Mitomycin C and etoposide in advanced colorectal carcinoma. A clinical and in vitro experience that focuses the problem of schedule dependence in combination therapy.

BACKGROUND: Aim of this study was to evaluate the activity of a combination regimen of chemotherapy containing mitomycin C (MMC) and etoposide (ETO) in advanced colorectal carcinoma. METHODS: Fourteen pretreated patients received MMC 2 mg/m2 and ETO 60 mg/m2, days 1-5 every 28 days. The clinical study was interrupted since no clinical response was observed in 14 patients following four courses of chemotherapy. An in vitro study was then performed on HTC-8 cell line. The cytotoxic activity of the MMC/ETO combination was tested by sulforhodamine B assay and the type of drug interaction was assessed using the method of Chou and Talalay. Cell cycle perturbations and apoptosis were evaluated by flow cytometry. RESULTS: While MMC and ETO were singularly active, the simultaneous exposure of cells to both drugs and the sequence MMC-->ETO ensued in antagonistic interaction at all levels of killed cell fraction. Conversely, the sequence ETO-->MMC produced a synergistic interaction. CONCLUSIONS: These results suggest that the activity of the MMC/ETO combination is highly schedule-dependent and that the experimental drug associations should be based on a preclinical rationale before clinical trials are designed.

[Colorectal carcinoma metastasis in livers infected with hepatitis B or C virus]. / Metastasi epatiche da carcinoma colo-rettale in pazienti con infezione da epatite B o C.

AIM: Metastases from colorectal cancers rarely occur in injured livers, however in western countries this phenomenon has not been investigated in patients with various forms of chronic hepatitis. Therefore in this study we evaluated the incidence of synchronous hepatic metastases of colorectal carcinomas in patients with hepatitis B (HBV) or C (HBC) infection. METHODS: Six hundred and thirty patients undergoing surgical treatment for colorectal carcinomas were analysed: the clinicopathological data of 87 patients with HBV or HCV infection (there were 29 patients with hepatitis C infection and 58 with hepatitis B infection) were compared to those of 543 non infected patients. RESULTS: Patients distribution was similar in both groups in terms of gender, age, type of operative procedures performed, histological grading and lymph node metastases. Stage I, II or III tumours were similarly represented in non infected and infected patients, while stage IV tumours were 33.1% in the non infection group and 17.2% in the infection group (P < 0.001). At the time of surgery, synchronous extrahepatic metastases were present in 14.9% of non infected patients and 15% of infected patients, while synchronous hepatic metastases were found in 32% and 17.2% of patients respectively (P < 0.01). CONCLUSIONS: Results of our study show that synchronous hepatic metastases of colorectal cancers are less frequently observed in chronic HBV or HCV infected patients than in non infected patients, while the incidence of extrahepatic metastases is comparable in both groups, suggesting that virus-related mechanisms and specific liver mediated immunity may have a protective role against neoplastic cell colonization of the liver.

[Occurrence of synchronous colorectal cancer metastasis in the cirrhotic or fatty liver]. / Metastasi epatiche sincrone da carcinoma colo-rettale in pazienti con cirrosi epatica o steatosi.

AIM: Metastases from colorectal cancers rarely occur in injured livers, however this phenomenon has not been fully investigated in patients with different degree of liver damage. Therefore in this study we evaluated the incidence of synchronous hepatic metastases in patients with fatty or cirrhotic liver submitted to surgery for colorectal neoplasms. METHODS: Seven hundred and forty-seven patients undergoing surgical treatment for colorectal neoplasms were evaluated: the clinicopathological data of 171 patients with liver cirrhosis and 33 with fatty liver were compared to those of 543 patients without liver damage. RESULTS: Gender, age, type of operative procedures performed and histological grading were similar in patients with or without liver damage. In patients with liver cirrhosis the incidence of stage II tumour was greater, while stage IV tumours (P < 0.001) and nodal involvement were significantly lower than in patients with non injured or fatty liver (P < 0.02 and P < 0.001 respectively) . At the time of surgery, synchronous hepatic metastases were present in 32% of patients with normal liver, in 15% of patients with fatty liver (P < 0.02) and in 4.7% of patients with liver cirrhosis (P < 0.001). CONCLUSIONS: Results of our study show that synchronous hepatic metastases of colorectal cancer are less frequently observed in patients with fatty or cirrhotic liver than in patients with non injured liver, indicating that chronically damaged livers are protected from the spread of secondary cancers.

[Surgical treatment of breast cancer in the elderly]. / Trattamento chirurgico del carcinoma della mammella in età avanzata.

AIM: The aim of this study is to evaluate the prognosis and survival of patients aged over 70 years and affected by breast cancer. METHODS: From January 1994 through December 2000, 56 patients with breast cancer aged 70 years or older were submitted to surgical treatment. Associated diseases were present in 24 patients, while no patient showed distant metastases at the time of hospital admission. All patients underwent breast preserving surgery regardless the tumour size and in 31 subjects out of 56, the surgical procedure was performed under local anesthesia. An axillary lymphectomy was associated in 46 patients. According to the TNM staging system, tumours were classified as follows: 10 T1Nx, 18 T1N0, 9 T1N1, 7 T2N0, 10 T2N1 and 2 T3N1. RESULTS: There was no postoperative mortality and in 6 cases an axillary seroma was observed. Radiotherapy and tamoxifen treatment followed surgery in all cases. The median follow-up was 44 months. Nineteen patients (34%) died during the follow-up: 6 patients of cancer progression with a specific cancer-death of 10.7% while 13 patients (23.2%) died because of concurrent diseases. A local relapse (1.8%) was observed in a single patient 2 years after the primary surgical treatment and, at 3 years, 37 patients (66%) are alive and disease-free. Long-term survival was significantly related to the stage of disease at the time of surgery, while our data do not allow any conclusions concerning the impact of axillary dissection on long-term outcome. CONCLUSIONS: In conclusion, results for breast cancer therapy are comparable in old and young patients and therefore strategies and treatment protocols should be similar, breast preserving surgery followed by radiotherapy and ormonal treatment being ''the gold standard''.

Guided biopsies of abnormalities on nuclear bone scans. Technique and indications.

A guided biopsy technique has been developed for evaluation of solitary bone abnormalities, identified by gallium 67 or technetium 99 bone scans, in patients with normal or ambiguous x-ray findings. Continuous gamma camera monitoring is used to guide staining of the bone abnormality and overlying tissues with methylene blue. This staining is followed by open biopsy of the marked bone. This technique was utilized in 15 patients, 12 of whom had bronchogenic carcinoma. The most commonly involved bones (13/15) were ribs. None of the patients had an identifiable, gross abnormality at operation, and the marked area was indistinguishable from neighboring tissues. Diagnostic tissue was obtained by each biopsy and there were no complications associated with this technique. The primary applicability of this technique is for both pretreatment and re-treatment staging of bronchogenic carcinoma in patients who have ambiguous nuclear bone scan abnormalities.

TNM staging in lung cancer: role of computed tomography.

Current procedures to determine the clinical staging of disease in patients with lung cancer are lacking in accuracy, particularly regarding the presence of metastatic disease. We have evaluated the use of computed tomography (CT) of the chest, brain, and upper abdomen for clinical staging of the extent of disease in 113 consecutive patients with histologically confirmed carcinoma of the lung. Comparisons with mediastinoscopy and surgical findings were made regarding the extent of primary tumor in 47 patients and nodal involvement in 41 patients. The CT scan showed a sensitivity of 86.9%, a specificity of 91.6%, and an accuracy of 89.3% for extrapulmonary extension of the primary tumor and a sensitivity of 50%, a specificity of 96.5% and an accuracy of 82.9% for mediastinal node involvement. Thirty-two of the 85 patients studied by total body CT scan had distant metastasis, of which 24 (75%) were clinically silent. Thus 28.2% of the 85 patients studied had asymptomatic metastatic disease. We conclude that CT of the chest, brain, and upper abdomen is a reliable procedure for staging lung cancer.

Use and prognostic value of staging mediastinoscopy in non-small-cell lung cancer.

One hundred sixty patients had preoperative mediastinoscopy, resection of the primary tumor, and complete mediastinal lymphadenectomy for non-small-cell carcinoma of the lung. Minimum follow-up was 24 months (mean 40 months). Postoperative staging based on histologic examination of the specimen of the lung and mediastinal lymphadenectomy categorized 59 patients in stage I, 28 in stage II, and 73 in stage III (20 T3N0, 12 T3N1, 29 T1 or T2N2, and 12 T3N2). The sensitivity rate of cervical mediastinoscopy for detection of mediastinal node metastasis was 48.7%. False-negative results of mediastinoscopy occurred in 21 of 41 patients with normal mediastinoscopy: unreachable nodes in eight patients, sampling error of reachable nodes in 11 patients, and error on frozen section in two patients. Eleven of 65 patients with clinical stage I disease and normal mediastinum on chest roentgenogram had mediastinal node involvement; only three were detected by mediastinoscopy, which resulted in a low sensitivity rate (27.3%) and a high rate of unnecessary mediastinoscopy (62/65 patients). The sensitivity of mediastinoscopy increased as the amount of disease present, as measured by the clinical stage of disease or positive gallium 67 scan of mediastinum, increased. Eleven of 29 patients with T1 to T2N2 disease discovered at mediastinoscopy had similar survival rates compared with 18 of 29 patients who had a normal mediastinoscopy examination and mediastinal node involvement discovered at thoracotomy.

Barrett's esophagus. Functional assessment, proposed pathogenesis, and surgical therapy.

Esophageal function was assessed with manometry and 24-hour pH monitoring of the distal esophagus in 22 patients with histologically proven Barrett's esophagus (BE), 31 consecutive patients with endoscopic grade 2 or 3 esophagitis, and 33 normal volunteers. Patients with BE had less lower esophageal sphincter (LES) pressure, but similar length of sphincter exposed to the abdomen, than patients with esophagitis. Both groups had significantly less LES pressure and abdominal length than normal subjects. Patients with BE had statistically more esophageal acid exposure than patients with esophagitis, and both differed markedly from normal subjects. They also had a greater number of reflux episodes lasting longer than five minutes than patients with esophagitis, suggesting that the severity of acid exposure was due to a defect in esophageal clearance. The extent of Barrett's mucosal change was related to the level of LES pressure and the number of reflux episodes that were five minutes or longer in duration. We concluded that BE is related to a mechanical incompetency of the cardia and a decrease in esophageal clearance that requires reconstruction of the cardia for effective therapy.

The use of serum albumin for further classification of Stage III non-oat cell lung cancer and its therapeutic implications.

The use of the preadmission serum albumin level for predicting survival was evaluated in 81 patients with Stage III disease, 59 with unresectable and 22 with resectable primary tumors. A serum albumin of less than 3.4 gm/dl in a patient with unresectable Stage III disease indicates a poor prognosis with an accuracy that supersedes that obtained from a clinical assessment of the anatomical extent of disease. Seventeen of the 22 patients with resectable Stage III disease had a preadmission level of albumin of 3.4 gm/dl or greater. The median survival was 20.5 months, which was statistically longer than 9.9 months for 12 patients with unresectable Stage III M0 disease and an albumin level of 3.4 gm/dl or greater (p less than 0.05). Five of the 22 patients who underwent resection had a preadmission albumin level of less than 3.4 gm/dl. The median survival for these patients was 9.7 months compared with 20.5 months for those with a level of 3.4 gm/dl or greater. These findings suggest that resection of Stage III disease in patients with an albumin level of 3.4 gm/dl or greater prolongs survival. Another group of 5 patients with resectable Stage III disease and an albumin level of less than 3.4 gm/dl were force-fed an elemental diet while undergoing a regimen of preoperative radiation therapy. There was no improvement in survival, and 3 died of the disease prior to resection.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

[Bronchopulmonary carcinoma: influence of type of resection on long term survival]. / Il carcinoma broncopolmonare: influenza del tipo di resezione sulla sopravvivenza a distanza.

A statistical comparison between survival and type of resection: Lobectomy and pneumonectomy was made out of 108 patients who had undergone curative resection for lung cancer (with a minimum 3 years follow-up). Analysis was first made on the whole series, then the patients were classified according to histological type (W-PL) or staging (TNM) and finally stratified in 2 control levels (stage and histological type). There was a better prognosis for lobectomy than for pneumonectomy, referring to a single subgroup, but not in a statistically significant way. There was a better prognosis for patients who had been operated for lobectomy S(2) 2 LOB with a 36 months survival for 85%. There were better results for squamous cell carcinoma stage I and II S(2) 1 PNE, for those patients who had been operated for pneumonectomy with a median survival of 32 months and over 3 years survival for 41.7%.

Diagnosis and treatment of Barrett's oesophagus. A general survey.

Barrett's oesophagus is an acquired condition with columnar metaplasia of the distal oesophagus. This condition represents the most serious consequence of chronic gastro-oesophageal reflux as it is associated with an increased incidence of oesophageal adenocarcinoma. Since the exact pathophysiology is not known, prevention is not possible. The diagnosis of Barrett's oesophagus requires the presence of intestinal metaplasia in at least one biopsy specimen from the lower oesophagus. Barrett's oesophagus is considered a premalignant condition and some cases progress from dysplasia to invasive adenocarcinoma. Medical or surgical antireflux treatment controls symptoms and oesophagitis, but Barrett's oesophagus remains. Patients are usually followed up by endoscopy for detection of dysplasia or early cancer. Several reports in the literature have assessed the effects of H2-blocker and proton pump inhibitors treatment on Barrett's epithelium, but none has clearly documented a significant and consistent regression of the metaplastic epithelium. Even with high doses of proton pump inhibitors given for a prolonged period of time, it does not appear that a significant regression of Barrett's epithelium can be achieved. Various studies have assessed the effects of antireflux surgery on the regression of columnar epithelium and dysplasia and its potential protective effect on the subsequent development of carcinoma. Overall, it appears from these reports that antireflux surgery, despite adequate symptomatic results, does not significantly and consistently lead to a reduction in length or disappearance of the Barrett's mucosa, and does not prevent the development of dysplasia and its progression to carcinoma. Recently, numerous reports have documented the regression of Barrett's mucosa by using various experimental techniques: these thermal therapies focus on the removal of the columnar epithelium with restoration of the squamous epithelium. Technological advances including laser and especially photodynamic therapy have allowed for endoscopic mucosal ablation. Long-term results are more encouraging when this mucosal ablation is associated with antireflux medical or surgical therapy. Currently, none of these approaches can obviate the need for continued endoscopic surveillance; however the photodynamic therapy seems to be a promising alternative in the future.

[Surgical treatment of recurrent gastroesophageal reflux]. / Terapia chirurgica del R.G.E. recidivato.

From 1972 to 1994, 66 patients underwent 67 Belsey MK IV antireflux repairs in our unit. Fifteen of the 67 patients or 22% had previously undergone antireflux surgery (10 hiatal repairs and 5 antireflux repairs). Obstructive symptoms were present in one patient who had previously undergone a Nissen fundoplication whereas all other patients presented recurrent reflux. There were no operative complications and only one hospital mortality (6.6%). Long-term results were good-to-excellent in 62% of all patients and fair in 15% of all patients; failures constituted 23% of all cases and were due to recurrent reflux symptoms. In the literature of the last 20 years, two groups can be identified, one group consisting of 142 patients treated surgically after unsuccessful Nissen fundoplication, the other group consisting of 438 patients who underwent 580 operations due to failure of the more common antireflux procedures used today. Recurrent reflux was the most frequent cause of failure in both groups (48% in the first and 58% in the second group). With respect to obstructing symptoms (26% and 32% respectively), these were due to a tight wrap in those patients who underwent a Nissen fundoplication and to peptic stenoses in those patients who underwent other surgical procedures. In 25% of patients who underwent a Nissen fundoplication, the cause of failure was the so-called "Slipped Nissen", responsible for both obstructing symptoms and reflux. In 60% of patients treated for failure following a Nissen fundoplication, the same surgical procedure was used. In the second group, only 20% of all patients underwent a Nissen fundoplication while 20% underwent esophageal resections and another 20% other antireflux surgical procedures. The differences in mortality and morbidity in the two groups (0-2% vs 0-12% and 0-33% vs 21-73%) are probably related to a higher incidence of the thoracic approach in the second group. Good-to-excellent results were achieved in 60-100% of patients treated for failure after a Nissen fundoplication and in 58-60% in those patients treated for failure of other various surgical procedures.

[Duplication of the gastrointestinal tract: a report of a rare case of mediastinal cyst]. / Duplicazione del tratto gastrointestinale: descrizione di un raro caso di cisti mediastinica.

An unusual case of alimentary tract duplication located in the left anterior mediastinum and observed in a 37-year-old woman is reported. Resection of the lesion through a left thoracotomy approach was resolutive and followed by an excellent long term outcome. Etiology, diagnosis and therapeutic problems as well as differential diagnosis with benign and malignant chest lesions of adult population are briefly discussed.

Carcinosarcoma and pseudosarcoma of the esophagus: two names, one disease--comprehensive review of the literature.

In the present review we have collected 127 carcinosarcomas and 56 pseudosarcomas of the esophagus from the literature. There were no significant differences in age, sex, symptoms, location, or stalk involvement between the two groups. Infiltrative lesions were observed in 7.5% and 4.0%, respectively. The rate of lymph node metastasis was 52.5% for carcinosarcoma and 45.0% for pseudosarcoma. The resectability was similar in the two groups, and the recurrence rates were 38.0% and 45.5%, respectively. Although recent immunohistochemical and electron microscopic studies suggested that carcinosarcoma and pseudosarcoma are a single pathologic entity of epithelial origin, no one has ever compared the clinical behavior of the two entities. Our study showed that the two neoplasms have similar clinical and behavioral outcomes. These findings support, once more, the unifying theory; and we suggest that the definition of "polypoid spindle cell carcinoma of the esophagus" be adopted.