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BACKGROUND A single state-wide upper gastrointestinal (GI) cancer video-linked multidisciplinary team (MDT) meeting guides management and evidence-based care for all newly diagnosed upper GI cancer patients in South Australia. This study determined the patterns of care and outcomes for patients diagnosed with gastric and gastro-oesophageal junction (GOJ) cancers. METHODS Patients diagnosed with gastric cancer and GOJ (Siewert III) cancer between June 2012 and June 2016 were included. Patient demographics, cancer stage, histology, diagnostic modalities and treatment data was analysed from a prospective database. Stage-specific survival outcomes were determined and analysed for each treatment modality. RESULTS The study included 218 patients and at diagnosis 132 (61%) patients had stage I-III and 86 (39%) patients had stage IV disease. One hundred and ninety-five (89%) patients had gastric cancer and 23 (11%) had GOJ cancer (Siewert III). One hundred and nine (50%) patients underwent surgery, with 92% R0 resection rate. Forty-six patients received perioperative chemotherapy and 111 (51%) patients received palliative intent treatment. Median overall survival for stage II, III and IV cancers was 57.6 (95% CI 57.6-NR), 22.8 (95% CI 20.4-43.2), and 6.0 months (95% CI 4.8-8.4) respectively (p

Advances in cancer biology and sequencing technology have enabled the selection of targeted and more effective treatments for individual patients with various types of solid tumour. However, only three molecular biomarkers have thus far been demonstrated to predict a response to targeted therapies in patients with gastric and/or gastro-oesophageal junction (G/GEJ) cancers: HER2 positivity for trastuzumab and trastuzumab deruxtecan, and microsatellite instability (MSI) status and PD-L1 expression for pembrolizumab. Despite this lack of clinically relevant biomarkers, distinct molecular subtypes of G/GEJ cancers have been identified and have informed the development of novel agents, including receptor tyrosine kinase inhibitors and monoclonal antibodies, several of which are currently being tested in ongoing trials. Many of these trials include biomarker stratification, and some include analysis of circulating tumour DNA (ctDNA), which both enables the noninvasive assessment of biomarker expression and provides an indication of the contributions of intratumoural heterogeneity to response and resistance. The results of these studies might help to optimize the selection of patients to receive targeted therapies, thus facilitating precision medicine approaches for patients with G/GEJ cancers. In this Review, we describe the current evidence supporting the use of targeted therapies in patients with G/GEJ cancers and provide guidance on future research directions. Despite considerable progress in the development of targeted therapies, only three biomarkers are currently used to guide the treatment of patients with gastric or gastro-oesophageal junction cancers using approved targeted therapies. Nonetheless, owing to advances in our understanding of tumour biology and sequencing technologies, several novel therapies are expected to soon become available. In this Review, the authors describe current and future biomarker-guided therapies for patients with G/GEJ cancers.

Background/Aim: We hypothesised that the prognostic nutrition index (PNI) is useful for evaluating host immunity and response to immune checkpoint inhibitors. We investigated the effect of PNI on nivolumab monotherapy efficacy in advanced or recurrent gastric cancer (GC) or gastro-oesophageal junction cancer (GOC) patients. Patients and Methods: We retrospectively examined 110 patients, divided them into a high-PNI group and a low-PNI group, and compared treatment efficacy, adverse events (AEs), and survival between the groups. Results: Median overall survival (OS) was significantly longer in the high-PNI group than in the low-PNI group (205 vs. 109 days; p < 0.001). Multivariate analysis revealed that low PNI was an independent risk factor for OS (hazard ratio=2.398; 95% confidence interval=1.384-4.154; p=0.002). The overall response rate and frequency of AEs were not significantly different between the groups. Conclusion: PNI could be a useful prognostic factor in GC or GOC patients undergoing nivolumab monotherapy.

Objectives To determine whether there is a benefit of using pre- and postoperative antacid treatment in dogs undergoing surgery for brachycephalic syndrome. To assess the use of an obstruction manoeuvre during endoscopy for the detection of dynamic gastro-oesophageal junction abnormalities. Materials and methods Thirty-six client-owned brachycephalic dogs were prospectively included in a randomised trial. Antacid treatment was randomly prescribed in 18 dogs before and after surgery while the other 18 dogs did not receive any gastrointestinal medical treatment. At presentation, at the time of surgery and at recheck, digestive clinical signs and gastro-oesophageal junction abnormalities were assessed using specific scores. Gastro-oesophageal junction abnormalities were assessed during endoscopy in standard conditions as well as during endotracheal tube obstruction. This manoeuvre was also applied in an unrelated control group. Results The results suggest a beneficial effect of antacid treatment on the improvement of digestive clinical signs and lesions in dogs with brachycephalic syndrome undergoing surgery. At postsurgical control 83% of dogs had a digestive clinical score ≤1 in the treated group in contrast to 44% in the non-treated group and 39% of dogs had a gastro-oesophageal abnormalities score (during obstruction manoeuvre) ≤1 in the treated group in contrast to 16.7% in the non-treated group. The use of the obstruction manoeuvre during endoscopic assessment in a control group revealed that gastro-oesophageal junction movements are negligible in healthy animals. Clinical significance The addition of antacid treatment during the pre- and postoperative period for brachycephalic dogs undergoing surgery may result in a faster and greater improvement in treated dogs. The obstruction manoeuvre is an interesting technique to improve detection of gastro-oesophageal junction abnormalities.

Simple Summary The optimal treatment strategy for locally advanced distal oesophageal and gastrooesophageal junction (GOJ) adenocarcinoma is currently not clear. Surgery as a main curative modality is usually combined with either preoperative chemoradiotherapy or perioperative chemotherapy. The aim of the review is to provide an overview of current treatment options in locally advanced oesophageal and GOJ adenocarcinomas based on the latest evidence, including the possible potential of predictive biomarkers in optimizing treatment. Abstract The following main treatment approaches are currently used in locally advanced adenocarcinomas of the oesophagus and gastrooesophageal junction (GOJ): preoperative chemoradiotherapy and surgery, and perioperative chemotherapy and surgery. While preoperative chemoradiotherapy is used primarily in oesophageal tumours, perioperative chemotherapy is the treatment of choice in Western countries for gastric cancer. The optimal treatment strategy for GOJ adenocarcinoma is still not clear. In comparison to other malignancies, biomarkers are used as predictive factors in distal oesophageal and GOJ adenocarcinomas in a very limited way, and moreover, only in metastatic stages (e.g., HER2 status, or microsatellite instability status). The aim of the article is to provide an overview of current treatment options in locally advanced adenocarcinomas of oesophagus and GOJ based on the latest evidence, including the possible potential of predictive biomarkers in optimizing treatment.

Background Most patients undergo follow-up after surgery for cancers of the gastro-oesophageal junction, stomach or pancreas, but data to support which modalities to use and the frequency of investigation are limited. Methods Patients in the EUFURO study were randomized to either visits to the outpatient clinic at 3, 6, 9, 12, 18, and 24 months after surgery (standard), or to the addition of [18F]fluorodeoxyglucose (FDG) PET–CT and endoscopic ultrasonography (EUS) with guided fine-needle aspiration biopsy to clinical assessments (intervention). Data from the intervention arm were used to analyse the diagnostic performance of endosonography or [18F]FDG PET–CT in detecting recurrences. Results During the scheduled follow-up, 42 of 89 patients developed recurrence; PET–CT and EUS in combination detected 38 of these recurrences. EUS detected 23 of the 42 patients with recurrent disease during follow-up and correctly diagnosed 17 of 19 locoregional recurrences. EUS was able to detect isolated locoregional recurrence in 11 of 13 patients. In five patients, EUS was false-positive for isolated locoregional recurrence owing to missed distant metastases. PET–CT detected locoregional recurrence in only 12 of 19 patients, and isolated locoregional recurrence in only 7 of 13. False-positive PET–CT results in 23 patients led to a total of 44 futile procedures. Conclusion Accuracy in detecting recurrences by concomitant use of PET–CT and EUS was high (90 per cent). PET–CT had moderate to high sensitivity for overall recurrence detection, but low specificity. EUS was superior to PET–CT in the detection of locoregional and isolated locoregional recurrences., Endosonography and [18F]fluorodeoxyglucose PET–CT combined is highly accurate in detecting recurrent disease after radical operation for gastro-oesophageal, stomach or pancreatic cancers. PET–CT has a moderate to high sensitivity, but a low specificity, ultimately leading to a substantial number of additional and often futile examinations. Endosonography is highly sensitive and specific in detecting locoregional recurrences, and superior to PET–CT in detecting isolated locoregional recurrences, enabling potentially curative treatment. FP, false-positive; TP, true-positive.

For resectable adenocarcinoma (AC) of the gastro-oesophageal junction (GEJ), several treatment options are available including: perioperative chemotherapy and neoadjuvant chemoradiotherapy (nCRT) [...

Summary Oesophageal and gastro-oesophageal junction (GOJ) neoplasms, and their predisposing conditions, may be encountered by the practicing pathologist both as biopsy samples and as surgical specimens in daily practice. Changes in incidence of oesophageal squamous cell carcinomas (such as a decrease in western countries) and in oesophageal and GOJ adenocarcinomas (such as a sharp increase in western countries) are being reported globally. New modes of treatment have changed our histologic reports as specific aspects must be detailed such as in post endoscopic resections or with regards to post neo-adjuvant therapy tumour regression grades. The main aim of this overview is therefore to provide an up-to-date, easily available and clear diagnostic approach to neoplastic and pre-neoplastic conditions of the oesophagus and GOJ, based on the most recent available guidelines and literature.

Background Treatment for cancer of the gastro‐oesophageal junction (GOJ) can result in considerable and persistent impairment of physical fitness and health‐related quality of life (HRQoL). This controlled follow‐up study investigated the feasibility and safety of postoperative exercise training. Methods Patients with stage I–III GOJ cancer were allocated to 12 weeks of postoperative concurrent aerobic and resistance training (exercise group) or usual care (control group). Changes in cardiorespiratory fitness, muscle strength and HRQoL were evaluated. Adherence to adjuvant chemotherapy, hospitalizations and 1‐year overall survival were recorded to assess safety. Results Some 49 patients were studied. The exercise group attended a mean of 69 per cent of all prescribed sessions. After exercise, muscle strength and cardiorespiratory fitness were increased and returned to pretreatment levels. At 1‐year follow‐up, the exercise group had improved HRQoL (+13·5 points, 95 per cent c.i. 2·2 to 24·9), with no change in the control group (+3·7 points, −5·9 to 13·4), but there was no difference between the groups at this time point (+9·8 points, −5·1 to 24·8). Exercise was safe, with no differences in patients receiving adjuvant chemotherapy (14 of 16 versus 16 of 19; relative risk (RR) 1·04, 95 per cent c.i. 0·74 to 1·44), relative dose intensity of adjuvant chemotherapy (mean 57 versus 63 per cent; P = 0·479), hospitalization (7 of 19 versus 6 of 23; RR 1·41, 0·57 to 3·49) or 1‐year overall survival (80 versus 79 per cent; P = 0·839) for exercise and usual care respectively. Conclusion Exercise in the postoperative period is safe and may have the potential to improve physical fitness in patients with GOJ cancer. No differences in prognostic endpoints or HRQoL were observed. Registration number: NCT02722785 ( https://www.clinicaltrials.gov)., With concurrent aerobic exercise and resistance training twice a week during treatment, patients with cancer of the gastro‐oesophageal junction can return cardiopulmonary fitness and muscle strength to pretreatment levels at completion of treatment. This can be done without affecting prognostic endpoints and with positive effects on health‐related quality of life. Generally well tolerated and safe.

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 gastro-oesophageal 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. Long-term 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.

Benign surgical conditions of the oesophago-gastric junction (OGJ) are important causes of morbidity and in some cases mortality for patients. This chapter discusses both elective and emergency benign disorders of the OGJ, their investigation and management. Elective conditions include gastro-oesophageal reflux disease (GORD), giant para-oesophageal hiatal herniae (GPHH), achalasia and other motility disorders. These conditions are now usually all managed laparoscopically when operative intervention is required. Emergency conditions include acute presentations of giant para-oesophageal hiatal herniae and OGJ perforations including Boerhaave's syndrome. These conditions present diagnostic and management challenges to the surgeon and are associated with significant morbidity and mortality. Varices, gastro-intestinal stromal tumours (GISTs), ulcers and bleeding are not discussed in this article.

Aim To report a novel approach for tumours located at the gastro-oesophageal junction (GOJ) using a laparoscopic abdominal phase combined with a left thoracoabdominal approach. Background and Methods The standard left thoracoabdominal approach offers excellent exposure and access to GOJ and lower oesophagus. It also involves a single position for the procedure, shortening the operation time. The disadvantages are a large incision, dividing the costochondral junction, and a low level thoracotomy. Laparoscopic Left Thoracoabdominal Oesophagectomy (LLTA) is performed with the patient in the same right lateral decubitus position, but rolled away from the operator at 45xxx. allowing laparoscopic gastric mobilisation and lymphadenectomy. The thoracic phase uses an anterolateral left thoracotomy through the higher 5th intercostal space, giving a higher intrathoracic anastomosis, just below the aortic arch. No disruption of the costochondral junction is made. Consecutive patients treated for GOJ tumours with LLTA operated on during 2013-2019 were analysed and compared to national standards (NOGCA). Results This series of 70 consecutive patients had a mean age of 63 years. Median operation time was 235 minutes. Median inpatient hospital stay was 10 days (NOGCA 9 (11-17)). The majority were adenocarcinoma; predominantly located in the GOJ (Siewert Type1 (37.14%), Type2 (45.71%), Type3 (2.86%)); 90% of the tumours were T3 or T4. Postoperative morbidity was low (Clavien-Dindo 0 in 50% of the patients). The median number of total lymph nodes excised was 27.77 (NOGCA >15). Positive nodes were predominantly located in the lesser-curve (40%), Para-oesophageal 34.29%; Sub-carinal 2.86%. Positive circumferential resection margins ( Conclusion This series demonstrates a novel, safe and reproducible left sided approach for cancer of the GOJ. There is good exposure at the hiatus, without the division of the costochondral junction and low thoracotomy.

The aim of this manuscript is to discuss the viewpoint of the European Organisation for Research and Treatment of Cancer (EORTC) Gastric Cancer Taskforce and Japan Clinical Oncology Group (JCOG) Gastric Cancer Study Group on the current challenges in the multidisciplinary management of stage II-III gastric and gastro-oesophageal junction (GEJ) cancer. We seek to outline how these challenges are addressed in current trials of both groups. Key elements of future trials of EORTC and JCOG in this indication are described, and a joint vision on how multidisciplinary research of gastric and GEJ cancer patients should be organised is outlined. ispartof: EUROPEAN JOURNAL OF CANCER vol:124 pages:67-76 ispartof: location:England status: published

Chronic acid-biliary reflux and Helicobacter pylori infection are instrumental environmental drivers of cancer initiation and progression in the upper gastrointestinal tract. Remarkably, although these environmental carcinogens are quite dissimilar, the tumour progression cascade these carcinogens engender is highly comparable. For this reason, studies of malignant progression occurring at the anatomic borderland between the oesophagus and the stomach have traditionally lumped junctional adenocarcinomas with either oesophageal adenocarcinoma or gastric adenocarcinoma. Whilst studies have revealed remarkable epidemiological and genetic similarities of these cancers and their associated premalignant conditions, these works have also revealed some key differences. This highlights that further scientific effort demands a dedicated focus on the understanding of the cell-cell interaction between the epithelium and the local microenvironment in this anatomic region. We here review available evidence with regards to tumour progression occurring at the gastro-oesophageal junction and contrast it with available data on cancer evolution in the metaplastic oesophagus and distal stomach.

immune checkpoint inhibitors(ICIs) have shown contradictory results in patients with advanced gastro-oesophageal junction/gastric cancer(GOJ/GC).to identify specific patient subgroups that would derive survival benefit from ICIs.a subgroup meta-analysis of randomised clinical trials(RCTs) was carried out.four phase-III-RCTs were identified with data on the following variables: primary location(Gastric vs GOJ); age(≤ 65 vs65); gender(male vs female); ECOG PS(0 vs 1); ethnicity (Asian vs non-Asian), histology(intestinal vs diffuse), PD-L1 expression(≥ 1% vs1%). PD-L1 positivity was significantly associated with survival benefit from ICIs (HR: 0.82, p 0.047), with a significant interaction between PD-L1 expression and ICI efficacy (interaction HR: 1.41, p 0.02). Numerically, the second most relevant interaction was ICI efficacy and gender, with ICI being more effective in males.The PD-L1 positive patient subgroup derives significant survival benefit from ICI in GOJ/GC, however other predictors are eagerly needed to further refine patient selection.

Background and scope The management of GOJ cancers remains controversial and may vary between countries. Evidence-based attitudes and guidelines are not easy to elaborate since most of the trials and studies reported mixed cases of oesophageal (both adenocarcinoma and squamous cell tumours), GOJ and gastric cancers. The aim of this expert discussion and position paper is to elaborate practical recommendations that integrate evidence-reported literature and experience-based attitude covering all clinical aspects of GOJ cancer across different specialities and countries in Europe. Methodology Opinion leaders, selected on scientific merit were asked to answer to a prepared set of questions covering the approach of GOJ tumours from definition to therapeutic strategies. All answers were then discussed during a plenary session and reported here in providing a well-balanced reflection of both clinical expertise and updated evidence-based medicine. Results Definition, classification, diagnosis and staging of GOJ tumours were updated and debated. Therapeutic aspects including endoscopic therapy, surgical management, both multimodal curative and palliative management were also reviewed for proposing practical and consensual positions and recommendations whenever possible. Conclusion GOJ tumours deserve specific attention,not only for uniformising clinical management across countries but also for performing specific clinical and translational research,mainly in the curative perioperative setting.

BACKGROUND Cancer of the oesophagus is the ninth most common malignancy, causes 2% of all cancer-related deaths worldwide. This study was aimed to determine the type of malignancy more common in gastro oesophageal junction as well as to know the age and gender distribution of malignancy. METHODS Longitudinal study was done by including all the diagnosed cases of carcinoma of gastro oesophageal junction who had undergone oesophagectomy. The resected specimen of the subset of patients with adenocarcinoma was examined for the presence of intestinal metaplasia using haematoxylin and eosin stain. RESULTS A total of 36 patients were studied. Among the 36 cases, 21 cases (58.33%) were squamous cell carcinoma with 13 patients (61.9%) between 50 years and 70 years of age and rest 15 cases (41.66%) were adenocarcinoma with 8 patients (53.3%) between 50 to 60 years of age. All the adenocarcinomas were presented in late stage (T3 or T4), 60% with lymph node metastasis and 20% of patients had intestinal metaplasia. Among the patients with squamous cell carcinoma, 62% presented with T3 disease and 33% presented with T2 disease and only 19% of patients had lymph node metastasis. CONCLUSION Among the malignancy at the gastro oesophageal junction, squamous cell carcinoma with female dominance was more common than adenocarcinoma with male dominance. Most of the cases were with well differentiated tumours presenting at a late stage of the disease either T3 or T4 with low incidence of lymph node metastasis. Adenocarcinoma showed a low incidence of specialized intestinal metaplasia.

Advanced squamous cell carcinoma of the oesophagus and gastroesophageal junction usually requires palliative treatment, and the method of choice is stenting. There are several types of stents currently available, including: self-expandable metallic stents (fully or partially covered); self-expandable plastic stents; biodegradable stents. Each of the mentioned stents has its advantages and limitations, and requires a proper, patient-tailored selection. Due to the close anatomical relationship between the oesophagus and bronchial tree, some patients may require bilateral stenting. Oesophageal stenting may not only be considered as a palliative procedure, but can also be implemented to alleviate dysphagia during preoperative chemotherapy and/or radiotherapy.

Oesophageal cancer remains a malignancy with a poor prognosis. However, in the recent 10-15 years relevant progress has been made by the introduction of chemoradiotherapy (CRT) for tumours of the oesophagus or gastro-oesophageal junction. The addition of neo-adjuvant CRT to surgery has significantly improved survival and locoregional control, for both adenocarcinoma and squamous cell carcinoma. For irresectable or medically inoperable patients, definitive CRT has changed the treatment intent from palliative to curative. Definitive CRT is a good alternative for radical surgery in responding patients with squamous cell carcinoma and those running a high risk of surgical morbidity and mortality. For patients with an out-of-field solitary locoregional recurrence after primary curative treatment, definitive CRT can lead to long term survival.

417 Background: ICIs demonstrated improved overall survival (OS) in heavily pre-treated mGOJ/GC pts. Pts selection exclusively based on PD-L1 tissue expression appears to be suboptimal, despite data from subgroup analyses of KEYNOTE trials. Strong rationale suggests a potential predictive role of inflammatory biomarkers in ICIs treated mGOJ/GC pts. Methods: 11 systemic inflammatory markers [platelets, monocytes, neutrophil/lymphocyte ratio (NLR), platelets-lymphocyte ratio, lymphocytes, sum of mononuclear cells, albumin, lactate dehydrogenase, alkaline phosphatase (ALP), c-reactive protein (CRP) and serum globulin] were retrospectively analyzed at baseline in 57 mGOJ/GC pts with unknown PD-L1 status treated in second-line with ICIs, and correlated with OS. Least Absolute Shrinkage and Selection Operator (LASSO) method was used to select variables (preliminarily subject to optimal coding using HR smoothed curves for OS) with the highest prognostic value.Selected variables were then analysed in a multivariate Cox Regression Model and used to build a GIPI nomogram. Results: NLR and CRP taken as continuous variables and ALP categorized as < vs > 150 IU/L were found as the most meaningful independent predictors of OS [(HR 1.30 (95%CI 1.02-1.65), 2.00 (95%CI 1.09-3.66), 2.82 (95%CI 1.29-6.20) and p values 0.04, 0.01, 0.02, respectively)] and used to build the GIPI nomogram. Nomogram-based lowest(l), mid and highest(h) risk tertiles were associated with median(m)OS of 14.5,10.6 and 2.4 months(mos), respectively [HR of l vs h 0.26 (95%CI 0.12-0.53), p 0.0002]. By optimally dichotomizing CRP and NLR, pts with one or more of the following risk factors: NLR > 6, CRP > 15 mg/L, ALP < 150 IU/L (n: 31) had a mOS of 3.9mos vs 14.5mos of pts with no risk factor (n: 26) (HR 2.72, p 0.0005). Conclusions: GIPI, combining NLR, CRP and ALP, is the first inflammatory index with a significant prognostic value in mOGJ/GC pts receiving second line ICIs. Its implementation with analysis of PD-L1 expression in the present cohort is ongoing. GIPI merits validation in external cohorts and prospective clinical trials.

The RAINBOW Phase III study established the efficacy of the combination of paclitaxel and ramucirumab, a monoclonal antibody targeting VEGF receptor-2 (VEGF-R2), as second-line therapy. We retrospectively analyzed the data of patients treated with ramucirumab plus paclitaxel at our Institution to evaluate the impact of clinical heterogeneous figures on the efficacy and safety of this combination paclitaxel/ramucirumab in a real- life cohort of patients. After a median follow-up of 10.74 months, the median progression-free survival (PFS) was 5.8 months (95% CI: 3.04 - 5,63). Disease control rate (DCR) was 61% and the median duration of response (DOR) was 5.8 months. Median overall survival (OS) was 8.3 months. A trend toward better outcome was observed in HER2 positive patients. In multivariate analysis, nutritional status (p = 0.0001) and number of metastatic sites (p = 0.0266) resulted significantly related with longer PFS. Our analysis confirmed the efficacy and safety of the combination of ramucirumab with paclitaxel also in the real-life practice and the median PFS is significantly longer than that reported for Western population in previous studies. Subgroup analysis confirms the key-role of nutritional status as prognostic factor and suggests a possible interaction between EGF and angiogenesis pathways that deserves further investigations.

In The Lancet Oncology, Josep Tabernero and colleagues 1 report the final analysis of the JACOB trial, which tested the efficacy and safety of pertuzumab (a monoclonal antibody targeting HER2 receptors) combined with trastuzumab and chemotherapy in previously untreated patients with HER2-positive metastatic gastric or gastrooesophageal junction cancer. JACOB was the first trial to investigate a dual HER2 blockade in metastatic gastric cancer; unfortunately, no significant improvement in overall survival was observed in the group treated with the dual-HER2 targeted combination.

Adenocarcinomas at the gastro-oesophageal junction (GOJ) are currently stratified by tumour location. This retrospective study examines the association of preneoplastic conditions and inflammation of the gastric mucosa with GOJ cancer at different locations and compares them with nonjunctional gastric cancers.A total of 520 patients with junctional and nonjunctional gastric cancer were assessed for the presence and degree of intestinal metaplasia, glandular atrophy and inflammation in the stomach. Histopathological data were complete for 428 patients (68.9% men, median age 67.7 years), including 172 patients with GOJ cancer (GOJ1: 1-5 cm proximal to the junction, GOJ2: 'true' junctional, GOJ3: 2-5 cm distal to the junction). Gastric inflammation and preneoplastic conditions were scored according to the updated Sydney classification and further stratified into respective operative link on gastritis assessment (OLGA) and operative link on gastritis assessment on intestinal metaplasia (OLGIM) stages.The prevalence and degree of gastric atrophy and intestinal metaplasia were significantly lower in GOJ1 than GOJ3 (P0.01). Preneoplastic conditions in the stomach were similar in GOJ3 compared with nonjunctional gastric cancer. GOJ1 were almost exclusively (98.4%) of the intestinal type, whereas GOJ2 and GOJ3 were the diffuse type in 22.6 and 22.4% of the patients (P0.001). Of all patients, only 8.5 and 12.7% presented with stage III/IV according to OLGA and OLGIM, respectively. However, data for OLGA and OLGIM staging were only available in 61.2 and 67.9% of patients, respectively.GOJ1 are less likely to be associated with gastric pathology compared with GOJ3 or nonjunctional gastric cancer. OLGA or OLGIM staging in patients with advanced gastro-oesophageal cancer seems to be of limited value.

Adenocarcinomas of the lower oesophagus and gastro-oesophageal junction are a complex clinico-pathological setting. Multimodality therapy is considered mandatory in most disease presentations. Nevertheless, the most appropriate treatment package has yet to be established. We herein summarize the evidence derived from randomized phase III trials on pre-operative treatments in this oncological scenario.

Objective To compare chemotherapy first (group 1) versus self-expanding metal stent first (group 2) for the management of malignant dysphagia in unresectable oesophageal or gastro-oesophageal junction cancer. Methods Patients from two university hospitals with severe malignant dysphagia (dysphagia score ≥ 2) uneligible for surgery or radiochemotherapy were evaluated retrospectively. Results Forty-two patients were included in group 1, and 29 in group 2. After 4 weeks, dysphagia scores improved by at least 1 point in 67% of patients in group 1 versus 93% in group 2 ( p = 0.01); 48% of patients in group 1 were able to eat solid food versus 68% in group 2 ( p = 0.054). In group 1, a self-expanding metal stent was secondarily placed in 18 patients (42.9%), whereas in group 2 dysphagia required a second self-expanding metal stent placement in 33.3% of patients. Conclusion Chemotherapy as the first treatment may be a valid option, avoiding self-expanding metal stent insertion in half of the patients.

OBJECTIVES The current (7th) International Union Against Cancer (UICC) pN staging system is based on the number of positive lymph nodes but does not take into consideration the characteristics of the metastatic lymph nodes itself. In particular, it has been suggested that tumour penetration beyond the lymph node capsule in metastatic lymph nodes, which is also called extracapsular lymph node involvement, has a prognostic impact. The aim of the current study was to assess the prognostic value of extracapsular (EC) and intracapsular (IC) lymph node involvement (LNI) in adenocarcinoma of the oesophagus and gastro-oesophageal junction (GOJ) and to assess its potential impact on the 7th edition of the UICC TNM manual. METHODS From 2000 to 2010, all consecutive adenocarcinoma patients with primary R0-resection (n = 499) were prospectively included for analysis. The number of resected lymph nodes, number of positive lymph nodes and number of EC-LNI/IC-LNI were determined. Extracapsular spread was defined as infiltration of cancer cells beyond the capsule of the positive lymph node. RESULTS Two hundred and eighteen (43%) patients had positive lymph nodes. Cancer-specific 5-year survival in lymph node-positive patients was significantly (P < 0.0001) worse compared with lymph node-negative patients, being 88.3 vs 28.7%, respectively. In 128 (58.7%) cases EC-LNI was detected. EC-LNI showed significantly worse cancer-specific 5-year survival compared with IC-LNI, 19.6 vs 44.0% (P < 0.0001). In the pN1 category (1 or 2 positive LN's-UICC stages IIB and IIIA), this was 30.4% vs 58%; (P = 0.029). In higher pN categories, this effect was no longer noticed. Integrating these findings into an adapted TNM classification resulted in improved homogeneity, monotonicity of gradients and discriminatory ability indicating an improved performance of the staging system. CONCLUSIONS EC-LNI is associated with worse survival compared with IC-LNI. EC-LNI patients show survival rates that are more closely associated with the current TNM stage IIIB, while IC-LNI patients have a survival more similar to TNM stage IIB. Incorporating the EC-IC factor in the TNM classification results in an increased performance of the TNM model. Further confirmation from other centres is required within the context of future adaptations of the UICC/AJCC (American Joint Committee on Cancer) staging system for oesophageal cancer.

Introduction The Siewert classification has been used to plan treatment for tumours of the gastro-oesophageal junction since its proposal in the 1980s. The purpose of this study was to assess its continued relevance by evaluating whether there were differences in the biology and clinical characteristics of adenocarcinomas by Siewert type, in a contemporary cohort of patients, in whom the majority had received neoadjuvant chemotherapy. Methods A prospective database was reviewed for all patients who underwent resection from 2005 to 2011 and analysed with regard to Siewert classification determined from the pathological specimen, treatment and clincopathological outcomes. Results Two hundred and sixteen patients underwent oesophagogastric resection: 133 for type I, 51 for type II and 33 for type III tumours. 135 Patients (62.5%) received neoadjuvant chemotherapy with no difference between groups. There were no significant differences in age, sex, pT stage, pN stage, pM stage, ASA, or inpatient complications between patients with adenocarcinoma based on their Siewert classification. There was a significant increase in maximum tumour diameter (P = 0.023), perineural invasion (P = 0.021) and vascular invasion (P = 0.020), associated with more distal tumours (Type III > Type II > Type I). Median overall survival was significantly shorter for more distal tumours (Type I: 4.96 years vs. Type II: 3.3 years vs. Type III: 2.64 years; P = 0.04). The surgical approach did not influence survival. Conclusion In the era of multi-modal treatment pathological Siewert tumour type is of prognostic value, as patients with Type III disease are likely to have larger and more aggressive tumours that lead to worse outcomes. J. Surg. Oncol. 2014;109:202–207.

The two most commonly occurring oesophageal tumours are squamous cell carcinomas and adenocarcinomas. These differ in their aetiology, pathogenesis and response to treatment. The incidence of oesophageal adenocarcinoma is rapidly increasing and, for both tumours, the prognosis remains poor. Here, we discuss the management of these tumours as well as the current recommendations for screening and surveillance. © 2007 Elsevier Ltd. All rights reserved.

Background. The standard of care for patients with operable gastric and gastro-oesophageal junction (GOJ) tumours involves neoadjuvant chemotherapy. This improves survival and reduces risk of tumour recurrence following surgery. The various grading criteria published to assess histological response to neoadjuvant treatments have never been compared in terms of their reproducibility and ability to predict survival. Methods. A study was carried out of 66 patients with gastric and GOJ (types II and III) adenocarcinoma treated with neoadjuvant chemotherapy according to the MAGIC protocol. Histology slides were reviewed independently by two histopathologists using three published grading systems (Mandard, Japanese, and Becker). Histological, demographic, and survival data were collected. The kappa statistic was used to assess interobserver reproducibility. Results. Three (5%) patients had a complete pathological response. There was reasonable interobserver agreement for the grading systems: κ-scores = 0.44 (Mandard), 0.28 (Japanese), and 0.51 (Becker). Only Mandard and Becker scores provided prognostic information: 5-year overall survival rates of 100% for complete or near complete responders versus 35% for nonresponders () for both. Positive lymph nodes () and resection margins () were associated with poor survival. Conclusion. Becker’s score is most reproducible for the evaluation of histological response. Furthermore, lymph node and resection margins status provides prognostic information.

This article discusses the investigation and management of gastro-oesophageal reflux disease, para-oesophageal hernias and achalasia.

Background NeoRes I is a randomized phase II trial comparing neoadjuvant chemoradiotherapy with neoadjuvant chemotherapy in the treatment of resectable oesophageal cancer. Methods Patients with biopsy-proven adenocarcinoma or squamous cell carcinoma in the oesophagus or gastro-oesophageal junction (Siewert type I and II), T1N1 or T2–3N0–1 and M0-M1a (AJCC 6th edition) were randomized to receive three 3-weekly cycles of cisplatin 100 mg/m2 day 1 and fluorouracil 750 mg/m2/24 hours, days 1–5 with or without the addition of concurrent radiotherapy 40 Gy, 2 Gy/fraction, 5 days a week, followed by oesophageal resection with two-field lymphadenectomy. Primary endpoint was complete histopathological response rate. Survival and recurrence patterns were evaluated as secondary endpoints. Results Between 2008 and 2013, 181 patients were enrolled in 10 participating institutions in Sweden and Norway. Patients were well matched for pre-treatment characteristics T3: 64,1%, T2: 34,8%, T1: 1,1%. Adenocarcinoma: 72,4%, squamous cell carcinoma: 27,6%. Proximal/middle: 16,6%, distal: 65,2%, cardia (Siewert type II): 18,2%. Conclusion This is to our knowledge the largest completed randomized trial comparing neoadjuvant chemotherapy with neoadjuvant chemoradiotherapy followed be oesophageal resection in patients with cancer in the oesophagus or gastro-oesophageal junction. We found no overall or progression-free survival advantages by adding radiotherapy, despite better tumour tissue response. Disclosure All authors have declared no conflicts of interest.

Ramucirumab, a fully humanized monoclonal antibody directed against vascular endothelial growth factor receptor 2, is the first targeted agent to have demonstrated an improvement in survival, as a single agent or in combination, in a molecularly unselected population in gastro-oesophageal cancer. Now that second-line treatment is routinely considered for patients with advanced gastro-oesophageal cancer, ramucirumab, with its favourable toxicity profile compared with cytotoxic treatment, provides a valuable additional treatment option.

Summary HER2 is amplified/overexpressed in a subset of gastric and gastro-oesophageal junction cancers. Addition of anti-HER2 therapy has been shown to provide survival benefit in this setting. However, there are limited data assessing the concordance of HER2 status between primary and metastatic sites. A total of 113 samples from 43 paired primary and metastatic tumours were tested for HER2 status, by immunohistochemistry (IHC) for protein expression and silver in situ hybridisation (SISH) for gene amplification. Primary sites tested included endoscopic biopsies (n = 30) and resections (n = 24). Metastatic samples included lymph nodes (n = 29), peritoneal effusions (n = 21) and miscellaneous sites (n = 9). The overall HER2+ rate was 11%. Of 41 (95%; 95% CI 88.5–100%) concordant cases, 38 were HER2– and three were HER2+. There were two (5%) discordant cases, one of which showed heterogeneity of HER2 expression. This series confirms a high concordance rate of 95%, supporting that testing of primary tumours and metastases is equally valid and providing clinical rationale for the addition of anti-HER2 therapy in HER2+ disseminated disease.

To systematically identify utility values associated with advanced gastric cancer (GC), oesophageal cancer (OC), or gastro-oesophageal junction (GEJ) cancer. Utility values relating to health states are an essential component for cost-utility analysis (CUA).MEDLINE, Embase, Cochrane Library, and EconLit databases were reviewed for relevant studies using a pre-defined search strategy. Studies eligible for inclusion reported health state utility values (HSUVs) using direct (standard gamble [SG] and time-trade-off [TTO]) and indirect (such as EuroQol 5D [EQ-5D], short-form 6D [SF-6D], and the 15-dimensional instrument [15D]) methods for patients with advanced GC, OC, or GEJ cancer.A total of 539 unique publications were identified, of which eight met the inclusion criteria (GC, n = 2; mixed population [gastrointestinal cancers], n = 4; OC, n = ). The most commonly used instrument to estimate HSUVs was the EQ-5D (n = 7). Utilities were also estimated using the SF-6D and the 15D in the same study (n = 1). Direct elicitation methods included the TTO (n = 2) and SG (n = 1). Across the eight identified publications, health states and study populations were heterogeneous and sample sizes were limited.This review, as with all summaries of this nature, is only as robust as the data derived from the identified studies. The systematic review process does not resolve any design issues or biases associated with the original studies.Limited data estimate HSUVs in patients with advanced GC, OC, or GEJ cancer. Utilities for advanced GC alone and advanced OC alone were reported in only two publications for each cancer type. No publications considered advanced GEJ utilities alone, and four publications considered utilities for a mixed population of gastrointestinal cancer types. Comparisons are confounded by heterogeneity across the identified publications. Further research into HSUVs associated with advanced GC and OC is required to improve the evidence available for use in CUAs.

The topographical anatomy of the gastro-oesophageal junction was evaluated in six Greyhounds and six Beagles with particular emphasis on the inter-relationship of anatomic structures and landmarks. Significant variation existed between individuals, and a standard topography could not be identified. It was not possible to document the consistent presence of an intra-abdominal oesophagus in either breed examined; in the majority of cases the oesophagus was contained entirely within the thoracic cavity such that no portion of the oesophagus could be subject to abdominal pressures. This has implications for understanding the pathogenesis of hiatal hernia associated gastro-oesophageal reflux disease.

BACKGROUNDHiatus hernia and lower oesophageal sphincter hypotension are often viewed as opposing hypotheses for gastro-oesophageal junction incompetence.AIMSTo examine the interaction between hiatus hernia and lower oesophageal sphincter hypotension.METHODSIn seven normal subjects and seven patients with hiatus hernia, the squamocolumnar junction and intragastric margin of the gastro-oesophageal junction were marked with endoscopically placed clips. Axial and radial characteristics of the gastro-oesophageal junction high pressure zone were mapped relative to the hiatus and clips during concurrent fluoroscopy and manometry. Responses to inspiration and abdominal compression were also analysed.RESULTSIn normal individuals the squamocolumnar junction was 0.5 cm below the hiatus and the gastro-oesophageal junction high pressure zone extended 1.1 cm distal to that. In those with hiatus hernia, the gastro-oesophageal junction high pressure zone had two discrete segments, one proximal to the squamocolumnar junction and one distal, attributable to the extrinsic compression within the hiatal canal. Inspiration and abdominal compression mainly augmented the distal one. Simulation of hernia reduction by algebraically summing the proximal segment pressures with the hiatal canal pressures restored normal maximal pressure, radial asymmetry, and dynamic responses of the gastro-oesophageal junction.CONCLUSIONSHiatus hernia reduces lower oesophageal sphincter pressure and alters its dynamic responsiveness by spatially separating pressure components derived from the intrinsic lower oesophageal sphincter and the extrinsic compression of the oesophagus within the hiatal canal.

The anatomy of the GE junction is represented by computer synthetised pictures. This method allows to represent different organs from different angles, emphasis being put on the laparoscopic angle of vision. This should improve anatomical comprehension. The synthetic pictures have been constructed in a figurative representation. Fatty tissues have been omitted whereas the peritoneal layers covering organs and defining spaces are enhanced.