Sporadic pedunculated duodenal adenomas. Clinical presentations and endoscopic management: a case series.

The prevalence of sporadic duodenal polyps is estimated to be 0.3%-4.6% in patients referred for an upper endoscopy. Most of patients are asymptomatic (66-80%) at the time of diagnosis though bleeding, anemia and abdominal pain are the most commonly reported symptoms. These are related to the polyp's size, location and histological characteristics. We describe three cases of big, pedunculated nonampullary sporadic duodenal polyps (tubulovillous low-grade dysplasia adenomas) located in the second part of the duodenum and characterized by different clinical presentations, managed in our Endoscopic Unit within one year (between 2016 and 2017). Polypectomies were performed, either piece-meal or en-bloc using various endoscopic instruments. In one of our patients (case 1), a delayed bleeding (36 hours after the procedure) occurred eventually managed conservatively with two units of blood transfusion. In the same patient, in the following months after polypectomy, the pre-procedural state of anemia misclassified as Mediterranean anemia has improved with a significant rise of hemoglobin value (14.1g/dl). In a patient who previously underwent a renal transplant (case 2), endoscopy was indicated, based on the positive fecal occult blood test. In another patient (case 3), a big polyp induced pancreatitis since it exerted a strong traction on the duodenal wall during peristaltic movements. The removal of the polyp has led to the resolution of pancreatitis and associated symptoms.

Effects of dark chocolate on NOX-2-generated oxidative stress in patients with non-alcoholic steatohepatitis.

BACKGROUND: Activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is considered a pathogenetic mechanism determining fibrosis and disease progression in non-alcoholic steatohepatitis (NASH). Polyphenols exert antioxidant action and inhibit NADPH oxidase in humans. AIM: To analyse the effect of cocoa polyphenols on NADPH oxidase isoform 2 (NOX2) activation, oxidative stress and hepatocyte apoptosis in a population affected by NASH. METHODS: In a cross-sectional study comparing 19 NASH and 19 controls, oxidative stress, as assessed by serum NOX2 activity and F2-isoprostanes, and hepatocyte apoptosis, as assessed by serum cytokeratin-18 (CK-18) levels, were measured. Furthermore, the 19 NASH patients were randomly allocated in a crossover design to 40 g/day of dark chocolate (>85% cocoa) or 40 g/day of milk chocolate (<35% cocoa), for 2 weeks. sNOX2-dp, serum isoprostanes and CK-18 were assessed at baseline and after 2 weeks of chocolate intake. RESULTS: Compared to controls, NASH patients had higher sNOX2-dp, serum isoprostanes and CK-18 levels. A significant difference for treatments was found in subjects with respect to sNOX2-dp, serum isoprostanes and serum CK-18. The pairwise comparisons showed that, compared to baseline, after 14 days of dark chocolate intake, a significant reduction in sNOX2-dp serum isoprostanes and CK-18 M30 was found. No change was observed after milk chocolate ingestion. A simple linear regression analysis showed that ∆ of sNOX2-dp was associated with ∆ of serum isoprostanes. CONCLUSION: Cocoa polyphenols exert an antioxidant activity via NOX2 down-regulation in NASH patients.

Expression level of quiescin sulfhydryl oxidase 1 (QSOX1) in neuroblastomas.

Neuroblastoma is the most common extracranial solid malignant tumor observed during childhood. Although these tumors can sometimes regress spontaneously or respond well to treatment in infants, genetic alterations that influence apoptosis can, in some cases, confer resistance to chemotherapy or result in relapses and adversely affect prognosis for these patients. The aim of this study was to correlate immunohistochemical expression of the protein QSOX1 (quiescin sulfhydryl oxidase 1) in samples obtained from untreated neuroblastomas with the patients' clinical and pathological prognostic factors and clinical course. Neuroblastoma samples (n=23) obtained from histology blocks were arrayed into tissue microarrays and analysed by immunohistochemistry. The cases were classified according to the following clinical and pathological prognostic factors: age at diagnosis greater or less than/equal to 18 months; location of the lesion at diagnosis (abdominal or extra-abdominal); presence or absence of bone-marrow infiltration; tumor differentiation (well or poorly differentiated); Shimada histopathologic classification (favourable or unfavourable); state of the tumor extracellular matrix (Schwannian-stroma rich or poor); amplification of the MYCN oncogene; and clinical course (dead or alive with or without relapses/residual lesions). Twelve of the cases were female, 9 children were over 18 months old, 9 cases presented with extra-abdominal tumors and 9 cases exhibited tumors with unfavourable histologies. Fifteen patients underwent bone-marrow biopsy, and 4 of these were positive for metastasis. Nine patients died. The higher immunohistochemical expression of QSOX1 was more common in well-differentiated samples (P=0.029), in stroma-rich samples (P=0.029) and in samples from patients with a high prevalence of relapses/residual disease. The functions of QSOX1 include extracellular matrix maturation and the induction of apoptosis. Therefore, QSOX1 may be involved in neuroblastoma differentiation and regression and may thus function as a biomarker for identifying risk groups for this neoplasm.

Lymphadenectomy in gastric cancer: influence on prognosis of lymph node count.

To better understand the role of the number of lymph nodes retrieved on long-term outcome of gastric cancer treatment, 154 patients who had undergone curative resection, with dissection of >15 nodes were retrospectively studied. Dissection of perigastric and extraperigastric lymph nodes, defined as 'extended' (>26 nodes dissected) in 39 cases and 'limited' (< or = 26 nodes dissected) in 115 cases, was performed. A total of 3479 lymph nodes (mean 22.6 per specimen), were dissected and of these 721 showed metastases. A mean of 8.1 lymph node metastases, per metastatic case, was found. Regression analysis showed no independent factor associated with the extent of lymphadenectomy. Depth of wall invasion (p=0.000) and histological growth pattern (p=0.044) were independently associated with the number of lymph nodes involved (pN0, pN1 1-7, pN2 >7). The cumulative 5-year survival rate was 47% in patients without lymph node metastases; 29% in those with 1-7 nodes involved and 17% in those with >8 nodes involved (p=0.002). Receiver operating characteristic (ROC) curve analysis, in 65 nodenegative cancer cases, demonstrated an area under the curve for vital status (alive or dead) of 0.602 (95% CI: 0.473 - 0.721). All node-negative cases with a number equivalent to or exceeding the cutoff point of 23 nodes were alive. ROC analysis showed 11 to be the cutoff number of metastasized lymph nodes in correlation with vital status. Almost all those patients in whom the number of positive nodes was equivalent to, or exceeded the cutoff point had died (area under the ROC curve 0.633; 95% CI: 0.524 - 0.733). ROC analysis showed that the cutoff lymph node ratio, in relation to vital status, was 0.33. The majority of patients at or above this cutoff point had died (area under ROC curve 0.682; 95% CI: 0.574 - 0.776). Multivariate survival analysis showed that lymph node ratio was the only independent prognostic factor (p=0.001). The present findings suggest that, in lymphadenectomy with at least 15 nodes, the number and status of regional nodes dissected, irrespective of the location, provide reliable prognostic information on curatively resected gastric carcinomas.

Maximum gastric cancer diameter as a prognostic indicator: univariate and multivariate analysis.

It was suggested that there are no stronger prognostic factors in gastric cancer than nodal involvement or depth of wall invasion. The present paper evaluated the influence of maximum tumor diameter (MTD) value, measured on fixed resected specimens, on the extent of disease progression and the outcome in gastric cancer patients. Clinicopathological data were retrospectively retrieved from records of 122 patients who underwent curative gastrectomy. The patients' MTD values were grouped as follows: MTD1, up to 26 mm; MTD2, between 26 and 50 mm; and MTD3, over 50 mm. The three groups evidenced significant differences with regard to 5 year survival (MTD1: 54%, MTD2: 31%, MTD3: 20%; p = 0.00027), furthermore they were significantly different with respect to the type of gastrectomy (p = 0.021), depth wall invasion (p = 0.000), lymphatic microinvasion (p = 0.014), perineural microinvasion (p = 0.017), stromal reaction (p = 0.025), and stage (p = 0.035). ROC curve analysis individuated a best accurate MTD threshold value for nodal involvement of 32 mm (sensitivity = 56.6%; specificity = 60.9%; positive predictive value = 52.6%; negative predictive value = 64.6%). The logistic regression analysis suggested that the depth of wall invasion was the only independent variable associated with MTD value (p = 0.0005). Multivariate analysis showed that independent prognostic risk factors were sex (p < 0.0025), number of involved nodes (p < 0.001) and MTD (p < 0.001). In conclusion, the maximum tumor diameter value of gastric cancer may be a factor with greater prognostic implications than previously believed.

Low rectal cancer--what is the choice?

In patients operated on for low rectal cancer, the functional results, disease recurrence, and survival have been evaluated with respect to the type of surgery performed. Particular attention was paid to analysis of the pathologic aspects, considered in our opinion, as risk factors for recurrence. The investigation was carried out on 131 patients, of whom 70 received anterior resection, 55 abdominoperineal resection, and 6 local treatment. Abdominoperineal resection was carried out in more advanced disease. Postoperative mortality was 2.1 percent after anterior resection and 0 after abdominoperineal resection or local treatment. Follow-up, carried out in 96 patients (44 anterior resections, 46 abdominoperineal resections, and 6 local treatments), ranged from 12 to 84 (mean, 33.3) months. Recurrence rate was 53.3 percent after abdominoperineal resection and 28.9 percent after anterior resection. Recurrence appears not be related to the treatment performed, but rather depend on certain aspects of the neoplasm such as diameter exceeding 5 cm, extraparietal infiltration, lymphangitis, and tumor indifferentiation. We observed anastomotic recurrence in 28.6 percent of patients with a margin of less than 2 cm. An intensive follow-up scheme enabled us to recognize this type of recurrence early and to reoperate with radical intent. One year after anterior resection functional results were encouraging. No severe incontinence was reported. Local treatment was performed in carefully selected patients (T1, N0) and no cases of mortality or recurrence were observed.

Gastrointestinal cancer follow-up: the effectiveness of sequential CEA, TPA and Ca 19-9 evaluation in the early diagnosis of recurrences.

One-hundred and seventy-four consecutive patients who underwent curative resection for gastric and colorectal cancer between 1983 and 1985 were studied prospectively to evaluate the roles of sequential carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA) and Ca 19-9 determinations and independent clinical examinations, in the early diagnosis of resectable recurrences. Sixty-six recurrences (33 from gastric and 33 from colorectal cancer) were detected between 6 and 42 months after primary surgery. In gastric cancer CEA, TPA and Ca 19-9 showed a sensitivity of 64%, 73% and 60% respectively and a specificity of 67%, 65% and 54% respectively. Nine patients (27%) underwent surgical treatment for recurrent disease, and four of these (44.4%) had resectable recurrence, for a total resectability rate of 12%. Of these four patients, three are still living after 12, 36 and 44 months respectively from re-operation without evidence of neoplastic disease. In one of these patients, re-operation was performed on the basis of the elevation of the three markers, without any other clinical sign of disease. This patient had a resectable solitary hepatic recurrence. In colorectal cancer. CEA, TPA and Ca 19-9 showed a sensitivity of 73%, 73% and 49% respectively, and a specificity of 77%, 87% and 97% respectively. Fourteen patients (42.4%) underwent surgical treatment for recurrent disease and eight of these (57%) showed resectable recurrence, for a total resectability rate of 24.2%. Six patients are still living after 9, 16, 21, 31, 41 and 53 months respectively from re-operation without evidence of neoplastic disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Patient selection and factors affecting results following resection for hepatic metastases from colorectal carcinoma.

Personal experience is reported of 47 consecutive liver resections for metastatic colorectal carcinoma treated in the I Clinica Chirurgica of the University of Rome for the purpose of contributing to treatment and evaluating the clinical factors and possible determinants of prognosis that could be potentially predictive of outcome and length of survival after liver resection: Duke's stage of primary colorectal cancer, synchronous or metachronous disease, number of hepatic lesions. Patients were classified according to the proposed staging system of the "Istituto Nazionale Tumori" in Milan. For Stage I and II patients the median survival time was 15 months, while in Stage III patients survival time was reduced to only 4.5 months. The 3- and 5-year survival rate was 20% and 12% respectively for Stage I patients; no patients at stage II or III survived more than 3 years.

Effect of preoperative colonoscopy on the incidence of synchronous and metachronous neoplasms.

Colonoscopy and air-contrast barium enema performed preoperatively in 389 patients with colorectal cancer revealed synchronous cancer in 4% and polyp in 14%. Nine of the 16 synchronous cancers were located in other surgical segments than the index cancer, and six of the nine were in stage A or B1. Of the 54 synchronous polyps, 28 were located in such other segments. Half of the synchronous cancers and almost half of the synchronous polyps were missed at double-contrast barium enema. All synchronous cancers and three-fourths of the synchronous polyps were detected at colonoscopy. No patient with preoperative colonoscopy presented with metachronous cancer within 3 years from surgery, and only two were subsequently found to have adenocarcinoma arising from an adenomatous polyp. Endoscopic polypectomy was performed in 21 cases during follow-up. Extensive use of preoperative colonoscopy is recommended in the evaluation of colorectal cancer, in order to promote detection of synchronous tumors, reduce the incidence of 'early metachronous' cancer and avoid malignant degeneration of adenomatous polyp.

The role of CEA, TPA and CA 19-9 in the early detection of recurrent colorectal cancer.

Eighty-eight consecutive patients who underwent curative resection for colorectal cancer between 1983 and 1985 were studied prospectively to evaluate the roles of sequential CEA, TPA and CA 19-9 determinations and independent clinical examination in the early diagnosis of resectable recurrences. Twenty nine recurrences were detected between 8 and 38 months after primary surgery. CEA, TPA and CA 19-9 showed a sensitivity of 72%, 62% and 38%, and a specificity of 78%, 86% and 97%, respectively. Of eight recurrences in which CEA was not raised, five induced a rise in TPA and two a rise in CA 19-9. The rise in the serum concentration of one of the three markers was the first sign of relapse in 23 (79%) patients. Two second-look laparotomies based solely on a rise in serum markers were performed. In one case diffuse recurrent disease was found, and in the other a resectable solitary hepatic metastasis was found.

Colorectal cancer in young patients.

Colorectal cancer is rare in patients under 40 years of age. We reviewed all colorectal cancer patients treated at the First Department of Surgery of the University of Rome, to determine the true incidence of large bowel cancer in young patients. During the period 1978-1984 a total of 571 patients were indexed. Out of these 44 were 39 years of age or less. A group of 527 patients 40 years of age or over served as a control. Neoplasms were localized in the right colon in 19 cases and in the left colon in 25 patients, in the young group. In the control group 178 patients presented neoplasms localized in the right colon, while 349 presented tumors localized in the left colon. According to tumor advancement in the young group tumor classification from A stage tumor through D stage was: 4, 6, 14, 5, 9, 6. In the control group 22 patients presented A stage tumors, 106 B1, 139 B2, 50 C1, 118 C2, 92 D tumors. The operability rate was 93.2% in the young group, and 92% in the old one. The operative mortality rate was 0% in the young group, and 2.5% in the old one. Four complications occurred in the young patients, and 57 in the old patients. The five years survival rate was 56.7% and 52.1% in young and old patients respectively. The results of our study indicate that there are no significant differences in prognosis and five years survival in young patients with colorectal cancer.

Relationship of symptom duration and survival in patients with colorectal carcinoma.

An early diagnosis in asymptomatic patients and a prompt treatment lead to an improved survival rate in patients with carcinoma of the colon. Patients with a short symptomatic history of colon cancer do not have a better prognosis than patients with a long history. Between 1978 and 1984 a consecutive series of 571 patients with colorectal cancer were admitted to the First Department of Surgery of the University of Rome. All patients were classified into five groups according to the duration of specific intestinal symptoms. In Group 1 (51 cases) asymptomatic patients were included, or patients with no specific symptoms such as asthenia, anemia, occult fecal blood. In Group 2 there were 129 patients with intestinal symptoms of less than 3 months' duration before treatment. In Group 3 there were 192 patients with symptoms of between 4 and 6 months' duration; 151 patients with symptoms of between 6 and 12 months were included in Group 4, and finally 48 patients who presented with symptoms of more than 1 year were included in Group 5. No relationship was noted between tumor site and duration of symptoms. Similarly, no relationship was noted between the duration of intestinal symptoms and stage and tumor differentiation. On the other hand, asymptomatic patients showed a higher incidence of T1N0M0 stage tumor and a lower percentage of undifferentiated neoplasms. The resectability rate was 79% and it was significantly related to the absence of intestinal symptoms. Follow-up data were available in 454 patients (80%). The overall survival rate was 52.4%. In Group 1 through Group 5 the 5-year survival rate was: 83.7%, 50%, 50%, 46.3%, 46.9%. The results of our study indicate that patients admitted in asymptomatic phase presented less-advanced stage tumors and, thus, best survival rate. On the other hand, from our data the duration of intestinal symptoms is not related to the stage and prognosis of tumors.

Right colon cancer: long-term results after curative surgery and prognostic significance of duration of symptoms.

Between 1976 and 1986, a consecutive series of 195 patients with right colon cancer were admitted at the First Department of Surgery of the University of Rome. Patients were divided into five groups according to the absence of intestinal symptoms (group 1) and the duration of the symptomatic phase (groups 2-5). Analysis of the preoperative investigation showed that colonoscopy was able to identify 33 (26.2%) of tumors misdiagnosed by double contrast X-ray barium enema. We did not notice any correlation among symptom duration and tumor stage, tumor differentiation, operability rate, and survival. Patients admitted in the asymptomatic phase presented tumors of less advanced stage and, thus, had the best survival rate (71.4%). In this group, patients promptly treated had a better survival rate (87.5%) than those treated after 2 months (50%). Our study suggests that only neoplasms diagnosed in asymptomatic patients and treated promptly are related to a good survival rate. We, therefore, emphasize the importance of education of patients and family physicians about right colon cancer and the necessity to investigate all patients with a suspected right colon cancer by means of colonoscopy.

Synchronous large bowel cancer: a series of 47 cases.

The incidence of synchronous cancer has been reported to be 1.5% to 7.6%. A retrospective review of all colorectal cancer patients was conducted to determine the incidence of synchronous cancers. 47 synchronous cancers were identified in an operative series of 2586 patients with an incidence of 1.8%. The patients were divided into two groups based on preoperative diagnostic examinations. The first group included 1608 patients examined by double contrast x-ray barium enema (1141) and/or single contrast barium enema (381) and/or rigid sigmoidoscopy (112). The second group included 978 patients examined by double contrast barium enema (459) and/or flexible sigmoidoscopy (631) and/or colonoscopy (389). The incidence of synchronous tumors was 1.6% for patients evaluated only with double contrast roentgenographic study and 4.1% for patients who underwent preoperative colonoscopy. Fifty percent of synchronous cancers detected by colonoscopy were missed at double contrast x-ray barium enema. While twenty two percent of synchronous tumors detected by barium enema were located in different surgical segments and were all "advanced" tumors, when preoperative colonoscopy was performed, 56.2% of synchronous tumors were not located in the same surgical segment, and 66.7% of these were "early" cancers. None of the patients who underwent preoperatively colonoscopy developed a metachronous tumor within 3 years. One percent of patients undergoing flexible sigmoidoscopy or double contrast barium enema developed a second tumor 3 years after surgery. An extended use of preoperative colonoscopy in the diagnosis of colorectal cancers, to increase the detection od synchronous tumors and to decrease the incidence of the so-called "early" metachronous cancers, is stressed.

Tissue CEA as prognostic indicator in a series of 31 cases of gastric cancer.

The role of tissue CEA localization as a complementary factor in prognosis of patients affected by gastric cancer is analyzed. In a group of 31 gastric tumors, tissue CEA was always present in the apical portion of the tumor cell cytoplasm and in the glandular lumen, while in 23 cases it was found in the stroma, and in superficial and deep cell cytoplasm in 26 and 20 cases respectively. The serum marker levels were over 3 ng/ml in 19 patients. A relationship between CEA localization and tumor stage was observed. The more the tumors were advanced, the more the marker was found in the stroma and in the cytoplasm of superficial and deep cells. The same was found for CEA localization and serum CEA levels. The opposite trend was evidenced for the degree of tumor differentiation. In well differentiated tumors in a high percentage of cases the marker was present in the stroma and in the cytoplasm of superficial and deep cells as compared with undifferentiated tumors. No relationship between the histologic type and CEA localization was found.

Surgical treatment of metachronous colorectal cancers.

Thirty-four patients with metachronous colorectal cancer who underwent surgical procedures at the First and Fourth Department of Surgery of the University of Rome were reviewed. 55.9% of the patients developed a second carcinoma within five years after the first operation, and the time interval for the entire group ranged from 13 to 228 months. Adenomatous polyps occurred in 14 patients. Two patients developed a third metachronous cancer. We followed up eight patients using colonoscopy regularly. In this group we found two early cancers, five submucosal cancers and only one advanced tumor. In the other group we found 16 advanced cancers and ten submucosal cancer. The curability rate at second operation was 88.2%, and at the third 50%. The management of metachronous tumors should imply total colonoscopy, at a mean interval of 12-18 months.