Echo-guided injection of botulinum toxin versus blind endoscopic injection in patients with achalasia: final report.

AIM: Achalasia, also known as Esophageal achalasia, is an esophageal motility disorder involving the smooth muscle layer of the esophagus and the lower esophageal sphincter (LES). It is characterized by incomplete LES relaxation, increased LES tone, and lack of peristalsis of the esophagus (inability of smooth muscle to move food down the esophagus) in the absence of other explanations like cancer or fibrosis. In our experience, the echo-guided injection technique is the first procedure to implement to cure patients. After endoscopic-echo-guided injection technique, in patients presenting with refractory symptoms, the authors believe in surgical technique (extramucosal myotomy) as a good alternative technique to be implemented. METHODS: From 1999 to 2010, the authors have treated 36 patients (Group A), 24 male and 12 female (age 26-78) with diagnosis of esophageal achalasia. Patients underwent botulinum toxin injection during echo-guided identification of the lower esophageal sphincter. Results were compared with 32 patients (Group B) (age 36-78) who underwent blind treatment. RESULTS: Patients of Group A presented complete relief of obstruction, patients of Group B had an obstruction remission in the 86% of the cases. Results were confirmed by manometric assessments in the early months after endoscopic treatment. CONCLUSION: The authors emphasize the importance of the injection of botulinum toxin into the thicker area of the muscle layer of the lower esophageal sphincter. Patients undergoing echo-guided injection technique presented complete relief of obstruction, confirmed by manometric assessments in the early months after treatment.

From mininvasive to maxinvasive surgery in colorectal cancer: modem evolution of oncologic specialized units.

In the last years a wide range of new technique offers the possibility to have R0 resection in colorectal cancer. We report our experience about Single Port Laparoscopic Surgery (SPL) for not advanced right colon cancer and about pelvectomy with cilindric Abdominal Perineal Resection (APR) for advanced rectal cancer. SPL offer mainly cosmetic advantages but also quicker recovery. No touch technique with adequate surgical margin and lymphectomy were respected. Operative time of SPL was 85-115 minutes, the incision was 5 cm long. There were no complications. Length of hospital stay was 4-6 days. With advanced pelvic cancer, pelvic exenteration with en-bloc resection is indicated. Then we propose a case of a 55 years old woman with a pelvic recurrence from a metastatic rectal cancer involving the right obturator fossa, the vaginal stump, the right ureter. Modern surgical technique give us the chance to offer the most appropriate oncologic surgical treatment.

Molecular alterations at chromosome 9p21 in melanocytic naevi and melanoma.

BACKGROUND: The chromosome 9p21 and its CDKN locus, with the p16 tumour suppressor gene (CDKN2A), are recognized as the genomic regions involved in the pathogenesis of melanoma. OBJECTIVES: To elucidate further the role of such regions during the different phases of melanocytic tumorigenesis. METHODS: Tissue sections from naevi, primary and metastatic melanomas were investigated by fluorescence in situ hybridization for allelic loss at the 9p21 chromosome and by immunochemistry for p16CDKN2A expression. RESULTS: Dysplastic naevi and primary or secondary melanomas were found to carry hemizygous deletions within the entire 9p21 region at similar frequencies (varying from 55% to 62%). Allelic deletion spanning the CDKN locus was observed at significantly increased rates moving from early (7%) to advanced (28%) primary melanomas and to secondary melanoma lesions (37%) (P=0.018). Also, inactivation of the p16 gene (CDKN2A) was absent in naevi and present at steadily increasing rates moving from primary melanomas (7% early lesions to 17% advanced lesions) to melanoma metastases (62%) (P=0.004). CONCLUSIONS: Our findings indicate that, in a model of sequential accumulation of genetic alterations, 9p21 deletions may play a role in melanocytic transformation and tumour initiation whereas rearrangements at the CDKN locus, and p16 gene (CDKN2A) inactivation may contribute to tumour progression.

Combined multistep approach in a locally advanced rectal cancer with sacral invasion: case report.

Composite pelvic resection with sacrectomy may provide good local control in case of locally advanced rectal cancer infiltrating the sacral bone. A combined multidisciplinary approach including chemotherapy and radiotherapy is here presented for a case of rectal tumor invading the sacrum.

[Early evaluation using PET-FDG of the efficiency of neoadjuvant radiochemotherapy treatment in locally advanced neoplasia of the lower rectum]. / Valutazione precoce con PET-FDG della efficacia del trattamento radiochemioterapico neoadiuvante nelle neoplasie del retto inferiore localmente avanzate.

BACKGROUND AND PURPOSE: Preoperative chemoradiation allows downstaging of locally advanced rectal cancer and in selected patients also a sufficient downsizing to ensure sphincter preservation. Selection of patients warranting a preoperative approach is improved by magnetic resonance imaging (MRI) which is able to define the involvement of mesorectal circumferential margin. Similarly it would be crucial to define the response to chemoradiation during the treatment but traditional morphologic imaging techniques may fail in differentiating neoplastic tissue from scarring. PET-FDG has been successfully used in the detection of metastatic colorectal cancer allowing imaging of deposits as small as 0.5 cm and may have a role in evaluating early response to chemoradiation. METHODS: In the present study, in patients with T3-T4 rectal cancer undergoing preoperative chemoradiation PET-FDG and flow cytometry analysis on endoscopic biopsy specimen have been performed before, during and after preoperative chemoradiation. RESULTS: Chemoradiation treatment has been successful in terms of downsizing and downstaging of the tumor. PET-FDG was able to demonstrate local response at only ten-fifteen days after the beginning of neoadjuvant therapy, also identifying non responding patients. CONCLUSIONS: FDG-PET may have a role in defining the response to chemoradiation and modulate the treatments strategy in patients with advanced rectal cancer.

Impact of surgical treatment on quality of life of patients with gastrointestinal tumors.

Quality-of-life assessment is becoming an important concern even of surgeons. The new trend applies specifically to surgical oncology, where particular attention is now being paid to the outcome of surgical treatment. Gastrointestinal cancers are heterogeneous in their presentation and in treatment, but they share common aspects related to the surgical approach. A functional outcome is fundamental in all the operations performed for gastrointestinal cancers and many improvements have been made thanks to the increased rate of conservative approaches and the amelioration of the technology applied to surgery. The measurement of the surgical outcome and the methods to be applied is still undergoing extensive evaluation but the flourishing interest in the issues concerning quality of life all over the surgical community will rapidly lead to a better definition of goals and results.

Detection of circulating tumor cells in carcinoma patients by a novel epidermal growth factor receptor reverse transcription-PCR assay.

The epidermal growth factor receptor (EGFR) is overexpressed in 50-70% of human primary breast, lung, and colon carcinomas, whereas it is not usually expressed in hematopoietic cells. We developed a novel reverse transcription-PCR (RT-PCR)-Southern blot assay for the detection of circulating, EGFR mRNA-expressing tumor cells in carcinoma patients. The assay was set up by increasing the amount of cDNA step by step in the PCR reaction. The highest sensitivity and specificity were found when using 800 ng of cDNA in the PCR reaction. Peripheral blood samples from 91 patients with either colon (38), lung (30), or breast (23) carcinomas and from 38 healthy volunteers were analyzed. EGFR transcripts were found in 44 of 75 (59%) patients with metastatic carcinoma and in 4 of 38 (10.5%) healthy donors (P < 0.001; chi2 test). The expression of EGFR, cytokeratin 19, and carcinoembryonic antigen mRNA in blood samples from patients with metastatic colon carcinoma was compared. EGFR, cytokeratin 19, and carcinoembryonic antigen transcripts were found in 8 of 11 (73%), 3 of 11 (27%), and 5 of 11 (45%) patients, respectively. Furthermore, two of seven (29%) Dukes' B and five of nine (55%) Dukes' C colon carcinoma patients were found to express EGFR mRNA in the peripheral blood. All patients that expressed EGFR transcripts in the peripheral blood were found to express the EGFR protein in the corresponding primary carcinoma, as assessed by immunohistochemistry. These data suggest that the EGFR assay that we developed is a highly specific and sensitive technique to detect circulating tumor cells in patients affected by different carcinoma types.

Major surgery for a gastric cancer in a haemophilic with high inhibitor titre successfully performed by the use of recombinant FVIIa.

A total gastrectomy with omentectomy and resection of the distal oesophagus in a 69-year-old haemophilia A patient with high inhibitor of 128 Bethesda units is described. Surgery was successfully performed after infusion of 112 microg kg-1 bw of recombinant FVIIa. Ninety-two microg kg-1 were given thereafter at time intervals of 2 h until 12 h, then every 3 h until 24 h, and every 4 h until 48 h after surgery. Doses were gradually reduced in the following days and finally discontinued on day 28 after surgery. The complete treatment schedule required the administration of a total of 708 mg of recombinant FVIIa. Using this approach, we observed normal haemostasis, and there were no signs of excessive postoperative bleeding or wound haematoma. No clinical side-effects or evidence of systemic activation of coagulation occurred during the treatment. As judged from the clinical course of this major surgery, recombinant FVIIa appears to be highly efficacious and safe and should be used as first line treatment in high titre inhibitor patients with cross-reactivity to porcine factor VIII, undergoing surgery.

Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies: results in 123 patients.

OBJECTIVE: To describe the safety and efficacy of radiofrequency ablation (RFA) to treat unresectable malignant hepatic tumors in 123 patients. BACKGROUND: The majority of patients with primary or metastatic malignancies confined to the liver are not candidates for resection because of tumor size, location, or multifocality or inadequate functional hepatic reserve. Local application of heat is tumoricidal; therefore, the authors investigated a novel RFA system to treat patients with unresectable hepatic cancer. PATIENTS AND METHODS: Patients with hepatic malignancies were entered into a prospective, nonrandomized trial. The liver tumors were treated percutaneously or during surgery under ultrasound guidance using a novel LeVeen monopolar array needle electrode and an RF 2000 generator. All patients were followed to assess complications, treatment response, and recurrence of malignant disease. RESULTS: RFA was used to treat 169 tumors (median diameter 3.4 cm, range 0.5 to 12 cm) in 123 patients. Primary liver cancer was treated in 48 patients (39.1%), and metastatic liver tumors were treated in 75 patients (60.9%). Percutaneous and intraoperative RFA was performed in 31 patients (35.2%) and 92 patients (74.8%), respectively. There were no treatment-related deaths, and the complication rate after RFA was 2.4%. All treated tumors were completely necrotic on imaging studies after completion of RFA treatments. With a median follow-up of 15 months, tumor has recurred in 3 of 169 treated lesions (1.8%), but metastatic disease has developed at other sites in 34 patients (27.6%). CONCLUSIONS: RFA is a safe, well-tolerated, and effective treatment to achieve tumor destruction in patients with unresectable hepatic malignancies. Because patients are at risk for the development of new metastatic disease after RFA, multimodality treatment approaches that include RFA should be investigated.

[Surgical options in the palliative treatment of pancreatic cancer]. / L'approccio chirurgico nella palliazione del carcinoma pancreatico.

Pancreatic carcinoma is an aggressive disease and its prognosis is dismal. Patients present with an advanced stage of disease and only a small number of patients undergo resection with a curative intent; thus the 5 years survival rate is very low. Several improvements have been made in the surgical approach with a decrease in perioperative morbidity and mortality. Results offered by chemotherapy and radiotherapy remain unsatisfactory despite a number of new drugs and considerable advancements in irradiation techniques. Jaundice, pain and gastrointestinal obstruction are the main clinical problems to be dealt with in advanced patients. Surgical palliation still represents a widely preferred option but non surgical approaches appear promising. The Authors analyse the possible options in palliation for pancreatic carcinoma. The various surgical procedures for biliary by-pass are described. Hepaticojejunostomy is the operation of choice and offers the best results in terms of quality of life and time of palliation. A possible role for resective operation also in advanced cases has been proposed by some groups and is gaining wide acceptance in referral centres where low morbidity and mortality are now routine. Percutaneous and endoscopic approaches to jaundice represent a valid alternative in some patients with a low life expectancy and in those centres with a high experience. Gastrointestinal by-pass in symptom-free patients or advanced cases only is an unsolved dilemma. New approaches such as locoregional chemotherapy with curative or neoadjuvant intent are also described in this paper. Many chemotherapic agents have been tested in various settings and appear to offer promising results in palliation and also, in some cases, in downstaging tumors then amenable to resection. Pain control is a major aspect in management of advanced pancreatic carcinoma. Appropriate pain therapy has to be established in all patients in order to obtain a better quality of life. Various options are available such as intraoperative alcohol injection or CT guided percutaneous splanchnicectomy. Palliation in patients with pancreatic carcinoma is a major aspect of management because of the high percentage of non curable cases; multimodality approach is mandatory and all possible problems have to be dealt with in order to increase survival and, more importantly, quality of life.

Soluble interleukin-2 receptor levels in hepatocellular cancer: a more sensitive marker than alfa fetoprotein.

BACKGROUND: Worldwide, the majority of cases of hepatocellular cancer (HCC) arise in individuals with chronic hepatitis B or C virus infections. Early detection of HCC in these patients provides the best chance for curative treatment, but serum alfa fetoprotein (AFP) levels are frequently normal in patients with small HCCs. The purpose of this study was to determine: (1) whether soluble interleukin-2 receptor (sIL-2R) levels are elevated more frequently than AFP levels in HCC patients and (2) whether sIL-2R levels are useful as a marker of successful treatment and recurrence of disease. PATIENTS AND METHODS: We are performing a prospective screening program with high-risk, chronic hepatitis virus-infected patients to detect HCC. Patients are screened by using abdominal ultrasonography, serum AFP measurements, and serum sIL-2R measurements. Normal serum sIL-2R levels were established using results from 174 healthy volunteers with no evidence of hepatitis virus infection or HCC. RESULTS: HCC has been diagnosed in 99 patients from a cohort of 1520 screened patients. Serum AFP levels were elevated in 79 patients (80%), whereas sIL-2R levels were elevated in 98 of the 99 patients (99%, P < .01, chi2 test). For 27 of the 99 patients (27%), HCC was diagnosed at an early stage and complete resection or ablation was performed. Serum sIL-2R levels returned to normal in all 27 patients after treatment, whereas AFP levels remained slightly elevated in 5 of the 27 (18%). Among the 16 patients in this group of 27 who developed recurrent HCC, sIL-2R levels became elevated in all 16, whereas AFP levels were elevated at diagnosis of recurrence for only 10 (P < .05). CONCLUSIONS: This study with chronic hepatitis B or C virus-infected patients indicates that (1) serum sIL-2R levels are abnormal in patients with HCC with a significantly greater frequency, compared with AFP levels, and (2) sIL-2R levels are a more sensitive marker of successful treatment and recurrence of HCC. Based on these findings, we now use serum sIL-2R measurements both to screen high-risk patients and to monitor treatment responses in patients with hepatitis who develop HCC.

Outcome of 67 patients with hepatocellular cancer detected during screening of 1125 patients with chronic hepatitis.

OBJECTIVE: We performed this prospective screening trial in chronic hepatitis virus-infected patients to determine the incidence of hepatocellular cancer (HCC) and the resectability and long-term survival rates of these HCC patients. SUMMARY BACKGROUND DATA: Chronic hepatitis B or C virus infection is a major etiologic factor in human HCC. It is not clear if routine screening of chronic viral hepatitis patients improves the survival of patients who develop HCC. METHODS: Screening for HCC was offered to patients chronically seropositive (>5 years) for hepatitis B or C infection. All patients underwent percutaneous core liver biopsy to assess the histologic severity of chronic liver injury. Patients were screened initially and every 3 months thereafter with serum alpha-fetoprotein and transabdominal ultrasound evaluations; HCC was confirmed by needle biopsy of liver tumors. RESULTS: Screening was performed on 1125 hepatitis-positive patients (804 with hepatitis C, 290 with hepatitis B, 31 with both). On liver biopsy, 800 patients had mild chronic active hepatitis and 325 had severe chronic active hepatitis, cirrhosis, or both. Initial screening detected HCC in 61 patients. HCC was detected in six more patients during follow-up; thus, the incidence of HCC was 5.9% (67/1125). However, 66 of the 67 HCC cases (98.5%) arose in the 325 patients with severe chronic active hepatitis or cirrhosis (66/325 [20.3%] vs. 1/800 [0.1%], p < 0.0001 [Wilcoxon signed rank]). Median follow-up of the 67 HCC patients was 24 months. Locally advanced or metastatic, unresectable HCC occurred in 43 patients (64.2%); 24 patients (35.8%), including the 6 patients detected during follow-up screening, underwent margin-negative resection. The median survival for the 24 resected patients was 26 months, compared to 6 months for the 43 patients with unresectable cancer (p < 0.0001, Wilcoxon signed rank). CONCLUSIONS: HCC was found to arise in 20.3% of patients with chronic hepatitis B or C infection and severe liver injury. Initial screening detected resectable lesions in less than half the HCC patients. Routine screening of chronic hepatitis B or C virus-infected patients with ultrasound and alpha-fetoprotein determination should be reserved for patients with severe chronic active hepatitis, cirrhosis, or both.

[Positron emission tomography (PET) with fludeoxyglucose F 18 in the study of adrenal masses: comparison of benign and malignant lesions]. / La tomografia con emissione di positroni (PET) con F-18 FDG nello studio delle formazioni espansive con sede surrenalica: confronto tra lesioni benigne e maligne.

In this study, 15 patients (4 men and 11 women, mean age: 50 +/- 13 years) with unilateral adrenal masses detected on ultrasound (US), Computed Tomography (CT) and/or Magnetic Resonance (MR) studies were submitted to positron emission tomography (PET) with fluorine-18 deoxyglucose (FDG). Histology demonstrated 3 adenomas, 1 myelolipoma, 1 angiolipoma, 1 neurinoma, 1 cyst, 1 malignant pheochromocytoma, 4 carcinomas and 3 metastases. The patient population was divided into two groups. Group 1 (n = 7) consisted of benign adrenal lesions. Group 2 consisted of malignant adrenal tumors. Lesion measurements were performed on the basis of the results of US, CT and/or MR images. In Group 1, no FDG uptake was observed in adrenal masses. Conversely, in Group 2 adrenal lesions showed abnormally increased FDG uptake, suggesting high glucose tumor metabolism. No significant difference in lesion size was observed between Groups 1 and 2 (5.6 +/- 4.0 vs 6.3 +/- 3.0 cm). Furthermore, in 6 patients of Group 2, total body PET images showed abnormal FDG uptake in extra-adrenal locations, such as chest (n = 2) and abdominal (n = 5) lymph nodes, lungs (n = 6), liver (n = 5), pancreas (n = 1), bone (n = 1) and muscle (n = 1) tissues. In conclusion, the results of this study suggest that PET imaging with FDG can characterize adrenal masses. In particular, abnormally increased FDG uptake in adrenal malignancies allows to differentiate these abnormalities from benign lesions. Furthermore, total body imaging PET can identify extra-adrenal tumor sites in patients with malignant tumors.