, and 10 (25%) showed progression of disease. Median duration of partial remissions was 10 months, and median survival was 15 months for responders and 5 months for nonresponders. A fall in WBC (less than 2500/microliter) occurred in 7% and of platelets (less than 80,000/microliter) in 4.5%. Total alopecia occurred in 20 of 40 patients and nausea and or weakness were common findings. No drug-related infection, bleeding or death was observed. Patients with advanced gastric carcinoma can derive useful palliation from FAM2 chemotherapy.

Twelve patients with metastatic clear cell renal cancer received a course of tamoxifen. Three showed stable disease for a period from 2 to 12 months and 1 a mixed response for a short time. It does not appear that tamoxifen may be a useful agent in the treatment of metastatic renal cell carcinoma.

Serum copper level (SCL) was studied by the atomic absorption technique in 103 patients with non-Hodgkin's lymphoma. SCL was increased in 61% of patients at diagnosis or during active disease; values within normal range were found in 88% of patients in complete remission. The difference between mean SCL during active disease and in remission was highly significant, independently of stage and histologic type, so that: a) Within the same clinical stage high SCL at diagnosis was associated with poorer response to therapy in stage II and stage III (respectively P = 0.033 and P = 0.049), but not in stage IV, where the complete remissions were only 8 out of 42. A shorter 5-year survival was also shown in stages III and IV with high SCL at diagnosis (respectively P less than 0.025 and P less than 0.05), but not in stage II where the deaths were only 3 out of 24. b) Within histologic types, SCL is a useful prognostic index of response to therapy and survival, although a statistically significant difference was only reached for poorly differentiated lymphocytic lymphoma. We conclude that SCL may be a good parameter of disease activity and a useful index of response to therapy and survival in non-Hodgkin's lymphoma.

Twenty-four-hour urinary hydroxyproline excretion (HOP) (normal values: 6-22 mg/day/m2) was measured by the Hypronosticon test in 50 untreated patients with plasma cell myeloma. At diagnosis, HOP was elevated in 36 of 50 patients (72%) with a mean value of 35.9 mg/day/m2. Extent of bone lesions and clinical stage were accurately assessed in all patients. Higher HOP values were found in patients with a higher degree of bone lesions (multiple lytic areas and/or destruction of skeletal segments). According to clinical stages, HOP was very elevated only in stage III (mean value: 43.7); in stages I and II the mean value (25.2) was just above the normal range. Our data indicate that HOP in multiple myeloma at diagnosis is closely related to the extension of skeletal lesions and that during the clinical course it may be useful in the follow-up of bone disease.

Serum lipid-bound sialic acid (LSA) was measured with a recently described procedure in 108 healthy subjects and in 138 patients with a variety of solid tumors and hematologic malignancies. At the time of serum sampling, 128 patients had active disease and 10 patients had no evidence of disease. LSA was elevated in 104 of 128 (81.2%) patients with active disease, while carcinoembryonic antigen, analyzed in 74, was elevated only in 21 (28.4%) (P less than 0.05). Sensitivity of the serum LSA test ranged from 66% for breast and gastrointestinal cancer to 92% for lung cancer. In patients with lung cancer, ovarian cancer or Hodgkin's disease, LSA was correlated with the extent of disease and it also proved to be useful in following the course of disease. Our preliminary data indicate that this test can be used as a monitor of tumor burden.

Twenty-one patients with plasma cell tumors received vindesine (VDS) at the dose of 3 mg/m2 i.v. on day 1 plus prednisone at the dose of 100 mg p.o. from day 1 to 5, recycling every 8 days 3 times and then every 10-12 days. In 3 patients with gastric or duodenal ulcer prednisone was not administered. All but one patient were heavily pretreated and resistant to M-2 regimen. Overall there were 4 objective responses (19%): 2 among 15 patients (13%) with multiple myeloma and 2 among 6 patients (33%) with extramedullary plasmacytoma (EMP). The responses lasted for 2, 12, 15 and 48+ months. One previously untreated EMP patient received VDS without prednisone and obtained a complete long-lasting remission. The association of VDS with high-dose prednisone seems to have some activity in plasma cell tumors; probably in multiple myeloma the objective responses are due to the high dose of cortisone rather than to VDS. On the contrary, in EMP patients, VDS may be an active agent, even if administered without cortisone.

From December 1971 to December 1976 224 patients with Hodgkin's disease underwent diagnostic laparotomy and splenectomy under a multidisciplinary protocol of treatment. In 149/224 (66.5%) the clinical stage of the disease was confirmed, whereas in 75/224 (33.5%) it was modified after surgery. In 7.6% of the patients (17/224) there were postoperative complications. One patient died of myocardial infarction. The rate of complications in the last 100 cases was 5%. Preoperative patient selection, excluding those definitely in stage IV, is of relevance, and it can be done by iliac crest biopsy and laparoscopy. Although a better exploitation of some diagnostic procedures (lymphangiography, laparoscopy) and the expanding use of chemotherapy may reduce in the future the need for staging laparotomy and splenectomy, diagnostic laparotomy is still indicated for the selection and preparation of patients for radiation therapy in stages I, II and III.

We conducted a phase II trial of Vindesine in 24 patients, mostly pretreated (23/24 fully evaluable for therapeutic response) with advanced hematologic malignancies. The drug was administered at weekly bolus doses of 3 mg/m2 i.v. Overall, objective tumor regressions were seen in 9 of 23 patients. The drug appeared effective in extraosseous plasmacytoma (1 complete response, 1 partial response and 1 minor response in 6 patients). Further phase II trials in these 2 diseases are justified. In addition, 3 partial responses in 7 patients with advanced lymphoma were also obtained. Previous vinca-alkaloid exposure did not adversely affect the response rate: 8 of 9 responsive patients had previously received vincristine and/or vinblastine. Drug-related toxic effects were mainly represented by manageable and reversible neurotoxicity and by moderate leukopenia with apparent lack of thrombocytopenia. In heavily pretreated patients, leukopenia may be occasionally severe: in these conditions a starting dose of 2 mg/m2 seems more appropriate.

86 postmenopausal women with disseminated breast cancer have been treated orally with 30 mg of Tamoxifen per day (ICI 46474, Nolvadex) for periods of 2 months or more. The overall responders were 28/86 (32.5%) with a median remission duration of 9 months. In 30 patients already shown to be resistant to cytotoxic chemotherapy. Tamoxifen was used as first hormonal agent; the remission rate in this group was 12/30 (40%), while it was 28.5% (16/56) in the others who had already received different hormonal treatments. In 6 early menopausal cases, the treatment had to be stopped for a dangerous "worsening syndrome". Other side effects were trivial. In 28/35 cases (80%), we have found the reappearance of a pattern of estrogenic activity in vaginal smears during treatment. Hence a "simil-estrogen", more than an "anti-estrogen" mechanism of action is postulated and a selection of patients for treatment in the "mid postmenopausal age" is recommended.