Uncharted Territory: Frequent Relapsing, Steroid Sensitive Secondary Minimal Change Nephrotic Syndrome Cause by Solid Tumor of the Gastro-Esophageal Junction —(Case Presentation and Review of the Literature)

We reported a biopsy proved case of minimal change nephrotic syndrome in a 72-year-old patient. The minimal change nephrotic syndrome has been steroid sensitive, but the patient had 7 relapses over a span of 5 years. Each time the dose of steroid is tapered, a relapse of the nephrotic syndrome occurred. Eventually, the patient was complaining of dysphagia and difficulty swallowing. Hospital work-up with barium swallow, endoscopy, and CT of the chest, abdomen and pelvis, revealed a focal stenotic lesion with mild to moderate esophageal dysmotility 7/15/2022. A diagnosis of an ulcerating lesion with biopsy confirmed a neuro-endocrine carcinoma of the gastro-esophageal junction was entertained. The CT of the chest/abdomen/pelvis, 7/19/2022, has shown, an esophageal mass of 5.1 × 5.6 × 7 cm of the gastro-esophageal junction with ulceration. No evidence of spread beyond the esophagus and stomach. The histology revealed a poorly differentiated neuroendocrine tumor of the gastro-esophageal junction. The patient underwent several rounds of chemotherapy, radiation, and surgery culminating in tumor control. His nephrotic syndrome was resolved after the tumor has been controlled by surgery and chemotherapy.

Overlap of functional heartburn and gastroesophageal reflux disease with irritable bowel syndrome

Several studies indicate a significant degree of overlap between irritable bowel syndrome(IBS)and gastroesophageal reflux disease(GERD).Likewise,both functional heartburn(FH)and IBS are functional digestive disorders that may occur in the same patients.However,data establishing a solid link between FH and IBS are lacking,mainly because the clinical definition of FH has undergone substantial changes over the years.The available literature on the overlap between GERD or FH and IBS highlights considerable heterogeneity in terms of the criteria and diagnostic procedures used to assess heartburn and IBS.In particular,several epidemiological studies included patients with concomitant IBS and GERD without any attempt to distinguish FH(as defined by the RomeⅢcriteria)from GERD via pathophysiological investigations.Independent of these critical issues,there is preliminary evidence supporting a significantdegree of FH-IBS overlap.This underscores the need for studies based on updated diagnostic criteria and accurate pathophysiological classifications,particularly to distinguish FH from GERD.This distinction would represent an essential starting point to achieving a better understanding of pathophysiology in the subclasses of patients with GERD and FH and properly assessing the different degrees of overlap between IBS and the subcategories of heartburn.The present review article intends to appraise and critically discuss current evidence supporting a possible concomitance of GERD or FH with IBS in the same patients and to highlight the pathophysiological relationships between these disorders.

Laparoscopic fundoplication for gastroesophageal reflux disease

Gastroesophageal reflux disease(GERD) is a condition that develops when the reflux of gastric contents into the esophagus leads to troublesome symptoms and/or complications. Heartburn is the cardinal symptom, often associated with regurgitation. In patients with endoscopy-negative heartburn refractory to proton pump inhibitor(PPI) therapy and when the diagnosis of GERD is in question, direct reflux testing by impedance-pH monitoring is warranted. Laparoscopic fundoplication is the standard surgical treatment for GERD. It is highly effective in curing GERD with a 80% success rate at 20-year follow-up. The Nissen fundoplication, consisting of a total(360°) wrap, is the most commonly performed antireflux operation. To reduce postoperative dysphagia and gas bloating, partial fundoplications are also used, including the posterior(Toupet) fundoplication, and the anterior(Dor) fundoplication. Currently, there is consensus to advise laparoscopic fundoplication in PPI-responsive GERD only for those patients who develop untoward side-effects or complications from PPI therapy. PPI resistance is the real challenge in GERD. There is consensus that carefully selected GERD patients refractory to PPI therapy are eligible for laparoscopic fundoplication, provided that objective evidence of reflux as the cause of ongoing symptoms has been obtained. For this purpose, impedance-pH monitoring is regarded as the diagnostic gold standard.

Gastro-esophageal reflux disease and obesity, where is the link?

The confluence between the increased prevalence of gastro-esophageal reflux disease(GERD)and of obesity has generated great interest in the association between these two conditions.Several studies have addressed the potential relationship between GERD and obesity,but the exact mechanism by which obesity causes reflux disease still remains to be clearly defined.A commonly suggested pathogenetic pathway is the increased abdominal pressure which relaxes the lower esophageal sphincter,thus exposing the esophageal mucosal to gastric content.Apart from the mechanical pressure,visceral fat is metabolically active and it has been strongly associated with serum levels of adipocytokines including interleukin-6 and tumor necrosis factorα,which may play a role in GERD or consequent carcinogenesis.This summary is aimed to explore the potential mechanisms responsible for the association between GERD and obesity,and to better understand the possible role of weight loss as a therapeutic approach for GERD.

Overlapping gastroesophageal reflux disease and irritable bowel syndrome:Increased dysfunctional symptoms

AIM:To investigate the association of gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS) in Iranian patients and examine the prevalence of functional symptoms of the gastrointestinal tract in patients presenting with either IBS, GERD or both.METHODS: Six thousand four hundred and seventy six patients presented to the Gastro-intestinal (GI) clinic with symptoms of functional dysfunction of GI tract, 1419 patients (62.0% women, 38.0% men; mean age: 37.4±11.5 years) met Rome or Rome criteria(depending on the year of diagnosis)for IBS.2658 patients were diagnosed with GERD based on clinical presentation and endoscopic findings.We assessed other functional symptoms(epigastric pain,nausea,vomiting,belching,constipation and diarrhea)in patients suffering from GERD,IBS or both.RESULTS: Among IBS subjects, 63.6% (69.0% women, 31.0% men; mean age: 36.4±10.3 years) also hadGERD, whereas 34.7% of the non-IBS patients had GERD [odds ratio (OR) =3.2, 95% confidence interval (CI): 2.9-3.7, P<0.0001]. Among patients with GERD, 33.9% of subjects met Rome criteria compared to 13.5% of non-GERD patients (OR=3.6, 95% CI: 3.1-4.3, P<0.0001). Prevalence of all functional symptoms was higher in overlapping GERD and IBS subjects, when compared with their prevalence in the IBS subjects without GERD or GERD only subjects (P<0.05).CONCLUSION: This finding shows that in overlapping GERD and IBS, other functional abnormalities of the GI tract are also highly prevalent, suggesting a common underlying dysfunction.

Review on sedation for gastrointestinal tract endoscopy in children by non-anesthesiologists

AIM: To present evidence and formulate recommendations for sedation in pediatric gastrointestinal(GI) endoscopy by non-anesthesiologists.METHODS: The databases MEDLINE, Cochrane and EMBASE were searched for the following keywords "endoscopy, GI", "endoscopy, digestive system" AND "sedation", "conscious sedation", "moderate sedation", "deep sedation" and "hypnotics and sedatives" for publications in English restricted to the pediatric age. We searched additional information published between January 2011 and January 2014. Searches for(upper) GI endoscopy sedation in pediatrics and sedation guidelines by non-anesthesiologists for the adult population were performed. RESULTS: From the available studies three sedation protocols are highlighted. Propofol, which seems to offer the best balance between efficacy and safety is rarely used by non-anesthesiologists mainly because of legal restrictions. Ketamine and a combination of a benzodiazepine and an opioid are more frequently used. Data regarding other sedatives, anesthetics and adjuvant medications used for pediatric GI endoscopy are also presented.CONCLUSION: General anesthesia by a multidisciplinary team led by an anesthesiologist is preferred. The creation of sedation teams led by non-anesthesiologists and a careful selection of anesthetic drugs may offer an alternative, but should be in line with national legislation and institutional regulations.

Therapeutic angiography for giant bleeding gastro-duodenal artery pseudoaneurysm

We present the case of an 18-year-old female transferred to our center from an outside hospital due to persistent gastrointestinal bleeding. Two weeks prior to her transfer she underwent duodenal omentopexy for a perforated duodenal peptic ulcer. The patient underwent a computed tomography angiogram which identified the source of bleeding as a giant gastroduodenal artery (GDA) pseudoaneurysm. The patient was taken to interventional radiology where successful microcoil embolization was performed. We present this rare case of a giant GDA pseudoaneurysm together with imaging and a review of the medical literature regarding prevalence, etiology and treatment options for visceral arterial aneurysms.

Proton pump inhibitor resistance, the real challenge in gastro-esophageal reflux disease

Gastro-esophageal reflux disease(GERD)is one of the most prevalent chronic diseases.Although proton pump inhibitors(PPIs)represent the mainstay of treatment both for healing erosive esophagitis and for symptom relief,several studies have shown that up to 40%of GERD patients reported either partial or complete lack of response of their symptoms to a standard PPI dose once daily.Several mechanisms have been proposed as involved in PPIs resistance,including ineffective control of gastric acid secretion,esophageal hypersensitivity,ultrastructural and functional changes in the esophageal epithelium.The diagnostic evaluation of a refractory GERD patients should include an accurate clinical evaluation,upper endoscopy,esophageal manometry and ambulatory pH-impedance monitoring,which allows to discriminate non-erosive reflux disease patients from those presenting esophageal hypersensitivity or functional heartburn.Treatment has been primarily based on doubling the PPI dose or switching to another PPI.Patients with proven disease,not responding to PPI twice daily,are eligible for anti-reflux surgery.

Transjugular intrahepatic portosystemic shunt combined with esophagogastric variceal embolization in the treatment of a large gastrorenal shunt

AIM: To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt(TIPS) combined with stomach and esophageal variceal embolization(SEVE) in cirrhotic patients with a large gastrorenal vessel shunt(GRVS).METHODS: Eighty-one cirrhotic patients with gastric variceal bleeding(GVB) associated with a GRVS were enrolled in the study and accepted TIPS combined with SEVE(TIPS + SEVE), by which portosystemic pressuregradient(PPG), biochemical, TIPS-related complications, shunt dysfunction, rebleeding, and death were evaluated. RESULTS: The PPGs before TIPS were greater than 12 mmH g in 81 patients. TIPS + SEVE treatment caused a significant decrease in PPG(from 37.97 ± 6.36 mmH g to 28.15 ± 6.52 mm Hg, t = 19.22, P < 0.001). The percentage of reduction in PPG was greater than 20%from baseline. There were no significant differences in albumin, alanine aminotransferase, aspartate aminotransferase, bilirubin, prothrombin time, or Child-Pugh score before and after operation. In all patients, rebleeding rates were 3%, 6%, 12%, 18%, and 18% at 1,3, 6, 12, and 18 mo, respectively. Five patients(6.2%)were diagnosed as having hepatic encephalopathy. The rates of shunt dysfunction were 0%, 4%, 9%, 26%,and 26%, at 1, 3, 6, 12, and 18 mo, respectively. The cumulative survival rates in 1, 3, 6, 12, and 18 mo were100%, 100%, 95%, 90%, and 90%, respectively.CONCLUSION: Our preliminary results indicated that the efficacy and safety of TIPS + SEVE were satisfactory in cirrhotic patients with GVB associated with a GRVS(GVB + GRVS).

Gender difference in gastro-esophageal reflux diseases

The incidence of esophageal adenocarcinoma(EAC) has risen sharply in western countries over the past 4 decades. This type of cancer is considered to follow a transitional process that goes from gastro-esophageal reflux disease(GERD) to Barrett's esophagus(BE,a metaplastic condition of the distal esophagus), a precursor lesion and ultimately adenocarcinoma. This spectrum of GERD is strongly predominant in males due to an unidentified mechanism. Several epidemiologic studies have des cribed that the prevalence of GERD, BE and EAC in women is closely related to reproductive status, which suggests a possible association with the estrogen level. Recently, we revealed in an in vivo study that the inactivation of mast cells by the anti-inflammatory function of estrogen may account for the gender difference in the GERD spectrum. Other studies have described the contribution of female steroid hormones to the gender difference in these diseases. Estrogen is reported to modulate the metabolism of fat, and obesity is a main risk factor of GERDs. Moreover, estrogen could confer esophageal epithelial resistance to causative refluxate. These functions of estrogen might explain the approximately 20-year delay in the incidence of BE and the subsequent development of EAC in women compared to men, and this effect may be responsible for the male predominance. However, some observational studies demonstrated that hormone replacement therapy exerts controversial effects in GERD patients. Nevertheless, the estrogen-related endocrine milieu may prevent disease progression toward carcinogenesis in GERD patients. The development of innovative alternatives to conventional acid suppressors may become possible by clarifying the mechanisms of estrogen.

Bloating and functional gastro-intestinal disorders: Where are we and where are we going?

Bloating is one of the most common and bothersome symptoms complained by a large proportion of patients. This symptom has been described with various definitions, such as sensation of a distended abdomen or an abdominal tension or even excessive gas in the abdomen, although bloating should probably be defined as the feeling(e.g. a subjective sensation) of increased pressure within the abdomen. It is usually associated with functional gastrointestinal disorders, like irritable bowel syndrome, but when bloating is not part of another functional bowel or gastrointestinal disorder it is included as an independent entity in Rome Ⅲ criteria named functional bloating. In terms of diagnosis, major difficulties are due to the lack of measurable parameters to assess and grade this symptom. In addition, it is still unclear to what extent the individual patient complaint of subjective bloating correlates with the objective evidence of abdominal distension. In fact, despite its clinical, social and economic relevance, bloating lacks a clear pathophysiology explanation, and an effective management endorsement, turning this common symptom into a true challenge for both patients and clinicians. Different theories on bloating etiology call into questions an increased luminal contents(gas, stools, liquid or fat) and/or an impaired abdominal empting and/or an altered intra-abdominal volume displacement(abdomino-phrenic theory) and/or an increased perception of intestinal stimuli with a subsequent use of empirical treatments(diet modifications, antibiotics and/or probiotics, prokinetic drugs, antispasmodics, gas reducing agents and tricyclic antidepressants). In this review, our aim was to review the latest knowledge on bloating physiopathology and therapeutic options trying to shed lights on those processes where a clinician could intervene to modify disease course.

Sleep,immunity and inflammation in gastrointestinal disorders

Sleep disorders have become a global issue,and discovering their causes and consequences are the focus of many research endeavors.An estimated 70 million Americans suffer from some form of sleep disorder.Certain sleep disorders have been shown to cause neurocognitive impairment such as decreased cognitive ability,slower response times and performance detriments.Recent research suggests that individuals with sleep abnormalities are also at greater risk of serious adverse health,economic consequences,and most importantly increased all-cause mortality.Several research studies support the associations among sleep,immune function and inflammation.Here,we review the current research linking sleep,immune function,and gastrointestinal diseases and discuss the interdependent relationship between sleep and these gastrointestinal disorders.Different physiologic processes including immune system and inflammatory cytokines help regulate the sleep.The inflammatory cytokines such as tumor necrosis factor,interleukin-1(IL-1),and IL-6 have been shown to be a significant contributor of sleep disturbances.On the other hand,sleep disturbances such as sleep deprivation have been shown to up regulate these inflammatory cytokines.Alterations in these cytokine levels have been demonstrated in certain gastrointestinal diseases such as inflammatory bowel disease,gastro-esophageal reflux,liver disorders and colorectal cancer.In turn,abnormal sleep brought on by these diseases is shown to contribute to the severity of these same gastrointestinal diseases.Knowledge of these relationships will allow gastroenterologists a great opportunity to enhance the care of their patients.

Characterisation and risk assessment of venous thromboembolism in gastrointestinal cancers

AIM To characterise venous thromboembolism(VTE) in gastrointestinal cancer and assess the clinical utility of risk stratification scoring. METHODS We performed a retrospective analysis using electronic patient records of 910 gastro-oesophageal(GO) cancer and 1299 colorectal cancer(CRC) patients referred to a tertiary cancer centre to identify the incidence of VTE, its relationship to chemotherapy and impact on survival.VTE risk scores were calculated using the Khorana index. Patients were classified as low risk(0 points), intermediate risk(1 to 2 points) or high risk(3 points). Data was analysed to determine the sensitivity of the Khorana score to predict VTE. RESULTS The incidence of VTE was 8.9% for CRC patients and 9.7% for GO cancer patients. Pulmonary emboli(PE) were more common in advanced than in localised CRC(50% vs 21% of events respectively) and lower limb deep vein thrombosis(DVT) were more common in localised than in advanced CRC(62% vs 39% of events respectively). The median time to VTE from cancer diagnosis was 8.3 mo for CRC patients compared to 6.7 mo in GO cancer. In localised CRC median time to VTE was 7.1 mo compared with 10.1 mo in advanced CRC. In contrast in GO cancer, the median time to VTE was 12.5 mo in localised disease and 6.8 mo in advanced disease. No survival difference was seen between patients with and without VTE in this cohort. The majority of patients with CRC in whom VTE was diagnosed had low or intermediate Khorana risk score(94% for localised and 97% in advanced CRC). In GO cancer, all patients scored either intermediate or high risk due to the primary site demonstrating a limitation of the risk assessment score in discriminating high and low risk patients with GO cancers. Additional risk factors were identified in this cohort including surgery, chemotherapy or hospital admission. Overall, 81% of patients with CRC and 77% of patients with GO cancer had one or more of these factors within 4 wk prior to diagnosis VTE. These should be factored into clinical risk assessment scores. CONCLUSION The Khorana score has low sensitivity for thrombotic events in CRC and cannot discriminate low risk patients in high risk cancer sites such as GO cancer.

Facing the challenge of venous thromboembolism prevention in patients undergoing major abdominal surgical procedures for gastrointestinal cancer

Venous thromboembolism(VTE)refers to a hypercoa-gulable state that remains an important and preven-table factor in the surgical treatment of malignancies.VTE includes two identical entities with regards to deep vein thrombosis and pulmonary embolism.The incidence of VTE after major abdominal interventions for gastro-intestinal,hepato-biliary and pancreatic neoplastic disor-ders is as high as 25%without prophylaxis.Prophylactic use of classic or low-molecular-weight heparin,anti-Xa factors,antithrombotic stocking,intermittent pneumatic compression devices and early mobilization have been described.Nevertheless,thromboprophylaxis is often dis-continued after discharge,although a serious risk may persist long after the initial triggering event,as the coagu-lation system remains active for at least 14 d post-opera-tively.The aim of this review is to evaluate the results of the current practice of VTE prevention in cancer patients undergoing major abdominal surgical operations,with special attention to adequately elucidated guidelinesand widely accepted protocols.In addition,the recent literature is presented in order to provide an update on the current concepts concerning the surgical manage-ment of the disease.

Upper aerodigestive tract disorders and gastro-oesophageal reflux disease

A wide variety of symptoms and diseases of the upper aerodigestive tract are associated to gastro-oesophageal reflux disease(GORD). These disorders comprise a large variety of conditions such as asthma, chronic otitis media and sinusitis, chronic cough, and laryngeal disorders including paroxysmal laryngospasm. Laryngopharyngeal reflux disease is an extraoesophageal variant of GORD that can affect the larynx and pharynx. Despite numerous research efforts, the diagnosis of laryngopharyngeal reflux often remains elusive,unproven and controversial, and its treatment is then still empiric. Aim of this paper is to review the current literature on upper aerodigestive tract disorders in relation to pathologic gastro-oesophageal reflux, focusing in particular on the pathophysiology base and results of the surgical treatment of GORD.

Transoral incisionless fundoplication for gastro-esophageal reflux disease: Techniques and outcomes

Gastro-esophageal reflux disease(GERD)is a verycommon disorder that results primarily from the loss of an effective antireflux barrier,which forms a mechanical obstacle to the retrograde movement of gastric content.GERD can be currently treated by medical therapy,surgical or endoscopic transoral intervention.Medical therapy is the most common approach,though concerns have been increasingly raised in recent years about the potential side effects of continuous longterm medication,drug intolerance or unresponsiveness,and the need for high dosages for long periods to treat symptoms or prevent recurrences.Surgery too may in some cases have consequences such as longlasting dysphagia,flatulence,inability to belch or vomit,diarrhea,or functional dyspepsia related to delayed gastric emptying.In the last few years,transoral incisionless fundoplication(TIF)has proved an effective and promising therapeutic option as an alternative to medical and surgical therapy.This review describes the steps of the TIF technique,using the Esophy X&#174;device and the MUSETM system.Complications and their management are described in detail,and the recent literature regarding the outcomes is reviewed.TIF reconfigures the tissue to obtain a full-thickness gastroesophageal valve from inside the stomach,by serosato-serosa plications which include the muscle layers.To date the procedure has achieved lasting improvement of GERD symptoms(up to six years),cessation or reduction of proton pump inhibitor medication in about 75%of patients,and improvement of functional findings,measured by either p H or impedance monitoring.

Clinical Study on Therapy of Clearing Hallow Viscera in Treating Critical Patients with Gastro-enteric Function Disorder

Objective： To explore the clinical effect of therapy of clearing hallow viscera in treating critical patients with gastro-enteric function disorder （GEFD）. Methods： Retrospective analysis was carried out on 96 critical patients. They were 48 patients in the treated group treated with Dachengqi Decoction （ 大承气汤） and 48 patients in the control group treated with Western medicine for promoting gastric dynamic force. The recovery rate, recovery time of gastro-enteric function, incidence rate and fatality rate of multiple organ dysfunction syndrome （MODS）, as well as the level of plasma endotoxin （ET） before and after treatment between the two groups were compared. Results： Comparison between the two groups in gastro-enteric function recovery rate （81.3% vs 45.8 %）, functional disorder sustaining time in patients who got recovered （1.2± 0.3 daysvs4.0±1.1 days）, incidence rate （29. 17% vs 52.08%） and fatality rate （28.57% vs 56.00%） of MODS all showed significant difference （ P〈0.05 or P〈0.01 ）. The plasma level of ET after treatment in the treated group was significantly lower than that in the control group （P〈0.05）. Conclusion： Therapy of clearing hallow viscera has a good effect in treating critical patients with gastro-enteric function disorder, and could reduce the incidence and fatality of MODS.

Human leukocyte antigen DQ2/8 prevalence in non-celiac patients with gastrointestinal diseases

AIM: To investigate the prevalence of human leukocyte antigen (HLA) DQ2/8 alleles in Southern Italians with liver and gastrointestinal (GI) diseases outside of celiac disease. METHODS: HLA DQ2/8 status was assessed in 443 patients from three ambulatory gastroenterology clinics in Southern Italy (University of Federico Ⅱ, Naples, Loreto Crispi Hospital, Ruggi D'Aragona Hospital, Salerno). Patients were grouped based on disease status [pre-post transplant liver disease, esophageal/gastric organic and functional diseases, irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD)] and DQ2/8 alleles, which correspond to a celiac disease genetic risk gradient. Subject allele frequencies were compared to healthy Italian controls. RESULTS: One hundred and ninety-six out of four hundred and forty-three (44.2%) subjects, median age 56 years and 42.6% female, were DQ2/8 positive. When stratifying by disease we found that 86/188 (45.7%) patients with liver disease were HLA DQ2/8 positive, 39/73 (53.4%) with functional upper GI diseases and 19/41 (46.3%) with organic upper GI diseases were positive. Furthermore, 38/105 (36.2%) patients with IBS and 14/36 (38.9%) with IBD were HLA DQ2/8 positive (P = 0.21). Compared to healthy controls those with functional upper GI diseases disorders had a 1.8 times higher odds of DQ2/8 positivity. Those with liver disease had 1.3 times the odds, albeit not statistically significant, ofDQ2/8 positivity. Both those with IBS and IBD had a lower odds of DQ2/8 positivity compared to healthy controls. CONCLUSION: The proportion of individuals HLA DQ2/8 positive is higher in those with liver/upper functional GI disease and lower in IBS/IBD as compared to general population estimates.

Medical treatment for gastro-entero-pancreatic neuroendocrine tumours

Gastro-entero-pancreatic neuroendocrine neoplasms(GEPNENs) represents a various family of rare tumours. Surgery is the first choice in GEP-NENs patients with localized disease whilst in the metastatic setting many other treatment options are available. Somatostatin analogues are indicated for symptoms control in functioning tumours. Furthermore they may be effective to inhibit tumour progression. GEP-NENs pathogenesis has been extensively studied in the last years therefore several driver mutations pathway genes have been identified as crucial factors in their tumourigenesis. GEP-NENs can over-express vascular endothelial growth factor(VEGF), basic-fibroblastic growth factor, transforming growth factor(TGF-α and-β), platelet derived growth factor(PDGF), insulin-like growth factor-1(IGF-1) and their receptors PDGF receptor, IGF-1 receptor, epidermal growth factor receptor, VEGF receptor, and c-kit(stem cell factor receptor) that can be considered as potential targets. The availability of new targeted agents, such as everolimus and sunitinib that are effective in advanced and metastatic pancreatic neuroendocrine tumours, has provided new treatment opportunities. Many trials combing new drugs are ongoing.

Impact of postoperative TNM stages after neoadjuvant therapy on prognosis of adenocarcinoma of the gastro-oesophageal junction tumours

AIM To compare prognostic relevance of postoperative tumour/node/metastasis(TMN) stages between patients with and without neoadjuvant treatment. METHODS Data from patients with adenocarcinoma of the gastrooesophageal junction(AEG) who had undergone surgical resection at a single German university centre were retrospectively analysed. Patients with or without neoadjuvant preoperative treatment were selected by exact matching based on preoperative staging. Standard assessment of preoperative(c)TNM stage was based on endoscopic ultrasound and computed tomography of the thorax and abdomen, according to the American Joint Committee on Cancer/Union for International Cancer Control classification system. Patients with cT1cN0cM0 and cT2cN0cM0 stages were excluded from the study, as these patients are generally not recommended for pretreatment. Longterm survival among the various postoperative TNM stages was compared between the groups of patients with or without neoadjuvant treatment. For statistical assessments, a P-value of ≤ 0.05 was considered significant.RESULTS The study included a total of 174 patients. The group of patients who had received preoperative neoadjuvant treatment included more cases of AEG(Siewert) type 1 carcinoma(P < 0.001), and consequently oesophagectomy was performed more frequently among these patients(P < 0.001). The two groups(with or without preoperative neoadjuvant treatment) had comparable preoperative T stages, but the group of patients with preoperative neoadjuvant treatment presented a higher rate of preoperative N-positive disease(P = 0.020). Overall long-term survival was not different between the two groups of patients according to tumours of different AEG classifications, receipt of oesophagectomy or gastrectomy, nor between patients with similar postoperative TNM stage, resection margin and grading. However, an improvement of long-term survival was found for patients with nodal down-staging after neoadjuvant therapy(P = 0.053).CONCLUSION The prognostic relevance of postoperative TNM stages is similar for AEG in patients with or without neoadjuvant preoperative treatment, but treatment-related nodal down-staging prognosticates longer-term survival.