The Role of Probe-Based Confocal Laser Endomicroscopy (pCLE) in the Diagnosis of Sustained Clinical Complete Response Under Watch-and-Wait Strategy After Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Adenocarcinoma: a Score Validation.

BACKGROUND: Watch-and-wait strategy has been increasingly accepted for patients with clinical complete response (cCR) after multimodal treatment for locally advanced rectal adenocarcinoma. Close follow-up is essential to the early detection of local regrowth. It was previously demonstrated that probe-based confocal laser endomicroscopy (pCLE) scoring using the combination of epithelial and vascular features might improve the diagnostic accuracy of cCR. AIM: To validate the pCLE scoring system in the assessment of patients with cCR after neoadjuvant chemoradiotherapy (nCRxt) for advanced rectal adenocarcinoma. METHODS: Digital rectal examination, pelvic magnetic resonance imaging (MRI), and pCLE were performed in 43 patients with cCR, who presented either a scar (N = 33; 76.7%) or a small ulcer with no signs of tumor, and/or biopsy negative for malignancy (N = 10; 23.3%). RESULTS: Twenty-five (58.1%) patients were men, and the mean age was 58.4 years. During the follow-up, 12/43 (27.9%) patients presented local regrowth and underwent salvage surgery. There was an association between pCLE diagnostic scoring and final histological report (for patients who underwent surgical resection) or final diagnosis at the latest follow-up (p = 0.0001), while this association was not observed with MRI (p = 0.49). pCLE sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 66.7%, 93.5%, 80%, 88.9%, and 86%, respectively. MRI sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 66.7%, 48.4%, 66.7%, 78.9%, and 53.5%, respectively. CONCLUSIONS: pCLE scoring system based on epithelial and vascular features improved the diagnosis of sustained cCR and might be recommended during follow-up. pCLE might add some valuable contribution for identifying local regrowth. Trial Registration This protocol was registered at the Clinical Trials (ClinicalTrials.gov identifier NCT02284802).

Impact of radiotherapy on adverse events of self-expanding metallic stents in patients with esophageal cancer.

Self-expanding metallic stents (SEMS) are considered the treatment of choice for the palliation of dysphagia and fistulas in inoperable esophageal neoplasms. However, the safety of SEMSs in patients who received or who will be submitted to radiotherapy (RT) is uncertain. The study aimed to evaluate the impact of RT on adverse events (AEs) in patients with esophageal cancer with SEMSs. This is a retrospective study conducted at a tertiary cancer hospital from 2009 to 2018. We collected information regarding RT, the histological type of the tumor, the model of SEMSs and AEs after stent placement. Three hundred twenty-three patients with malignant stenosis or fistula were treated with SEMSs. The predominant histological type was squamous cell carcinoma (79.6%). A total of 282 partially covered and 41 fully covered SEMSs were inserted. Of the 323 patients, 182 did not received RT, 118 received RT before SEMS placement and 23 after. Comparing the group that received RT before stent insertion with the group that did not, the first one presented a higher frequency of severe pain (9/118 7.6% vs. 3/182 1.6%; P = 0.02). The group treated with RT after stent placement had a higher risk of global AEs (13/23 56.5% vs. 63/182 34.6%; P = 0.019), ingrowth/overgrowth (6/23 26.1% vs. 21/182 11.5%; P = 0.045) and gastroesophageal reflux (2/23 8.7% vs. 2/182 1.1%; P = 0.034). Treatment with RT before stent placement in patients with inoperable esophageal neoplasm prolongs survival and is associated with an increased risk of severe chest pain. Treatment with RT of patients with an esophageal stent increases the frequency of minor, not life-threatening AEs.

Underwater versus conventional EMR for nonpedunculated colorectal lesions: a randomized clinical trial.

BACKGROUND AND AIMS: Conventional endoscopic mucosal resection (CEMR) is the standard modality for removing nonpedunculated colorectal lesions. Underwater endoscopic mucosal resection (UEMR) has emerged as an alternative method. There are few comparative studies between these techniques, especially evaluating recurrence. Therefore, the purpose of this trial was to compare CEMR and UEMR for the resection of colorectal lesions with respect to efficacy, safety, and recurrence rate. METHODS: This was a randomized controlled trial of UEMR versus CEMR for naïve and nonpedunculated lesions measuring between 10 and 40 mm. The primary outcome was adenoma recurrence at 6 months after the resection. Secondary outcomes were rates of technical success, en bloc resection, and adverse events. Block randomization was used to assign patients. Tattooing was performed to facilitate localization of the scars and eventual recurrences. Endoscopic follow-up was scheduled at 6 months after the procedure. The sites of resections were examined with white-light imaging, narrow-band imaging (NBI), and conventional chromoscopy with indigo carmine followed by biopsies. RESULTS: One hundred five patients with 120 lesions were included, with a mean size of 17.5 ± 7.1 (SD) mm. Sixty-one lesions were resected by UEMR and 59 by CEMR. The groups were similar at baseline regarding age, sex, average size, and histologic type. Lesions in the proximal colon in the CEMR group corresponded to 83% and in the UEMR group to 67.8% (P = .073). There was no difference between groups regarding success rate (1 failure in each group) and en bloc resection rate (60.6% UEMR vs 54.2% CEMR, P = .48). Intraprocedural bleeding was observed in 5 CEMRs (8.5%) and 2 UEMRs (3.3%) (P = .27). There was no perforation or delayed hemorrhage in either groups. Recurrence rate was higher in the CEMR arm (15%) than in the UEMR arm (2%) (P = .031). Therefore, the relative risk of 6-month recurrence rate in the CEMR group was 7.5-fold higher (95% CI, 0.98-58.20), with a number needed to treat of 7.7 (95% CI, 40.33-4.22). The higher recurrence rate in the CEMR group persisted only for lesions measuring 21 to 40 mm (35.7% vs 0%; P = .04). CONCLUSION: This study demonstrated that UEMR was associated with a lower adenoma recurrence rate than was CEMR. Both endoscopic techniques were effective and had similar rates of adverse events for the treatment of nonpedunculated colorectal lesions.

UNDERWATER ENDOSCOPIC MUCOSAL RESECTION FOR SMALL RECTAL NEUROENDOCRINE TUMORS.

BACKGROUND: A common site of neuroendocrine tumors (NETs) is the rectum. The technique most often used is endoscopic mucosal resection with saline injection. However, deep margins are often difficult to obtain because submucosal invasion is common. Underwater endoscopic mucosal resection (UEMR) is a technique in which the bowel lumen is filled with water rather than air, precluding the need for submucosal lifting. OBJECTIVE: This study aimed to evaluate the efficacy and safety of UEMR for removing small rectal neuroendocrine tumors (rNETs). METHODS: Retrospective study with patients who underwent UEMR in two centers. UEMR was performed using a standard colonoscope. No submucosal injection was performed. Board-certified pathologists conducted histopathologic assessment. RESULTS: UEMR for small rNET was performed on 11 patients (nine female) with a mean age of 55.8 years and 11 lesions (mean size 7 mm, range 3-12 mm). There were 9 (81%) patients with G1 rNET and two patients with G2, and all tumors invaded the submucosa with only one restricted to the mucosa. None case showed vascular or perineural invasion. All lesions were removed en bloc. Nine (81%) resections had free margins. Two patients had deep margin involvement; one had negative biopsies via endoscopic surveillance, and the other was lost to follow-up. No perforations or delayed bleeding occurred. CONCLUSION: UEMR appeared to be an effective and safe alternative for treatment of small rNETs without adverse events and with high en bloc and R0 resection rates. Further prospective studies are needed to compare available endoscopic interventions and to elucidate the most appropriate endoscopic technique for resection of rNETs.

Ressecção endoscópica sob imersão d'água de pequenos tumores neuroendócrinos retais / Underwater endoscopic mucosal resection for small rectal neuroendocrine tumors

ABSTRACT BACKGROUND: A common site of neuroendocrine tumors (NETs) is the rectum. The technique most often used is endoscopic mucosal resection with saline injection. However, deep margins are often difficult to obtain because submucosal invasion is common. Underwater endoscopic mucosal resection (UEMR) is a technique in which the bowel lumen is filled with water rather than air, precluding the need for submucosal lifting. OBJECTIVE: This study aimed to evaluate the efficacy and safety of UEMR for removing small rectal neuroendocrine tumors (rNETs). METHODS: Retrospective study with patients who underwent UEMR in two centers. UEMR was performed using a standard colonoscope. No submucosal injection was performed. Board-certified pathologists conducted histopathologic assessment. RESULTS: UEMR for small rNET was performed on 11 patients (nine female) with a mean age of 55.8 years and 11 lesions (mean size 7 mm, range 3-12 mm). There were 9 (81%) patients with G1 rNET and two patients with G2, and all tumors invaded the submucosa with only one restricted to the mucosa. None case showed vascular or perineural invasion. All lesions were removed en bloc. Nine (81%) resections had free margins. Two patients had deep margin involvement; one had negative biopsies via endoscopic surveillance, and the other was lost to follow-up. No perforations or delayed bleeding occurred. CONCLUSION: UEMR appeared to be an effective and safe alternative for treatment of small rNETs without adverse events and with high en bloc and R0 resection rates. Further prospective studies are needed to compare available endoscopic interventions and to elucidate the most appropriate endoscopic technique for resection of rNETs.

RESUMO CONTEXTO: Um local comum de tumores neuroendócrinos (TNEs) é o reto. A técnica mais utilizada é a ressecção endoscópica da mucosa com injeção de solução salina. No entanto, as margens profundas costumam ser difíceis de ressecar porque a invasão da submucosa é comum. A ressecção endoscópica sob imersão d'água (RESI) é uma técnica em que o lúmen intestinal é preenchido com água em vez de ar, evitando a necessidade de elevação submucosa. OBJETIVO: Este estudo teve como objetivo avaliar a eficácia e segurança da RESI para a remoção de pequenos TNEs retais (rTNEs). MÉTODOS: Estudo retrospectivo com pacientes que realizaram RESI em dois centros. RESI foi realizada usando um colonoscópio padrão. Nenhuma injeção submucosa foi realizada. Patologistas certificados conduziram avaliação histopatológica. RESULTADOS: RESI foi realizada para pequenos rTNEs em 11 pacientes (nove mulheres) com média de idade de 55,8 anos e 11 lesões (tamanho médio de 7 mm, variando de 3-12 mm). Havia 9 (81%) pacientes com G1 rTNEs e dois pacientes com G2, sendo que todos os tumores invadiam a submucosa sendo apenas um restrito a mucosa. Nenhum caso mostrou invasão vascular ou perineural. Todas as lesões foram removidas em bloco. Nove (81%) ressecções tiveram margens livres. Dois pacientes tiveram envolvimento de margens profundas; um teve biópsias negativas por meio de vigilância endoscópica e o outro perdeu o acompanhamento. Não ocorreram perfurações ou sangramento tardios. CONCLUSÃO: A RESI parece ser uma alternativa eficaz e segura para o tratamento de pequenos rTNEs sem eventos adversos e com altas taxas de ressecção em bloco e R0. Mais estudos prospectivos são necessários para comparar as intervenções endoscópicas disponíveis e para elucidar a técnica endoscópica mais adequada para ressecção de rTNEs.

UNDERWATER ENDOSCOPIC MUCOSAL RESECTION FOR NON-PEDUNCULATED COLORECTAL LESIONS. A PROSPECTIVE SINGLE-ARM STUDY.

BACKGROUND: Underwater endoscopic mucosal resection (UEMR) has emerged as a revolutionary method allowing resection of colorectal lesions without submucosal injection. Brazilian literature about this technique is sparse. OBJECTIVE: The aim of this study was evaluate the efficacy and safety of UEMR technique for removing non-pedunculated colorectal lesions in two Brazilian tertiary centers. METHODS: This prospective study was conducted between June 2016 and May 2017. Naïve and non-pedunculated lesions without signs of submucosal invasion were resected using UEMR technique. RESULTS: A total of 55 patients with 65 lesions were included. All lesions, except one, were successfully and completely removed by UEMR (success rate 98.5%). During UEMR, two cases of bleeding were observed (3.0%). One patient had abdominal pain on the day after resection without pneumoperitoneum. There was no perforation or delayed bleeding. CONCLUSION: This study supports the existing data indicating acceptable rates of technical success, and low incidence of adverse events with UEMR. The results of this Brazilian study were consistent with previous abroad studies.

Probe-based confocal endomicroscopy is accurate for differentiating gastric lesions in patients in a Western center.

OBJECTIVE: Probe-based confocal laser endomicroscopy (pCLE) technique may improve the diagnosis of gastric mucosal lesions allowing acquisition of high-resolution in vivo images at the cellular and microvascular levels. This study aims to evaluate the accuracy of pCLE for the differential diagnosis of non-neoplastic and neoplastic gastric lesions. METHODS: Twenty gastric mucosal lesions from 10 patients were evaluated during endoscopic procedure and were examined by pCLE. Diagnostic pCLE was followed by biopsies or endoscopic resection of suspected lesions. A senior pathologist evaluated the specimens and was blinded to the pCLE results. RESULTS: Patients' mean age was 68.3 (range, 42-83) years and six were men. Thirteen suspicious flat or elevated lesions (classified as 0-Is, 0-IIa or 0-IIa + IIc) and seven pre-malignant lesions (atrophy and intestinal metaplasia) were evaluated. One patient was studied during his long-term follow-up after partial gastrectomy and presented severe atrophy, intestinal metaplasia, and xanthomas at the stump mucosa. The location of gastric lesions was in the body (n=10 lesions), the antrum (n=9) and the incisura angularis (n=1). All neoplastic lesions and all but one benign lesion were properly diagnosed by pCLE. pCLE incorrectly diagnosed one small antrum lesion as adenoma, however the final diagnosis was intestinal metaplasia. The final histological diagnosis was neoplastic in 9 and benign lesions in 11. In this small case series, pCLE accuracy was 95% (19/20 lesions). CONCLUSIONS: pCLE is accurate for real time histology of gastric lesions. pCLE may change the management of patients with gastric mucosal lesions, guiding biopsies and endoscopic resection, and avoiding further diagnostic workup or unnecessary therapy.

Comparison of the pull and introducer percutaneous endoscopic gastrostomy techniques in patients with head and neck cancer.

BACKGROUND AND STUDY AIMS: Percutaneous endoscopic gastrostomy (PEG) in head and neck cancer (HNC) patients is associated with higher complication and mortality rates when compared to a general patient population. The pull technique is still the preferred technique worldwide but it has some limitations. The aim of this study is to compare the pull and introducer PEG techniques in patients with HNC. PATIENTS AND METHODS: This study is based on a retrospective analysis of a prospectively collected database of 309 patients with HNC who underwent PEG in the Cancer Institute of São Paulo. RESULTS: The procedure was performed with the standard endoscope in 205 patients and the introducer technique was used in 137 patients. There was one procedure-related mortality. Age, sex and albumin level were similar in both groups. However in the introducer technique group, patients had a higher tumor stage, a lower Karnofsky status, and presented more frequently with tracheostomy and trismus. Overall, major, minor, immediate and late complications and 30-day mortality rates were similar but the introducer technique group presented more minor bleeding and tube dysfunctions. CONCLUSION: The push and introducer PEG techniques seem to be both safe and effective but present different complication profiles. The choice of PEG technique in patients with HNC should be made individually.

Argon plasma coagulation for the endoscopic treatment of gastrointestinal tumor bleeding: A retrospective comparison with a non-treated historical cohort.

BACKGROUND: The endoscopic use of argon plasma coagulation (APC) to achieve hemostasis for upper gastrointestinal tumor bleeding (UGITB) has not been adequately evaluated in controlled trials. This study aimed to evaluate the efficacy of APC for the treatment of upper gastrointestinal bleeding from malignant lesions. METHODS: Between January and September 2011, all patients with UGITB underwent high-potency APC therapy (up to 70 Watts). This group was compared with a historical cohort of patients admitted between January and December 2010, when the endoscopic treatment of bleeding malignancies was not routinely performed. Patients were stratified into two categories, grouping the Eastern Cooperative Oncology Group (ECOG) performance status scale: Category I (ECOG 0-2) patients with a good clinical status and Category II (ECOG 3-4) patients with a poor clinical status. RESULTS: Our study had 25 patients with UGITB whom underwent APC treatment and 28 patients whom received no endoscopic therapy. The clinical characteristics of the groups were similar, except for endoscopic active bleeding, which was more frequently detected in APC group. We had 15 patients in the APC group whom had active bleeding, and initial hemostasis was obtained in 11 of them (73.3%). In the control group, four patients had active bleeding. There were no differences in 30-day re-bleeding (33.3% in the APC group versus 14.3% in the control group; p = 0.104) and 30-day mortality rates (20.8% in the APC group, versus 42.9% in the control group; p = 0.091). When patients were categorized according to their ECOG status, we found that APC therapy had no impact in re-bleeding and mortality rates (Group I: APC versus no endoscopic treatment: re-bleeding p = 0.412, mortality p = 0.669; Group II: APC versus no endoscopic treatment: re-bleeding p = 0.505, mortality p = 0.580). Hematemesis and site of bleeding located at the esophagus or duodenum were associated with a higher 30-day mortality. CONCLUSIONS: Endoscopic hemostasis of UGITB with APC has no significant impact on 30-day re-bleeding and mortality rates, irrespective of patient performance status.

A new technique for performing endoscopic pyloromyotomy by gastric submucosal tunnel dissection.

AIM: To investigate the feasibility of a new endoscopic pyloromyotomy technique. MATERIALS AND METHODS: Endoscopic pyloromyotomy through a gastric submucosal tunnel was performed in 6 pigs. At the greater curvature, 2 cm proximal to the pylorus, we incised the mucosa and dissected the submucosal tunnel up to the pyloric ring. The pyloric muscular ring was sectioned, and then the gastric mucosal incision was closed with metallic clips. The pigs were then euthanized and necropsies were performed. RESULTS: Section of the pyloric ring was successful in all 6 pigs. Small perforations occurred in 2 of the pigs, and there was limited bleeding in 1 pig. Necropsy and histologic evaluation confirmed the pyloric section. CONCLUSIONS: This technique is feasible, easy to perform, and maybe alternative to pyloroplasty in selected cases. Experimental comparative studies with other techniques still must be performed.

Stents for benign and malignant esophageal strictures.

This paper presents commentaries on endotherapy for esophageal perforation/leaks; treatment of esophageal perforation; whether esophageal stents should be used for treating benign esophageal strictures; what determines the optimal stenting period in benign esophageal strictures/leaks; how to choose an esophageal stent; how a new fistula secondary to an esophageal stent should be treated; which strategy should be adopted when a fistula of a cervical anastomosis occurs; intralesional steroids for refractory esophageal strictures; balloon and bougie dilators for esophageal strictures and predictors of response to dilation; whether refractory strictures from different etiologies respond differently to endotherapy; surgical therapy of benign esophageal strictures; and whether stenoses following severe esophageal burns should be treated by esophageal resection or esophageal bypass.

Estesioneuroblastoma / Esthesioneuroblastoma

O estesioneuroblastoma é uma neoplasia maligna incomum, que tem origem no epitélio olfatório e corresponde de 4% a 6% dos tumores malignos dos seios paranasais. A última grande revisão sobre esses tumores mostra que, desde sua descoberta, há oitenta anos, menos de mil casos foram publicados na literatura mundial. As manifestações clínicas usuais constituem-se por anosmia, obstrução nasal e epistaxe. Devido às características microscópicas serem bastante variadas e inespecíficas, é importante que o diagnóstico seja bem estabelecido pela histoquímica e imunoistoquímica, pois disso dependerá o prognóstico do paciente. Por se tratar de uma doença rara, ainda não há consenso quanto ao melhor tipo de tratamento, mas os relatos de casos bem sucedidos incluíram tratamento multidisciplinar com quimioterapia, ressecção cirúrgica e radioterapia. Em um período de seis anos (janeiro/ 2000 a janeiro/2006), ocorreram quatro casos no serviço do Hospital e Maternidade Celso Pierro, que são aqui reportados

Esthesioneuroblastoma is an uncommon malignant neoplasm that arises from the olfactory epithelium and corresponds to 4% - 6% of all malignant tumors in the paranasal sinuses. The last extensive review on these tumors reveals that less than one thousand cases have been published in the literature since its discovery eighty years ago. The common clinical manifestations are anosmia, nasal obstruction and epistaxis. Since its microscopic characteristics vary greatly and are unspecific, a precise diagnosis using histochemical and immunohistochemical techniques cannot be overemphasized as the patient?s prognosis depends on the diagnosis. As it is a rare disease, there is no consensus regarding the best treatment, but reports of cases treated successfully cite a multidisciplinary approach, which includes chemotherapy, surgical resection and radiation therapy. Our service has treated four cases over a period of six years (January 2000 - January 2006) that are reported here