Search

The benefit of resection of liver metastases depends on primary diseases. Neuroendocrine tumors are associated with favorable prognosis after resection of liver metastases. Gastric cancer has worse tumor biology, and resection of gastric liver metastases should be performed in selected patients. A multidisciplinary approach is well established for colorectal liver metastases (CLMs). Resection remains the only curative treatment of CLM. Chemotherapy and molecular-targeted therapy have improved survival in unresectable metastatic colorectal cancer. Understanding of the following two strategies, conversion therapy and two-stage hepatectomy, are important to make this patient group to be candidates for curative-intent surgery.

Background Patients with prior colon cancer have increased risk of metachronous colorectal neoplasms; therefore, endoscopic surveillance is indicated. Current recommendations are not risk-stratified. We investigated predictive factors for colorectal neoplasms to build a model to spare colonoscopies for low-risk patients. Methods This was a multicenter, retrospective study including patients who underwent surgery for colon cancer in 2001 – 2008 (derivation cohort) and 2009 – 2013 (validation cohort). A predictive model for neoplasm occurrence at second surveillance colonoscopy was developed and validated. Results 421 and 203 patients were included in derivation and validation cohort, respectively. At second surveillance colonoscopy, 112 (26.6 %) and 55 (27.1 %) patients had metachronous neoplasms in derivation and validation groups; three cancers were detected in the latter. History of left-sided colon cancer (OR 1.64, 95 %CI 1.02 – 2.64), ≥ 1 advanced adenoma at index colonoscopy (OR 1.90, 95 %CI 1.05 – 3.43), and ≥ 1 adenoma at first surveillance colonoscopy (OR 2.06, 95 %CI 1.29 – 3.27) were independently predictive of metachronous colorectal neoplasms at second surveillance colonoscopy. For patients without such risk factors, diagnostic accuracy parameters were: 89.3 % (95 %CI 82.0 %-94.3 %) and 78.2 % (95 %CI 65.0 %-88.2 %) sensitivity, and 28.5 % (95 %CI 23.5 %-33.9 %) and 33.8 % (95 %CI 26.2 %-42.0 %) specificity in derivation and validation group, respectively. No cancer would be missed. Conclusions Patients with prior left-sided colon cancer or ≥ 1 advanced adenoma at index colonoscopy or ≥ 1 adenoma at first surveillance colonoscopy had a significantly higher risk of neoplasms at second surveillance colonoscopy; patients without such factors had much lower risk and could safely skip the second surveillance colonoscopy. A prospective, multicenter validation study is needed.

INTRODUCTION Most studies predicting survival after resection, transarterial chemoembolization (TACE), and ablation analyzed diameter and number of hepatocellular carcinomas (HCCs) as dichotomous variables, resulting in an underestimation of risk variation. We aimed to develop and validate a new prognostic model for patients with HCC using largest diameter and number of HCCs as continuous variables. METHODS The prognostic model was developed using data from patients undergoing resection, TACE, and ablation in 645 Japanese institutions. The model results were shown after balanced using the inverse probability of treatment-weighted analysis and were externally validated in an international multi-institution cohort. RESULTS Of 77,268 patients, 43,904 patients, including 15,313 (34.9%) undergoing liver resection, 13,375 (30.5%) undergoing TACE, and 15,216 (34.7%) undergoing ablation, met the inclusion criteria. Our model (http://www.u-tokyo-hbp-transplant-surgery.jp/about/calculation.html) showed that the 5-year overall survival (OS) in patients with HCC undergoing these procedures decreased with progressive incremental increases in diameter and number of HCCs. For patients undergoing resection, the inverse probability of treatment-weighted-adjusted 5-year OS probabilities were 10%-20% higher compared with patients undergoing TACE for 1-6 HCC lesions

Data to guide surveillance following oncologic extended resection (OER) for gallbladder cancer (GBC) are lacking. Conditional recurrence-free survival (C-RFS) can inform surveillance. We aimed to estimate C-RFS and identify factors affecting conditional RFS after OER for GBC. Patients with ≥ T1b GBC who underwent curative-intent surgery in 2000–2018 at four countries were identified. Risk factors for recurrence and RFS were evaluated at initial resection in all patients and at 12 and 24 months after resection in patients remaining recurrence-free. Of the 1071 patients who underwent OER, 484 met the inclusion criteria; 290 (60%) were recurrence-free at 12 months, and 199 (41%) were recurrence-free at 24 months. Median follow-up was 24.5 months for all patients and 47.21 months in survivors at analysis. Five-year RFS rates were 47% for the overall population, 71% for patients recurrence-free at 12 months, and 87% for the patients without recurrence at 24 months. In the entire cohort, the risk of recurrence peaked at 8 months. T3–T4 disease was independently associated with recurrence in all groups: entire cohort [hazard ratio (HR) 2.16, 95% confidence interval (CI) 1.49–3.13, P

Background The refusal of blood transfusions compels surgeons to face ethical and clinical issues. A single-institution experience with a dedicated perioperative blood management protocol was reviewed to assess feasibility and short-term outcomes of true bloodless pancreatic surgery. Methods The institutional database was reviewed to identify patients who refused transfusion and were scheduled for elective pancreatic surgery from 2010 through 2018. A protocol to optimize the hemoglobin values by administration of drugs stimulating erythropoiesis was systematically used. Results Perioperative outcomes of 32 Jehovah’s Witnesses patients were included. Median age was 67 years (range, 31–77). Nineteen (59.4%) patients were treated with preoperative erythropoietin. Twenty-four (75%) patients underwent pylorus-preserving pancreaticoduodenectomy, 4 (12.5%) distal pancreatectomy (DP) with splenectomy, 3 (9.4%) spleen-preserving DP, and 1 (3.1%) total pancreatectomy. Median estimated blood loss and surgical duration were 400 mL (range, 100–1000) and 470 min (range, 290–595), respectively. Median preoperative hemoglobin was 13.9 g/dL (range, 11.7–15.8) while median postoperative nadir hemoglobin was 10.5 g/dL (range, 7.1–14.1). The most common histological diagnosis (n = 15, 46.9%) was pancreatic ductal adenocarcinoma. Clavien-Dindo grade I-II complications occurred in fourteen (43.8%) patients while one (3.1%) patient had a Clavien-Dindo grade IIIa complication wich was an abdominal collection that required percutaneous drainage. Six (18.8%) patients presented biochemical leak or postoperative pancreatic fistula grade B. Median hospital stay was 16 days (range, 8–54) with no patient requiring transfusion or re-operation and no 90-day mortality. Conclusions A multidisciplinary approach and specific perioperative management allowed performing pancreatic resections in patients who refused transfusion with good short-term outcomes.

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 Current evidence supports the curative resection of colorectal cancer and synchronous liver and lung metastases in selected patients.1,2 This video shows simultaneous left colectomy, bilobar liver resection, and lung metastasectomy via a transdiaphragmatic approach for stage IV colorectal cancer.3 PATIENT: A 57-year-old man with a stage IV colonic adenocarcinoma was considered for simultaneous resection of primary, liver, and lung metastases without thoracic incision. The tumor mutational status was KRAS, NRAS, and BRAF wild-type, and the patient underwent preoperative chemotherapy. Technique After performing a midline laparotomy, atypical liver resection of segments 8/4a was performed under the guidance of intraoperative ultrasonography and intermittent Pringle maneuver using the two-surgeon's technique. A small capsular lesion in segment 3 also was intraoperatively detected and resected. Lung metastasectomy of the right lower lobe was performed via a transdiaphragmatic approach using an endoscopic stapler. Sigmoid colectomy with transanal circular-stapled anastomosis was performed. Duration of surgery and blood loss were 358 min and 400 ml, respectively. Histopathological examination showed metastatic colonic adenocarcinoma with negative surgical margins and final stage was T3N2aM1b. The patient was discharged on postoperative day 6 without complication. He was alive and free of disease at 90-day follow-up. Conclusions Simultaneous colon, liver, and lung resection via a transdiaphragmatic approach is a feasible and safe surgical strategy in selected patients with peripheral lung metastases and favorable tumor biology.4 This surgical strategy avoids thoracic incision, multiple operations, and may reduce the healthcare costs and the recovery time to early implement postoperative therapy.

Hepatocellular carcinoma (HCC) de-differentiation is thought to correlate with size, therefore well-differentiated HCC ≥3 cm are considered rare and not fully understood.Patients who underwent hepatectomy for HCC between 1998-2016 were retrospectively analyzed. Patient's characteristics and recurrence-free (RFS) and overall (OS) survival were compared between those with atypical- (well-differentiated-HCC ≥3 cm) and typical-HCC (moderate-to-poorly-differentiated HCC ≥3 cm).Of 176 patients included in this study, 37 (21%) had atypical-HCC. Patients with atypical-HCC were less likely to be Asian ethnicity (3% vs. 17%, p = 0.062), have lower rate of viral infection (14% vs. 43%, p = 0.003), cirrhosis (8% vs. 27%, p = 0.015). The tumors were less likely to demonstrate vascular invasion (30% vs. 59%, p = 0.002), and were associated with a lower alpha-fetoprotein level (3.5 ng/ml vs. 33.2 ng/ml, p 0.001). Patients with atypical-HCC had a longer RFS (5-y RFS: 58.3% vs. 35.7%, p = 0.016) and OS (5-y OS: 79.1% vs 53.3%, p = 0.029) as compared to those with typical-HCC following univariate analysis, however this did not appear following multivariate analysis.Patients with atypical-HCC have different characteristic in terms of epidemiology, etiology, cirrhosis and vascular invasion as compared to typical-HCC. The etiology of atypical-HCC may be non-alcoholic fatty liver disease-related and/or malignant transformation of hepatocellular adenoma.

Background Patients with prior colorectal cancer (CRC) are at slightly increased risk of metachronous colorectal neoplasms, therefore endoscopic surveillance is indicated. Current recommendations of repeating examinations at 1, 3 and 5 years after surgery, are not tailored according to risk stratification. Our aim was to find predictive factors of colorectal neoplasms to build a predictive model, to spare colonoscopies for low-risk patients. Methods Multicenter retrospective study including patients with colon carcinoma surgically resected from 2001 to 2008 (training cohort) and from 2009 to 2013 (validation cohort). A predictive model for neoplasms occurrence at second surveillance colonoscopy was developed and externally validated. Results 396 and 131 patients were included in training and validation cohort respectively. Patients with ≥1 adenoma at the 2nd surveillance colonoscopy were 113/396 (28.5%) and 21/131 (16.5%) in the two groups. In the validation cohort, 3 cancers were found. Four variables were associated with higher risk of metachronous colorectal adenomas at 2nd surveillance colonoscopy on multivariate analysis: age >65 years old, left colectomy, ≥1 advanced adenoma at basal colonoscopy and ≥1 adenoma at first surveillance colonoscopy (table 1). The predictive model showed fair discrimination, with an area under the ROC curve of 0.69 and 0.64, in training and validation cohort respectively. In validation group, If patients with a low-risk profile (i.e. none of the risk factors) skip the 2nd surveillance colonoscopy, 25/131 (19.1%) exams would be saved while missing 2/21 (9.5%) patients with ≥1 adenoma; no cancer would be missed. Conclusions We provided a risk-stratification tool for adenoma occurrence after colon surgery, which could prove cost-effective to select patients who could skip the second surveillance colonoscopy.

Background: Laparoscopic Incisional and Ventral Hernia Repair (LIVHR) is a safe and worldwide accepted procedure performed using absorbable tacks. The aim of the study was to evaluate recurrence rate in a long term follow-up and whether the results of laparoscopic IVH repair in the elderly (≥65 years old) are different with respect to results obtained in younger patients. Methods: One hundred and twenty-nine consecutive patients (74 women and 55 men, median age 67 years, range = 30-87 years) with ventral (N = 42, 32.5%) or post incisional (N = 87, 67.5%) hernia were enrolled in the study. Patients were divided into two groups according to their age: group A (N = 55, 42.6%) aged Results: The mean operative time was not significantly different between groups (66.7 ± 37 vs. 74 ± 48.4 min, p = 0.4). To the end of 2016, seven recurrences had occurred (group A = 3, group B = 4, p = 1). Complications occurred in 8 (16%) patients in group A and 21 (28.3%) patients in group B. Conclusion: In conclusion, our results confirm that the use of absorbable tacks does not increase recurrence frequency and laparoscopic incisional and ventral repair is a safety procedure also in elderly patients.

Irreversible electroporation is a new ablation modality. Our purpose was to describe the MRI findings after irreversible electroporation treatment of hepatocellular carcinoma (HCC).In an 18-month period, we treated 24 HCC lesions in 20 patients who were not candidates for surgery. MRI was performed before and 1 month after irreversible electroporation. We used the liver-specific contrast medium gadoxetic acid. We evaluated the size, shape, signal intensity (T1-weighted, T2-weighted, and diffusion-weighted imaging), dynamic contrast enhancement pattern, and signal behavior during the liver-specific phase. Changes in the perilesional parenchyma, perfusion abnormalities, and complications were also recorded.According to the modified Response Evaluation Criteria in Solid Tumors system, 22 of 24 lesions had a complete response, and two lesions showed a partial response and were retreated. The lesions showed a mean size increase of 10%, with a round or oval shape. On the T1-weighted images, we observed a hyperintense core and a hypointense rim. On the T2-weighted sequences, the signal was heterogeneously hypointense. On diffusion-weighted images, 83% of lesions showed restricted diffusion, with b values of 0-800 s/mm(2), whereas in 17% of the lesions, the signal was not clearly discernible for different b values. The apparent diffusion coefficient values did not show statistically significant differences between the baseline (800-1020 × 10(-3) mm(2)/s) and the reassessment after 1 month (900-1100 × 10(-3) mm(2)/s). The necrotic area did not show a signal increase after contrast material injection. Perfusion abnormalities, such as areas of transient hepatic intensity difference, were present in the tissue adjacent to six treated lesions. In two patients, a reduced or absent concentration of the contrast medium was observed during the liver-specific phase around the ablation zone. One patient had an arteriovenous shunt and another had biliary duct dilatation.MRI detects characteristic morphologic and functional changes after irreversible electroporation treatment.

The majority of currently available oesophageal metal stents are partially covered to reduce migration risk. Preliminary experiences with fully covered stents seem to indicate an increased risk of migration in patients treated for malignant dysphagia. The aim of our study was to determine, in this setting, the safety and efficacy of a new, recently introduced stent with anti-migration proprieties.We designed a prospective, multicentre, non-randomized, follow-up study in nine tertiary referral centres. Eighty-two patients with dysphagia due to inoperable or metastatic oesophageal cancer were included. In all of them the fully covered WallFlex(®) stent was placed. Main outcome measurements included functional outcome, recurrent dysphagia, complications, and mortality.Dysphagia score improved from a median of 3, before stenting, to 1 at 4 weeks after stent placement (P0.001). Perforation occurred in 1 patient after 39 days, while bleeding was reported in 3. In total, 19 patients (23.1%) developed recurrent dysphagia because of stent migration (N=10, 12.2%), tissue overgrowth (N=7; 8.5%), and food impaction (N=2; 2.4%).Placement of the fully covered WallFlex(®) stent resulted in safe and effective palliation of malignant dysphagia, with migration and tissue overgrowth rates comparable to previously reported data on partially covered stents.

BACKGROUND: Despite the improvements in diagnosis and treatment, colorectal cancer (CRC) is the second cause of cancer deaths in both sexes. Therefore, research in this field remains of great interest. The approval of bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, in combination with a fluoropyrimidine-based chemotherapy in the treatment of metastatic CRC has changed the oncology practice in this disease. However, the efficacy of bevacizumab-based treatment, has thus far been rather modest. Efforts are ongoing to understand the better way to combine bevacizumab and chemotherapy, and to identify valid predictive biomarkers of benefit to avoid unnecessary and costly therapy to nonresponder patients. The BRANCH study in high-risk locally advanced rectal cancer patients showed that varying bevacizumab schedule may impact on the feasibility and efficacy of chemo-radiotherapy. METHODS/DESIGN: OBELICS is a multicentre, open-label, randomised phase 3 trial comparing in mCRC patients two treatment arms (1:1): standard concomitant administration of bevacizumab with chemotherapy (mFOLFOX/OXXEL regimen) vs experimental sequential bevacizumab given 4 days before chemotherapy, as first or second treatment line. Primary end point is the objective response rate (ORR) measured according to RECIST criteria. A sample size of 230 patients was calculated allowing reliable assessment in all plausible first-second line case-mix conditions, with a 80% statistical power and 2-sided alpha error of 0.05. Secondary endpoints are progression free-survival (PFS), overall survival (OS), toxicity and quality of life. The evaluation of the potential predictive role of several circulating biomarkers (circulating endothelial cells and progenitors, VEGF and VEGF-R SNPs, cytokines, microRNAs, free circulating DNA) as well as the value of the early [(18)F]-Fluorodeoxyglucose positron emission tomography (FDG-PET) response, are the objectives of the traslational project. DISCUSSION: Overall this study could optimize bevacizumab scheduling in combination with chemotherapy in mCRC patients. Moreover, correlative studies could improve the knowledge of the mechanisms by which bevacizumab enhance chemotherapy effect and could identify early predictors of response. EudraCT Number: 2011-004997-27 TRIAL REGISTRATION: ClinicalTrials.gove number, NCT01718873.

OBJECTIVE. The goal of this article is to discuss and show the common complications of biliary and gastrointestinal stents as depicted by MDCT in cancer patients. Major complications include stent misplacement or displacement, bleeding, obstruction, perforation, stent fracture or collapse, and infection. This topic encompasses several relevant issues, including interpretative difficulties, therapeutic decisions, and potential malpractice concerns. CONCLUSION. Awareness and methodical assessment of stents could allow detection of stenting complications, potentially sparing the patient from associated morbidity and mortality.

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.

Part I of this review in the previous issue of Gastrointestinal Endoscopy outlined the key points of tissue sampling at ERCP and considered intraductal bile aspiration cytology, cytologic/histologic analysis of retrieved plastic biliary stents and fine needle aspiration cytology. Specimen adequacy, slide preparation, and accuracy of slide interpretation, which is often influenced by the interpretation “philosophy” of individual cytopathologists, are fundamental to the effort to optimize cancer detection by using tissue sampling techniques at ERCP. Intraductal bile aspiration is simple and inexpensive but adds little to the other methods, which have higher rates of cancer detection. Therefore, bile aspiration is recommended only when other sampling techniques cannot be used. Cytologic evaluation of material from retrieved plastic biliary stents is relatively insensitive (32%) and impractical as a firstline approach to the diagnosis of malignant biliary obstruction because diagnosis is delayed until the stent is removed. However, it can be considered in patients undergoing stent exchange when other methods of tissue sampling fail to confirm the suspected diagnosis of malignancy. Endoscopic fineneedle aspiration (FNA) cytology has a lower rate of cancer detection (33%) than initially reported and is technically difficult. It is usually used to supplement other simpler methods. Part II of this review considers the remaining tissue sampling methods for use at ERCP: brush cytology, endobiliary forceps biopsy, and the multimodal tissue sampling. Methods for improving diagnostic yield are discussed. BRUSH CYTOLOGY

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.

Flexible endoscopy plays a fundamental role in the clinical monitoring of surgical digestive anastomosis. Endoscopic examination is essential for the recognition and for the description of the type of anastomosis (end to end, end to side, side to side), providing both an accurate evaluation of the new digestive anatomy and the early detection of any postsurgical complications or recurrence. Close monitoring of the surgically treated disease, both neoplastic and nonneoplastic, can be realized by an accurate and scheduled follow-up which should consider all the imaging modalities nowadays available in the clinical practice, such as radiology and endoscopic ultrasonography. On the other hand, prompt detection of any pathologic pattern of the anastomosis (stenosis, dehiscence, fistula, recurrence) is the key factor for the choice of any further and appropriate treatment. Our chapter is aimed at defining the key factors of an accurate endoscopic evaluation of surgical anastomosis and at discussing the clinical criteria for an accurate follow-up.

Experimental studies have shown that vinorelbine is a powerful radiosensitizer in vitro. To date, no reports on clinical activity of the single agent vinorelbine as radiosensitizer have been published. The aim of the present phase I study was to determine the maximum tolerated dose (MTD) of vinorelbine administered daily concurrently with thoracic radiotherapy, with or without amifostine support, in the treatment of locally advanced non small cell lung cancer. In vitro studies have shown that vinorelbine can potentiate the antitumor effects of radiation therapy. Amifostine is a sulphydril compound that has shown to protect normal tissues from chemotherapy and radiotherapy-induced toxicities. Radiotherapy lasted 6 weeks and the total dose was 55 Gy. The daily fraction was 1.8 Gy, administered 5 days a week for 5 weeks and increased to 2.0 Gy during the sixth and last week. Concurrent vinorelbine was administered daily with a planned escalation of the dose from 4, to 5 and 6 mg/m 2 . Fourteen patients were enrolled in the study. The first dose of vinorelbine was 4 mg/m 2 and it showed to be feasible without dose-limiting toxicity (DLT). Instead, the second dose level of 5 mg/m 2 was unfeasible because three out of six patients had DLT (grade 4 neutropenia, treatment interruption longer than 2 weeks for prolonged grade 2 neutropenia and treatment interruption longer than 2 weeks for prolonged grade 3 esophagitis together with grade 4 dyspnea). At that time, the study continued adding amifostine to vinorelbine in order to increase its MTD. Amifostine was administered by means of subcutaneous injection 15 min before each radiotherapy fraction at the fixed dose of 300 mg/m 2 . However, 5 mg/m 2 of vinorelbine were considered unfeasible even with amifostine support because three out of five patients showed DLT (grade 4 neutropenia, febrile grade 4 neutropenia and grade 3 liver toxicity). Among 14 patients enrolled in the study, eight completed the planned treatment because six patients experienced DLT, which determined treatment interruption. Overall, four partial and two complete responses were observed. Two partial and one complete response were observed in those three patients who had been treated with the first dose of vinorelbine. In conclusion, our data show that the MTD of daily vinorelbine is 4 mg/m 2 . Therefore, this is the recommended dose of daily vinorelbine to be administered with concurrent thoracic radiotherapy in a phase II trial. Finally, amifostine administered subcutaneously failed to increase the MTD of daily vinorelbine.

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.

Gastrointestinal stromal tumors (GISTs) are rare tumors, that are usually discovered incidentally during endoscopy. Occasionally, however, they are symptomatic and present mainly with gastrointestinal bleeding.

arct S [1] Fuccio L. Comment on “Self-expandable metal stents for malignant colonic obstruction: data from a retrospective regional SIED-AIGO study” by R. Di Mitri, F. Mocciaro, M. Traina et al. [Digestive and Liver Disease 2014;46:279–82]. Digestive and Liver Disease 2014;46:859–60. [2] Di Mitri R, Mocciaro F, Traina M, et al. Self-expandable stents for malignant colonic obstruction: data from a retrospective regional SIED-AIGO study. Digestive and Liver Disease 2014;46:279–82. [3] Sanoff HK. Therapy for metastatic colorectal cancer in elderly patients and those with a poor performance status; 2014. Uptodate.com. our ts: 7.

Background Surveillance in hereditary non-polyposis colorectal cancer (HNPCC) family members recommends baseline colonoscopy starting at age 20 and then surveillance colonoscopy every 1–2 years. Aims To verify adherence to the guidelines for HNPCC family members enrolled in endoscopic surveillance. Methods Data regarding 11 HNPCC families was retrieved from our database. Excluding 11 probands, 106 family members were evaluated and 40 underwent surveillance. Results At baseline colonoscopy, 7 colorectal cancers (CRC), 14 polyps (PO) [1 inflammatory, 2 hyperplastic, 10 adenomas with low grade dysplasia (LGD-AD) and 1 adenoma with high-grade dysplasia (HGD-AD)] were diagnosed in sixteen individuals. Twenty-eight HNPCC family members underwent endoscopic surveillance, with a total of 94 surveillance colonoscopies. Of these, 45 were positive (4 CRC, 3 inflammatory PO, 34 hyperplastic PO, 21 LGD-AD and 5 HGD-AD). Mean time between two consecutive surveillance colonoscopies was 24.6 months (range 4–168). Median time to first positive surveillance colonoscopy was 84 months for HNPCC family members with negative baseline colonoscopy, and 60 months for those with positive baseline colonoscopy ( p = 0.21). Conclusions Our data suggests that surveillance colonoscopy every 2 years is adequate to diagnose advanced lesions in HNPCC family members, and improves their compliance with surveillance.

Since laparoscopic cholecystectomy was first performed by Mouret, in March 1987, laparoscopic surgery has rapidly evolved as a major innovation in the history of surgery. Minimally invasive surgery has become an important specialty and has contributed to the drastic reduction of incisional hernia, which is a typical complication associated with open surgery [1,2]. However, laparoscopic surgery is also associated with a specific type of incisional hernia that occurs at the trocar site [2,3]. Trocar-site hernia was first described in 1968 by Fear, who reported this complication after diagnostic laparoscopy performed to rule out gynaecologic diseases [4].

Background: The sensitivity for cancer detection or brush cytology at ERCP is relatively low. Manipulation of the stricture and repeated tissue sampling may increase the yield. This study compared the cancer detection rate of brush cytology before and after biliary stricture dilation. Methods: In patients with a biliary structure at ERCP of suspected malignant origin, the stricture was sampled with a cytology brush and then dilated with either a graduated dilating catheter or a dilating balloon (4–8 mm). Brushing was then repeated in all patients. Specimens were interpreted as normal, atypical (benign), highly atypical (suspicious for cancer), and malignant. Final diagnoses were based on cytology plus surgery, EUS, percutaneous biopsy, autopsy, or clinical follow-up. Results: A total of 139 patients with suspected malignant obstructive jaundice underwent 143 ERCPs (116 ultimately found to have mallgnant obstruction, and 27 benign disease). Dilation was performed with a catheter in 68 cases, balloon in 73, and both in 2. Brush cytology had a sensitivity of 34.5% (40/116) before dilation and 31% (36/116) after dilation (p=NS). However, sensitivity with predilation and postdilation brushing specimens combined was 44% (51/116), which was higher than that for either the predilation or postdilation brush cytology (p=0.001). Cancer detection rates were 34.7% (17/49) after dilation with the catheter and 27.7% (18/65) after balloon dilation (p=NS). Conclusions: Stricture dilation does not improve the sensitivity of brush cytology for the detection of cancer, which remains relatively low. However, repeat brushing increases the diagnostic yield and should be performed when sampling biliary strictures with a cytology brush at ERCP.

Background: In some patients with pancreas divisum, minor papilla cannulation is difficult because of uncertain identification of the papilla or its orifice, even after pancreatic secretory stimulation with secretin or cholecystokinin agonist. Methods: Two techniques with methylene blue were used to identify the minor papilla and its orifice more clearly in a series of patients: spraying methylene blue over duodenal mucosa in the region suspected to contain the minor papilla with/without secretin or cholecystokinin agonist administration, and injection of contrast medium containing methylene blue into the ventral pancreatic duct by means of the major papilla in cases of incomplete pancreas divisum. Results were reviewed retrospectively. Results: From January 2001 to May 2002, minor papilla cannulation with conventional methods initially failed in 38 of 305 patients with pancreas divisum because of an inconspicuous minor papilla orifice. Methylene blue was used to identity the minor papilla orifice in 14 of 38 patients (spraying, 13; injection, 1). Minor papilla cannulation was successful in 12 of 14 (86%) patients (spraying 11, injection 1). Mild pancreatitis developed in 1 patient. Conclusions: Methylene blue spraying or injection appears to be a helpful technique for identification of the inconspicuous minor papilla orifice in patients with pancreas divisum. (Gastrointest Endosc 2003;57:358-63.)

Granular cell tumors are uncommon, usually benign tumors that can be located anywhere in the body. They commonly occur in the oral cavity and in subcutaneous tissue. In the gastrointestinal tract, granular cell tumors are uncommon and are quite rare in the colon. To date, 55 patients diagnosed with granular cell tumors of the colon have been reported in the literature, only 15 had multiple tumors. We describe the case of a 38-year-old man with a family history of colon cancer who was diagnosed with multiple colonic granular cell tumors after a screening colonoscopy. This seems to be the first report of this type. However, in our patient, the diagnosis of colonic granular cell tumors was incidental and there is no data that correlates adenomas or colorectal cancer with granular cell tumors of the colon. Finally, since granular cell tumors are usually benign, we suggest a conservative approach to patients with multiple granular cell tumors of the colon by means of endoscopic resection and a strict endoscopic follow-up.

Gastroesophageal reflux (GER) can develop in patients with esophageal achalasia either before treatment or following pneumatic dilatation or Heller myotomy. In this study we assessed the value of pre- and postoperative pH monitoring in identifying GER in patients with esophageal achalasia. Ambulatory pH monitoring was performed preoperatively in 40 patients with achalasia (18 untreated patients and 22 patients after pneumatic dilatation), 27 (68%) of whom complained of heartburn in addition to dysphagia (group A), and postoperatively in 18 of 51 patients who underwent a thoracoscopic (n=30) or laparoscopic (n=21) Heller myotomy (group B). The DeMeester reflux score was abnormal in 14 patients in group A, 13 of whom had been treated previously by pneumatic dilatation. Two types of pH tracings were seen: (1) GER in eight patients (7 of whom had undergone dilatation) and (2) pseudo-GER in six patients (all 6 of whom had undergone dilatation). Therefore 7 (32%) of 22 patients had abnormal GER after pneumatic dilatation. Postoperatively (group B) seven patients had abnormal GER (6 after thoracoscopic and 1 after laparoscopic myotomy). Six of the seven patients were asymptomatic. These findings show that (1) approximately one third of patients treated by pneumatic dilatation had GER; (2) symptoms were an unreliable index of the presence of abnormal GER, so pH monitoring must be performed in order to make this diagnosis; and (3) the preoperative detection of GER in patients with achalasia is important because it influences the choice of operation.

A Multicenter Prospective Study of Management of Inoperable Malignant Esophageal Strictures With a New Fully Covered Metal Stent Alessandro Repici, Giacomo Rando, Fabio Romeo, Biagio Solito, Roberto Di Mitri, Federico Buffoli, Giovanni Macri, Diego Fregonese, Mario De Bellis, Vincenzo Cennamo, Peter D. Siersema Servizio di Endoscopia Digestiva, IRCCS Istituto Clinico Humanitas, Rozzano (MI), Italy; Pisa Osp. Santa Chiara, Pisa, Italy; Palermo Hospital, Palermo, Italy; Cremona Hospital, Cremona, Italy; Acireale Hospital, Acireale, Italy; Ospedale di Camposampiero, Campio S. Piero, Italy; S. Orsola Hospital University of Bologna, Bologna, Italy; University Medical Center Utrecht, Utrecht, Italy; Pascale Hospital, Napoli Pascale, Italy Background and aim: self expanding covered metal stent are frequently indicated for palliation of malignant dysphagia. This multicentric prospective study was undertaken to assess the technical and clinical success and complications using the fully covered Wallflex esophageal stent (boston scientific, MA, USA) in patients with inoperable esophageal cancer. Methods: from January 2010 patients with dysphagia secondary to a primary esophageal cancer were considered eligibile for the study. Exclusion criteria was presence of respiratory fistula, previous stent placement, previous upper GI surgery, Karnofsky status 50%. Data were prospectively collected from 9 centers trough a dedicated electronic database. Pre and post-stent dysphagia symptoms were graded on a scale from 0 to 4. Follow-up with clinical visit or telephone interview was scheduled at 14 days, and then, at monthly interval, until death. Results: A total of 52 patient with a M/F ratio 36/16, median age 74.6 (range 37-95 years) were treated with Wallflex fully covered esophageal stent. The median tumor length was 6.2 (range 3-12 cm). The site of malignant stricture was: upper third 8, middle 14, lower third 16, GEJ 14. Eighteen patients had a squamous cancer, 30 had adenocarcinoma and 4 undifferentiated cancer. The stent was successfully placed in 50 patients, while in 2 cases stent release was too distal and required repositioning in 1 case and second stent placement. Dysphagia score improved from a median of 3.7 before stenting to 1.5 four weeks after stent placement (p 0.0001).Perforation occurred after 39 days in 1 patient. Bleeding in 2 patients. In total 12 patients (23%) developed recurrent dysphagia because of stent migration (n 4, 7.6%), tissue overgrowth (N 6; 11.5%) and food impaction (N 2; 3.8%). Conclusions: Placement of fully covered Wallflex stent resulted in safe and effective palliation of malignant dysphagia, with a migration and tissue overgrowth rates comparable to previous published data.

Systemic chemotherapy can be complicated by colonic toxicity, which usually determines the onset of pseudomembranous colitis and, rarely, of ischemic colitis in patients with cancer. This report describes the case of a 49-year-old woman with liver metastases from a neuroendocrine tumor of unknown origin who developed mild ischemic colitis after chemotherapy with carboplatin and paclitaxel. The patient developed symptoms of gastrointestinal toxicity with abdominal pain and bloody diarrhea, which resolved in about 10 days. She had a normal white blood cell count throughout her illness; the assay of stool specimens for Clostridium difficile toxins and the stool cultures were both negative. A sigmoidoscopy showed a mild, transient ischemic colitis, which was confirmed by pathologic examination of the biopsy specimens. Although carboplatin is not related to severe colonic cytotoxicity, it has been previously reported that paclitaxel induces necrosis of the gastrointestinal mucosa and inhibits angiogenesis. Pseudomembranous colitis is the most frequent complication in patients with cancer who undergo paclitaxel-based chemotherapy and develop gastrointestinal toxicity. Once C. difficile infection has been excluded, a diagnosis of ischemic colitis should be considered, especially in patients with cancer who have normal white blood cell counts.