Prognostic role of hERG1 Potassium Channels in Neuroendocrine Tumours of the Ileum and Pancreas.

hERG1 potassium channels are widely expressed in human cancers of different origins, where they affect several key aspects of cellular behaviour. The present study was designed to evaluate the expression and clinical relevance of hERG1 protein in cancer tissues from patients suffering from neuroendocrine tumours (NETs) of ileal (iNETs) and pancreatic (pNETs) origin, with available clinicopathological history and follow-up. The study was carried out by immunohistochemistry with an anti-hERG1 monoclonal antibody. In a subset of samples, a different antibody directed against the hERG1/ß1 integrin complex was also used. The analysis showed for the first time that hERG1 is expressed in human NETs originating from either the ileum or the pancreas. hERG1 turned out to have a prognostic value in NETs, showing (i) a statistically significant positive impact on OS of patients affected by ileal NETs, regardless the TNM stage; (ii) a statistically significant positive impact on OS of patients affected by aggressive (TNM stage IV) disease, either ileal or pancreatic; (iii) a trend to a negative impact on OS of patients affected by less aggressive (TNM stage I-III) disease, either ileal or pancreatic. Moreover, in order to evaluate whether ERG1 was functionally expressed in a cellular model of pNET, the INS1E rat insulinoma cell line was used, and it emerged that blocking ERG1 with a specific inhibitor of the channel (E4031) turned out in a significant reduction in cell proliferation.

Incidence and prognostic impact of para-aortic lymph nodes metastases during pancreaticoduodenectomy for peri-ampullary cancer.

BACKGROUND: Standard lymphadenectomy during pancreaticoduodenectomy (PD) for peri-ampullary cancer does not include the routine removal of para-aortic lymph nodes (PALN) (station 16, according to the JPS staging system). The aim of this study was to report the incidence and the prognostic value of PALN metastases in patients undergoing PD for peri-ampullary cancer. MATERIALS AND METHODS: One hundred thirty-five consecutive patients who underwent PD and PALN dissection for peri-ampullary cancer were prospectively evaluated. The relationship between clinicopathological factors, including PALN metastases and survival was evaluated at univariate and multivariate analysis. RESULTS: PALN metastases (N16+) were found in 11.1% of cases. At univariate analysis, R1 resection, metastatic nodes different from para aortic (N1) and N16+ significantly affected patients' prognosis. Compared with N16+, the median overall survival (OS) of N0 patients was significantly longer (32 versus 69 months, respectively; P < 0.05), whereas no difference was found between N16+ and N1 patients (32 versus 34 months, respectively) (P > 0.05). At multivariate analysis, only R1 resection reached statistical significance and was confirmed an independent prognostic factor. CONCLUSIONS: Neoplastic involvement of PALN in peri-ampullary cancer is frequent and, so, their removal during PD could be justified. Moreover, PALN metastases should be not considered an absolute contraindication to radical surgery.

Long-term patient-reported outcomes after anti-reflux surgery for gastroesophageal reflux disease and hiatal hernia repair: a single-center experience.

BACKGROUND: Patients with gastroesophageal reflux disease (GERD) and hiatal hernia who are candidates for surgery should be treated with minimally invasive partial or total fundoplication. As data on long-term clinical and functional outcomes after laparoscopic surgery for GERD are limited, the aim of this study was to evaluate the long-term effectiveness of fundoplication in terms of patient-reported symptoms and proton pump inhibitor (PPI) use. METHODS: The data of 88 patients who underwent laparoscopic anti-reflux surgery for GERD between January 2007 and September 2020 were retrospectively reviewed. Preoperative and postoperative patient-reported outcomes were investigated after surgery using a 13-items Likert-Scale questionnaire based on the frequency (events/week) and severity of typical and atypical symptoms, dysphagia, and dyspepsia. Furthermore, variations in the use of PPIs were investigated as a secondary endpoint. RESULTS: A total of 76 patients participated in the questionnaire survey. The median follow-up duration was 77 (2-165) months. The postoperative rate of mild and severe typical symptoms was significantly lower than the preoperative rate (P<0.01). Similarly, the atypical symptom rates decreased after surgery (P<0.05). Dysphagia was more frequent after fundoplication (P<0.01). Before the anti-reflux surgery, 94.7% of the patients were prescribed a PPI. At the time of follow-up, this proportion had decreased to 73.7% (P<0.01). However, the PPI intake rate was 90.9% in the group of patients interviewed >10 years after surgery. CONCLUSIONS: In this cohort of patients, laparoscopic anti-reflux fundoplication reduced the rate typical and atypical symptoms of GERD. However, surgery appeared to have no impact on PPI intake over time.

The Role of Pathological Method and Clearance Definition for the Evaluation of Margin Status after Pancreatoduodenectomy for Periampullary Cancer. Results of a Multicenter Prospective Randomized Trial.

BACKGROUND: There is extreme heterogeneity in the available literature on the determination of R1 resection rate after pancreatoduodenectomy (PD); consequently, its prognostic role is still debated. The aims of this multicenter randomized study were to evaluate the effect of sampling and clearance definition in determining R1 rate after PD for periampullary cancer and to assess the prognostic role of R1 resection. METHODS: PD specimens were randomized to Leeds Pathology Protocol (LEEPP) (group A) or the conventional method adopted before the study (group B). R1 rate was determined by adopting 0- and 1-mm clearance; the association between R1, local recurrence (LR) and overall survival (OS) was also evaluated. RESULTS: One-hundred-sixty-eight PD specimens were included. With 0 mm clearance, R1 rate was 26.2% and 20.2% for groups A and B, respectively; with 1 mm, R1 rate was 60.7% and 57.1%, respectively (p > 0.05). Only in group A was R1 found to be a significant prognostic factor: at 0 mm, median OS was 36 and 20 months for R0 and R1, respectively, while at 1 mm, median OS was not reached and 30 months. At multivariate analysis, R1 resection was found to be a significant prognostic factor independent of clearance definition only in the case of the adoption of LEEPP. CONCLUSIONS: The 1 mm clearance is the most effective factor in determining the R1 rate after PD. However, the pathological method is crucial to accurately evaluate its prognostic role: only R1 resections obtained with the adoption of LEEPP seem to significantly affect prognosis.

Intra-anal condyloma: surgical or topical treatment?

Human Papillomavirus infections are the strongest risk factors for genital cancer and are the causative agents of anogenital warts. Although the viral types associated with condylomata usually do not cause carcinoma, in women with a history of these lesions there is an increased risk of intraepithelial neoplasia and cancer. Generally the lesions are not life-threatening, but they provoke significant morbidity, are difficult to treat, and are a source of psychosocial stress. Thus, condylomata represent not only a health problem for the patient but also an economic burden for the society. Considering the individual episodes of care, men experience a longer duration of the lesions and incur greater costs than women. We report a case of a male patient with external and intra-anal condyloma resistant to laser therapy. Initially, surgical intervention appeared required because of florid and intra-anal growth. HPV DNA testing and sequencing revealed the presence of HPV 6. After initial discomfort, the lesions were successfully cleared with topical imiquimod 5 percent cream therapy.

Pancreatic intraductal papillary mucinous neoplasms: a paradigmatic case. A case report and review of the literature.

Pancreatic intraductal papillary mucinous neoplasms constitute an increasingly frequent clinical entity. The definition and clinical behaviour of these tumours are still a subject of debate. As a consequence, their clinical management is also presents controversial aspects ranging from follow-up to the advisability or otherwise of an aggressive surgical approach, even in the case of small non-malignant lesions. In 2002 we observed a patient affected by a large pancreatic mass with the endoscopic and radiological features of an intraductal papillary mucinous tumour. Over a 20-year clinical history the patient had been considered and treated as affected by chronic pancreatitis. In spite of the tumour size and possible vascular infiltration, surgical exploration was considered. Total pancreatectomy was performed and final histology revealed a non-invasive papillary mucinous carcinoma of the pancreas. Twenty-six months after surgical resection the patient is alive and free of disease. In the present paper we re-assess the clinical history of this patient and review the most recent literature on such tumours.

Taste intensity and hedonic responses to simple beverages in gastrointestinal cancer patients.

Changes in the taste of food have been implicated as a potential cause of reduced dietary intake among cancer patients. However, data on intensity and hedonic responses to the four basic tastes in cancer are scanty and contradictory. The present study aimed at evaluating taste intensity and hedonic responses to simple beverages in 47 anorectic patients affected by gastrointestinal cancer and in 55 healthy subjects. Five suprathreshold concentrations of each of the four test substances (sucrose in black current drinks, citric acid in lemonade, NaCl in unsalted tomato juice, and urea in tonic water) were used. Patients were invited to express a judgment of intensity and pleasantness ranging from 0 to 10. Mean intensity scores directly correlated with concentrations of sour, salty, bitter, and sweet stimuli, in both normals and those with cancer. Intensity judgments were higher in cancer patients with respect to sweet (for median and high concentrations, P<0.05), salty (for all concentrations, P<0.05), and bitter tastes (for median concentration, P<0.01). Hedonic function increased with the increase of the stimuli only for the sweet taste. A negative linear correlation was found between sour, bitter, and salty concentrations and hedonic score. Both in cancer patients and in healthy subjects, hedonic judgments increased with the increase of the stimulus for the sweet taste (r=0.978 and r=0.985, P=0.004 and P=0.002, respectively), and decreased for the salty (r=-0.827 and r=-0.884, P=0.084 and P=0.047, respectively) and bitter tastes (r=-0.990 and r=-0.962, P=0.009 and P=0.001, respectively). For the sour taste, the hedonic scores remained stable with the increase of the stimulus in noncancer controls (r=-0.785, P=0.115) and decreased in cancer patients (r=-0.996, P=0.0001). The hedonic scores for the sweet taste and the bitter taste were similar in cancer patients and healthy subjects, and these scores were significantly higher in cancer patients than in healthy subjects for most of the concentrations of the salty taste and all the concentrations of the sour taste. The present study suggests that cancer patients, compared to healthy individuals, have a normal sensitivity, a normal liking for pleasant stimuli, and a decreased dislike for unpleasant stimuli. Moreover, when compared to controls, they show higher hedonic scores for middle and high concentrations of the salty taste and for all concentrations of the sour taste. Further studies are needed to evaluate whether these changes observed in cancer patients translate into any alteration in dietary behavior and/or food preferences.

Percutaneous ultrasound-guided ablation of BW7756-hepatoma using ethanol or acetic acid in a rat model.

BACKGROUND: To compare tumor necrosis in hepatoma induced in rats by a single percutaneous injection of ethanol (PEI) or acetic acid (PAI). METHODS: BW7756 hepatomas of 1 mm3 were implanted in the liver of 40 male healthy rats. After 14 days, the 36 surviving rats were treated, in a single session, by ultrasound-guided injection of 300 microl of 95% ethanol (n = 17) or 100 microl of 50% acetic acid (n = 19). They were sacrificed 14 days after treatment and explanted tumoral livers were examined. The same PAI procedure was repeated on 13 additional rats to exclude a suspected occurrence of technical failures during the experiment, due to a surprisingly high rate of deaths within 30 minutes after PAI. RESULTS: Four rats died within four days after tumor implantation; after PEI, 1/17 (6%) died, whereas after PAI 9/19 (47%) died. The remaining 26 rats, after 14 days post-percutaneous ablation, were sacrificed. Gross and microscopic examinations showed that the hepatoma's nodules treated with PEI had 45.3 +/- 19.4% tumor necrosis compared to 49 +/- 23.3% (P = NS) for those treated with PAI. Complete tumor necrosis was not found in any animal. Peritoneal invasion was present in 4/16 (25%) and 2/10 (20%) rats treated with PEI or PAI, respectively (P = NS). Autopsy was performed in the 5 additional rats that died within 30 minutes after PAI. CONCLUSION: Our results show that there is no significant difference in the percentage of tumor necrosis between two local ablation methods in spite of the different dosages used. However, mortality in the PAI-treated group was greater than in PEI-treated group, presumably due to greater acetic acid systemic diffusion and its metabolic side effects. In human subjects, HCC occurs in the setting of cirrhosis, where the non-tumoral tissue is firmer than the tumor structure, with consequent reduction of drug diffusion. This could be the reason why some human studies have concluded similar or even better safety and efficacy with PAI compared to PEI.

COX-2 expression of ampullary carcinoma: correlation with different histotypes and clinicopathological parameters.

Epidemiological studies suggest that regular intake of nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with reduced incidence of gastrointestinal cancer. Several lines of evidence indicate that the antineoplastic effect of NSAIDs is attributable to COX-2 inhibition. The aim of our study was to assess COX-2 expression in a series of primary untreated ampullary carcinomas and its possible correlation with clinicopathological parameters. In the present study, 45 surgical specimens of invasive ampullary carcinomas were histologically classified into pancreaticobiliary, intestinal, and unusual types. COX-2 expression by immunohistochemical method was analyzed. High COX-2 expression was detected in 35 (77.8%) ampullary carcinomas. Among these, 20/21 (95.2%) were classified as intestinal, 9/18 (50%) pancreaticobiliary, and 6/6 (100%) unusual type. A significant statistical difference in terms of COX-2 expression was found between pancreaticobiliary vs intestinal type (P=0.002). Furthermore, a negative significant statistical correlation was found between T factor and COX-2 expression (P=0.047). The different COX-2 expression among histopathological types supports the concept of histogenetical difference of ampullary carcinomas. Furthermore, the high rate of COX-2 expression in the intestinal subtype of ampullary carcinoma may represent the rational for a histotype-tailored therapy targeting COX-2.

Cyclooxygenase-2 overexpression is associated with a poor outcome in resected ampullary cancer patients.

PURPOSE: To identify potential prognostic molecular factors in ampullary adenocarcinoma that could be of significant importance. To this end, we examined the possible prognostic significance of cyclooxygenase-2 (Cox-2) and Survivin expression and the apoptotic index in a cohort of uniformly treated patients with ampullary cancer treated with radical surgical excision. EXPERIMENTAL DESIGN: The entry criteria were that the patients have a pathologic diagnosis of ampullary cancer which had been resected. Expression analysis for Cox-2 and Survivin was done by immunohistochemical staining. Apoptotic cells were identified by the terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method. RESULTS: Thirty-nine tumor specimens from resected ampullary adenocarcinoma patients were included. By univariate analysis, overall survival was affected by Cox-2 expression and TUNEL staining (respectively, P = 0.0003 and 0.03). Survivin expression did not influence the overall survival in our patient population (P = 0.123). Patients' clinicopathologic features (gender, age, and T and N factors) did not influence outcome. In multivariate Cox regression analysis, Cox-2 expression (relative risk, 4.330; P = 0.005) was the only variable that significantly affected overall survival. CONCLUSIONS: The results of the present article provide, for the first time, evidence that Cox-2 expression, but not Survivin expression, may represent a significant prognostic factor after surgical resection in patients affected by cancer of the ampulla of Vater. Further studies are required to determine whether Cox-2 inhibitors may be useful for the therapy or prevention of ampullary carcinoma.

Microscopic Residual Tumor After Pancreaticoduodenectomy: Is Standardization of Pathological Examination Worthwhile?

OBJECTIVES: R1 resection rate after pancreaticoduodenectomy (PD) for cancer is highly variable. The aim of this study was to verify if a standardized histopathological work-up of the specimen affects the rate of R1 resection after PD for cancer. METHODS: Two groups of specimens were managed with (standardized method [SM] group) or without (non-standardized method [NSM] group) a SM of histopathological work-up. Each group included 50 cases of PD for periampullary cancer. Differences in terms of R1 resection rate between the 2 groups were evaluated. Correlation between R1 status and local recurrence was also evaluated. RESULTS: The cohort of 100 patients consisted of 66 pancreatic ductal adenocarcinoma, 15 cholangiocarcinoma, and 19 ampullary cancer. The R1 resection rate resulted statistically higher in the SM group (66% vs 10%). Local recurrence was more frequently related to R1 resection in the SM group (34.3% of cases) than in NSM group (20% of cases). CONCLUSIONS: The use of the SM of pathological evaluation of the specimen after PD for cancer determines a significant increase of R1 resection. This remarkable difference seems to be due to the different definition of minimum clearance. The SM seems to better discriminate patients in terms of risk of local recurrence.

DNA end binding activity and Ku70/80 heterodimer expression in human colorectal tumor.

AIM: To determine the DNA binding activity and protein levels of the Ku70/80 heterodimer, the functional mediator of the NHEJ activity, in human colorectal carcinogenesis. METHODS: The Ku70/80 DNA-binding activity was determined by electrophoretic mobility shift assays in 20 colon adenoma and 15 colorectal cancer samples as well as matched normal colonic tissues. Nuclear and cytoplasmic protein expression was determined by immunohistochemistry and Western blot analysis. RESULTS: A statistically significant difference was found in both adenomas and carcinomas as compared to matched normal colonic mucosa (P<0.00). However, changes in binding activity were not homogenous with approximately 50% of the tumors showing a clear increase in the binding activity, 30% displaying a modest increase and 15% showing a decrease of the activity. Tumors, with increased DNA-binding activity, also showed a statistically significant increase in Ku70 and Ku86 nuclear expression, as determined by Western blot and immunohistochemical analyses (P<0.001). Cytoplasmic protein expression was found in pathological samples, but not in normal tissues either from tumor patients or from healthy subjects. CONCLUSION: Overall, our DNA-binding activity and protein level are consistent with a substantial activation of the NHEJ pathway in colorectal tumors. Since the NHEJ is an error prone mechanism, its abnormal activation can result in chromosomal instability and ultimately lead to tumorigenesis.

Persisting perianal ulcer after radiotherapy for anal cancer: recurrence of disease or late radiation-related complication?

We report the case of a 47-year-old HIV-negative male affected by a perianal ulcer which occurred after chemoradiation delivered for anal cancer. In spite of a negative biopsy the lesion was highly suspected to be a disease recurrence. Uncontrollable pain and anal stenosis were also present; abdominoperineal resection with a large excision of perianal tissues and reconstruction with bilateral musculocutaneous gracilis flaps was therefore performed. Histology did not confirm tumor recurrence. Thirteen months after surgery, the patient is still alive and free of disease. The introduction of radiotherapy and concomitant chemotherapy has revolutionized the treatment of anal cancer, avoiding demolitive surgery in a large subset of patients. Radionecrosis is an uncommon but potentially devastating event occurring in up to 10% of patients undergoing radiotherapy for anal cancer. It causes clinical (pain, anal stenosis, mucositis and diarrhea) and diagnostic problems (recurrence vs. benign post-attinic lesion). In the present article we review this uncommon complication, discuss the technical surgical aspects associated with a very large perianal tissue removal, and data of the most recent literature in this field.

Prospective study of cetuximab and gemcitabine in combination with radiation therapy: feasibility and efficacy in locally advanced pancreatic head cancer.

BACKGROUND: Radio-chemotherapy is one of the steps of multidisciplinary management in locally advanced pancreatic cancer. The Epidermal Growth Factor Receptor (EGFR) plays an important role in the disease pathway. The purpose of this prospective study is to evaluate the feasibility and the efficacy of radiotherapy in combination with gemcitabine and EGFR targeting therapy for patients with locally advanced disease. MATERIALS AND METHODS: From November 2008 through January 2012, 34 patients were included in this study. In all cases an accurate pre-treatment staging including CT scan, Endoscopic Ultra-Sonography (EUS), 18F - fluorodeoxyglucose (18F-FDG) PET-CT and laparoscopy with peritoneal washing was performed. External beam radiation was delivered with a total dose of 50.4 Gy (1.8 Gy per fraction). Patients were treated using 3D- conformal radiotherapy, and the clinical target volume was the primary tumor and involved lymph nodes. Gemcitabine 300 mg/m(2) and Cetuximab were given weekly during radiation therapy. RESULTS: Ten patients (29.4 %) were excluded from the protocol because of the evidence of metastatic disease at the pre-treatment staging. Three patients refused radiochemotherapy. Twenty-one patients completed the therapy protocol. During the combined therapy grade 3-4 toxicities observed were only haematological (leukopenia 47,6 %, trombocytopenia 4.8 %, elevated gamma-GT 23.8 %, elevated alkaline phosphatase 4,8 %). Non-haematological toxicity grade 3-4 was never reported. Post-treatment workup showed partial response in five patients (24 %), stable disease in 11 patients (52 %) and disease progression in 5 patients (24 %). Two-year Local Control was 49 % (median, 18.6 months), 2-year Metastases Free Survival was 24 % (median, 10.8 months). One and two-year Overall Survival were 66 % and 28 % respectively, with a median survival time of 15.3 months. CONCLUSIONS: The combination of cetuximab and gemcitabine with concurrent radiation therapy provides a feasible and well tolerated treatment for locally advanced pancreatic cancer. Patients' selection is crucial in order to treat patients appropriately.

Fever after zoledronic acid administration is due to increase in TNF-alpha and IL-6.

The most common adverse event typically associated with bisphosphonate therapy is transient fever. The aim of this study was to define the role of the main cytokines of the acute-phase reaction interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) involved in the pathogenesis of zoledronic acid-induced fever. Eighteen consecutive cancer patients with bone metastases were treated, for the first time, with a single dose of 4 mg zoledronic acid infusion. They were prospectively evaluated for circulating TNF-alpha, interferon-gamma (IFN-gamma), and IL-6 levels at different times, just before and 1, 2, 7, and 21 days after diphosphonate infusion. Clinical and standard laboratory parameters were recorded at the same time points. TNF-alpha circulating levels increased significantly 1 and 2 days after zoledronic acid infusion (respectively, p = 0.002 and p < 0.001) and then decreased to levels similar to the basal levels. IL-6 levels increased significantly 1 day after the infusion (p = 0.007), returning to values similar to the median basal values 2 days after zoledronic acid administration. Moreover, in patients who experienced fever, the TNF-alpha and IL-6 increases were higher than in patients without fever. No statistically significant differences in IFN-gamma were identified at different time points in patients with and without fever. Our results show that zoledronic acid induces transient TNF-alpha and IL-6 increases and that these increases are higher in patients who have developed fever, suggesting that these cytokines could be responsible for fever pathogenesis. The sharp reduction in serum calcium levels observed in patients with fever may be related to zoledronic acid pharmacokinetic modifications.

Radiofrequency ablation of hepatic tissue: a new experimental animal model.

BACKGROUND/AIMS: Experimental radiofrequency ablation has already been performed in healthy livers of porcine models, but not in less expensive and easy-to-manage rats, with devices capable of delivering radiofrequency ablation in the 20-30 g liver of such small animals being so far unavailable. METHODOLOGY: We experimented with a modified system of radiofrequency ablation of liver tissue in rat models developing a custom-made needle-microelectrode of very small dimensions (0.3x2 mm) and an electrode-tip cooling technique, based on saline solution infusion. We adjusted duration (seconds) and power (watts) of radiofrequency ablation letting them range between 5-50 seconds and 5-25 W, respectively, to obtain the greatest lesions with the least side effects. After sacrificing the animals, an accurate histological examination of the liver was made. RESULTS: It is possible to establish beforehand the diameter of thermal liver lesion on the basis of joules of applied energy. The greatest increase of liver thermal lesion diameter (8 mm) is obtained with a 250-joule (10 W for 25 seconds) thermal energy cooling the electrode-tissue interface. CONCLUSIONS: Experimental radiofrequency ablation in rat liver is an effective and cheap way to study its effects on healthy hepatic tissues. It might be the first step to treat experimentally caused liver tumors.

Infusion of bevacizumab increases the risk of intestinal perforation: results on a series of 143 patients consecutively treated.

Bevacizumab is largely used in colorectal cancer patients. Postsurgical healing complications have been described for patients following treatment with Bevacizumab. We report three cases of spontaneous intestinal perforation following infusion of Bevacizumab. From January 2002 through October 2010, Bevacizumab was delivered in 143 patients. Spontaneous intestinal perforation occurred in 3 cases (2.1 %). Bevacizumab may result in severe complications. Therefore, it is important to consider every patient treated with Bevacizumab at risk for life-threatening gastro-intestinal complications.

Carcinoma of the ampulla of Vater: morphological and immunophenotypical classification predicts overall survival.

OBJECTIVES: The objective of the study was to verify if histopathological differentiation of ampullary carcinoma after surgical resection may be related to survival. METHODS: The prognostic role of an accurate histological and immunohistochemical classification has been investigated in a multicentric series of carcinoma of the ampulla of Vater. Immunohistochemical expression of cytokeratin 7 (CK7) and CK20 were analyzed in the different morphological histotypes of ampullary cancers, and results were compared with overall survival. RESULTS: Of 72 ampullary cancers, 48.6% were classified as pancreaticobiliary-type carcinomas, 43.1% were classified as intestinal-type carcinomas, and 8.3% were classified as "unusual"-type carcinomas. Cytokeratin 20 was expressed in 28 (90.3%) of the 31 intestinal-type carcinomas, whereas it was always negative in the pancreaticobiliary histotype; CK7 was expressed in 32 (91.4%) of the 35 pancreaticobiliary-type carcinomas and in 18 (58.1%) of the 31 intestinal-type carcinomas. By univariate analysis, overall survival was influenced significantly by pathological T factor, lymph node involvement, and histological/immunohistochemical subtyping. Furthermore, using a multivariate Cox regression model, lymph node metastasis and CK20 were identified as significant independent factors related to prognosis. CONCLUSION: Our results prove the clinical use of ampullary cancer subclassification based on different histotypes and indicate the useful role of the CK7/CK20 expression profile for consistent histopathological classification and prognostic relevance.

Pancreatic arteriovenous malformation involving the duodenum embolized with ethylene-vinyl alcohol copolymer (Onyx).

Arteriovenous malformation (AVM) of the pancreas is a rare condition. Most patients are asymptomatic or alternatively may present with a wide spectrum of symptoms. Traditionally, surgery has been considered the treatment of choice; however, alternative approaches, such as transcatheter embolization (TAE), may be proposed. We report a case of a 48-year-old man with a pancreatic head AVM, presenting with upper abdominal pain and slight anemia. The patient refused surgery and underwent TAE by means of ethylene-vinyl alcohol copolymer (EVOH). At 3 months follow-up, the patient was able to eat regularly, with no residual pain and no signs of anemia.