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.

[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''.

[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.

Use of radioisotopic esophageal transit in the assessment of patients with symptoms of reflux and non-specific esophageal motor disorders.

The purposes of this study were to assess the esophageal clearance of a radioisotopic bolus in patients with symptoms of reflux and evaluate the impact of manometric abnormalities on scintigraphic esophageal transit. Esophageal clearance was assessed in a supine position and indicated by the retained radioactivity in the esophagus at 10, 20, 30 and 40 s after the ingestion of a liquid bolus labeled with 2 mCi 99 mTc-SC. The study included 214 consecutive patients with symptoms of reflux and 11 normal controls. The results were compared to the motility findings detected on manometry performed on a separate occasion. Esophageal manometry was normal in 93 patients. Nonspecific esophageal motor disorders were identified in 121 patients and were classified into: 'predominantly nonpropagated activity', 'predominantly low-amplitude peristaltic contractions' and 'miscellaneous disorders' diagnosed in 27, 47 and 47 patients, respectively. The radionuclide clearance was significantly delayed in the overall group of patients compared with that of normal controls (P < 0.001); in patients with reflux symptoms and nonspecific esophageal motor disorders compared with patients with reflux symptoms and 'normal manometry' (P < 0.01 at 20 s); and in patients with reflux symptoms and 'normal manometry' compared with the control group (P < 0.01 at 20 s). Abnormal radioisotope clearances were detected in 88% of patients with 'predominantly nonpropagated activity', in 70% of patients with 'predominantly low-amplitude peristaltic contractions' and in 57% of patients with 'miscellaneous disorders'. Radioisotopic esophageal clearance abnormalities are frequently observed in patients with reflux symptoms and are more likely to be associated to hypomotility disorders, i.e. nonpropagated motor activity or low-amplitude contractions.

Esophagogram and CT vs endoscopic and surgical specimens in the diagnosis of esophageal carcinoma.

PURPOSE: Aim of our study was to assess the accuracy of diagnostic imaging in establishing site, morphology and size of the neoplasm comparing surgical specimens or endoscopic examination with esophagograms and CT in patients with esophageal cancer. CT accuracy in defining TNM staging was also evaluated. MATERIAL AND METHODS: From 1993 to 2000 we examined 39 patients with esophageal cancer: 30 males (77%) and 9 females (23%), age range 41-85 years. All patients underwent esophagogram, digestive endoscopy, and chest and abdominal CT. In 22 patients who underwent surgery, we evaluated the correlation between diagnostic imaging and surgical specimens. Patients were divided into 3 groups on the basis of discrepancy between pathological and radiological measurements: =/<1 cm (considered as no discrepancy); 1 to 3 cm; > 3 cm. RESULTS: Esophagogram identified neoplasm in 38 patients out of 39, while CT identified neoplasm in all patients. Location and morphology of the neoplasm established at endoscopy were confirmed in all patients. Lesion length measured at esophagogram corresponded to length of surgical specimens in 13 of the 22 surgically treated patients (59%). In this group there was a dominance of polypoid and stenotic tumor forms. In the remaining 9 cases there was a dominance of ulcerative tumor forms. CT measurement corresponded in 7 patients (32%) with a dominance of polypoid and stenotic tumor forms. T staging performed with CT corresponded to surgical specimens in 12 patients (54%, T3-T4). N staging correlated in 19 patients (86%). CT identified distant metastases in 6 patients (27%). DISCUSSION AND CONCLUSIONS: Our study proves a high sensitivity of esophagogram and CT in the diagnosis of esophageal carcinoma. Esophagogram presented a higher accuracy in establishing tumor length (59% of cases, as compared to CT 32%). Tumor morphology influenced the accuracy of the esophagogram, and highest accuracy was obtained in polypoid and stenotic tumors. T staging performed with CT corresponded to surgical specimens in advanced stages (T3-T4), while accuracy was poorer in smaller superficial lesions (T1-T2) due to the inability of CT to differentiate the layers of the esophageal wall. N understaging in 14% of cases did not modify surgical management. CT presented a high sensitivity in the identification of loco-regional lymph nodes and identified distant metastases in 6 patients. In conclusion, these techniques are accurate and non-invasive and their role in establishing the correct management is therefore important.

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.

Recurrent gastric carcinoma causing pseudoachalasia: case report.

We report the case of a patient with a gastric remnant relapse of an antral carcinoma resected 5 years before and presenting with the clinical feature of a secondary achalasia (pseudoachalasia). In spite of the patient's 4-month history of dysphagia and weight loss that suggested a malignant lesion, barium swallow, repeated endoscopic biopsies and computed tomography (CT) scan of the upper abdomen did not reveal any abnormalities to indicate a recurrence. However, in the following months, because of worsening symptoms, a further CT scan was performed and revealed thickening of the cardia and gastric wall. The patient underwent an exploratory laparotomy that showed an unresectable lesion involving the gastric fundus, the diaphragm and penetrating into the mediastinum, and therefore a palliative jejunostomy was performed.

Cross-sectional imaging in a case of adventitial cystic disease of the popliteal artery.

Adventitial cystic disease of the popliteal artery is an unusual condition of uncertain etiology, in which a mucin-containing cyst forms in the wall of the artery and produces lower extremity claudication, typically in young and middle-aged men. A diagnosis of adventitial cystic disease of the popliteal artery was made preoperatively in a 47-year-old man by means of several imaging modalities, including angiography, magnetic resonance imaging, and ultrasound. The pathological findings confirmed the suggested diagnosis.

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.

[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.

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.

Heller-Belsey and Heller-Nissen operations for achalasia of the esophagus.

From 1972 to 1985, 101 consecutive patients underwent Heller's myotomy and Belsey repair (H + B) (n = 43) or Nissen fundoplication (H + N) (n = 58) for achalasia of the esophagus. There was no operative mortality after either operation; minor pulmonary complications occurred after H + B procedure in 9.3 per cent of the patients. Good to excellent long term results were achieved in 87 per cent of the patients after H + B repair and 83 per cent of the patients undergoing H + N. The failure rates were 2.5 and 11.3 per cent, respectively. The analyses of postoperative esophageal symptoms showed that the incidence of heartburn was greater after H + B repair and the incidence of obstructive symptoms was greater after H + N. The inability to vomit or belch, or both, was 10.2 per cent in the H + B group and 13.1 per cent in the H + N group. Finally, 56.4 per cent of patients after H + B repair and 41.0 per cent of those after myotomy and H + N were considered to be cured after the operative procedure was performed. Patients were improved in 41.0 and 47.3 per cent, respectively.

Chronic respiratory symptoms and occult gastroesophageal reflux. A prospective clinical study and results of surgical therapy.

Seventy-seven patients with a primary complaint of persistent cough, wheezing, and/or recurrent pneumonia were evaluated for the presence of occult gastroesophageal reflux disease. Fifty-four patients (70%) had increased esophageal acid exposure on 24-hour pH monitoring of the distal esophagus. In 28% of these patients the respiratory symptoms were thought to be due to aspiration because they occurred during or within 3 minutes after a reflux episode. In the other patients, the respiratory symptoms were either induced by or were unrelated to reflux episodes. The number of respiratory symptoms reported by the patients with increased esophageal acid exposure was directly related to the presence of a nonspecific esophageal motility abnormality (p less than 0.05). This suggested that a motility disorder contributes to aspiration by promoting the aboral flow of refluxed gastric juice. Seventeen patients with increased esophageal acid exposure had an antireflux operation to relieve their respiratory complaints. Patients whose respiratory symptoms induced reflux episodes were not helped by the procedure. Of the other patients, symptoms were abolished by the procedure only in those with normal esophageal motility. It is concluded that the majority of patients suffering from chronic unexplained respiratory symptoms have occult gastroesophageal reflux disease, but only a minority of them are helped by surgery. Carefully performed esophageal function studies are needed to select those patients who will benefit from a surgical antireflux procedure.

Belsey and Nissen operations for gastroesophageal reflux.

From 1972 to 1985, 37 consecutive patients underwent primary Belsey repair and 40 consecutive patients underwent primary Nissen fundoplication because of reflux disease. The operative procedures were performed by a single surgeon in each group. For the purpose of comparison, both groups were divided into two subsets: (1) patients with proved reflux, and (2) patients with different indications. The first subset consisted of 30 patients in the Belsey series and 32 in the Nissen series. The remaining patients were included in the second subset. One death occurred in the Belsey series; morbidity consisted of minor pulmonary complications in the Belsey series (10.8%) and spleen injuries requiring splenectomy (5%) in the Nissen series. In patients with proved reflux good-to-excellent results were achieved in 89.3% of subjects of the Belsey series and 86.6% of patients of the Nissen group. The failures rates were 7.1% and 10%, respectively. Inability to vomit and/or belch was reported in 7.1% of patients with proved reflux of the Belsey group and 10% of patients with proved reflux of the Nissen group. In patients with different indications there were no failures after either operation. Finally 82.2% of subjects in the Belsey group and 73.3% of patients in the Nissen group declared that they were satisfied with the operative results. In conclusion the Belsey and the Nissen procedures are equally able to achieve long-term control of reflux disease in comparable groups of patients. Failures and gastrointestinal symptoms are equally frequent after either procedure and do not affect the overall patient acceptance of antireflux surgery.

Cisapride versus placebo in reflux esophagitis. A multicenter double-blind trial.

In a 6 to 12-week double-blind trial, the effect of cisapride (10 mg q.i.d.) was compared with that of placebo in 63 patients with esophagitis confirmed by endoscopy and/or biopsy. In only one patient (3%) in the cisapride group but in 43% of the placebo patients (p = 0.001), symptoms had not improved after 6 weeks. Forty patients continued treatment until week 12. At that time, control endoscopy showed a significantly (p = 0.005) higher rate of healing (no erosions, ulcers, or bleeding mucosa) in the cisapride patients (63%) than in the placebo patients (12%). At week 12, only three of the 21 cisapride patients still had moderate reflux symptoms, whereas eight of the 19 placebo patients had moderate or severe symptoms (p less than 0.05). Cisapride patients also took significantly (p less than 0.001) less antacids during the trial. These results show that cisapride, 10 mg q.i.d., heals esophagitis lesions and greatly reduces associated symptoms. The treatment was well tolerated.