Magnet and wire remodeling for the treatment of candy cane syndrome: first case series of a new approach (with video).

BACKGROUND AND AIMS: Candy cane syndrome (CCS) is an adverse event (AE) from gastrectomy or gastric bypass and end-to-side anastomosis to a jejunal loop. Preferential passage of food to the blind loop induces early satiety, pain, and regurgitation. An endoscopic device that combines 2 magnets and a self-retractable wire was designed to perform progressive septotomy with marsupialization. We evaluated the clinical safety and efficacy of this treatment in CCS. METHODS: Consecutive patients presenting with symptoms associated with CCS after gastrectomy or Roux-en-Y gastric bypass were treated with the MAGUS (Magnetic Gastrointestinal Universal Septotome) system. Weight, dysphagia, pain scores, 12-item Short Form Survey quality of life physical and mental scores, GERD Health-Related Quality of Life, and Eckardt score were measured at baseline and 1 and 3 months postprocedure. Satisfaction with therapy and AEs were monitored during follow-up. RESULTS: Fourteen consecutive patients with CCS were enrolled in the study. Thirteen MAGUS systems migrated within 28 days after achieving uneventful complete septotomy. In 1 patient the magnet had to be collected from the right-sided colon after 1 month. Treatment was completed in a single endoscopy session. Dysphagia score (2 [1-3] vs 1 [1-1], P = .02), pain score (7 [6-8] vs 1 [0-1], P = .002), Eckardt score (5 [3-8] vs 1 [0-2], P = .002), GERD Health-Related Quality of Life score (37 [29-45] vs 8 [6-23], P = .002), and quality of life physical and mental scores were all significantly improved at 3 months. No device or procedure-related serious AEs were observed. One patient died during follow-up from evolution of oncologic disease. CONCLUSIONS: Endoluminal septotomy using a retractable wire and magnet system in CCS is feasible and safe, with rapid improvement of symptoms. (Clinical trial registration number: NCT04480216.).

Magnets and a self-retractable wire for endoscopic septotomies: from concept to first-in-human use.

BACKGROUND: A medical device that allows simple and safe performance of an endoscopic septotomy could have several applications in the gastrointestinal (GI) tract. We have developed such a device by combining two magnets and a self-retractable wire to perform a progressive septotomy by compression of the tissues. We describe here the concept, preclinical studies, and first clinical use of the device for the treatment of symptomatic epiphrenic esophageal diverticulum (EED). METHODS: The MAGUS (MAgnetic Gastrointestinal Universal Septotome) device was designed based on previous knowledge of compression anastomosis and currently unmet needs. After initial design, the feasibility of the technique was tested on artificial septa in pigs. A clinical trial was then initiated to assess the feasibility and safety of the technique. RESULTS: Animal studies showed that the MAGUS can perform a complete septotomy at various levels of the GI tract. In two patients with a symptomatic EED, uneventful complete septotomy was observed within 28 and 39 days after the endoscopic procedure. CONCLUSIONS: This new system provides a way of performing endoluminal septotomy in a single procedure. It appears to be effective and safe for managing symptomatic EED. Further clinical applications where this type of remodeling of the GI tract could be beneficial are under investigation.

Systematic review and meta-analysis of endoscopic ultrasound drainage for the management of fluid collections after pancreas surgery.

BACKGROUND: The outcomes of endoscopic ultrasonography-guided drainage (EUSD) in treatment of pancreas fluid collection (PFC) after pancreas surgeries have not been evaluated systematically. The current systematic review and meta-analysis aim to evaluate the outcomes of EUSD in patients with PFC after pancreas surgery and compare it with percutaneous drainage (PCD). METHODS: PubMed and Web of Science databases were searched for studies reporting outcomes EUSD in treatment of PFC after pancreas surgeries, from their inception until January 2022. Two meta-analyses were performed: (A) a systematic review and single-arm meta-analysis of EUSD (meta-analysis A) and (B) two-arm meta-analysis comparing the outcomes of EUSD and PCD (meta-analysis B). Pooled proportion of the outcomes in meta-analysis A as well as odds ratio (OR) and mean difference (MD) in meta-analysis B was calculated to determine the technical and clinical success rates, complications rate, hospital stay, and recurrence rate. ROBINS-I tool was used to assess the risk of bias. RESULTS: The literature search retrieved 610 articles, 25 of which were eligible for inclusion. Included clinical studies comprised reports on 695 patients. Twenty-five studies (477 patients) were included in meta-analysis A and eight studies (356 patients) were included in meta-analysis B. In meta-analysis A, the technical and clinical success rates of EUSD were 94% and 87%, respectively, with post-procedural complications of 14% and recurrence rates of 9%. Meta-analysis B showed comparable technical and clinical success rates as well as complications rates between EUSD and PCD. EUSD showed significantly shorter duration of hospital stay compared to that of patients treated with PCD. CONCLUSION: EUSD seems to be associated with high technical and clinical success rates, with low rates of procedure-related complications. Although EUSD leads to shorter hospital stay compared to PCD, the certainty of evidence was low in this regard.

Portuguese Pancreatic Club Perspective on the Surveillance Strategy for Pancreatic Neuroendocrine Tumours: When and How to Do It?

Background: Pancreatic neuroendocrine tumours (pNETs) are a highly heterogeneous group of tumours with widely variable biological behaviour. The incidence of pNETs has risen exponentially over the last three decades, particularly for asymptomatic small pNETs (≤2 cm), due to the widespread use of cross-sectional imaging in clinical practice. Summary: Current consensus guidelines suggest that incidentally discovered pNETs ≤2 cm can be selectively followed due to the overall low risk of malignancy. Nevertheless, the "watch-and-wait" management strategy for small asymptomatic pNETs is still not widely accepted due to the lack of long-term data on the natural history of these small lesions. Additionally, it is clear that a subset of small pNETs may show malignant behaviour. Key Message: Given the non-negligible risk of malignancy even in small pNETs, it is of the utmost importance to identify other preoperative factors, other than size, that may help to stratify the risk of malignant behaviour and guide clinical management. In this article, the Portuguese Pancreatic Club reviews the importance of risk stratification of pNETs and presents an updated perspective on the surveillance strategy for sporadic well-differentiated pNETs.

Contexto: Os tumores neuroendócrinos do pâncreas (pNETs) correspondem a um grupo heterogéneo de tumores com comportamento biológico variável. A sua incidência aumentou exponencialmente nas últimas três décadas, particularmente à custa do diagnóstico incidental de pNETs de reduzidas dimensões (≤2 cm) devido à utilização crescente de exames de imagem seccional na prática clínica. Sumário: As normas de consenso internacionais sugerem que os pNETs ≤2 cm poderão ser seletivamente vigiados, dado o seu baixo risco global de comportamento maligno. No entanto, a estratégia proposta de "watch and wait" na abordagem dos pNETs assintomáticos ≤2cm não tem sido amplamente aceite devido à ausência de dados a longo-prazo relativos à sua história natural. Adicionalmente, é hoje evidente que um subgrupo destes pequenos tumores poderá apresentar comportamento maligno. Mensagens Chave: Dado o risco não desprezível de agressividade biológica mesmo nos pNETs incidentais de reduzidas dimensões, torna-se essencial identificar fatores pré-operatórios, para além da dimensão do tumor, que permitam estratificar o seu risco de malignidade e guiar a abordagem clínica. No presente artigo o Clube Português de Pâncreas apresenta uma perspectiva atual sobre a estratificação do risco e a estratégia a adoptar na vigilância dos pNETs esporádicos bem-diferenciados.

Portuguese Pancreatic Club Perspectives on Endoscopic Ultrasound-Guided and Surgical Treatment of Pancreatic Neuroendocrine Tumors.

Pancreatic neuroendocrine tumors (panNETs) are a group of neoplasms with heterogenous biological and clinical phenotypes. Although historically regarded as rare, the incidence of these tumors has been increasing, mostly owing to improvements in the detection of small, asymptomatic tumors with imaging. The heterogeneity of these lesions creates significant challenges regarding diagnosis, staging, and treatment. Endoscopic ultrasound (EUS) has improved the characterization of pancreatic lesions. Furthermore, EUS nowadays has evolved from a purely diagnostic modality to allow the performance of minimally invasive locoregional therapy for pancreatic focal lesions. The choice of treatment as well as the treatment goals depend on several factors, including tumor secretory status, grading, staging, and patient performance status. Surgery has been the mainstay for the management of these patients, particularly for localized, low-grade, large panNETs >2 cm. Over the last decade, a significant body of evidence has been accumulated evaluating the role of EUS for the ablative therapy of panNETs, namely by the use of chemoablative agents and radiofrequency. Although endoscopic techniques are not routinely recommended by international guidelines, they may be considered for the treatment of smaller lesions in patients who are unwilling or unfit for pancreatic surgery. In this review, we summarize the existing evidence on the interventional techniques for the treatment of patients with panNETs, focusing on the EUS-guided and surgical approaches.

Os tumores neuroendócrinos do pâncreas (panNETs) são um grupo de neoplasias com comportamento biológico e clínico heterogéneo. Embora historicamente considerados raros, a incidência desses tumores tem aumentado, algo que se atribui principalmente à melhoria na deteção de pequenos tumores assintomáticos em exames de imagem. A heterogeneidade destas lesões cria desafios significativos no que respeita ao seu diagnóstico, estadiamento e tratamento. A ultrassonografia endoscópica melhorou a caracterização das lesões pancreáticas. Concomitantemente, a ultrassonografia endoscópica, para além da vertente diagnóstica, evoluiu no sentido do desenvolvimento de capacidades terapêuticas, permitindo a realização de terapêutica locorregional de lesões pancreáticas focais de forma minimamente invasiva.A seleção do tratamento, bem como a definição dos seus objetivos, depende de diversos fatores, incluindo a atividade secretora da neoplasia, a sua atividade mitótica, o estadiamento e o status funcional do doente. A cirurgia é considerada a pedra basilar do tratamento destes doentes, particularmente para panNETs localizados, de baixo grau, com >2 cm. Ao longo da última década foi gerado um conjunto significativo de evidência relativamente ao papel da ultrassonografia endoscópica na terapêutica ablativa dos panNETs, nomeadamente através da utilização de agentes quimioablativos e de radiofrequência. Embora as recomendações internacionais não recomendem a utilização rotineira destas técnicas para o tratamento dos panNETs, as mesmas podem ser consideradas no tratamento de lesões de menores dimensões em doentes que não desejem ou que sejam considerados inaptos para cirurgia pancreática. Esta revisão visa resumir a evidência existente relativa às técnicas de intervenção para o tratamento de pacientes com panNETs, com foco nas abordagens cirúrgica e guiada por ultrassonografia endoscópica.

Portuguese Pancreatic Club Perspectives on Pancreatic Neuroendocrine Neoplasms: Diagnosis and Staging, Associated Genetic Syndromes and Particularities of Their Clinical Approach.

Pancreatic neuroendocrine neoplasms (panNENs) have been historically regarded as rare, but their incidence has raised more than 6-fold over the last 3 decades, mostly owing to improvement in the detection of small asymptomatic tumours with imaging. Early detection and proper classification and staging are essential for the prognosis and management of panNENs. Histological evaluation is mandatory in all patients for the diagnosis of panNEN. Regarding localization and staging, multiphasic contrast-enhanced computer tomography is considered the imaging study of choice. Nevertheless, several other diagnostic modalities might present complementary information that can help in diagnosis and staging optimization: magnetic resonance imaging, somatostatin receptor imaging using positron emission tomography in combination with computed tomography (PET/CT), PET/CT with fluorodeoxyglucose (18F-FDG), and endoscopic ultrasound. Approximately 10% of panNENs are due to an inherited syndrome, which includes multiple endocrine neoplasia type 1, von Hippel-Lindau disease, neurofibromatosis type 1 (NF-1), tuberous sclerosis complex, and Mahvash disease. In this review, the Portuguese Pancreatic Club summarizes the classification, diagnosis, and staging of panNENs, with a focus on imaging studies. It also summarizes the characteristics and particularities of panNENs associated with inherited syndromes.

As neoplasias neuroendócrinas pancreáticas (panNENs) são historicamente consideradas raras, embora a sua incidência tenha aumentado mais de 6 vezes nas últimas três décadas, principalmente devido à otimização do diagnóstico de tumores pequenos e assintomáticos em exames de imagem. A deteção precoce, a classificação e o estadiamento adequados são essenciais para o prognóstico e abordagem dos panNENs. A avaliação histológica é obrigatória em todos os doentes para o diagnóstico de panNENs. Para a localização e estadiamento, ​​a TC multifásica com contraste é considerada o estudo de imagem de eleição. Contudo, várias outras modalidades diagnósticas podem apresentar informações complementares que podem auxiliar no diagnóstico e na otimização do estadiamento: ressonância magnética, PET/CT dos receptores da somatostatina, PET/CT [18F]FDG e ecoendoscopia. Aproximadamente 10% dos panNENs estão relacionados com síndromes hereditários, que incluem neoplasia endócrina múltipla tipo 1 (MEN1), doença de von Hippel-Lindau (VHL), neurofibromatose tipo 1 (NF1), complexo de esclerose tuberosa (TSC) e doença de Mahvash. Neste artigo, o Clube Português de Pâncreas aborda a classificação, diagnóstico e estadiamento de panNENs, ​​com foco nos estudos de imagem, bem como resume as características e particularidades dos panNENs associados aos síndromes hereditários.

Candy cane syndrome: A systematic review.

BACKGROUND: Candy cane syndrome (CCS) is a condition that occurs following gastrectomy or gastric bypass. CCS remains underrecognized, yet its prevalence is likely to rise due to the obesity epidemic and increased use of bariatric surgery. No previous literature review on this subject has been published. AIM: To collate the current knowledge on CCS. METHODS: A literature search was conducted with PubMed and Google Scholar for studies from May 2007, until March 2023. The bibliographies of the retrieved articles were manually searched for additional relevant articles. RESULTS: Twenty-one articles were identified (135 patients). Abdominal pain, nausea/vomiting, and reflux were the most reported symptoms. Upper gastrointestinal (GI) series and endoscopy were performed for diagnosis. Surgical resection of the blind limb was performed in 13 studies with resolution of symptoms in 73%-100%. In surgical series, 9 complications were reported with no mortality. One study reported the surgical construction of a jejunal pouch with clinical success. Six studies described endoscopic approaches with 100% clinical success and no complications. In one case report, endoscopic dilation did not improve the patient's symptoms. CONCLUSION: CCS remains underrecognized due to lack of knowledge about this condition. The growth of the obesity epidemic worldwide and the increase in bariatric surgery are likely to increase its prevalence. CCS can be prevented if an elongated blind loop is avoided or if a jejunal pouch is constructed after total gastrectomy. Diagnosis should be based on symptoms, endoscopy, and upper GI series. Blind loop resection is curative but complex and associated with significant complications. Endoscopic management using different approaches to divert flow is effective and should be further explored.

Mediastinal Abscess Formation after EUS-Guided Sampling in a Young Patient with Sarcoidosis: Be Aware of the Increased Risk!

International guidelines establish EUS-guided sampling as safe and accurate for the evaluation of mediastinal solid lesions, such as lymphadenopathies of unknown origin, and point out an increased risk of severe infectious complications induced by needle puncture in mediastinal cystic lesions. A retrospective case series and a systematic review documented an increased risk of mediastinal abscess formation after EUS-guided lymph nodes sampling in patients with sarcoidosis. The authors describe a case of a 38-year-old male patient with a final diagnosis of sarcoidosis, who developed a large mediastinal abscess after EUS-guided fine-needle biopsy of mediastinal lymphadenopathies. Endoscopists should be aware of the potential increased risk of severe infectious complications when sampling mediastinal lymph nodes in suspected sarcoidosis, and a strategy to minimize such risk should be pursued.

As normas de consenso internacionais estabelecem a biopsia guiada por ecoendoscopia como segura e precisa no diagnóstico de lesões sólidas do mediastino, tais como adenopatias de origem indeterminada, e sublinham o risco significativo de complicações infecciosas graves associado à punção de lesões mediastínicas quísticas. Uma série retrospectiva e uma revisão sistemática apontaram para um risco aumentado de abcesso mediastínico após punção guiada por ecoendoscopia de gânglios linfáticos em doentes com sarcoidose. Os autores descrevem o caso cínico de um jovem de 38 anos, com o diagnóstico final de sarcoidose, que desenvolveu um volumoso abcesso mediastínico após biopsia guiada por ecoendoscopia de adenopatias mediastínicas. Os endoscopistas deverão reconhecer o risco aumentado de complicações infeciosas graves aquando da punção de adenopatias mediastínicas na suspeita de sarcoidose e procurar definir uma estratégia preventiva para minimizar o referido risco.

Pilot study of an endoluminal-suturing device as a treatment for patients with gastroesophageal reflux disease.

Background and study aims Endoscopic therapy is a promising option for patients with gastroesophageal reflux disease (GERD). The aim of this study was to assess safety and feasibility of the Endomina suturing platform as a treatment for GERD. Patients and methods This was a two-center study of patients with chronic GERD symptoms that responded at least partially to proton pump inhibitors (PPIs). Primary endpoints were to assess the safety of the procedure and persistence of the sutures. Secondary endpoints were to assess esophageal pH-impedance and manometry parameters changes at 6 months, as well as GERD symptoms and PPI use up to 12 months of follow-up. Results Fourteen patients were treated (13 males, mean of 43±12 years), with a mean number of three plications per patient. Thirteen, 10, and nine patients were analyzed at 3, 6, and 12 months of follow-up, respectively. One device-related adverse event occurred (loss of needle tip requiring endoscopic retrieval 1 week later). A mean of two plications persisted at 3 and 12 months. A decrease in median acid exposure time and reflux episodes was observed after the procedure. Mean Reflux Symptom Index and GERD-Health-Related Quality of Life scores decreased during follow-up visits and 90% of the patients discontinued PPI use at 1 year. Conclusions Endoscopic full-thickness suturing of the esophagogastric junction with the Endomina suturing platform is feasible, allowing persistence of two-thirds of the plications, with promising results for decreasing reflux and improving GERD symptoms.

A comparison of the temporary placement of 3 different self-expanding stents for the treatment of refractory benign esophageal strictures: a prospective multicentre study.

BACKGROUND: Refractory benign esophageal strictures (RBESs) have been treated with the temporary placement of different self-expanding stents with conflicting results. We compared the clinical effectiveness of 3 types of stents: self-expanding plastic stents (SEPSs), biodegradable stents, and fully covered self-expanding metal stents (FCSEMSs), for the treatment of RBES. METHODS: This study prospectively evaluated 3 groups of 30 consecutive patients with RBESs who underwent temporary placement of either SEPSs (12 weeks, n = 10), biodegradable stents (n = 10) or FCSEMSs (12 weeks, n = 10). Data were collected to analyze the technical success and clinical outcome of the stents as evaluated by recurrent dysphagia, complications and reinterventions. RESULTS: Stent implantation was technically successful in all patients. Migration occurred in 11 patients: 6 (60%) in the SEPS group, 2 (20%) in the biodegradable group and 3 (30%) in the FCSEMS group (P = 0.16). A total of 8/30 patients (26.6%) were dysphagia-free after the end of follow-up: 1 (10%) in the SEPS group, 3 (30%) in the biodegradable group and 4 (40%) in the FCSEMS group (P = 0.27). More reinterventions were required in the SEPS group (n = 24) than in the biodegradable group (n = 13) or the FCSEMS group (n = 13) (P = 0.24). Multivariate analysis showed that stricture length was significantly associated with higher recurrence rates after temporary stent placement (HR = 1.37; 95% CI = 1.08-1.75; P = 0.011). CONCLUSIONS: Temporary placement of a biodegradable stent or of a FCSEMS in patients with RBES may lead to long-term relief of dysphagia in 30 and 40% of patients, respectively. The use of SEPSs seems least preferable, as they are associated with frequent stent migration, more reinterventions and few cases of long-term improvement. Additionally, longer strictures were associated with a higher risk of recurrence.

Endoscopic Management of Symptomatic Duodenal Duplication Cysts: Two Case Reports.

Background: Duodenal duplication cysts (DDCs) are rare congenital anomalies typically manifesting during childhood. Clinical manifestations are uncommon in adulthood. DDCs were classically treated surgically, but endoscopic treatment has been increasingly reported. Endoscopic cyst marsupialization establishes a communication between the cyst cavity and the duodenal lumen so that the cystic content can be drained continuously into the duodenum. We herein describe two cases of symptomatic DDCs diagnosed in adulthood and submitted to endoscopic marsupialization using different techniques and devices. Case Summary: Case 1: A 23-year-old female patient was admitted with the diagnosis of acute pancreatitis. Endoscopic ultrasound revealed a 35-mm duodenal subepithelial lesion whose proximal limit was immediately distal to the ampulla of Vater and filled with fluid and calcifications. Using a duodenoscope, deroofing of the lesion was made with a diathermic snare. Pathology confirmed the diagnosis of DDC. Case 2: A 41-year-old female, submitted to laparoscopic cholecystectomy 1 month earlier due to suspected lithiasic acute pancreatitis, was admitted due to suspicion of iatrogenic biliary fistula. An endoscopic retrograde cholangiopancreatography was performed and the bile leak was treated. Immediately distal to the papillary orifice, a 20-mm subepithelial lesion was also detected. A biopsy forceps was used to fenestrate its wall, allowing the exit of mucous fluid and stones, and a sphincterotome was used to expand the incision. No recurrence was documented in both cases. Conclusion: These cases highlight DDC as a potential cause for acute pancreatitis in adults and endoscopy as an easy treatment option.

Introdução: Os quistos de duplicação duodenais (QDD) são anomalias congénitas raras que tipicamente se manifestam durante a infância. As manifestações clínicas são pouco frequentes em adultos. Os QDD eram classicamente tratados cirurgicamente, mas o tratamento endoscópico tem sido crescentemente reportado. A marsupialização endoscópica do quisto estabelece uma comunicação entre a cavidade do quisto e o lúmen duodenal, permitindo que o conteúdo do quisto drene continuamente para o duodeno. Reportamos 2 casos de QDD diagnosticados em adultos e submetidos a marsupialização endoscópica, utilizando diferentes técnicas e dispositivos. Casos clínicos: Caso 1: Doente do sexo feminino, 23 anos, internada por pancreatite aguda. Por ecoendoscopia documentou-se lesão subepitelial duodenal com 35 mm com limite proximal imediatamente distal à ampola de Vater, preenchida por líquido e calcificações. Usando um duodenoscópio, foi feita marsupialização da lesão com ansa diatérmica. Histologia confirmou o diagnóstico de QDD. Caso 2: Doente do sexo feminino, 41 anos, submetida a colecistectomia laparoscópica 1 mês antes por suspeita de pancreatite aguda litiásica, foi internada por suspeita de fístula biliar iatrogénica. Por CPRE confirmouse fuga biliar que foi tratada. Imediatamente distal ao orifício papilar, foi também detetada uma lesão subepitelial com 20 mm. Uma pinça de biopsia foi usada para fenestrar a sua parede, permitindo a saída de fluido mucoso e cálculos e um esfincterótomo foi usado para expandir a incisão. Não se registou recorrência em nenhum dos casos. Conclusão: Estes casos destacam os QDD como causa potencial de pancreatite aguda em adultos e a endoscopia como possível opção terapêutica.

Endoscopic Reconstruction of an Oral Feeding Route Using a Rendezvous Approach.

Background: The approach to esophageal obstruction or discontinuity remains challenging and often involves complex reconstructive surgeries. The rendezvous endoscopic technique might be interesting in cases of complete esophageal obstruction. Case Presentation: Herein we describe a successful case of endoscopic recanalization of the esophageal lumen in a patient with a long-standing esophageal discontinuity resulting from several surgeries and chemoradiation for a squamous cell carcinoma of the hypopharynx, ending in a major cervical amputation, construction of a neopharynx, and definitive surgical closure of the superior esophagus with a PEG placement. With a rendezvous technique (peroral and through the gastrostomy) and under radiographic guidance, puncture from the neopharynx into the distal esophagus was performed, followed by balloon dilation and covered metal stent placement in order to reconstruct a neoesophagus. Five weeks later, the stent was removed (using a stent-in-stent technique). No complications occurred. The patient has been able to eat soft food and is being kept under regular endoscopic surveillance to control/treat a luminal stenosis of the neoesophagus. Conclusions: This case report illustrates a successful endoscopic treatment of post-surgical complete esophageal obstruction. This approach should be considered in the therapeutic armamentarium of these difficult clinical settings.

Introdução: A abordagem da descontinuidade esofágica permanece desafiante e frequentemente envolve cirurgias reconstrutivas complexas. A técnica endoscópica de rendez-vous pode ser interessante em casos de obstrução esofágica completa. Apresentação do caso: Descrevemos um caso de sucesso de recanalização endoscópica do lúmen esofágico de um doente com descontinuidade esofágica de longa duração, em resultado de múltiplas cirurgias e quimioradiação por um carcinoma pavimento-celular da hipofaringe, que resultou numa amputação cervical major, construção de uma neofaringe e encerramento cirúrgico definitivo do esófago com colocação de PEG. Por técnica de rendez-vous (peroral e por gastrostomia) e sob apoio radiológico, foi realizada punção da neofaringe, seguido de dilatação com balão e colocação de prótese metálica coberta para criar um neo-esófago. Cinco semanas depois, a prótese foi removida (por técnica stent-in-stent). Não ocorreram complicações. O doente tem mantido capacidade de ingerir comida pastosa e é submetido a vigilância regular endoscópica para controlar/tratar uma estenose do lúmen do neo-esófago. Conclusão: Este caso ilustra o tratamento endoscópico bem-sucedido de um doente com obstrução pós-cirúrgica completa do esófago. Esta abordagem deverá ser considerada no arsenal terapêutico destes quadros clínicos complexos.

Zebrafish Avatars of rectal cancer patients validate the radiosensitive effect of metformin.

Neoadjuvant chemoradiation (nCRT) followed by surgery represents the standard of care in patients with locally advanced rectal cancer. Increasing radiotherapy (RT) doses and chemotherapy cycles with 5FU have been associated with increased rates of complete response, however these strategies imply significant toxicity. In the last years, epidemiologic findings have demonstrated that metformin is associated with significantly higher rates of pathological complete response to nCRT. Also, pre-clinical studies using cell lines provide evidence for the radiosensitive effect of metformin. However, no studies have been performed using rectal cancer patient samples to test this radiosensitive effect of metformin and compared it to the standard 5FU. Here, we designed an experimental study to compare both radiosensitizers in the zebrafish xenograft model (zAvatar), using rectal cancer surgical specimens and diagnostic biopsies. Patient zAvatars confirmed that metformin has indeed a powerful in vivo radiosensitizer effect, similar to 5FU. Our work confirms that metformin constitutes a promising less toxic alternative to the standard 5FU, which could be game changing in elderly/frail patients to optimize tumor regression.

Efficacy of Technical Modifications to the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) Procedure: A Systematic Review and Meta-Analysis.

To compare the outcomes of modified-Associating Liver Partition and Portal vein Ligation for Staged hepatectomy (ALPPS) techniques with those of conventional-ALPPS. Background: ALPPS is an established technique for treating advanced liver tumors. Methods: PubMed, Web of Science, and Cochrane databases were searched. The outcomes were assessed by single-arm and 2-arm analyses. Results: Seventeen studies containing 335 modified-ALPPS patients were included in single-arm meta-analysis. The estimated blood loss was 267 ± 29 mL (95% confidence interval [CI], 210-324 mL) during the first and 662 ± 51 mL (95% CI, 562-762 mL) during the second stage. The operation time was 166 ± 18 minutes (95% CI, 131-202 minutes) during the first and 225 ± 19 minutes (95% CI, 188-263 minutes) during the second stage. The major morbidity rate was 14% (95% CI, 9%-22%) after the first stage. The future liver remnant hypertrophy rate was 65.2% ± 5% (95% CI, 55%-75%) and the interstage interval was 16 ± 1 days (95% CI, 14-17 days). The dropout rate was 9% (95% CI, 5%-15%). The overall complication rate was 46% (95% CI, 37%-56%) and the major complication rate was 20% (95% CI, 14%-26%). The postoperative mortality rate was 7% (95% CI, 4%-11%). Seven studies containing 215 patients were included in comparative analysis. The hypertrophy rate was not different between 2 methods (mean difference [MD], -5.01; 95% CI, -19.16 to 9.14; P = 0.49). The interstage interval was shorter for partial-ALPPS (MD, 9.43; 95% CI, 3.29-15.58; P = 0.003). The overall complication rate (odds ratio [OR], 10.10; 95% CI, 2.11-48.35; P = 0.004) and mortality rate (OR, 3.74; 95% CI, 1.36-10.26; P = 0.01) were higher in the conventional-ALPPS. Conclusions: The hypertrophy rate in partial-ALPPS was similar to conventional-ALPPS. This shows that minimizing the first stage of the operation does not affect hypertrophy. Moreover, the postoperative overall morbidity and mortality rates were lower following partial-ALPPS.

Endoscopic Treatment of Post-Cholecystectomy Biliary Leaks.

Postcholecystectomy leaks may occur in 0.3-2.7% of patients. Bile leaks associated with laparoscopy are often more complex and difficult to treat than those occurring after open cholecystectomy. Furthermore, their incidence has remained unchanged despite improvements in laparoscopic training and technological developments. The management of biliary leaks has evolved from surgery into a minimally invasive endoscopic procedural approach, namely, endoscopic retrograde cholangiopancreatography (ERCP), which decreases or eliminates the pressure gradient between the bile duct and the duodenum, thus creating a preferential transpapillary bile flow and allowing the leak to seal. For simple leaks, the success rate of endotherapy is remarkably high. However, there are more severe and complex leaks that require multiple endoscopic interventions, and clear strategies for endoscopic treatment have not emerged. Therefore, there is still some debate regarding the optimal time point at which to intervene, which technique to use (sphincterotomy alone or in association with the placement of stents, whether metallic or plastic stents should be used, and, if plastic stents are used, whether they should be single or multiple), how long the stents should remain in place, and when to consider treatment failure. Here, we review the types and classification of postoperative biliary injuries, particularly leaks, as well as the evidence for endoscopic treatment of the latter.

As fugas biliares pós colecistectomia podem ocorrer em 0,3 a 2,7% dos casos, sendo frequentemente mais complexas e difíceis de tratar quando comparamos as lesões provocadas pela abordagem laparoscópica versus cirurgia clássica. Associadamente a sua incidência não tem diminuído apesar da melhoria do treino em laparoscopia e do desenvolvimento tecnológico. O tratamento das fugas biliares evoluiu da cirurgia para a endoscopia permitindo, através da colangiopancreatografia retrógrada endoscópica (CPRE), executar vários procedimentos que têm como objetivo divergir preferencialmente o fluxo biliar através da papila para o duodeno e assim reduzir ou eliminar a pressão no sistema biliar, eliminando o fluxo de bílis através da perfuração e criando condições para o seu encerramento. Para fugas simples a taxa de sucesso da CPRE é muito elevada. Contudo, existem fugas mais graves e complexas com necessidade de múltiplas intervenções, não estando definidas estratégias claras para o tratamento endoscópico, persistindo alguma discussão em relação ao timing ideal para intervir, à melhor técnica a utilizar (esfincterotomia isolada ou associada à colocação de próteses biliares, se estas devem ser metálicas ou plásticas e, neste ultimo caso, se únicas ou múltiplas), ao período de tempo em que devem permanecer as próteses biliares, e quando assumir a falência do tratamento. Neste artigo iremos rever os tipos e a classificação das lesões pós-cirúrgicas das vias biliares, nomeadamente das fugas, assim como a evidência para o tratamento endoscópico destas últimas.

The Role of Endoscopic Ultrasound in Pancreatic Cancer Staging in the Era of Neoadjuvant Therapy and Personalised Medicine.

Precise staging of pancreatic cancer is crucial for treatment choice. In clinical practice, this includes the TNM staging and determination of tumour resectability, based on a multimodality imaging workup. International guidelines recommend multi-detector computed tomography (CT), with a dedicated pancreatic protocol, as the first-line tool for TNM staging and evaluation of tumour-vessel relationships. In non-metastatic disease upon initial CT assessment, both magnetic resonance imaging and endoscopic ultrasound (EUS) may add relevant information, potentially changing treatment sequence. EUS may have distinct advantages in pancreatic cancer diagnosis and staging when compared with other modalities, being particularly valuable in the determination of portal venous confluence involvement (particularly in small and ill-defined/isoattenuating tumours on CT), in locoregional nodal staging and in the detection of ascites. As we step forward to a more frequent use of neoadjuvant chemotherapy and to personalised medicine, the importance of EUS-guided fine-needle biopsy (EUS-FNB) also increases. The recent availability of third-generation biopsy needles significantly increased the diagnostic yield of EUS-guided tissue acquisition, providing diagnostic cell blocks in approximately 95% of cases with only two dedicated passes and allowing ancillary testing, such as immunohistochemistry and molecular profiling of the tumour. In this article, the authors present an updated perspective of the place of EUS and EUS-FNB in the staging algorithm of pancreatic cancer. Data supporting the increasing role of neoadjuvant therapy and the importance of a patient-tailored treatment selection, based on tumoural subtyping and molecular profiling, are also discussed.

No cancro do pâncreas é fundamental um estadiamento preciso para a decisão terapéutica. Na prática clínica, istoinclui o estadiamento TNM e a avahação da ressecabilidade cirúrgica, baseada numa avahação imagiológica multimodal. As recomendações de consenso recomendam a tomografia computorizada (TC) multi-detector, com protocolo pancreático, como exame de primeira linha para o estadiamento TNM e determinação de invasão vascular loco-regional. Na doença loco-regional não-metastática (após TC inicial), a ressonância magnética e a ecoendoscopia poderão acrescentar informação relevante, com potencial impacto na decisão terapéutica. A ecoendoscopia apresenta vantagens únicas comparativamente a outros métodos de estadiamento, sendo particularmente útil na avahação da relação do tumor com a confluência espleno-portal (especialmente na presença de tumores pequenos e isodensos/mal-definidos na TC), no estadiamento ganglionar loco-regional (N) e na detecção de ascite. À medida que caminhamos no sentido da utilização crescente de quimioterapia neoadjuvante e da Medicina personalizada, a relevância da biopsia guiada por ecoendoscopia também aumenta. A recente disponibilização de agulhas de biopsia de terceira geração aumentou significativamente a rentabilidade diagnóstica da punção guiada por ecoendoscopia, obtendo cell-blocks para avahado histológica em cerca de 95% dos casos (com apenas duas passagens), permitindo a realização de estudos ancilares, como avahação imuno-histoquímica e caracterização molecular do tumor. No presente artigo os autores apresentam uma perspetiva do papel atual da ecoendoscopia e da biopsia guiada por ecoendoscopia no algoritmo de estadiamento do cancro do páncreas. É ainda analisada a evidência atual que favorece o papel crescente da terapéutica neoadjuvante e a importância da seleção individualizada do tratamento, baseada na definição do subtipo de tumor e na caracterizado molecular.

The Impact of Recent Advances in Endoscopic Ultrasound-Guided Tissue Acquisition on the Management of Pancreatic Cancer.

Over the last few decades, endoscopic ultrasound (EUS)-guided tissue acquisition has become the method of choice for the pathological diagnosis of solid pancreatic lesions. Due to its high diagnostic yield and low complication rate, EUS-guided tissue acquisition has surpassed percutaneous sampling techniques. For many years, EUS-guided fine-needle aspiration (EUS-FNA) was traditionally used to obtain cytological aspirates of solid pancreatic lesions, with sensitivity values ranging from 80 to 90% for the diagnosis of malignancy. Nevertheless, despite numerous technical advances, EUS-FNA still presents some limitations. Therefore, EUS-guided fine-needle biopsy (EUS-FNB) has been introduced to provide tissue core biopsies, allowing histological assessment. A newly developed generation of FNB needles has demonstrated an outstanding diagnostic accuracy of over 95% for solid pancreatic lesions and provides samples appropriate for ancillary testing, such as immunohistochemistry and tumour molecular profiling. As a result, EUS-FNB is rapidly replacing EUS-FNA and is now the recommended technique for EUS-guided tissue acquisition in pancreatic cancer. Furthermore, with the recent expansion of neoadjuvant treatment criteria and with the advent of novel and personalised anti-cancer therapies, EUS-FNB is gaining a pivotal role in pancreatic cancer management and might soon be generalised to all patients, independent of disease stage. In this article, the authors present an updated review of the role of EUS-guided tissue acquisition in pancreatic cancer. Current indications, several technical aspects and new applications of EUS-FNA and EUS-FNB are discussed.

Nas últimas décadas, a aquisição de tecido por ecoendoscopia tornou-se o método de eleição para o diagnóstico patológico de lesões sólidas do pâncreas. Devido à sua elevada capacidade diagnóstica e baixa taxa de complicações, a aquisição de tecido por ecoendoscopia ultrapassou as técnicas de biópsia por via percutânea. Durante muito anos, a aspiração com agulha fina guiada por ecoendoscopia (EUS-FNA) foi tradicionalmente usada para obter aspirados citológicos de lesões sólidas do pâncreas, com valores de sensibilidade que variam entre os 80% e os 90% no diagnóstico de malignidade. Contudo, apesar de numerosos avanços técnicos, a EUS-FNA apresenta ainda algumas limitações. Assim, a biópsia com agulha fina guiada por ecoendoscopia (EUS-FNB) foi introduzida para obter biópsias com cores de tecido, permitindo avaliação histológica. Uma nova geração de agulhas de FNB recentemente desenvolvida demonstra uma acuidade diagnóstica excecional acima de 95% nas lesões sólidas do pâncreas e obtém amostras adequadas para estudos ancilares, designadamente imunohistoquímica e caracterização molecular tumoral. Por conseguinte, a EUS-FNB está rapidamente a substituir a EUS-FNA e é hoje a técnica recomendada para aquisição de tecido no cancro do pâncreas. Além disso, com a recente expansão dos critérios para tratamento neoadjuvante e com o advento de terapias anti-tumorais novas e personalizadas, a EUS-FNB está a adquirir um papel essencial na abordagem do cancro do pâncreas e poderá em breve ser generalizada a todos os doentes, independentemente do estádio da doença. Neste artigo, os autores apresentam uma revisão atualizada do papel da aquisição de tecido por ecoendoscopia no cancro do pâncreas. As indicações atuais, vários aspetos técnicos e novas aplicações da EUS-FNA e EUS-FNB são discutidos.

Developments in zebrafish avatars as radiotherapy sensitivity reporters - towards personalized medicine.

BACKGROUND: Whereas the role of neoadjuvant radiotherapy in rectal cancer is well-established, the ability to discriminate between radioresistant and radiosensitive tumors before starting treatment is still a crucial unmet need. Here we aimed to develop an in vivo test to directly challenge living cancer cells to radiotherapy, using zebrafish xenografts. METHODS: We generated zebrafish xenografts using colorectal cancer cell lines and patient biopsies without in vitro passaging, and developed a fast radiotherapy protocol consisting of a single dose of 25 Gy. As readouts of the impact of radiotherapy we analyzed proliferation, apoptosis, tumor size and DNA damage. FINDINGS: By directly comparing isogenic cells that only differ in the KRASG13D allele, we show that it is possible to distinguish radiosensitive from radioresistant tumors in zebrafish xenografts, even in polyclonal tumors, in just 4 days. Most importantly, we performed proof-of-concept experiments using primary rectum biopsies, where clinical response to neoadjuvant chemoradiotherapy correlates with induction of apoptosis in their matching zebrafish Patient-Derived Xenografts-Avatars. INTERPRETATION: Our work opens the possibility to predict tumor responses to radiotherapy using the zebrafish Avatar model, sparing valuable therapeutic time and unnecessary toxicity.