Feasibility of intraperitoneal Trastuzumab treatment in a patient with peritoneal carcinomatosis from gastric cancer.

OBJECTIVES: This case report evaluates the feasibility and efficacy of intraperitoneal (IP) trastuzumab administration in gastric cancer (GC) patients with peritoneal carcinomatoses. METHODS: Peritoneal metastasis is a common sign of advanced tumor stage, tumor progression or disease recurrence in patients with GC. Recently, the role of HER2 overexpression in GC, occurring in about 20% of cases, is correlated with a worse prognosis. We report the case of 61-years old female, admitted to our Hospital after curative surgery for GC with over-expression of HER2. Seven months after the start of first line chemotherapy treatment a pleuro-peritoneal disease progression occurred, documented by cytological exam; according to HER2 status, we decided to treat the patient with IP trastuzumab administration. RESULTS: Between September and October 2012, the patient (ECOG performance status was 0), underwent to 6 cycles of IP trastuzumab. Trastuzumab was administered weekly at a dose of 150 mg for each cycle after paracentesis. The safety was good, no local complications (e.g. abdominal pain, peritonitis) occurred. The clinical revaluation evidenced a stable peritoneal disease. CONCLUSIONS: To our knowledge this is the first report on Trastuzumab use to treat IP metastases from GC, with acceptable toxicity and local disease control.

MTHFR polymorphisms in gastric cancer and in first-degree relatives of patients with gastric cancer.

Two common mutations, 677 C-->T and a1298 A-->C, in the methylenetetrahydrofolate reductase gene (MTHFR) reduce the activity of MTHFR and folate metabolism. Familial aggregation in a variable but significant proportion of gastric cancer (GC) cases suggests the importance of genetic predisposition in determining risk. In this study, we evaluate MTHFR polymorphisms in 57 patients with a diagnosis of GC, in 37 with a history of GC in first-degree relatives (GC-relatives), and in 454 blood donors. Helicobacter pylori (HP) infection was also determined. An increased risk was found for 677TT in GC patients with respect to blood donors (odds ratio (OR) = 1.98), and statistical significance was sustained when we compared sex-age-matched GC patients and donors (OR = 2.37). The 677TT genotype association with GC was found in women (OR = 3.10), while a reduction in the 667C allele frequency was present in both the sex. No statistically significant association was detected when 677-1298 genotype was stratified by sex and age. Men of GC-relatives showed a higher 1298C allele frequency than donors (OR = 4.38). Between GC and GC-relatives, HP infection frequency was similar. In conclusion, overall findings support the hypothesis that folate plays a role in GC risk. GC-relatives evidence a similar 677TT frequency to that found in the general population.

Small-bowel neoplasms in patients undergoing video capsule endoscopy: a multicenter European study.

BACKGROUND AND STUDY AIM: Small-bowel tumors account for 1% - 3% of all gastrointestinal neoplasms. Recent studies with video capsule endoscopy (VCE) suggest that the frequency of these tumors may be substantially higher than previously reported. The aim of the study was to evaluate the frequency, clinical presentation, diagnostic/therapeutic work-up, and endoscopic appearance of small-bowel tumors in a large population of patients undergoing VCE. PATIENTS AND METHODS: Identification by a questionnaire of patients with VCE findings suggesting small-bowel tumors and histological confirmation of the neoplasm seen in 29 centers of 10 European Countries. RESULTS: Of 5129 patients undergoing VCE, 124 (2.4%) had small-bowel tumors (112 primary, 12 metastatic). Among these patients, indications for VCE were: obscure gastrointestinal bleeding (108 patients), abdominal pain (9), search for primary neoplasm (6), diarrhea with malabsorption (1). The main primary small-bowel tumor type was gastrointestinal stromal tumor (GIST) (32%) followed by adenocarcinoma (20%) and carcinoid (15%); 66% of secondary small-bowel tumors were melanomas. Of the tumors, 80.6% were identified solely on the basis of VCE findings. 55 patients underwent VCE as the third procedure after negative bidirectional endoscopy. The lesions were single in 89.5% of cases, and multiple in 10.5%. Retention of the capsule occurred in 9.8% of patients with small-bowel tumors. After VCE, 54/124 patients underwent 57 other examinations before treatment; in these patients enteroscopy, when performed, showed a high diagnostic yield. Treatment was surgery in 95% of cases. CONCLUSIONS: Our data suggest that VCE detects small-bowel tumors in a small proportion of patients undergoing this examination, but the early use of this tool can shorten the diagnostic work-up and influence the subsequent management of these patients.

Genetic insights into the disease mechanisms of type II mixed cryoglobulinemia induced by hepatitis C virus.

The ability of the immune system to distinguish between self and non-self is critical to the functioning of the immune response. A breakdown in these mechanisms can lead to the onset of autoimmune disease. Clinical and molecular data suggest that shared immunogenetic mechanisms lead to the autoimmune process. The most studied part of the autoimmune process is the human leukocyte antigen (HLA) region. Recently, progress has been made in narrowing down HLA cluster classifications based on structural and functional features of HLA alleles. Using this approach we have investigated 175 patients with hepatitis C virus (HCV)-induced type II cryoglobulinemia (MC), and compared them to a control group of 14,923 bone marrow donors. Additionally, we investigated the frequency of HLA homozygosity in the same groups of subjects. Our results provide evidence of a role for DR5 and DQ3 HLA class II clusters and a higher frequency of HLA homozygous leading to the clinical outcome of type II mixed cryoglobulinemic autoimmune disease. The DR5 cluster is characterized by a Glu in beta 9 and its polymorphism is connected with preferred anchors at beta 9 of the binding peptide, while the DQ3 cluster is characterized by Glu B86 and Leu B87, which allows the binding of large hydrophobic amino acids at p1 of the binding peptide. The mechanisms by which variations in HLA lead to autoimmunity remain unknown, although they are likely to be mediated by continuous presentation of HCV epitopes to T cells and a genetic background that limits the effective clearance of HCV. The results presented in this paper have increased our knowledge of the mechanism of autoimmune disease and B-cell lymphoproliferation during HCV infection. The work was performed in accordance with the principles of the 1983 Declaration of Helsinki. There is no conflict of interest.

Proteins specifically hyperexpressed in a coeliac disease patient with aberrant T cells.

An aberrant T cell population is the basis for diagnosis of refractory coeliac disease and determines the risk of enteropathy-associated T cell lymphoma. This disease is serious with a poor survival. Pathogenetic mechanisms sustaining aberrant T cell proliferation remain unknown. Recently, alemtuzumab has been proposed as a promising new approach to treat these patients. Only few single cases have been tested at present; nevertheless, in all the cases a clinical improvement was observed. However, whether intraepithelial lymphocytes have been targeted effectively by alemtuzumab is still debated. This study reports, using two-dimensional difference gel electrophoresis (2D DIGE), hyperexpressed proteins associated specifically with aberrant T cells found in a patient with coeliac disease by comparison of the protein expression of this sample with that of patients with coeliac disease and polyclonal T cells or with control subjects. The data demonstrated a significantly higher expression of IgM, apolipoprotein C-III and Charcot-Leyden crystal proteins in a duodenal biopsy specimen of the patient with clonal T cells compared with that of other patients. These preliminary results allow hypothesizing different clinical effects of alemtuzumab in patients with coeliac disease and aberrant T cell proliferation, because as well as the probable effect on T cells, alemtuzumab could exert its effect by acting on inflammatory associated CD52(+) IgM(+) B cells and eosinophil cells, known to produce IgM and Charcot-Leyden crystal proteins, that we demonstrated to be altered in this patient. The results also emphasize the possible association of apolipoprotein with aberrant T cell proliferation.

Hepatitis C virus-related hepatocellular carcinoma and B-cell lymphoma patients show a different profile of major histocompatibility complex class II alleles.

Comparison of human leukocyte antigen (HLA) frequencies in patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) and in patients with HCV-associated non-Hodgkin's lymphoma (NHL) has not been addressed previously. To this aim, we investigated the distribution of HLA class II alleles in two selected groups of HCV-infected patients. Group 1 included 50 patients with HCV-associated NHL; group 2 included 29 patients with HCV-associated HCC. A control group included 144 hospitalized patients without NHL or HCC and who were negative for HCV, hepatitis B virus, and human immunodeficiency virus antibodies. Polymerase chain reaction sequence DRB1 and DQB1 specific-primer methods were used. DRB1*1101/DQB1*0301 haplotype, which mainly favors the spontaneous clearance of HCV infection, was lower in HCC subjects than in controls, whereas HLA-DRB1*1104/DQB1*0301, was higher in NHL patients. These findings suggest different pathogenic pathways in HCC and in NHL development. In patients with HCV-associated HCC, a major protective role of DQB1*0301 allele, rather than DRB1*11, was found, probably because of a better HLA class II-associated virus clearance. By contrast, the same allele as HLA-DRB1*04 showed an increase in HCV-associated NHL. These data suggest that NHL and HCC development may be associated to a different response with respect to chronic HLA class II-restricted antigen presentation (perhaps a switch toward CD4+Th2 response in NHL?) or, alternatively, that these alleles could be in linkage disequilibrium to unrelated gene(s), or are in synergy with other immunomodulatory genes that may confer increased risk for NHL.

Utility of combined use of plasma levels of chromogranin A and pancreatic polypeptide in the diagnosis of gastrointestinal and pancreatic endocrine tumors.

BACKGROUND: Chromogranin A (CgA) is considered the most accurate marker in the diagnosis of gastro-entero-pancreatic (GEP) endocrine tumors. Pancreatic polypeptide (PP) has also been proposed to play this role, but then not used due to its low sensitivity. The aim of the present study was to determine whether the assessment of PP would improve the diagnostic reliability of CgA in patients with GEP tumors. PATIENTS AND METHODS: Both markers were assessed in 68 patients [28 functioning (F), 40 non functioning (NF)]. Twenty-seven patients disease-free (DF) after surgery, and 24 with non-endocrine tumors (non-ETs) were used as control groups. RESULTS: CgA sensitivity was: 96% in F, 75% in NF, 74% in pancreatic, and 91% in gastrointestinal (GI) tumors. Specificity was 89% vs DF, and 63% vs non-ETs. PP sensitivity was: 54% in F, 57% in NF, 63% in pancreatic, and 53% in GI tumors. Specificity was 81% vs DF, and 67% vs non-ETs. By combining the two markers a significant gain in sensitivity vs CgA alone was obtained: overall in GEP tumors (96% vs 84%, p = 0.04), in NF (95% vs 75%, p = 0.02), and in pancreatic (94% vs 74%, p = 0.04). More specifically, a 25% gain of sensitivity was obtained in the subgroup of NF pancreatic tumors (93% vs 68%, p = 0.04). CONCLUSION: The combined assessment of PP and CgA leads to a significant increase in sensitivity in the diagnosis of GEP tumors, particularly in pancreatic NF.

Somatostatin receptor scintigraphy versus chromogranin A assay in the management of patients with neuroendocrine tumors of different types: clinical role.

BACKGROUND: Current diagnosis and staging of neuroendocrine tumors (NETs) are significantly improved by the introduction of the chromogranin A (CgA) assay in plasma or serum as a tumor marker, and by the use of somatostatin receptor scintigraphy (SRS) for tumor localization. However, the clinical role of CgA assay compared with SRS in the management of NETs has not been well elucidated. PATIENTS AND METHODS: Sixty-three consecutive patients with a histological diagnosis of NET underwent plasma CgA assay and SRS for tumor staging (23 cases), evaluation of tumor response (18 cases) and evaluation of tumor recurrence on follow-up (22 cases). Twenty-one patients had well-differentiated neuroendocrine tumors (WDNETs: 18 gastroenteropancreatic tumors and three lung NETs); 22 patients had well-differentiated neuroendocrine carcinomas (WDNECs: 17 gastroenteropancreatic carcinomas, two lung neuroendocrine carcinomas and three neuroendocrine carcinomas of unknown origin) and 20 patients had poorly differentiated neuroendocrine carcinomas (PDNECs: 14 extra-pulmonary small-cell carcinomas and six Merkel cell carcinomas). Almost all (58 of 63) NETs were non-functioning. The quantitative determination of CgA was performed in plasma using an enzyme immunoassay with a cut-off value fixed at 34 U/l. Scintigraphies with indium 111-DTPA-octreotide ((111)In-pentetreotide) included whole-body images and single photon emission computed tomography (SPECT) scans of the chest and abdomen. RESULTS: SRS results were compared with CgA findings and final clinical data. The overall sensitivity of SRS and CgA, based on the final clinical data, was 77% and 55%, respectively, whereas the specificity of both SRS and CgA was 94%. Concerning tumor type, SRS accuracy was 95% for WDNETs, 86% for WDNECs and 60% for PDNECs; CgA accuracy was 76% for WDNETs, 68% for WDNECs and 50% for PDNECs. With regard to disease extent, SRS sensitivity was 100% for limited disease and 72% for advanced disease; CgA sensitivity was 43% for limited disease and 57% for advanced disease. CONCLUSIONS: In our NET series, SRS proved to be more sensitive than CgA, with equivalent specificity. Tumor differentiation influences the sensitivity of SRS and CgA analysis. In addition, the plasma CgA level is related to tumor secretory activity. Nevertheless both SRS and CgA should be considered useful tools in the diagnostic work-up of NET patients.

Digestive neuroendocrine tumours: diagnosis and treatment in Italy. A survey by the Oncology Study Section of the Italian Society of Gastroenterology (SIGE).

BACKGROUND: New insights in the diagnosis and treatment of digestive neuroendocrine tumours have prompted a renewed interest in these rare and complex diseases. AIM: To establish how many new cases of digestive neuroendocrine tumours were diagnosed, and how they were treated, at gastroenterological centres across Italy during a two-year period (1997-1998). METHODS: The 12 centres taking part filled in a data collection form reporting type of tumour, methods of diagnosis and therapeutic strategies adopted in each case. Data were collected and analysed by the authors of the present report. RESULTS: Data refer to 98 patients, 22 with functioning and 76 with non-functioning digestive neuroendocrine tumours [50 carcinoids, 48 pancreatic endocrine tumour syndromes]. Primary tumours were localised in 96% (38% with metastases) of non-functioning and 81% (50% with metastases) of functioning tumours. These were surgically removed in >80% of patients in both groups. Somatostatin analogue treatment, with or without interferon, was administered in 35% of patients, while chemotherapy was used in 9% and 23% of functioning and non-functioning tumours, respectively. The imaging study always included a computed tomography scan (20% helical computed tomography). Magnetic resonance and somatostatin receptor scintigraphy were also performed, the former in 41% and 21% of the two (functioning and non-functioning tumour) groups, the latter in 45% and 30%. CONCLUSIONS: The number of functioning digestive neuroendocrine tumours reported was lower than expected. Surgery plays a major role in the treatment of these tumours in all centres. Overall, in only a small number of patients was a multidisciplinary approach applied.

Percutaneous endoscopic gastrostomy (PEG) in palliative treatment of non-operable intestinal obstruction due to gynecologic cancer: a review.

Percutaneous endoscopic gastrostomy (PEG) is a relatively simple method in achieving non-surgical gastric decompression in patients with upper gastrointestinal tract obstruction from metastatic pelvic and abdominal tumors.

Pre-malignant and malignant lymphoproliferations in an HCV-infected type II mixed cryoglobulinemic patient are sequential phases of an antigen-driven pathological process.

Type II mixed cryoglobulinemia (MC) is a systemic vasculitis characterized by the presence in the serum of a monoclonal cryoprecipitable IgM with rheumatoid factor (RF) activity. Hepatitis C virus (HCV) has been recognized as its major etiologic factor. Because MC frequently evolves into overt B-cell non-Hodgkin's lymphoma (NHL), chronic HCV infection is hypothesized to lead to both benign and malignant lymphoproliferative disease. In this study, we investigated mutations in the V(H) and V(K) genes of the B-cell clone originating the overt B-cell lymphoma in a subject with MC. Mutational patterns were analyzed longitudinally in two bone marrow biopsies obtained at the stage of MC, as well as in multiple involved tissues (bone marrow, liver, and peripheral blood cells) at the stage of overt NHL. Hybridization of variable-diversity-joining (VDJ) PCR products with a probe specific for the neoplastic clone indicated that the lymphoma originated from one of the clones over-stimulated during MC. This clone producing an IgM highly homologous to a protein with RF specificity may explain the MC syndrome in the patient. Moreover, the presence of an IgH ongoing mutation process and the expression of an Ig antigen receptor significantly homologous to an anti-HCV protein support the hypothesis that the MC syndrome and the subsequent evolution to NHL are antigen-driven lymphoproliferative processes possibly sustained by HCV. Furthermore, the marked reduction in intra-clonal diversity in the last bone marrow biopsy obtained at the stage of overt NHL points out a minor dependence of the cells on the antigen-driven mechanism, although an intrinsic propensity of the neoplastic cell to undergo replacement mutations cannot be excluded.

[Usefulness of chromogranin A determination in the diagnosis of neuroendocrine neoplasia]. / Utilità del dosaggio della cromogranina A nella diagnosi delle neoplasie neuroendocrine.

Neuroendocrine gastroenteropancreatic tumor diagnosis is a very difficult and expensive procedure. This study compared Chromogranin A (CgA) to Neuron-specific enolase (NSE) in 55 patients affected by neuroendocrine tumors. Advanced local or metastatic neoplasia was found in 43 patients. Radical operation was performed in 12 patients. Seventeen cases of lung microcystoma, 23 cases of other intestinal tumors and 19 patients affected by irritable bowel syndrome were used as controls. CgA sampling demonstrated sensitivity of 73% and specificity of 66%, a positive predictive value of 77% and a negative predictive value of 61% while NSE sampling showed sensitivity of 100%, specificity of 36%, a positive predictive value of 15% and a negative predictive value of 100%. CgA values demonstrated a statistically significant difference between patients with neuroendocrine tumors and tumor-free resected patients (p = 0.0015), microcystoma patients (p = 0.0087), other types of neoplasia (p = 0.01) and irritable bowel syndrome patients (p = 0.0004). No significant difference was found among the same groups when NSE values were analyzed. The high diagnostic accuracy of CgA sampling renders it very useful in early neoplastic detection, even in cases of nonfunctioning neoplasms or absence of liver metastases. In addition, CgA sampling may be an effective screening test in patients with irritable bowel syndrome or with liver or lung metastases when there is no evidence of the primitive tumor.

Pharmacokinetics of oral etoposide in patients with hepatocellular carcinoma.

Etoposide dosage in patients with liver dysfunction remains controversial. Since etoposide has a hepatic component to its clearance (CL) and shows a high degree of protein binding, hepatic impairment could affect etoposide disposition. However, the empiric recommendation that the dose of etoposide be decreased in such patients may reduce systemic exposure and be detrimental to its antitumor activity. To address these issues we studied the pharmacokinetics (PK) of etoposide in patients with hepatocellular carcinoma (HCC) and underlying cirrhosis (n = 17) treated with daily oral etoposide. Unbound etoposide was obtained by ultrafiltration. Etoposide concentrations (total and free drug) were measured by high-performance liquid chromatography (HPLC) and analyzed by noncompartmental equations. The patients had mild or moderate liver dysfunction. Albuminemia was in the normal range for all the patients. Creatininemia was normal in all but two patients. PK results (mean and range) showed that etoposide disposition was unchanged in patients with liver dysfunction. We found slightly high etoposide bioavailability [F, 61% (17-95%)] and clearance [CL, 1.1 (0.7-2.3)l h(-1) m(-2)] resulting in a normal degree of systemic exposure (AUC(oral) 27 microg h ml(-1)). Normal protein binding [PB 93.2% (84.4-98.1%)] contributed to a normal level of exposure to free drug (AUC(f, oral) 1.9 microg h ml(-1)). The distribution volume [V(SS) 8.4 (6.1-13.2) l/m2] and the effective half-life [t1/2eff, 5.1 (3.0-9.6) h] were normal. Median CL and protein binding did not differ in the seven patients with total bilirubin value of > 1.2 mg/dl as compared with the ten patients with total bilirubin levels of < or = 1.2 mg/dl (1.3 versus 1.01 h(-1) m(-2) and 92.5% versus 93.4%, respectively). In agreement with this PK finding, we observed no clinical evidence of increased toxicity in patients with hyperbilirubinemia as compared with patients with normal bilirubinemia (mean WBC decrease 38% versus 47%). The only case of severe (grade 4) hematological toxicity was observed in one patient with reduced glomerular filtration. Since the pharmacological effects of etoposide correlate with the level of systemic exposure to the free drug, our data suggest that no dose reduction is needed in patients with HCC. It is even possible to increase the dose intensity in patients with favorable PK parameters under appropriate hematological and therapeutic drug monitoring.

Evaluation of the risk for metachronous colorectal neoplasms following intestinal polypectomy: a clinical, endoscopic and pathological study.

BACKGROUND/AIMS: Surveillance programs are recommended for patients with previous intestinal polypectomy because of the high rate of adenomatous recurrences and risk of subsequent colorectal cancer. The parameters to identify patients at higher risk and the length and schedules of follow-up have not yet been established. We considered some clinical, endoscopic and pathological parameters in order to assess the probability of developing new colorectal neoplasms and eventually to schedule proper surveillance programs. METHODOLOGY: Patients with removed adenomas were enrolled into a clinico-endoscopic follow-up, comprehensive of two colonoscopies the first at 1 year and the second at 3 years. We evaluated the risk of new neoplasms dividing the patients into four groups according to the number and size of the adenomas removed and the parameters considered. RESULTS: Of 164 patients enrolled 156 completed the study. We had an overall 21.3% of adenomatous recurrences at 1 year and 12.8% at 3 years. Most of the adenomas removed were tubular and small in size (< 1 cm). The percentage of patients who had adenomas with advanced pathological features was 1.82% at 1 year and 0.64% at 3 years. The increase in number and size of the adenomas removed on the initial colonoscopic examination was the only one parameter statistically significant, X(2)1 (trend) 5.11; p<0.05 at the first follow-up and X(2)1 (trend) 4.87; p<0.05 at the second follow-up. CONCLUSIONS: Patients with previous single adenoma showed few recurrences of extremely benign histological features. Since they do not require short-term endoscopic examination, it would be reasonable to defer the next colonoscopy for at least another 5 years. During follow-up, patients with multiple polyps had adenomas with advanced pathological features so it was useful to follow-up at 1 year. The tendency for advanced pathological features of removed polyps was not seen at 3 years, suggesting the importance of long-term follow-up, but with longer intervals.

Early gastric cancer: diagnosis, surgical treatment and follow-up of 45 cases.

AIMS AND BACKGROUND: The 5-year survival rate of early gastric cancer (EGC) is 85%-100% after "curative" resection, as compared to 20%-30% in advanced gastric cancer (AGC). Because of this relatively high cure rate, the interest in the diagnosis and therapy of EGC has been steadily increasing. The present study, based on 45 EGCs, is aimed at a critical evaluation of the diagnostic procedures and surgical options. METHODS AND RESULTS: Forty-five patients with early gastric cancer (27 men and 18 women; median age, 62 years; range, 28-84) were diagnosed and operated on. They represented 22.5% of all patients with gastric cancer (200) treated in the period July 1987 to January 1998. Forty-one patients were from the northeastern part of Italy. The most frequent symptom was epigastric pain (84%). Barium upper gastrointestinal radiography findings were strongly suggestive of malignancy in 41 cases (91%). Preoperative histopathological diagnosis of adenocarcinoma was performed in 43 cases (95.5%). In two cases (4.5%) severe epithelial dysplasia (associated with ulcer) was the first diagnosis, but the final diagnosis on the basis of the resected specimens was a well differentiated adenocarcinoma. The primary surgical procedure included i) subtotal distal resection (37 cases) with Billroth 11 (33) and Billroth I (4) reconstructions; ii) total gastrectomy (3) for proximal neoplastic extension; iii) proximal gastric resection (2) for cardial cancer; iv) degastro-total gastrectomy (3) for cancer of the stump. Two patients, previously treated with conservative surgery, underwent degastro-total gastrectomy for neoplastic microfocal extension to the margin of resection and for early anastomotic recurrence, respectively. Mural infiltration was limited to the mucosa and submucosa in 27 and 18 cases, respectively. Lymph node metastases were found in three mucosal and five submucosal tumor cases, involving either the first or the second echelon. No operative deaths or postsurgical complications occurred in this series. In the follow-up period (median, 36 months; range, 3-120) four patients died due to other causes; one developed liver metastases, another developed oropharyngeal cancer and two died of biopsy-proven lung cancer without evidence of gastric cancer recurrence. CONCLUSIONS: The clinical presentation of EGC is aspecific. Preoperative endoscopy with biopsy remains the most sensitive diagnostic procedure. For treatment, subtotal distal gastric resection with lymphadenectomy is the "gold standard" but in some instances total gastrectomy may be indicated. Accurate pathological examination establishes the depth of infiltration, as well as the superficial extension of tumors and the lymph node status. Although the prognosis of EGC is favorable, a medium-term follow-up should be planned.

[Percutaneous endoscopic gastrostomy (PEG) in upper gastrointestinal tract occlusion in gynecologic oncology]. / La gastrostomia percutanea endoscopica (PEG) nelle occlusioni dell'alto tratto intestinale in ginecologia oncologica.

BACKGROUND AND AIMS: Intestinal obstruction is a frequent cause of death in patients suffering from gynecological cancer, who have undergone multiple treatment in the form of surgery and/or chemotherapy and/or radiotherapy. The usual form of rescue treatment consists in the use of a nasogastric tube to administer support and analgesic treatment. Surgical gastrostomy is not a viable proposition in these extremely weak patients with large masses compressing and displacing the stomach. Percutaneous endoscopic gastrostomy (PEG), a technique first introduced for nutritional purposes, can be beneficially used to achieve decompression in these patients. METHODS: PEG was performed in a total of 67 patients who had already undergone multiple treatment for abdominal-pelvic neoplasia with upper gastrointestinal obstruction, who could no longer be operated and who had a life expectancy of less than sixty days. In three cases positioning was not possible owing to the lack of transillumination of the gastric and abdominal wall. 54/64 patients had previously undergone at least two operations. RESULTS: Esophagogastric lesions were found in 29% of patients, some of which were attributed to the nasogastric tube. Symptomatic wellbeing was obtained in 76.5% a few days after PEG. PEG remained in situ from 4 to 472 days. Slight peristomal infection was observed in 9% of cases. In seven cases it was necessary to add octreotide owing to the reappearance of symptoms. CONCLUSIONS: PEG is relatively easy to use and allows obstructive symptoms to be resolved in the majority of patients. Special medical skills are not required and the patient may be easily managed at home together with support therapy and pain management. Once PEG has been performed, it is possible to take fluids and semi-liquid foods, offering the patient a chance to taste flavours which have often been forgotten. PEG enables neoadjuvant chemotherapy to be performed in patients with previously untreated intestinal obstruction.

Hepatitis C virus, non-Hodgkin's lymphomas and hepatocellular carcinoma.

In a case-control study in northeastern Italy hepatitis C virus infection seemed to increase by about 50-fold the risk of non-Hodgkin's lymphoma involving the liver and major salivary glands (i.e. larger than that for hepatocellular carcinoma) and by about fourfold the risk of lymphomas at other sites.

Palliative treatment of upper intestinal obstruction by gynecological malignancy: the usefulness of percutaneous endoscopic gastrostomy.

The usefulness of percutaneous endoscopic gastrostomy (PEG) for decompression in patients with unresolving intestinal obstruction by gynecological malignancy is examined. Between April 1993 and August 1995, 34 consecutive patients with small-bowel obstruction by gynecological cancer, heavily pretreated with surgery and chemotherapy, were admitted to our prospective study. PEG was performed in 32/34 patients (94.1%). Failure in the placing of the tube occurred in 2 patients (5.9%). Twenty-seven patients (84.4%) experienced symptomatic relief after a few days from PEG and tolerated soft and liquid foods. All of these patients were discharged from the hospital and underwent parenteral nutrition at home. The median postoperative hospital stay was 7 days (range 3-45). No major complications due to PEG placement itself occurred in our patients. Only 4 patients (12.5%) had postprocedure nausea and vomiting that was unresponsive to the conventional therapy. The use of Octreotide (0.6 mg/24 hr) obtained relief from symptoms until death. The gastrostomy remained in place for a median of 74 days (range 5-210). Relief from symptoms after PEG placement and total parenteral nutrition permitted continuation of palliative chemotherapy in 8 patients (25%). We suggest percutaneous endoscopic drainage gastrostomy technique as the procedure of choice for long-term drainage of unresolving small bowel obstruction in patient with metastatic abdominal gynecologic malignancy.