Role of reoperation in recurrence of adrenal cortical carcinoma: results from 188 cases collected in the Italian National Registry for Adrenal Cortical Carcinoma.

BACKGROUND: Recurrence of adrenal cortical carcinoma (ACC) after radical surgery is a common finding. Although successful reoperations have been reported with encouraging results, most published experiences are anecdotal and based on few cases. We report the results of surgical treatment for recurrent ACC in a multiinstitutional series. METHODS: One hundred eighty-eight cases of ACC were collected in a national registry. A complete follow-up was obtained in 179 cases. At initial diagnosis 92 patients had local disease (stage I or II). One hundred seventy patients underwent surgical treatment, considered radical in 140; in this group, recurrent disease was observed in 52 cases (37%) after a mean disease-free interval of 21.7 months. RESULTS: Adjuvant chemotherapy was ineffective in ameliorating the prognosis. The mean survival in 20 patients who underwent reoperation was significantly higher (15.85 +/- 14.9 months) than in nonreoperated cases (3.2 +/- 2.9 months). Five-year actuarial survival in reoperated patients is significantly better than in nonreoperated patients (49.7% versus 8.3%, respectively). CONCLUSIONS: Although the prognosis of this tumor is still poor, surgery is the only effective therapy; reoperation allows survival comparable to that observed in patients without recurrent disease. An aggressive strategy for recurrent ACC is advisable until prospective studies demonstrate a real effectiveness for chemotherapy.

Representation of vibrissae inputs through the climbing fiber pathway in lobule VII of the adult rat cerebellar vermis.

The present study gives a detailed description of the functional characteristics and of the topographic distribution of Purkinje cell (PC) responses, mediated through the climbing fiber pathway and elicited by mechanical stimulation of two different rows (A and C) of vibrissae in a circumscribed region of the posterior vermis of the rat cerebellum. Experiments were carried out on normal adult rats under barbiturate anesthesia. PCs were recorded in an area extending 1500 microns laterally to the midline in the vermal part of lobule VII contralateral to the stimulation. Using micromapping techniques and computer analysis, we located the cells on the map of the unfolded PC layer. Taking into account the mean latency of the responses and the probability of discharge of PCs, restricted areas of projection were found. For each row, these areas formed two longitudinal patches located between midline and plane 1100 microns and separated by a non-responsive plane at 500 microns. Cells having the best characteristics of responses to the stimulation of row C were located mainly in plane 200 microns. Cells giving the best responses to the stimulation of row A were located mainly in the posterior part of plane 200 microns which was therefore a zone of convergence for both rows.

Enlargement of olivo-cerebellar microzones in the agranular cerebellum of adult rats.

Previous work on normal adult rat showed that the vibrissae project, through the climbing fiber (CF) system, onto the Purkinje cells (PCs) of the contralateral cerebellar hemivermis of lobule VII. The highly elaborated CF projections from a given row of vibrissae delimit a narrow parasagittal zone which can be regarded as a functional olivo-cerebellar microzone. Interestingly, the adult one-to-one relationship between PCs and CFs is preceded by a transient phase during which each PC receives synaptic inputs from several CF collaterals which will be eliminated but one, when granule cells begin to establish synapses on PCs. Therefore, the question arose as to whether this synaptic elimination process could participate in the refinement of the topographical organization of CF projections and could contribute to the formation of such precise peripheral maps onto the cerebellum. In the present study, the topographical map of the CF-mediated projection of mystacial vibrissae onto the vermal PCs of lobule VII was determined in adult rats whose cerebellar PCs remain polyinnervated by olivary CFs due to degranulation by postnatal X-irradiation. Using intracellular recordings, we examined the responsiveness of PCs in lobule VII during mechanical stimulation of the 3rd row of contralateral vibrissae, and positioned cells responding to the stimulation on an averaged planar map of lobule VII. Comparison of the results to those obtained in our previous work on normal rats showed that the activated cells were more numerous and more diffusely distributed.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormal ipsilateral functional vibrissae projection onto Purkinje cells multiply innervated by climbing fibers in the rat.

We have previously shown that synapse elimination occurring in the climbing fiber (CF)-Purkinje cell (PC) relationships during normal postnatal development is likely involved in the refinement of vibrissae projections onto the cerebellar cortex. In normal adult rats, CF-mediated vibrissae projections onto cerebellar Purkinje cells of the vermis of lobule VII are strictly contralateral and located in a narrow microzone whereas they are widely distributed in rats whose PCs remained multiply innervated by CFs due to postnatal irradiation. Given the proximity of this microzone to the midline, the question arose as to whether this synapse elimination process could participate in the segregation of ipsilateral and contralateral projections. In the present study, we compared the topographical map of the ipsilateral and contralateral CF-mediated projections of the third row of vibrissae onto the vermal PCs of lobule VII in adult normal rats and in polyinnervated rats. Using intracellular electrophysiological recordings, we examined the responsiveness of PCs to mechanical stimulation of vibrissae, and positioned responsive cells on an averaged planar map of lobule VII. In normal rats no ipsilateral responses were found, while in irradiated rats ipsilateral responses were distributed evenly from the midline to 700 microns apart. These results suggest that synapse elimination participates in the segregation of ipsi and contralateral mystacial inputs to the vermis.

Esophagocardiomyotomy with Dor gastroplasty in the treatment of esophageal achalasia.

Thirteen patients affected by achalasia of the esophagus, undergoing esophagocardiomyotomy with Dor gastroplasty, are reported. No postoperative deaths or complications occurred. Overall long-term results were satisfactory: excellent or good in 92.3% of cases, fair in 7.7%. Manometry after esophagocardiomyotomy as compared to preoperative assessment showed a decreased resting pressure in the esophageal body, in all patients in whom it was elevated, and the appearance of some peristaltic waves in 23.1% of them (3 patients). As for lower esophageal sphincter, some relaxation after deglutition was observed in one patient. The 24h pH monitoring showed signs of gastroesophageal reflux only in one patient. Based on the obtained results which compare well with those of the literature, the authors be believe that the procedure represents an effective treatment of esophageal achalasia.

Thymostimulin effect on the immune response in neoplastic patients submitted to surgical treatment.

We selected the data from performance status, disease state, skin tests, circulating lymphocytes and relative subsets, serum immunoglobulin classes to evaluate the immune response in 29 neoplastic patients treated with surgery and undergoing Thymostimulin administration during long term follow-up. Moderate drug intolerance was observed in 3 patients. After treatment lymphocyte count increase (41% mean increase) in 61.5% of cases; CD3, CD4, CD8, CD16 respectively 95-74-87-82% of cases; immunoglobulin classes in about 90% of cases. A clear-cut improvement of Karnofsky's index was observed in 34.6% of cases, worsening in 11.5%. A manifest improvement in the delayed hypersensitivity skin test resulted in 36% of cases. Most patients (85%) have shown signs of complete disease remission. Disease progression was observed only in 3 patients. There were no infections during this study.

The usefulness of biliary drainage for restoring liver function in obstructive jaundice.

In eighty patients with obstructive jaundice treated with percutaneous or endoscopic drainage, the results of biochemical liver-function tests (serum bilirubin, transaminase, gamma-glutamyl transferase, alkaline phosphatase, and albumin) were analyzed to evaluate the return of liver function after biliary decompression. Before decompression all the patients had increased serum concentrations of all the liver-function indicators measured. Conjugated bilirubin normalized within 7 days in 67.5% of the patients and within 14 days in 94.5%. The other serum responses normalized as follows: glutamic oxaloacetic transaminase (7 days in 45%, 14 days in 100%); glutamic pyruvic transaminase (7 days in 46.2%, 14 days in 100%); gamma-glutamyl transferase (7 days in 56.2%, 14 days in 89.1%); alkaline phosphatase (7 days in 52.5%, 14 days in 90.4%); and albumin (7 days in 100%, 14 days in 90.4%). The low mortality and morbidity rates in this series of patients with obstructive jaundice: 0% and 7% after endoscopic and 2.1% and 10.4% after percutaneous drainage suggest that biliary drainage has a valuable place in the preparation of jaundiced patients for surgery and in some cases provides a definitive intervention.

The role of surgery in stage IIIa non-small cell lung cancer. Surgery in IIIa NSCLC.

The authors have reviewed the records of 50 consecutive patients resected for stage IIIa non-small cell lung cancer and included in a long-term follow-up study at the 1st Department of Surgery, University of Rome "La Sapienza". Overall survival was 60-20-16.6-16.6% at 1-5-7-10 years with an incidence of recurrence and/or metastasis respectively of 56-80-85.6-85.6%. These percentages were not influenced by the histological type. Tumours with the best prognosis were those classified as T1N2 and T3N0 (7-year survival rate: 33.3 and 29.4% respectively). Tumours with the worst prognosis were those classified as T3N2 with the highest incidence of relapse after 6 months (T3N0 vs T3N2 0.01 < p < 0.025) and no survival after 3 years (T3N0 vs T3N2 0.005 < p < 0.01). Regarding T3 tumours, infiltration of mediastinal pleura or pericardium was a negative prognostic factor implying no survival at 30 months. Involvement of chest wall or parietal pleura showed better survival overall although not statistically significant (10-year survival rate: 37.4 vs 24% respectively).

Neuroendocrine tumors of the gastroenteric canal. Anatomopathological and diagnostic-therapeutic definition. Description of a case with a rare cecal localisation.

The authors take the case of a neuroendocrine tumour of the cecum as the starting point for an analysis of the anatomopathological and diagnostic-therapeutic aspects of these neoplasms. Furthermore, the authors underline that neuroendocrine tumours (NET) of the colon represent an extremely rare nosological entity and that they are heterogeneous from a clinical and biochemical point of view, thus making a reliable preoperative diagnosis a problem that is still difficult to resolve today.

Thymostimulin effect on the immune response in pulmonary carcinoma with or without surgical treatment.

Experience with 54 patients affected by pulmonary carcinoma treated or not with surgery and undergoing thymostimulin administration during long-term follow-up (70 mg i.m. every other day for 3 months), is reported. Drug intolerance was observed in 5.5% of cases. In patients who were able to complete the therapeutic cycle (50 cases) objective improvement of Performance Status was obtained in 46% of cases and subjective improvement in nearly 90%. The course of neoplastic disease showed definite progression (presence of local recurrence or distant metastasis) in 20% of cases, remission in 6%. No case of onset of pulmonary or extrapulmonary infections was observed. After treatment, a significant increase (between 24% and 108%) in blood parameters (circulation lymphocytes, CD3, CD4, CD8, CD16, IgG, IgA, IgM) was observed in 28-56% of cases. As for CD4 increase, this was accompanied by concomitantly positive Merieaux test in 44.5% of cases. Quiescence or complete remission has appeared to occur together with high CD16 values, progression with high CD8 and low CD16 values.

Carcinoma of the duodenum: management and survival in 14 cases.

AIMS: The aim of this study is to evaluate the role of surgery in the treatment of adenocarcinoma of the duodenum. METHODS: From 1955 to 1994, 14 patients with primary adenocarcinoma of the duodenum underwent surgical treatment in our department. Presenting signs and symptoms were mainly related to obstruction and bleeding. Upper gastrointestinal contrast study, Computed Tomography (CT) and duodenoscopy were the primary diagnostic procedure modalities. All diagnoses were confirmed histologically. The tumors were staged pathologically according to the new TNM classification (UICC, 1992). Eight patients received palliative treatment or exploratory laparotomy. The remaining 6 patients were resectable for cure. RESULT: Operative mortality was 35.7%. The 5-year survival rate for patients who underwent curative resection was 33.3%. None of the patients who underwent palliative procedures or exploratory laparotomy survived for more than 11 months. CONCLUSIONS: In the management of resectable adenocarcinomas of the duodenum surgical radicality including lymphadenectomy should be pursued. Unresectable adenocarcinomas treated with palliative procedure had a very poor prognosis.

Lung cancer in young patients.

Despite the increasing frequency of lung cancer, the percentage occurring in young patients is very low (1.3-5.5% of all lung cancers). In 1992, of the 78,124 cases observed in Italy, 2.8% involved patients under 40 years of age. We reviewed a series of 800 patients with histologically proven lung cancer, candidates to a long-term follow-up. Of these, 23 (2.9%) were under 40 years of age, with a low male/female ratio (1.87:1). Fifty-two percent were smokers and 82.6% presented symptoms as the time of diagnosis. The most frequent histologic types were adenocarcinoma and large-cell type, which carried a better outcome (10-year survival of 28.5%) than epidermoid and small-cell types (p = 0.013). These tumors detected in 13% and 17.4% of cases, were unresectable (except for one epidermoid carcinoma), with a survival expectancy of 0% at two years. Considering all patients, resection was possible in nine cases, being curative in seven, with an overall 10-year survival rate of 44.4% (p = 0.002 vs non-resected patients). Stage I-II had the best prognosis with a 10-year survival rate of 80% (p = 0.022 vs resected stage III-IV). Patients undergoing primary chemotherapy and/or radiotherapy had the worst prognosis with no survivors at 30 months. In young patients clinical and pathological parameters had almost the same distribution except for sex and histologic type and offered almost the same survival probability as in patients over 40 years of age. When prognostic findings were tested by univariate analysis, only resectability was found to have an independent favourable impact on survival (hazard risk: 7.47; 95% confidence interval: 1.50-37.14).

Results of surgical treatment of stage IIIA non-small cell lung cancer.

From 1975 to 1993, 665 patients with non-small cell lung carcinoma (NSCLC) were studied in our Unit. Of the 55 stage IIIA patients submitted to resection, 50 were followed-up in order to evaluate the effectiveness of surgery and to identify which variables had a prognostic impact on survival. The expectancy of survival at 3,5 and 10 years was 31.7, 19.5 and 13.7%, respectively. When the analysis was limited to N2 patients, 3,5- and 10-year survival rates were 20.9, 14 and 7%, respectively. Regarding the "TN" factor, the T3N0 subset presented the highest expected survival (24.8 and 18.6% at 5 and 10 years). With regard to the "T3" factor and type of surgery, peripheral tumors submitted to en bloc resection of the chest wall showed the best 5-year survival rate (42.9%), whereas extrapleural resections--even for tumors confined to the parietal pleura--showed a 5-year survival rate of 14.3%. A slightly higher risk of death was observed in tumors originating in the superior sulcus (SST). No patients with mediastinal pleura and pericardium involvement survived more than 34 months. With univariate analysis, "N2" was the variable most significantly associated with a negative prognosis when related to T3 (T3N2 vs T3N0 0.025 < P < 0.05) or non-epidermoid tumor (no survivors at 3 years; N2 epidermoid vs N2 non-epidermoid tumor P < 0.05). Applying multivariate analysis, epidermoid cell type, even if exclusively for N2 tumors, was an independent prognostic factor, showing a favorable impact on survival expectancy (27.8% at 90 months).

Local and/or distant recurrences in T1-2/N0-1 non-small cell lung cancer.

Data from a series of 181 patients subjected to long-term follow-up after surgical resection for non-small cell stage I and II lung cancer were analyzed to evaluate the statistical incidence and the prognostic factors of recurrence. The recurrence rate/year was particularly high in the first 2 years after surgery: the 2-year recurrence rate was 35.1% in stage I tumors and 51.8% in stage II, whereas the 5- and 7-year recurrence rates were 46.1 and 55.9% and 65.8 and 70.7%, respectively, for the same groups. Recurrences were observed more frequently in non-epidermoid carcinomas with multiple nodules (100% at 5 years) and in carcinomas classified as stage II (70.7% at 5-7 years), particularly when defined as adenocarcinoma (100% at 3 years). In the overall recurrence rate we observed no significant difference dependent on the type of resection even though limited segmental or wedge resection appeared to be related to a higher risk rate (true recurrence rate ratio: 0.6). Over two-thirds of the first observed recurrences were located at a distant site, with a slightly higher incidence of non-epidermoid carcinoma (72.5%). Isolated local recurrence mostly occurred in epidermoid carcinoma (47.6%). The most frequent sites of recurrence were the brain, bone and mediastinum. On multivariate analysis, independently significant adverse prognostic factors regarding the recurrence incidence were: tumor size greater than 3 cm, bronchial or hilar lymph node involvement, tumor histologically defined as adenocarcinoma, and the presence of satellite nodules.

Neuroendocrine tumors of the gastroenteric canal. Anatomopathological and diagnostic-therapeutic definition. Description of a case with a rare cecal localisation.

The authors take the case of a neuroendocrine tumour of the cecum as the starting point for an analysis of the anatomopathological and diagnostic-therapeutic aspects of these neoplasms. Furthermore, the authors underline that neuroendocrine tumours (NET) of the colon represent an extremely rare nosological entity and that they are heterogeneous from a clinical and biochemical point of view, thus making a reliable preoperative diagnosis a problem that is still difficult to resolve today.

Pericardial cysts of the mediastinum.

Pericardial cysts are an uncommon benign disease. Their treatment, in the past, was based on excision by thoracotomy or, in selected cases, on percutaneous aspiration. The progress of video-assisted thoracoscopy gave new possibilities, but most surgeons still consider the thoracotomic approach as the treatment of choice. The aim of this study is to report our experience and to discuss the role of different therapeutic procedures in the management of pericardial cysts. Between 1970 and 1996, 24 patients with pericardial cysts were treated at the first Department of Surgery of the University of Rome <>. Of 24 cysts, six were located in the right cardiophrenic angle, three in the left cardiophrenic angle, two in the subcarenal areas, one in the paracardiac area and one on the posterior mediastinum. Ten patients were asymptomatic. Diagnosis was performed preoperatively only in patients with cysts typically located in the cardiophrenic angle. Twenty-three patients were surgically treated by a standard posterolateral thoracotomy or limited thoracotomy with sparing of muscles. One patient underwent CT-guided transparietal fine-needle aspiration. There were no cases of operative mortality. Morbidity was 12.5% and consisted of retained secretions, moderate hypoxemia and partial atelectasis. All patients were submitted to a long-term follow-up and no cyst recurrences were found. We conclude that excision via thoracotomy is an optimal treatment for pericardial cysts. Limited thoracotomy with sparing muscles offers a good cosmetic result and a rapid functional respiratory recovery. Percutaneous cyst aspiration may be, in selected patients, an attractive alternative to surgery.

Lung cancer surgery in elderly patients.

AIMS AND BACKGROUND: Bronchogenic carcinoma is the major cancer-related cause of death in patients aged 70 years and over, and its incidence is rising. The aim of our study was to compare the incidence and the prognostic effect of the parameters characterizing resected patients with non-small-cell lung cancer (NSCLC) when stratified by age. Of 283 NSCLC patients candidates to a long-term follow-up program and who underwent pulmonary resection in our Unit, 34 (12%) were older than 70 years. METHODS: All patients had been preoperatively selected to exclude those with severe or multiple organ system disease and staged in accordance with the UICC classification. RESULTS: When univariate and multivariate analyses were performed within the elderly group, exclusively epidermoid carcinoma and multiple tumor nodules emerged as independent poor prognostic factors (hazard risk, 5.77 and 7.33, respectively). In comparing the older and younger groups, a higher incidence of previous primary neoplastic disease (P = 0.001), epidermoid carcinoma (P < 0.05) and multiple tumor nodules (P < 0.001) was observed in the elderly. Postoperative death was similar (3% vs 4.8%) in the two age groups, as was survival expectancy when stratified by stage. However, univariate analysis showed that epidermoid carcinoma (P = 0.001) and pneumonectomy (P = 0.00001) had a worse outcome in the older early stage subset than in the younger group. When multivariate analysis was performed in all early stage patients, only lymph node involvement and multiple tumor nodules were independently related to survival (hazard risk, 1.82 and 3.76, respectively) and had a poor prognosis. In more advanced disease, elderly and younger patients had a similar outcome. CONCLUSIONS: Our results confirm that a patient's advanced age is not a risk factor in deciding on pulmonary resection, at least for stage I and II NSCLC, and suggest that in all patients, irrespective of age, stage and histologic cell type, the presence of multiple tumor nodules is the only true prognostic factor with a very low survival rate.

Role of surgery in ductal carcinoma of the pancreas.

Data of 111 patients with ductal carcinoma of the pancreas examined over a decade (1979-1989) at the 1st Department of Surgery, "La Sapienza" University of Rome, are presented. 21.6% of them underwent pancreatic resection and 40.5% biliodigestive diversion. Resectability was 26.5% for tumors of the head, 11.8% for tumors of the body and tail, nil for diffuse tumors. Overall operative mortality was 13.5%. Only stage I patients were shown to be resectable for cure and benefited from surgery with 21% probability of 5-year survival.

Assessment of the accuracy of diagnostic chest CT scanning. Impact on lung cancer management.

To evaluate the reliability of computed tomography (CT) scanning in detecting the locoregional extent of bronchogenic carcinoma, preoperative chest CT findings were compared with surgical and pathological findings (pTN) in 61 patients submitted to pulmonary resection for non-small cell lung carcinoma. Neoplastic disease was misdiagnosed in 3 cases. In the remaining 58 cases, CT showed a sensitivity, specificity and accuracy in delineating T factor of 66.6%, 96.1%, 93.1% for T1; of 84.6%, 68.4%, 79.3% for T2; of 66.6%, 95.9%, 91.3% for T3 and of 50.0%, 94.4%, 91.3% for T4. For N1 and N2 factors, sensitivity was 45.4% and 27.2%; and accuracy was 74.1% and 81.0% respectively. The highest incidence of false positive N1 and false positive N2 was found in tumors classified at CT as T2 and T4 respectively. Overall CT showed a good accuracy in discriminating between resectable tumours with better prognosis (postsurgical pathological stage I-II) and those with less favourable outcome (postsurgical pathological stage III).

Surgical treatment of multinodular goiter: incidence of lesions of the recurrent nerves after total thyroidectomy.

The problems concerning surgical goiter treatment are discussed, particularly the morbidity of total thyroidectomy and possible injury to recurrent nerves in comparison to the partial resection of the gland. We discuss our case material and review the literature. We conclude that total thyroidectomy seems to be the most effective surgical procedure with lower morbidity than subtotal thyroidectomy.