[Esophageal cancer: standards and innovations in multidisciplinary treatment]. / Cancer de l'œsophage : standards et innovations du traitement multidisciplinaire.

Esophageal cancer is a severe disease that requires a combined therapeutic approach to improve the prognosis. Once the initial assessment is completed, the patient's case should be discussed in a multidisciplinary conference in a specialized center to decide on an appropriate therapeutic strategy taking into account the stage of the disease and the patient's general condition. Several advances in treatment, both from a surgical technique standpoint, with the advent of minimally invasive and robotic surgery, and from a medical perspective, with the use of immunotherapy under certain conditions, have dramatically improved mortality rates. In this article, we explore the standards and latest innovations in the multimodal treatment of esophageal cancer.

Le cancer de l'œsophage est une pathologie sévère nécessitant une approche thérapeutique combinée afin d'en améliorer le pronostic. Une fois le bilan initial réalisé, le cas du patient doit être discuté lors d'un colloque multidisciplinaire dans un centre spécialisé, afin de décider d'une stratégie thérapeutique adaptée tenant compte du stade de la maladie et de l'état général du patient. Plusieurs avancées en matière de traitement, tant du point de vue technique chirurgical, par l'avènement de la chirurgie minimalement invasive et robotique, que du point de vue médical, par le recours à l'immunothérapie sous certaines conditions, ont permis d'améliorer drastiquement le taux de mortalité. Dans cet article, nous explorons les standards ainsi que les dernières innovations dans le traitement multimodal du cancer de l'œsophage.

Predictive Value of Preoperative Endoscopic Ultrasound (EUS) After Neoadjuvant Chemotherapy in Locally Advanced Esophagogastric Cancer - Data From a Randomized German Phase II Trial.

PURPOSE: The role of EUS before or after neoadjuvant chemotherapy (nCTX) in advanced esophagogastric cancer (EGC) is still unclear. The phase II NEOPECX trial evaluated perioperative chemotherapy with or without panitumumab in this setting. The aim of this sub-study was to investigate the prognostic value of EUS-guided preoperative staging before and after nCTX. MATERIALS AND METHODS: Preoperative yuT/yuN stages by EUS were compared with histopathological ypT/ypN stages after curative resection. Reduction in T-stage from baseline to preoperative EUS was defined as downstaging (DS+) and compared to progression-free (PFS) and overall survival (OS) of patients without downstaging (DS-). In addition, preoperative EUS N-stages (positive N+ or negative N-) were correlated with clinical data. RESULTS: The preoperative yuT-stage correlated with the ypT-stage in 48% of cases (sensitivity 48%, specificity 52%), while the preoperative yuN-stage correlated with the ypN-stage in 64% (sensitivity 76%, specificity 52%). Within DS+ patients who were downstaged by ≥ 2 T-categories, a trend towards improved OS was detected (median OS DS+: not reached (NR), median OS DS-: 38.5 months (M), p=0.21). Patients with yuN+ at preoperative EUS had a worse outcome than yuN- patients (median OS yuN-: NR, median OS yuN+: 38.5 M, p = 0.013). CONCLUSION: The diagnostic accuracy of EUS to predict the response after nCTX in patients with advanced EGC is limited. In the current study the endosonographic detection of lymph node metastasis after nCTX indicates a poor prognosis. In the future, preoperative EUS with sectional imaging procedures may be used to tailor treatment for patients with advanced EGC.

[Modern Multimodal Concepts for Advanced and Metastatic Esophageal Cancer]. / Moderne multimodale Konzepte für fortgeschrittene und metastasierte Ösophaguskarzinome.

Modern Multimodal Concepts for Advanced and Metastatic Esophageal Cancer Abstract. In case of locally advanced esophageal carcinoma, the clear recommendation for multimodal therapy has been established in the guidelines. This also applies to systemic therapy in the palliative, metastatic situation. Against the background of increasing experience with multimodal concepts and a parallel trend towards more and more personalized tumor therapy, therapy options that go beyond this are increasingly being used. The most recent chapter here is the successful use of antibodies and immune checkpoint inhibitors in the adjuvant, additive or palliative setting. Salvage concepts and the salvage operation are also used. These are efficient options to be able to react surgically from a situation of clinical remission and close observation in case of tumor recurrence. The limited radical surgical procedures with reconstruction according to "Merendino" and the "double tract procedure" with limited resection of the distal esophagus and proximal stomach via abdominal approach are options for high-risk patients or very elderly patients. They show great advantages with regard to the operational stress and - especially the "double tract procedure" - with regard to the quality of life. The oligometastatic situation is also the subject of ongoing studies. Under strict clinical observation, it may make sense not to exclude patients with very limited metastases from a curative concept. Numerous cases of long-term survival encourage this. In the palliative setting, in addition to classic chemotherapy and best supportive care, immunotherapy is also playing an increasingly important role, and here, too, a conversion to a curative concept is possible if the response is good. Palliative esophageal resections in the case of disseminated metastases, infiltration of vertebral bodies, aorta or trachea or main bronchi must be strictly avoided and must unfortunately be described as incurable.

[Chemotherapy and Radio-Chemotherapy of Locally Advanced Esophageal Cancer]. / Chemotherapie und Radio-/Chemotherapie des lokal fortgeschrittenen Ösophaguskarzinoms.

Chemotherapy and Radio-Chemotherapy of Locally Advanced Esophageal Cancer Abstract. Surgical resection alone of locally advanced esophageal carcinoma leads to long-term survival in only about 30% of cases. The multimodal strategy for locally advanced tumors, especially neoadjuvant radiochemotherapy and chemotherapy, has significantly improved the long-term prognosis. Multimodal therapy concepts have been developed which improve overall survival. Therapy planning must be performed pretherapeutically in an interdisciplinary tumor board, preferably at a high-volume center. For squamous cell carcinomas, neoadjuvant radio/chemotherapy followed by resection or definitive radio/chemotherapy are currently the therapies of choice. For adenocarcinomas, neoadjuvant radio/chemotherapy followed by resection or perioperative chemotherapy are considered equivalent therapeutic standards. After neoadjuvant radiochemotherapy, adjuvant immunotherapy is currently recommended in case of only incomplete histopathological response.

[Esophageal and esophago-gastric junction cancer†: management and multimodal treatment]. / Cancer de l'œsophage et de la jonction œsogastrique†: prise en charge et traitement multidisciplinaire.

Esophageal cancer remains an oncological burden with a low survival rate. Multidisciplinary management is essential to offer an adjusted treatment to the patient general condition and the tumor stage. New minimally invasive surgical treatments help to reduce the surgical trauma and improve post-operative patient recovery. Oncological treatments have also evolved and definitive treatment by radio-chemotherapy can be proposed in specific cases.

Le cancer de l'œsophage reste un fardeau oncologique avec un taux de survie bas. Une prise en charge multidisciplinaire est primordiale afin d'offrir un traitement adapté à l'état général du patient et au stade de la tumeur. De nouvelles prises en charge minimalement invasives chirurgicales permettent de diminuer le traumatisme d'une chirurgie majeure et améliorent la récupération des patients en postopératoire. Les traitements oncologiques ont également évolué et un traitement définitif par radiochimiothérapie peut être proposé dans des cas précis.

Glucose transporters 1, 3, 6, and 10 are expressed in gastric cancer and glucose transporter 3 is associated with UICC stage and survival.

BACKGROUND: Due to proliferation and increased metabolism, cancer cells have high glucose requirements. The glucose uptake of cells is influenced by a group of membrane proteins denoted the glucose transporter family (Glut-1 to -12). Whereas increased expression and a negative correlation with survival have been described for Glut-1 in several types of cancer, the impact of other glucose transporters on tumor biology is widely unknown. METHODS: In this retrospective study, gastric cancer specimens of 150 patients who underwent total gastrectomy between 2005 and 2010 were stained for Glut-1, -3, -6, and -10 by immunohistochemistry. Expression of Glut-1, -3, -6, and 10 was correlated to prognosis as well as clinical and pathological parameters. RESULTS: Glut-1, Glut-3, Glut-6, and Glut-10 were expressed in 22.0, 66.0, 38.0, and 43.3 % of the analyzed samples. Whereas Glut-1, -6, and -10 did not show a correlation with prognosis, positive staining for Glut-3 was associated with higher UICC stage and inferior prognosis. The mean overall survival was 38.6 months for Glut-3 positive patients, as compared to 51.2 months for Glut-3 negative patients (p < 0.05). Coexpression of two or more of the analyzed glucose transporters was correlated to inferior prognosis. Glut-3 and UICC stage were significant prognostic factors in multivariate analysis. CONCLUSIONS: All of the analyzed glucose transporters were expressed in a significant proportion of the gastric cancer samples. Glut-3 was associated with higher UICC stage and inferior prognosis. These findings are relevant to therapeutic approaches that target glucose metabolism as well as to imaging using radioactively labeled glucose.

Premature mortality for patients after completely resected early adenocarcinoma of the esophagus or stomach.

OBJECTIVE: To establish the life expectancy burden of esophago-gastric cancer by analyzing years of life lost (YLL) for a Western patient population after treatment of early esophageal (EAC) or early gastric (GAC) adenocarcinoma. BACKGROUND: For patients with early EAC or GAC, the short-term prognosis after surgical resection is very good. Little data is available regarding long-term prognosis when compared to the general population. METHODS: Two hundred and fourteen patients with pT1 EAC (n = 112) or GAC (n = 102) were included in the study. Patients with EAC underwent transthoracic en-bloc esophagectomy; those with GAC had total or subtotal gastrectomy with D2-lymphadenectomy. Surviving patients had a median follow-up of approximately 14 years. YLL was calculated using average life expectancy data from Germany. RESULTS: Patients with EAC were younger (median age 61 years) than those with GAC (66 years) (p = 0.031). The male:female ratio was 10:1 for EAC and 3:2 for GAC (p < 0.001). Multivariate survival analysis showed the age of the patients ≥60 years and the existence of lymph node metastasis was associated with poor prognosis. The median YLL for all patients who died over follow-up was 8.0 years. For patients under 60 years, it was approximately 20 years, and for older patients, approximately 5 years (p < 0.001) without difference in tumor stage between these age cohorts. YLL did not differ for GAC vs. EAC. CONCLUSION: After surgical resection, the prognostic burden as measured by YLL is relevant for all patients with early esophageal and gastric adenocarcinomas and especially for younger patients. Reasons for YLL need further studies.

Impact of Nonalcoholic Steatohepatitis on the Outcome of Patients Undergoing Roux-en-Y Gastric Bypass Surgery: a Propensity Score-Matched Analysis.

PURPOSE: It is currently unknown whether NASH (nonalcoholic steatohepatitis), as compared to simple steatosis, is associated with impaired postoperative weight loss and metabolic outcomes after RYGB surgery. To compare the effectiveness of Roux-en-Y gastric bypass (RYGB) on patients with NASH versus those with simple nonalcoholic fatty liver (NAFL). MATERIALS AND METHODS: We retrospectively retrieved data from 515 patients undergoing RYGB surgery with concomitant liver biopsy. Clinical follow-up and metabolic assessment were performed prior to surgery and 12 months after surgery. We used multivariate analysis of variance (MANOVA) and propensity score matching and we assessed for changes in markers of hepatocellular injury and metabolic outcomes. RESULTS: There were 421 patients with simple NAFL, and 94 with NASH. Baseline alanine and aspartate aminotransferases were significantly higher in patients with NASH (p < 0.01). Twelve months after the RYGB surgery, as determined by both MANOVA and propensity score matching, patients with NASH exhibited a significantly greater reduction in alanine aminotransferase (ß-coefficient - 12 iU/l [- 22 to - 1.83], 95% CI, adjusted p = 0.021) compared to their NAFL counterparts (31 matched patients in each group with no loss to follow-up at 12 months). Excess weight loss was similar in both groups (ß-coefficient 4.54% [- 3.12 to 12.21], 95% CI, adjusted p = 0.244). Change in BMI was comparable in both groups (- 14 (- 16.6 to - 12.5) versus - 14.3 (- 17.3 to - 11.9), p = 0.784). CONCLUSION: After RYGB surgery, patients with NASH experience a greater reduction in markers for hepatocellular injury and similar weight loss compared to patients with simple steatosis.

[Treatment options for oligometastatic gastric cancer]. / Therapieoptionen beim oligometastasierten Magenkarzinom.

BACKGROUND: At the time of diagnosis of gastric cancer approximately one third of patients already have metastases. It is important to differentiate between oligometastasis and the diffuse metastatic situation. For the first time the definition of oligometastasis has been integrated into the German S3 guidelines. OBJECTIVE: Can multimodal treatment with tumor resection and metastasectomy combined with perioperative chemotherapy, increase the chances of survival in oligometastatic patients? MATERIAL AND METHODS: In this review article the data situation of the current literature is discussed. RESULTS: The Dutch D1/D2 trial reported an increased median survival for a subgroup of patients with single metastasis who underwent resection. Multimodal treatment with resection doubled the median survival of oligometastatic patients in the German AIO-FLOT 3 study and as a consequence, the AIO-FLOT 5 (RENAISSANCE) trial was designed. Patients with oligometastatic gastric and esophagogastric junction cancer are randomized after chemotherapy to either undergo resection followed by adjuvant chemotherapy or to undergo definitive chemotherapy. Further randomized trials investigate the benefit of antibodies and immune checkpoint inhibitors in locoregional and advanced metastatic gastric cancer with promising results. CONCLUSION: The results of the ongoing randomized trials will show if oligometastatic patients benefit from a multimodal treatment with resection. The clear definition of the oligometastatic state, assessment of the response to neoadjuvant chemotherapy and realistic estimation of the R0 resectability will be useful for patient selection.

Multimodal treatment in locally advanced gastric cancer.

According to the data of the GLOBOCAN-network of the World Health Organization, there were 952,000 (6.8% of the total) new cases of gastric cancer in 2012, making it the fifth most common malignancy in the world. It represents a substantive change since the very first estimates in 1975 when stomach cancer was the most common neoplasm. More than 70% of cases (677,000 cases) occur in developing countries, and half the world total occurs in Eastern Asia, mainly in China. Gastric cancer is the third leading cause of cancer death in both sexes worldwide (Globocan, Estimated cancer incidence, mortality and prevalence worldwide in 2012, http://globocan.iarc.fr , 2012). Annually, worldwide 723,000 patients die of this tumor entity. Interestingly, a strong change in incidence rates in relation to the anatomical-topographic localization of the primary tumors in the stomach and esophagus has been experienced. While the frequency of proximal gastric carcinoma and adenocarcinoma of the cardiac and subcardiac region in Europe and North America has been constantly rising, distal gastric carcinomas have become less common (Torre et al. in JAMA 65:87-108, 2015). Furthermore, the relative incidence of esophageal adenocarcinoma (mostly localized in the distal esophagus) has strongly increased (Jemal et al. in JAMA 58:71-96, 2008; Crew and Neugut 31:450-464, 2004; Pohl and Welch 97:142-146, 2005).

[Foreign-Body Ingestion: A Rare Cause of Abdominal Pain]. / Die Fremdkörperingestion ­ eine seltene Ursache persistierender, unklarer abdomineller Schmerzen.

HISTORY AND FINDINGS UPON ADMISSION: A 50-year-old man presented at the emergency unit with abdominal pain in the right lower quadrant and dysuria. He described an increase in pain during micturition. EXAMINATIONS: After multiple examinations (CT-scan, MR-scan, ileocolonoscopy) were performed to no avail, a toothpick was detected in the terminal ileum during an ultrasound scan of the small intestine. Prompted elevation of intra-abdominal pressure led to migration of the radiolucent sharp foreign body into the wall of the urinary bladder, inducing pain. TREATMENT: Median laparotomy revealed a two-sided perforation of the terminal ileum with ileosigmoidal fistula, which was induced by an ingested toothpick. The patient underwent en-bloc resection of the infectious tumor by segmental ileal resection and sigma resection. Anastomoses were performed as hand-sewn end-to-end ileoileostomy and end-to-end stapled colorectal anastomosis, respectively. CONCLUSION: Ingested foreign bodies and perforation of the gastrointestinal tract by foreign bodies are rare events but may cause serious gut injuries. The ingestion of foreign bodies should be kept in mind as an important differential diagnosis in patients with acute abdomen or chronic abdominal pain of unknown origin, especially in children. Abdominal ultrasound can be a useful diagnostic tool in identifying ingested foreign bodies.

Preoperative staging of nodal status in gastric cancer.

An accurate preoperative staging of nodal status is crucial in gastric cancer, because it has a great impact on prognosis and therapeutic decision-making. Different staging methods have been evaluated for gastric cancer in order to predict nodal involvement. So far, no technique could meet the necessary requirements, which include a high detection rate of infiltrated lymph nodes and a low frequency of false-positive results. This article summarizes different staging methods used to assess lymph node status in patients with gastric cancer, evaluates the evidence, and proposes to establish new methods.