Anterior gastric wall anastomosis may lead to lower rate of delayed gastric emptying after minimally invasive Ivor Lewis esophagectomy: a retrospective cohort study.

INTRODUCTION: In minimally invasive esophagectomy, a circular stapled anastomosis is common, but no evidence exists investigating the role of the specific localization of the anastomosis. The aim of this study is to evaluate the impact of an esophagogastrostomy on the anterior or posterior wall of the gastric conduit on the postoperative outcomes. MATERIAL AND METHODS: All oncologic minimally invasive Ivor Lewis procedures, performed between 2017 and 2022, were included in this study. The cohort was divided in two groups: a) intrathoracic esophagogastrostomy on the anterior gastric wall of the conduit (ANT, n = 285, 65%) and b) on the posterior gastric wall (POST, n = 154, 35%). Clinicopathological parameters and short-term outcomes were compared between both groups by retrieving data from the prospective database. RESULTS: Overall, 439 patients were included, baseline characteristics were similar in both groups, there was a higher proportion of squamous cell carcinoma in ANT (22.8% vs. 16.2%, P = 0.043). A higher rate of robotic-assisted procedures was observed in ANT (71.2% vs. 49.4%). Anastomotic leakage rate was similar in both groups (ANT 10.4% vs. POST 9.8%, P = 0.851). Overall complication rate and Clavien-Dindo > 3 complication rates were higher in POST compared to ANT: 53.2% vs. 40% (P = 0.008) and 36.9% vs. 25.7% (P = 0.014), respectively. The rate of delayed gastric emptying (20.1% vs. 7.4%, P < 0.001) and nosocomial pneumonia (22.1% vs. 14.8%, P = 0.05) was significantly higher in POST. CONCLUSION: Patients undergoing minimally invasive Ivor Lewis esophagectomy with an intrathoracic circular stapled anastomosis may benefit from esophagogastrostomy on the anterior wall of the gastric conduit, in terms of lower rate of delayed gastric emptying.

[Anastomotic techniques in minimally invasive esophageal and gastric surgery]. / Anastomosentechniken in der minimal-invasiven Ösophagus- und Magenchirurgie.

In specialized centers minimally invasive surgery has become established as the standard of care for esophageal and gastric surgery. Offering equal oncological outcome, patients benefit with respect to lower postoperative pain and complication rates. The creation of the anastomosis during minimally invasive surgery remains a critical step and the complications are decisive for the immediate postoperative course. So far no clear consensus exists in the literature regarding the recommended techniques for placement of an anastomosis after resections in the upper gastrointestinal tract. This article summarizes and compares the various established anastomotic techniques used in minimally invasive esophageal and gastric surgery.

Current Surgical Concepts in Lynch Syndrome and Familial Adenomatous Polyposis.

Background: Approximately 5% of colorectal cancers (CRCs) are associated with hereditary cancer syndromes. The natural history of these syndromes differs from sporadic cancers, and due to their increased risk of metachronous carcinomas, surgical approaches also differ. This review focuses on the current recommendations for surgical treatment and what evidence has led to these recommendations in the most clinically relevant hereditary CRC syndromes: Lynch syndrome (LS) and (attenuated) familial adenomatous polyposis (FAP). Summary: LS has no common phenotype and is caused by individual germline variants in one of the mismatch repair genes (MLH1, MSH2, MSH6, or PMS2). Because each gene is associated with a different risk of metachronous cancer, guidelines now differentiate between genes in their recommendations for oncology interventions. Classical and attenuated FAP are caused by germline mutations in the APC gene and have a characteristic phenotype. Although correlations exist between phenotype and genotype, the indication for surgery is predominantly based on clinical manifestation rather than specific gene mutations. Key Message: Currently, the recommendation on the two diseases tends to go in opposite directions: while some forms of FAP may require less extensive surgery, in some LS patients, more sophisticated knowledge of metachronous carcinoma risk leads to more extensive surgery.

[Achalasia Update]. / Update Achalasie.

Achalasia Update Abstract. The neurodegenerative disease achalasia (obsolete: "cardiac spasm") is the second most common functional disease of the esophagus after reflux disease. It is associated with an extremely high level of suffering for the patient. Pathophysiologically, it is a combination of a lack of swallowing-reflex relaxation at the gastric entrance and disturbed peristalsis of the tubular esophagus. The gold standard in diagnostics is high-resolution manometry. The disease cannot be cured, the therapeutic spectrum that alleviates the disease includes pharmaceutical, endoscopic-interventional and surgical procedures.

[Minimally Invasive Esophagectomy for Esophageal Cancer]. / Minimalinvasive Ösophagektomie für maligne Tumore der Speiseröhre.

Minimally Invasive Esophagectomy for Esophageal Cancer Abstract. Oncological esophagectomy with gastric pull up and intrathoracic represents the standard surgical procedure in the curative treatment of malignant tumors of the esophagus and the esophagogastric junction. The procedure, as two or three body cavities are accessed, has a natural level of invasiveness, which suggests lowering the surgical trauma using minimally invasive surgery (MIS). Because of the complexity of the surgical procedure, minimally invasive esophagectomy is an operation with relevant surgical learning curve. As of now, two principally different minimally invasive techniques for esophageal resection are established in clinical routine in specialized centers, the conventional laparoscopy/thoracoscopy based method and the robotic approach. Benefits of minimally invasive esophagectomy are reduced pulmonary complications and reduced postoperative pain. The surgical radicality of both minimally invasive techniques is at least comparable to the open approach and combined MIS/open approach, long-term survival outcomes from randomized controlled trials are pending. The robotic surgical technology has evolved dramatically over the last decade and oncological esophagectomy offers meaningful opportunity for application. Due to further technological progress, robotic surgery is expected to play an even more important role in the future. Focusing on the direct comparison of conventional minimally invasive esophagectomy and robotic-assisted esophagectomy, the randomized ROBOT-2 trial will reveal important evidence.

[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.

Robotic-assisted surgery for esophageal submucosal tumors: a single-center case series.

Esophageal submucosal tumors (SMTs) are rare heterogenous clinical entities. The surgical resection can be performed in different surgical approaches. However, the robotic surgical strategy is poorly documented in the treatment of SMTs. We present our series of operated esophageal SMTs approached via robotic-assisted surgery. Six patients with symptomatic esophageal submucosal tumors underwent robotic surgery within a 3-year period. The performed procedures were robotic-assisted enucleation, robotic esophagectomy (RAMIE) and reverse hybrid robotic esophagectomy. Patients' clinical data, intra/postoperative outcomes, and histopathological features were retrieved from the institution's prospective database. Five of six patients were scheduled for upfront surgery: four underwent robotic enucleation (three leiomyoma and one suspected GIST) and one underwent reverse hybrid robotic esophagectomy (suspected GIST). One patient, diagnosed with GIST, was treated with neoadjuvant Imatinib therapy, before undergoing a RAMIE. No major intra-operative complications were recorded. Median length of stay was 7 days (6-50), with a longer post-operative course in patients who underwent esophagectomy. Clavien-Dindo > 3a complications occurred in two patients, aspiration pneumonia and delayed gastric emptying. The final histopathological and immuno-histochemical diagnosis were leiomyoma, well-differentiated GIST, low-grade fibromyxoid sarcoma and Schwannoma. Robotic-assisted surgery seems to be a promising option for surgical treatment strategies of benign or borderline esophageal submucosal tumors.

End to side circular stapled anastomosis during robotic-assisted Ivor Lewis minimally invasive esophagectomy (RAMIE).

Robotic-assisted minimally invasive esophagectomy (RAMIE) represents an established approach for the treatment of esophageal cancer. Aim of this study is to evaluate the feasibility and safety of our technique for performing the intrathoracic anastomosis during RAMIE.All the procedures were performed by the same surgeon using the same technique for performing the intrathoracic anastomosis. Intraoperative and postoperative outcomes were recorded. Postoperative complications were classified according to the Esophagectomy Complications Consensus Group (ECCG); the primary outcome was the evaluation of the feasibility and safety of our technique. From 2016 to 2021, 204 patients underwent Ivor Lewis RAMIE at our Center. Two patients (0.9%) were converted during the thoracic phase. The anastomosis was completed in all the other patients forming complete anastomotic rings. The median duration for the robotic-assisted thoracoscopic phase was 224 minutes. Twenty-two of the RAMIE-Ivor Lewis patients had an anastomotic leakage (10.3%). The overall 90-day postoperative mortality was 1.9%. The procedure resulted to be feasible and safe in our cohort of patients.

Technical details of the abdominal part during full robotic-assisted minimally invasive esophagectomy.

The full robotic-assisted minimally invasive esophagectomy (RAMIE) is an upcoming approach in the treatment of esophageal and junctional cancer. Potential benefits are seen in angulated precise maneuvers in the abdominal part as well as in the thoracic part, but due to the novelty of this approach the optimal setting of the trocars, the instruments and the operating setting is still under debate. Hereafter, we present a technical description of the 'Mainz technique' of the abdominal part of RAMIE carried out as Ivor Lewis procedure. Postoperative complication rate and duration of the abdominal part of 100 consecutive patients from University Medical Center in Mainz are illustrated. In addition, the abdominal phase of the full RAMIE is discussed in general.

[Morphological and Quantitative Changes in Retinal and Optic Nerve Vessels in Experimental Glaucoma Model with Elevated IOP for 7 Weeks]. / Erhöhter Augeninnendruck für 7 Wochen induziert lokale Gefäßveränderungen im experimentellen Glaukommodell in vivo.

INTRODUCTION: Glaucoma is characterised by progressive loss of retinal ganglion cells and axons. Experimental research has concentrated on understanding the pathophysiological mechanisms involved in glaucomatous damage. It is still a matter of debate whether neurons or capillaries are primarily damaged by elevated intraocular pressure (IOP). The aim of this study was to detect IOP-induced vascular changes in the vessels of the optic nerve head and the main vessels of the retina in vivo. METHODS: Experimental glaucoma was induced in adult Sprague Dawley rats by cauterisation of three episcleral veins of the left eye (n = 3). In vivo, retinal vessel calibre was measured manually using a peripapillary scan with SD-OCT (Heidelberg Engineering) at baseline and after seven weeks of IOP elevation. The animals were then sacrificed and the optic nerve was fixed with 30% glutaraldehyde and cross-sections stained with paraphenylene diamine to mark the vessels. Contralateral eyes served as controls. Pictures were taken and number of vessels, vessel calibre and area were calculated and compared. RESULTS: IOP was significantly elevated (p < 0.001). In optic nerve cross sections, the number of capillaries did not differ significantly between animals with elevated IOP and controls. However, vessel calibre and area were significantly reduced (p < 0.001) in glaucomatous optic nerves. The calibre of the retinal vessels was significantly lowered - by 9.22% (p = 0.021). CONCLUSION: Retinal arterioles and optic nerve capillaries respond sensitively to abnormal pressure elevation in vivo, showing high and early vulnerability. The vascular responses may influence secondary neuronal responses, which culminate in the death of ganglion cells and blindness, as occurs in clinical glaucoma.

[Endothelial Cell Reaction to Elevated Hydrostatic Pressure and Oxidative Stress in Vitro]. / Reaktion der Endothelzellen auf kurzzeitig physiologisch erhöhte hydrostatische Drücke und oxidativen Stress in vitro.

INTRODUCTION: Endothelial dysfunction has become a strongly discussed factor regarding glaucoma pathogenesis. In addition to peripapillary bleedings as signs of vascular damage, there is a definite correlation between glaucoma and vascular dysregulation syndrome. The aim of this study was to evaluate endothelial cell reaction to moderately elevated hydrostatic pressure and oxidative stress in vitro. METHODS: In vitro, primarily dissociated brain microvascular endothelial cells (BMECs) were exposed to moderately elevated hydrostatic pressure (60 and 120 mmHg) in a special pressure chamber. Additionally, cells primarily exposed to pressure, and cells not exposed to pressure, were incubated with low amounts of H2O2. A live/dead assay was performed to evaluate cell viability. Immunohistochemical staining against actin was used for morphological evaluation. RESULTS: Neither 60 nor 120 mmHg of elevated pressure had a viability changing effect on primary endothelial cells. Secondary, no big morphological changes could be discovered. However, against a low concentration of oxidative stress, BMECs showed high vulnerability. A difference in reaction to cells stressed with high pressure before could not be shown. CONCLUSION: Direct effects, in terms of higher vulnerability or morphological changes of moderately elevated high pressure on endothelial cells, could not be shown. However, the reaction to low amounts of oxidative stress indicates the involvement of endothelial cells in the pathogenesis of glaucoma and the special role of oxidative stress when referring to endothelial dysfunction in glaucomatous disease.

Elevated Intraocular Pressure Causes Abnormal Reactivity of Mouse Retinal Arterioles.

OBJECTIVE: Glaucoma is a leading cause of severe visual impairment and blindness. Although high intraocular pressure (IOP) is an established risk factor for the disease, the role of abnormal ocular vessel function in the pathophysiology of glaucoma gains more and more attention. We tested the hypothesis that elevated intraocular pressure (IOP) causes vascular dysfunction in the retina. METHODS: High IOP was induced in one group of mice by unilateral cauterization of three episcleral veins. The other group received sham surgery only. Two weeks later, retinal vascular preparations were studied by video microscopy in vitro. Reactive oxygen species (ROS) levels and expression of hypoxia markers and of prooxidant and antioxidant redox genes as well as of inflammatory cytokines were determined. RESULTS: Strikingly, responses of retinal arterioles to stepwise elevation of perfusion pressure were impaired in the high-IOP group. Moreover, vasodilation responses to the endothelium-dependent vasodilator, acetylcholine, were markedly reduced in mice with elevated IOP, while no differences were seen in response to the endothelium-independent nitric oxide donor, sodium nitroprusside. Remarkably, ROS levels were increased in the retinal ganglion cell layer including blood vessels. Expression of the NADPH oxidase isoform, NOX2, and of the inflammatory cytokine, TNF-α, was increased at the mRNA level in retinal explants. Expression of NOX2, but not of the hypoxic markers, HIF-1α and VEGF-A, was increased in the retinal ganglion cell layer and in retinal blood vessels at the protein level. CONCLUSION: Our data provide first-time evidence that IOP elevation impairs autoregulation and induces endothelial dysfunction in mouse retinal arterioles. Oxidative stress and inflammation, but not hypoxia, appear to be involved in this process.

Fully robotic Ivor-Lewis esophagectomy (RAMIE4) for esophageal cancer after emergency surgery and ligation of the gastroduodenal artery.

We report a case of a 69-year-old patient with esophageal cancer and severe upper gastrointestinal bleeding during neoadjuvant radiochemotherapy who required mass transfusion followed by complex emergency procedures. Despite endoscopic stenting, the bleeding recurred, and thus emergency open surgery was required. Gastric wedge resection of the minor curvature necessitated by perforation caused by the endoscopic stent maneuver and duodenotomy with ligation of the gastroduodenal artery, as the cause of persistent intraluminal bleeding, were performed. The already prepared gastric conduit during the emergency operation did not become ischemic, even though the gastroduodenal artery, left gastric artery, and short gastric arteries were ligated during emergency surgery. After 2 months of recovery, a computed tomographic scan showed collateral perfusion of the conduit via the superior mesenteric artery. Therefore, a fully robotic (abdominal and thoracic) esophagectomy with pull-up of the gastric conduit was performed, with no post-surgical complications. The patient was discharged 10 days after the robotic esophagectomy. Six months after esophagectomy, the patient is in a good condition.

Correlation of Crystallin Expression and RGC Susceptibility in Experimental Glaucoma Rats of Different Ages.

PURPOSE: Glaucoma is one of the leading causes of blindness worldwide with age being an important risk factor. However, the pathogenesis remains poorly understood. Aim of this study was to focus on age-dependent molecular changes in an experimental animal model of glaucoma. METHODS: Intraocular pressure was elevated in Sprague-Dawley rats aged 3, 14, and 47 weeks for a period of 7 weeks by episcleral vein cauterization. Ganglion cell loss was monitored by an immunohistochemical staining of the Brain-specific homeobox/POU (Pit-1, Oct-2, Unc-86) domain protein 3A positive cells in retinal flat-mounts and spectral-domain optical coherence tomography measuring the retinal nerve fiber layer thickness. Molecular protein alterations were analyzed using a comprehensive mass spectrometric proteomics approach of the retina and vitreous body. RESULTS: While juvenile animals did not show a significant loss of retinal ganglion cells due to intraocular pressure elevation, adolescent animals showed a decrease up to 26% (p < 0.05). A shift of retinal crystallin protein expression levels within all protein-family subclasses (α, ß, γ) could be observed in the youngest animal group (p < 0.05), while the upregulation of crystallin proteins in older animals was less striking. In addition, numerous crystallin proteins were also detected in the vitreous body. CONCLUSION: These results provide insights of a potential correlation of age-related glaucomatous damage and the absence of crystallin proteins in the retina.

The Small Heat Shock Protein α-Crystallin B Shows Neuroprotective Properties in a Glaucoma Animal Model.

Glaucoma is a neurodegenerative disease that leads to irreversible retinal ganglion cell (RGC) loss and is one of the main causes of blindness worldwide. The pathogenesis of glaucoma remains unclear, and novel approaches for neuroprotective treatments are urgently needed. Previous studies have revealed significant down-regulation of α-crystallin B as an initial reaction to elevated intraocular pressure (IOP), followed by a clear but delayed up-regulation, suggesting that this small heat-shock protein plays a pathophysiological role in the disease. This study analyzed the neuroprotective effect of α-crystallin B in an experimental animal model of glaucoma. Significant IOP elevation induced by episcleral vein cauterization resulted in a considerable impairment of the RGCs and the retinal nerve fiber layer. An intravitreal injection of α-crystallin B at the time of the IOP increase was able to rescue the RGCs, as measured in a functional photopic electroretinogram, retinal nerve fiber layer thickness, and RGC counts. Mass-spectrometry-based proteomics and antibody-microarray measurements indicated that a α-crystallin injection distinctly up-regulated all of the subclasses (α, ß, and γ) of the crystallin protein family. The creation of an interactive protein network revealed clear correlations between individual proteins, which showed a regulatory shift resulting from the crystallin injection. The neuroprotective properties of α-crystallin B further demonstrate the potential importance of crystallin proteins in developing therapeutic options for glaucoma.

Hydrogen Sulfide Protects Retinal Ganglion Cells Against Glaucomatous Injury In Vitro and In Vivo.

Purpose: Hydrogen sulfide (H2S) is recognized as a novel third signaling molecule and gaseous neurotransmitter. Recently, cell protective properties within the central nervous and cardiovascular system have been proposed. Our purpose was to analyze the expression and neuroprotective effects of H2S in experimental models of glaucoma. Methods: Elevated IOP was induced in Sprague-Dawley rats by means of episcleral vein cauterization. After 7 weeks, animals were killed and the retina was analyzed with label-free mass spectrometry. In vitro, retinal explants were exposed to elevated hydrostatic pressure or oxidative stress (H2O2), with and without addition of a slow-releasing H2S donor Morpholin-4-ium-methoxyphenyl-morpholino-phosphinodithioate (GYY4137). In vivo, GYY4137 was injected intravitreally in animals with acute ischemic injury or optic nerve crush. Brn3a+ retinal ganglion cells (RGCs) were counted in retinal flat mounts and compared. Optical coherence tomography (OCT) was performed to examine the vessels. Comparisons were made by t-test and ANOVA (P < 0.05). Results: IOP elevation caused significant RGC loss (P < 0.001); 3-mercaptosulfurtransferase, an H2S producing enzyme, showed a 3-fold upregulation within the retina after IOP elevation. GYY4137 protected RGCs against elevated pressure and oxidative stress in vitro depending on the concentration used (P < 0.005). In vivo, intravitreal administration of GYY4137 preserved RGCs from acute ischemic injury and optic nerve crush (P < 0.0001). Retinal vessel diameters enlarged after intravitreal GYY4137 injection (P < 0.0001). Conclusions: H2S is specifically regulated in experimental glaucoma. By scavenging reactive oxygen species and dilating retinal vessels, H2S may protect RGCs from pressure and oxidative stress-induced RGC loss in vitro and in vivo. Therefore, H2S might be a novel neuroprotectant in glaucoma.