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Pancreatic cancer (PC) is one of the deadliest cancers, and it is responsible for a number of deaths almost equal to its incidence. The high mortality rate is correlated with several explanations; the main one is the late disease stage at which the majority of patients are diagnosed. Since surgical resection has been recognised as the only curative treatment, a PC diagnosis at the initial stage is believed the main tool to improve survival. Therefore, patient stratification according to familial and genetic risk and the creation of screening protocol by using minimally invasive diagnostic tools would be appropriate. Pancreatic cystic neoplasms (PCNs) are subsets of lesions which deserve special management to avoid overtreatment. The current PC screening programs are based on the annual employment of magnetic resonance imaging with cholangiopancreatography sequences (MR/MRCP) and/or endoscopic ultrasonography (EUS). For patients unfit for MRI, computed tomography (CT) could be proposed, although CT results in lower detection rates, compared to MRI, for small lesions. The actual major limit is the incapacity to detect and characterize the pancreatic intraepithelial neoplasia (PanIN) by EUS and MR/MRCP. The possibility of utilizing artificial intelligence models to evaluate higher-risk patients could favour the diagnosis of these entities, although more data are needed to support the real utility of these applications in the field of screening. For these motives, it would be appropriate to realize screening programs in research settings.

Hilar biliary strictures (HBS) are difficult to diagnose and treat, because their etiology is not always ascertained by all the available diagnostic tests. If a diagnosis cannot be made, HBS are classified as indeterminate. In recent years, both new imaging and endoscopic techniques, and a better understanding of hepato-biliary diseases have significantly reduced the number of patients diagnosed with indeterminate HBS. A complete work-up of these patients is mandatory to exclude malignancy and is based on laboratory tests, radiological imaging, and endoscopic procedures. Briefly, a decision-making process for the diagnosis of patients with HBS is discussed and a diagnostic algorithm is proposed.

Background Pancreas adenocarcinoma is the sixth cause of cancer-related death worldwide with an increasing mortality in the Western countries. Recently, the association between nab-paclitaxel (nab-P) and gemcitabine (GEM) has significantly improved progression-free and overall survival. Patients and methods Patients affected by metastatic pancreas adenocarcinoma were treated at the Department of Abdominal Oncology of the National Cancer Institute of Naples from July 2015 to July 2016 with nab-P at 125 mg per square meter of body-surface area followed by GEM at 1,000 mg per square meter on days 1, 8 and 15 every 4 weeks. Computed tomography (CT) was performed every three months of therapy. Toxicity was graded with National Cancer Institute-Common Toxicity Criteria (NCI-CTC) v4.0. Objective responses were evaluated with Response Evaluation Criteria in Solid Tumors (RECIST). Analysis of time-to-progression is only descriptive. Pain was evaluated with a visual analogue scale (VAS). Results Twenty-three patients were treated. Median age was 67 years (range=45-81); 8 patients were ≥70 years old. Performance status (PS) Eastern Cooperative Oncology Group (ECOG) was 2 in 8 patients, 1 in 10 and 0 in 5. Twelve patients presented with diffuse hepatic metastases, 4 with carcinosis, 7 with more than one organ involvement. Nab-P was reduced at 100 mg per square meter in all patients. The most common G3/G4 adverse events were neutropenia (13.0% G4, 8.6% G3; none was febrile), neuropathy (30.4% G3) and asthenia (G3 17.3%). The disease control rate was 43.4% (partial response+stable disease (PR+SD) 10/23). The median time-to-progression was 7.9 months (95% confidence interval (CI)=5.8-11.2). After three months of therapy the PS improved in 14 patients, as well as pain in 18 patients. Conclusion We present an experience with nab-P and GEM association in a series with poor PS and highly metastatic disease relatively to a previous randomized study. The schedule is feasible, with nab-P at 100 mg per square meter achieving a good disease control rate, as well as a clinical benefit.

Neuroendocrine tumors (NET), especially those of the pancreas and gastrointestinal tract, are frequently metastatic at the time of initial diagnosis. Because of a better knowledge of the molecular and cell-biological aspects as well as the clear pathological characterization of this tumor entity, a worldwide overall increase of these neuroendocrine tumors is reported. Therapeutic approaches for management of metastatic disease include surgical, medical, radiological, and nuclear medicine strategies. We present our experiences of management of three clinical cases of ileum, rectum, and gastric metastatic neuroendocrine tumors treated at the ENETS Center for Neuroendocrine Tumors of Naples, Italy. In the case of ileum-NET, we demonstrate the potent antiproliferative effect of SSA and the decisive role of the multidisciplinary approach which is able by itself to impact on survival. Then, in the case of gastric NET, we stress such awful consequences; a late and misunderstood diagnosis may have on prognosis and on the quality of life of a young patient. The role of a center of excellence devoted to NETs becomes crucial in these situations. Regarding the last case, it is a patient with G2 rectum NET. His clinical history, characterized by successive progressions of disease, is a paradigm of the G2 metastatic neuroendocrine tumors treatment. Three lines of therapy (SSA, chemotherapy, and PRRT) have followed ensuring a prolongation of survival of the patient and a good quality of life. The patient is in follow-up and maintains additional therapeutic chance.

The role of preoperative biliary drainage (PBD) in the management of jaundiced patients with resectable pancreatic cancer (RPC) is controversial. Obstructive jaundice determines hepatic dysfunction which can increase the operative risks. Experimental studies demonstrated that PBD could be associated with improved surgical outcomes. However, clinical studies did not confirm these findings. Initial clinical studies conducted with percutaneous approach failed to demonstrate a real advantage for patients undergoing PBD before pancreaticoduodenectomy. Overall morbidity was higher in patients undergoing PBD, because of procedure-related complications. Similar results were obtained with endoscopic PBD. Six meta-analyses have not clarified the role of PBD in the management of patients with malignant jaundice undergoing pancreaticoduodenectomy, because of lack of uniformity among all the studies published. Recently, the results of a large randomized controlled trial indicated that direct surgery should be the best therapeutic strategy for jaundiced patients with RPC. The debate whether jaundiced patients with RPC should undergo PBD continues and the advent of neoadjuvant chemoradiotherapy added some arguments in favor of PBD. The latter is still considered the first step for jaundiced patients when they present with cholangitis, intense pruritus or severe jaundice; surgery cannot be scheduled within 7-10 days from the diagnosis; neoadjuvant chemoradiation is planned, as part of the treatment. While endoscopic PBD is considered the preferred approach, there is still controversy about the type of biliary stent which should be used. Emerging data support the insertion of short (4-6 cm) biliary self-expandable metallic stent, especially if surgery is not immediately planned.

Summary Background To date, the role of endoscopic ultrasound (EUS) in restaging locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (NAT) have not been thoroughly investigated. Aim To evaluate accuracy and clinical usefulness of EUS for both staging and restaging LARC. Methods According to EUS staging, patients with LARC were enrolled in the study. Those who underwent surgery directly represented a control group useful for evaluating the accuracy of EUS in staging LARC. In the study group, EUS was repeated seven weeks after NAT, before surgery. The results of EUS were compared with the corresponding pTN stages. Results From 2000 to 2006, 212 consecutive patients with RC underwent EUS staging. Among them EUS diagnosed 162 LARC (M/F = 93/69; mean age: 60 years [range 40–80]). The final study group included 85 patients with LARC. EUS restaging had an overall accuracy of 61% and 59% for T and N-stage, respectively. In the control group, the accuracy of EUS in staging LARC was 86% and 58% for T and N-stage, respectively. Conclusion EUS accurately stages LARC and enables appropriate decision-making, with selection of those patients who need NAT. On the other hand, EUS restaging of LARC after NAT has low accuracy and should not be used in clinical practice.

Summary Background & aims Lactose malabsorption (LM) is a frequent condition in adults and is often associated with bowel symptoms. Although the diagnostic gold standard is represented by assessment of the tissue lactase activity, LM diagnosis is currently made non-invasively by hydrogen breath test. Alternatively, an accurate clinical and anamnestic evaluation of symptoms can suggest LM in many cases. The aim of the study was to evaluate the diagnostic accuracy of clinical variables for the diagnosis of LM when compared to the hydrogen breath test. Methods Forty consecutive patients with suspected LM performed a hydrogen breath test after oral load of lactose (25 g). Patients were requested to answer five questions on a visual-analogical scale (0–4): subjective correlation milk/symptoms; abdominal pain; bloating; soft stools; response after milk exclusion. Statistical analysis was performed by using the Mann–Whitney U-test and Cohen's k of agreement. Also, a ROC curve was constructed to identify the best diagnostic cut-off for the resulting clinical-anamnestic score. Results Breath test was positive in 16 out of 40 patients (40%). The mean clinical score was significantly higher in patients with LM (14 vs 8.5; p 10 showed a sensitivity of 91%, a specificity of 95%, positive and negative predictive values of 91% and of 95% for LM diagnosis. Additionally, a score >10 presented high concordance with the result of the breath test (k = 0.92). Conclusions Accurate evaluation of five clinical-anamnestic variables, with the use of a simple scoring system, is almost equivalent to the hydrogen breath test for the diagnosis of lactose malabsorption and could avoid breath testing in many cases.

Neuroendocrine tumors (NET) are rare malignancies, with the most common site of origin being from the gastrointestinal tract, particularly the pancreas, small bowel and appendix. Pancreatic neuroendocrine tumors (PNETs) can be functional, hormone secreting tumors, and can have distinctive symptoms leading to the diagnosis. In contrast nonfunctional tumors, the majority of PNETs, usually present later either incidentally or due to tumor bulk symptoms. Currently Everolimus, an inhibitor of mammalian target of rapamycin (mTOR), is the most promising drug for patients with unresectable, metastatic disease, in progressive well-differentiated PNETs and many studies are ongoing to demonstrate its effects on the other neuroendocrine histotipes. Food and Drug Administration (FDA) and European Medicines Agency (EMA) registered Everolimus in advanced/metastatic breast cancer, in advanced/metastatic renal cell carcinoma and in well/moderately differentiated pancreatic neuroendocrine tumors. Nevertheless only a subset of patients respond to the therapy due to the development of drug resistance. Thus the powerful Everolimus antitumor activity have prompted extensive efforts to overcome drug resistance and to maximize clinical benefit. In this review we aim to summarize current knowledge on mechanisms of Everolimus and other mTOR inhibitors molecules resistance with the intent to overcome it.

497 Background: Pancreas adenocarcinoma is the sixth cause of cancer-related death worldwide and the mortality is increasing in the Western Countries. Recently, the association between nab-paclitaxel (nab-P) and gemcitabine (GEM) has significantly improved progression-free (PFS) and overall survival (OS) compared to GEM monotherapy (PFS: 5.5 vs 3.7 months; OS: 8.5 vs 6.7 months). Methods: Patients affected by metastatic pancreas adenocarcinoma were treated at the Department of Abdominal Oncology of the National Cancer Institute of Naples from July 2015 to July 2016 with nab-P at 125 mg per square meter of body-surface area followed by GEM at 1000 mg per square meter on days 1, 8, and 15 every 4 weeks. Computed tomography (CT) was done every three months of therapy. Toxicity was graded with NCI-CTC criteria v4.0. Objective responses were evaluated with RECIST. Analysis of time-to-progression is only descriptive. Pain was evaluated with a visual analogic scale. Results: Twenty-three patients were treated. Median age was 67 years (range: 45-81); 8 patients were ≥ 70 years old. Performance Status (PS) ECOG was 2 in 8 patients, 1 in 10 and 0 in 5. Twelve patients presented with diffuse hepatic metastases, 4 with carcinosis, 7 with more than one organ involvement. They received a median number of 13 administrations (range: 3-32) of therapy. During therapy Nab-P was reduced at 100 mg per square meter in all patients. The most common G3/G4 adverse events were neutropenia (13.0% G4, 8.6% G3, none was febrile), neuropathy (30.4% G3) and asthenia (G3 17.3%). The disease control rate was 43.4% (PR+SD 10/23); PR was registered in three patients (response rate: 13.0%). Twelve patients progressed and seven dead at September 20. The median time-to-progression was 7.9 months (95% confidence interval 5.8-11.2). After three months of therapy the PS improved in 14 patients as well as pain in 18 patients. Conclusions: We present an experience with nab-P and GEM association in a series with poor PS and highly metastatic disease relatively to the previous randomized study. The schedule is feasible with nab-P at 100 mg per square meter and it achieves a good disease control rate as well as a clinical benefit.

The prognosis of rectal cancer (RC) is strictly related to both T and N stage of the disease at the time of diagnosis. RC staging is crucial for choosing the best multimodal therapy: patients with high risk locally advanced RC (LARC) undergo surgery after neoadjuvant chemotherapy and radiotherapy (NAT); those with low risk LARC are operated on after a preoperative short-course radiation therapy; finally, surgery alone is recommended only for early RC. Several imaging methods are used for staging patients with RC: computerized tomography, magnetic resonance imaging, positron emission tomography, and endoscopic ultrasound (EUS). EUS is highly accurate for the loco-regional staging of RC, since it is capable to evaluate precisely the mural infiltration of the tumor (T), especially in early RC. On the other hand, EUS is less accurate in restaging RC after NAT and before surgery. Finally, EUS is indicated for follow-up of patients operated on for RC, where there is a need for the surveillance of the anastomosis. The aim of this review is to highlight the impact of EUS on the management of patients with RC, evaluating its role in both preoperative staging and follow-up of patients after surgery.

Endoscopic follow-up (FU) after colorectal surgery is indicated mainly for patients operated on for cancer who are at risk for metachronous adenomas and/or recurrent cancer. Despite published guidelines, there is both overuse and underuse of endoscopic surveillance, and many institutions continue to have their own follow-up regimens. Therefore, endoscopic FU of colorectal cancer (CRC) survivors remains controversial, and there are several open issues regarding its appropriateness, timing, duration, and cost-effectiveness. Endoscopic FU should allow diagnosis of early anastomotic recurrences and metachronous adenomas and/or cancer in CRC patients after curative surgery. While endoscopic surveillance of the colonic anastomosis does not have any proven benefit, patients with prior rectal cancer should undergo flexible sigmoidoscopy ± endoscopic ultrasound at 3–6-month intervals for the first 3 years after resection, if not treated with neoadjuvant chemoradiation and mesorectal excision. All CRC survivors should undergo lifelong endoscopic FU to prevent metachronous CRCs, with surveillance colonoscopies at 1, 3, and 5 years after surgery and then every 5 years until the benefit is outweighed by comorbidity. Recently, it has been proposed that endoscopic FU should be tailored according to the personal risk of the individual CRC survivor, based on the presence or absence of synchronous adenomas at perioperative colonoscopy, the diagnosis of metachronous lesions during surveillance, and the features of both synchronous and metachronous adenomas. This strategy has been shown to be cost-effective, with a clear survival benefit for CRC survivors.

Peutz-Jeghers syndrome (PJS) is characterized by multiple hamartomatous polyps of the gastrointestinal tract and mucocutaneous pigmentation occurring around the body orifices [1, 2]. This autosomal dominant disease is caused by a germline mutation in the STK11/LKB1 gene and carries an increased risk of several types of cancer, such as gastrointestinal tumors, pancreatic cancer, genital tract malignancies and, especially, breast cancer [1, 2]. Approximately 50% of patients develop intussusception by the age of 15, because of jejunal and/or ileal polyps [3]. Previously, this complication was usually treated by surgery. Recently, video-capsule-endoscopy (VCE) and enteroscopy have changed both the diagnostic and the therapeutic management of small bowel hamartomas [4, 5, 6, 7, 8].

Gastrointestinal (GI) metastases of lung cancer are quite rare, ranging from 0.2% to 1.7% in clinical series, even if they occur in 7.3– 12.2% of autopsy cases [1, 2, 3]. The small bowel is the most frequent site of metastatic lung cancer in the GI tract [4, 5]. Mostly asymptomatic, small bowel metastases from lung cancer are usually diagnosed only in the presence of life threatening symptoms, such as small bowel obstruction, perforation or bleeding.

Colonic diverticulosis is characterized by abnormal thickening of the bowel wall, associated with luminal overpressure and increase of sigmoid contractility. However, patients with ulcerative colitis show chronic inflammatory alterations determining a reduction of both bowel wall muscle tone and contractility. Thus, we could presume ulcerative colitis and colonic diverticulosis as two pathophysiologically and mutually excluding diseases. This study was designed to evaluate the prevalence of colonic diverticulosis in patients with ulcerative colitis compared with a control endoscopic population.We prospectively analyzed the prevalence of colonic diverticulosis in 85 patients, older than aged 45 years, with known ulcerative colitis compared with that in 85 age/gender-matched patients without colitis. All patients underwent pancolonoscopy with ulcerative colitis and colonic diverticulosis diagnosis made by endoscopy and histopathology. The patients with ulcerative colitis also were divided in three subgroups according to the age at diagnosis (45 years) and extension of disease (sigmoiditis, left colitis, extensive colitis).Colonic diverticulosis was present in 7 of 85 patients with and in 24 patients without ulcerative colitis (8.2 vs. 28.2 percent; P < 0.001; relative risk, 3.4; 95 percent confidence interval, 1.56-7.52). All seven patients with both diseases were diagnosed with ulcerative colitis when older than age 45 years. No differences were found between the two groups in terms of extension of diverticula.Patients with ulcerative colitis show a significantly lower prevalence of colonic diverticulosis, with this finding probably reflecting the motor alterations caused by chronic bowel wall inflammation. In the patients affected by ulcerative colitis with late onset of the disease, the reduced prevalence of colonic diverticulosis is not evident.

Somatostatin analogs (SSAs) are typically used to treat the symptoms caused by neuroendocrine tumors (NETs), but they are not used as the primary treatment to induce tumor shrinkage. We report a case of a 63-year-old woman with a symptomatic metastatic NET of the ileum. Complete symptomatic response was achieved after 1 month of treatment with SSAs. In addition, there was an objective response in the liver, with the disappearance of secondary lesions noted on computed tomography scan after 3 months of octreotide treatment. Our experience suggests that SSAs could be useful for downstaging and/or downsizing well-differentiated NETs, and they could allow surgery to be performed. Such presurgery therapy could be a promising tool in the management of patients with initially inoperable NETs.

Abdominal ultrasound can assess the extent and localization of Crohn's disease, and an increased bowel wall thickness is the most common finding. Our aim was to correlate bowel wall thickness at ultrasound, with the risk of short-term surgical outcome in patients with Crohn's disease.From 1997 to 2000 we performed ultrasound in 174 consecutive patients with Crohn's disease. Surgical operations were recorded over a 1-yr follow-up. Logistic regression analysis was performed to identify clinical and ultrasound risk factors for surgery.Fifty-two patients underwent surgery within 1 yr. Indication for surgery was strictures in most of the cases. Median bowel wall thickness was higher in patients with surgery (8 mm) than those without surgery (6 mm) (p0.0001). A receiver operating characteristic (ROC) curve was constructed taking into account bowel wall thickness for selecting patients with a high risk of surgery. The optimized cut-off for equally important sensitivity and specificity was calculated at 7.008 mm. The binary regression analysis showed that CDAI150, absence of previous surgery, stricturing-penetrating pattern, the presence of intestinal complications, and intestinal wall thickness7 mm were associated with an increased risk of surgery. Patients with intestinal wall thickness7 mm at ultrasound had the highest risk (OR: 19.521, 95% CI: 5.362-71.065).Data suggest that bowel wall thickness7 mm at ultrasound is a risk factor for intestinal resection over a short period of time. Routine use of abdominal ultrasound during evaluation of patients with Crohn's disease may identify a subgroup that is at high risk for surgery. (Am J Gastroenterol 2004;99:1-7)