Atypical presentations and pitfalls of achalasia.

Achalasia is a rare disease with significant diagnostic delay and association with false diagnoses and unnecessary interventions. It remains unclear, whether atypical presentations, misinterpreted symptoms or inconclusive diagnostics are the cause. The aim of this study was the characterization of typical and atypical features of achalasia and their impact on delays, misinterpretations or false diagnoses. A retrospective analysis of prospective database over a period of 30 years was performed. Data about symptoms, delays and false diagnoses were obtained and correlated with manometric, endoscopic and radiologic findings. Totally, 300 patients with achalasia were included. Typical symptoms (dysphagia, regurgitation, weight loss and retrosternal pain) were present in 98.7%, 88%, 58.4% and 52.4%. The mean diagnostic delay was 4.7 years. Atypical symptoms were found in 61.7% and led to a delay of 6 months. Atypical gastrointestinal symptoms were common (43%), mostly 'heartburn' (16.3%), 'vomiting' (15.3%) or belching (7.7%). A single false diagnosis occurred in 26%, multiple in 16%. Major gastrointestinal misdiagnoses were GERD in 16.7% and eosinophilic esophagitis in 4%. Other false diagnosis affected ENT-, psychiatric, neurologic, cardiologic or thyroid diseases. Pitfalls were the description of 'heartburn' or 'nausea'. Tertiary contractions at barium swallows, hiatal hernias and 'reflux-like' changes at endoscopy or eosinophils in the biopsies were misleading. Atypical symptoms are common in achalasia, but they are not the sole source for diagnostic delays. Misleading descriptions of typical symptoms or misinterpretation of diagnostic studies contribute to false diagnoses and delays.

Optimization of anastomotic technique and gastric conduit perfusion with hyperspectral imaging and machine learning in an experimental model for minimally invasive esophagectomy.

INTRODUCTION: Esophagectomy is the mainstay of esophageal cancer treatment, but anastomotic insufficiency related morbidity and mortality remain challenging for patient outcome. Therefore, the objective of this work was to optimize anastomotic technique and gastric conduit perfusion with hyperspectral imaging (HSI) for total minimally invasive esophagectomy (MIE) with linear stapled anastomosis. MATERIAL AND METHODS: A live porcine model (n = 58) for MIE was used with gastric conduit formation and simulation of linear stapled side-to-side esophagogastrostomy. Four main experimental groups differed in stapling length (3 vs. 6 cm) and simulation of anastomotic position on the conduit (cranial vs. caudal). Tissue oxygenation around the anastomotic simulation site was evaluated using HSI and was validated with histopathology. RESULTS: The tissue oxygenation (ΔStO2) after the anastomotic simulation remained constant only for the short stapler in caudal position (-0.4 ± 4.4%, n.s.) while it was impaired markedly in the other groups (short-cranial: -15.6 ± 11.5%, p = 0.0002; long-cranial: -20.4 ± 7.6%, p = 0.0126; long-caudal: -16.1 ± 9.4%, p < 0.0001). Tissue samples from avascular stomach as measured by HSI showed correspondent eosinophilic pre-necrotic changes in 35.7 ± 9.7% of the surface area. CONCLUSION: Tissue oxygenation at the site of anastomotic simulation of the gastric conduit during MIE is influenced by stapling technique. Optimal oxygenation was achieved with a short stapler (3 cm) and sufficient distance of the simulated anastomosis to the cranial end of the gastric conduit. HSI tissue deoxygenation corresponded to histopathologic necrotic tissue changes. The experimental model with HSI and ML allow for systematic optimization of gastric conduit perfusion and anastomotic technique while clinical translation will have to be proven.

Mismatch repair deficiency, chemotherapy and survival for resectable gastric cancer: an observational study from the German staR cohort and a meta-analysis.

PURPOSE: In a post hoc analysis of the MAGIC trial, patients with curatively resected gastric cancer (GC) and mismatch repair (MMR) deficiency (MMRd) had better median overall survival (OS) when treated with surgery alone but worse median OS when treated with additional chemotherapy. Further data are required to corroborate these findings. METHODS: Between April 2013 and December 2018, 458 patients with curatively resected GC, including cancers of the esophagogastric junction Siewert type II and III, were identified in the German centers of the staR consortium. Tumor sections were assessed for expression of MLH1, MSH2, MSH6 and PMS2 by immunohistochemistry. The association between MMR status and survival was assessed. Similar studies published up to January 2021 were then identified in a MEDLINE search for a meta-analysis. RESULTS: MMR-status and survival data were available for 223 patients (median age 66 years, 62.8% male), 23 patients were MMRd (10.3%). After matching for baseline clinical characteristics, median OS was not reached in any subgroup. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd and MMRp had a HR of 0.67 (95% CI 0.13-3.37, P = 0.63) and 1.44 (95% CI 0.66-3.13, P = 0.36), respectively. The meta-analysis included pooled data from 385 patients. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd had an improved OS with a HR of 0.36 (95% CI 0.14-0.91, P = 0.03), whereas those with MMRp had a HR of 1.18 (95% CI 0.89-1.58, P = 0.26). CONCLUSION: Our data support a positive prognostic effect for MMRd in GC patients treated with surgery only and a differentially negative prognostic effect in patients treated with perioperative chemotherapy. MMR status determined by preoperative biopsies may be used as a predictive biomarker to select patients for perioperative chemotherapy in curatively resectable GC.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with peritoneal surface malignancies (PSM): a prospective single-center registry study.

PURPOSE: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new, palliative approach for patients with peritoneal surface malignancies (PSMs). Its main goals are to control symptoms and ascites. For this experimental procedure, treatment efficacy and patient safety need to be closely monitored. METHODS: We performed a prospective registry study for patients with PSMs. Cisplatin (C) (7.5 mg/m2 body surface) and doxorubicin (D) (1.5 mg/m2) were administered laparoscopically via PIPAC. RESULTS: Between November 2015 and June 2020, we recorded data from 108 patients and 230 scheduled procedures. Tumor burden, patient fitness, quality of life, operating time and in-hospital stay remained stable over consecutive procedures. We recorded 21 non-access situations and 14 intraoperative complications (11 intestinal injuries, and three aspirations while inducing anesthesia). Three or more previous abdominal surgeries or cytoreductive surgery (CRS) with intraperitoneal hyperthermic chemoperfusion (HIPEC) were risk factors for non-access and intestinal injuries (χ2, p ≤ 0.01). Five Grade IV and three Grade V postoperative complications according to the Clavien-Dindo Classification (CDC) occurred. Median overall survival was 264 days (interquartile range 108-586). Therapies were primarily discontinued because of death (34%), progressive (26%), or regressive (16%) disease. CONCLUSION: PIPAC is effective in stabilizing PSMs and retaining quality of life in selected patients. Earlier abdominal surgeries and CRS with HIPEC should be considered when determining the indication for PIPAC. Randomized controlled studies are needed to evaluate PIPAC's therapeutic benefits compared to systemic chemotherapy (sCHT) alone. TRIAL REGISTRATION: NCT03100708 (April 2017).

Combined indocyanine green and quantitative perfusion assessment with hyperspectral imaging during colorectal resections.

Anastomotic insufficiencies still represent one of the most severe complications in colorectal surgery. Since tissue perfusion highly affects anastomotic healing, its objective assessment is an unmet clinical need. Indocyanine green-based fluorescence angiography (ICG-FA) and hyperspectral imaging (HSI) have received great interest in recent years but surgeons have to decide between both techniques. For the first time, two data processing pipelines capable of reconstructing an ICG-FA correlating signal from hyperspectral data were developed. Results were technically evaluated and compared to ground truth data obtained during colorectal resections. In 87% of 46 data sets, the reconstructed images resembled the ground truth data. The combined applicability of ICG-FA and HSI within one imaging system might provide supportive and complementary information about tissue vascularization, shorten surgery time, and reduce perioperative mortality.

[Treatment recommendations for early esophageal cancer : Endoscopic and surgical options]. / Therapieempfehlungen beim Frühkarzinom des Ösophagus : Endoskopische und chirurgische Optionen.

BACKGROUND: Esophageal cancer represents a complex tumor entity with an increasing proportion of adenocarcinomas. Early esophageal cancer is staged as m1-m3 depending on the depth of infiltration into the mucosa and as sm1-sm3 depending on invasion into the submucosa. The risk of lymph node metastasis is strongly correlated with the depth of invasion and increases by leaps and bounds with submucosal infiltration. MATERIAL AND METHODS: This review is based on publications retrieved by a selective database search (MEDLINE, PubMed, Cochrane Library, International Standard Randomised Controlled Trial Number, ISRCTN, registry) on the current management of early esophageal cancer. RESULTS: The endoscopic diagnostics and evaluation of the dignity of superficial esophageal cancer by traditional staining techniques have been expanded by virtual chromoendoscopy. Endoscopic resection is the diagnostic and therapeutic procedure of choice for mucosal low risk adenocarcinomas (grade 1 or 2, no blood or lymph vessel invasion). Under certain prerequisites adenocarcinomas of the upper submucosa (sm1) can also be endoscopically removed. All other stages necessitate surgical treatment. In squamous cell carcinoma without risk factors a surgical oncological esophageal resection is indicated after infiltration of the third mucosal layer (m3). Endoscopic submucosal dissection (ESD) shows high rates of en bloc and R0 (curative) resections even with large lesions. CONCLUSION: Borderline cases between endoscopic and surgical treatment of early esophageal cancer necessitate an interdisciplinary approach and individually adapted management, which in the locally advanced stage are always embedded in a multimodal concept.

The Circular Stapled Esophagogastric Anastomosis in Esophagectomy: No Differences in Anastomotic Insufficiency and Stricture Rates Between the 25 mm and 28 mm Circular Stapler.

BACKGROUND: For patients undergoing an Ivor Lewis esophagectomy with a circular stapled anastomosis, the optimal diameter of the used circular stapler to restore continuity is unknown. The aim of this study was to compare the 25 mm stapled versus the 28 mm stapled esophagogastric anastomosis after Ivor Lewis esophagectomy, focusing on anastomotic insufficiency and postoperative anastomotic strictures. METHODS: Between February 2008 and June 2019, 349 consecutive patients underwent Ivor Lewis esophagectomy with gastric conduit reconstruction and circular stapled anastomosis. Patient characteristics and postoperative results, such as anastomotic insufficiency rates, postoperative anastomotic stricture rates, time to anastomotic stricture rate, and the number of dilatations, were recorded in a prospective database and analyzed. RESULTS: In 222 patients (64%), the 25 mm circular stapler was used and in 127 patients (36%) the 28 mm circular stapler was used. There were no differences in baseline characteristics. Anastomotic insufficiency rates were comparable between the 25 mm (12%) and the 28 mm groups (11%) (p = 0.751). There were no differences between postoperative anastomotic strictures in the 25 mm (14%) and the 28 mm groups (14%) (p = 0.863). Within patients with postoperative anastomotic strictures, a median number of 2 dilatations were observed in each group (p = 0.573) without differences in the time to first diagnosis (p = 0.412). CONCLUSION: There were no differences in anastomotic insufficiency and postoperative anastomotic stricture rates between the 25 mm and the 28 mm circular stapled esophagogastric anastomosis after Ivor Lewis esophagectomy. Both the 25 mm and 28 mm stapler can be safely used to create a circular stapled esophagogastric anastomosis to restore continuity after esophagectomy.

Fit-for-Discharge Criteria after Esophagectomy: An International Expert Delphi Consensus.

There are no internationally recognized criteria available to determine preparedness for hospital discharge after esophagectomy. This study aims to achieve international consensus using Delphi methodology. The expert panel consisted of 40 esophageal surgeons spanning 16 countries and 4 continents. During a 3-round, web-based Delphi process, experts voted for discharge criteria using 5-point Likert scales. Data were analyzed using descriptive statistics. Consensus was reached if agreement was ≥75% in round 3. Consensus was achieved for the following basic criteria: nutritional requirements are met by oral intake of at least liquids with optional supplementary nutrition via jejunal feeding tube. The patient should have passed flatus and does not require oxygen during mobilization or at rest. Central venous catheters should be removed. Adequate analgesia at rest and during mobilization is achieved using both oral opioid and non-opioid analgesics. All vital signs should be normal unless abnormal preoperatively. Inflammatory parameters should be trending down and close to normal (leucocyte count ≤12G/l and C-reactive protein ≤80 mg/dl). This multinational Delphi survey represents the first expert-led process for consensus criteria to determine 'fit-for-discharge' status after esophagectomy. Results of this Delphi survey may be applied to clinical outcomes research as an objective measure of short-term recovery. Furthermore, standardized endpoints identified through this process may be used in clinical practice to guide decisions regarding patient discharge and may help to reduce the risk of premature discharge or prolonged admission.

[Possibilities and perspectives of hyperspectral imaging in visceral surgery]. / Möglichkeiten und Perspektiven der Hyperspektralbildgebung in der Viszeralchirurgie.

HyperSpectral Imaging (HSI) technology enables quantitative tissue analyses beyond the limitations of the human eye. Thus, it serves as a new diagnostic tool for optical properties of diverse tissues. In contrast to other intraoperative imaging methods, HSI is contactless, noninvasive, and the administration of a contrast medium is not necessary. The duration of measurements takes only a few seconds and the surgical procedure is only marginally disturbed. Preliminary HSI applications in visceral surgery are promising with the potential of optimized outcomes. Current concepts, possibilities and new perspectives regarding HSI technology together with its limitations are discussed in this article.

[Pretherapeutic misclassification of esophageal cancer and adenocarcinoma of the esophagogastric junction : Possibilities and clinical consequences]. / Prätherapeutische Fehlklassifikationen bei Ösophaguskarzinomen und Adenokarzinomen des ösophagogastralen Übergangs : Möglichkeiten und klinische Konsequenzen.

During the course of a malignant disease, the tumor needs to be classified repeatedly in order to facilitate decision-making in treatment and to estimate patients prognosis; however, a wrong classification of tumors can occur in different stages of the disease course with tremendous consequences for the affected patients. This review discusses the possible misclassifications which can occur in patients with esophageal cancer or adenocarcinoma of the esophagogastric junction (EGJ), along with the consequences.

Cecal Resection with Bipolar Sealing Devices in a Rat Model.

Background: Bipolar sealing devices are routinely used to seal blood vessels. The aim of the study is to evaluate the feasibility and safety of colonic sealing with the use of the bipolar energy devices in rats as model for experimental appendectomy. Methods: Seventy-five male Wistar rats underwent a cecal resection with four different bipolar sealing devices or a linear stapler. The harvesting procedure was performed immediately or at postoperative day (POD) 7. The sealing front bursting pressure (BP) was measured in both groups. At POD7, the resection line was clinically examined and the hydroxyproline (HDP) levels were determined. Hematoxylin and Eosin (H&E) staining was used for histopathological evaluation of the sealing front as well. Results: There was no mortality and no insufficiency. The BPs between the bipolar sealing devices showed no statistical differences. The early phase of the seal (POD 0) provides a low BP with an 30.8% increase until POD 7. The BPs in the stapler group showed significant better values. The hydroxyproline levels did not differ statistically between the groups. Histopathologically, there were more signs of ischemic necrosis in the stapler group than in the sealing devices groups. Conclusion: The resection and sealing of the cecum as an experimental appendectomy model with the use of bipolar energy devices proved feasible and safe in rats. The different energy devices in this study produce comparable results. To justify clinical practice in humans, several studies on the underlying mechanisms of early stage wound healing are needed.

[Surgical treatment of esophagotracheal and esophagobronchial fistulas]. / Chirurgische Versorgung ösophagotrachealer und -bronchialer Fisteln.

BACKGROUND: Esophagotracheal and esophagobronchial fistulas are pathological communications between the airway system and the digestive tract, which often lead to major pulmonary complications with a high mortality. Endoscopic treatment is the primary therapeutic approach; however, in cases of failure early surgical treatment is obligatory. METHODS: This article describes the clinical course of patients with esophagotracheal and esophagobronchial fistulas treated in this hospital over a period of 10 years. Patients were retrospectively analyzed with respect to the etiology of fistulas, management, in particular to the operative procedures, complications and outcome. RESULTS: Between 2009 and 2019, a total of 15 patients with esophagotracheal and esophagobronchial fistula were treated in this hospital. Of these 12 underwent an endoscopic intervention, of which 5 were successful. In total, eight patients needed surgical intervention, six of the eight surgically treated patients recovered fully, one had a recurrent fistula, which was successfully treated by subsequent endoscopy after surgery and one patient died. DISCUSSION: Management of esophagotracheal and esophagobronchial fistulas is challenging. This retrospective analysis reflects the published data with a success rate of endoscopic treatment in approximately 50%. Surgical intervention should be carried out after unsuccessful endoscopic treatment or if endoscopic treatment is primarily not feasible. Direct closure with resorbable sutures or reconstruction with alloplastic or allogeneic material should be preferred. For larger defects or high proximal esophagotracheal fistulas local transposition of muscular flaps or free muscular flaps play a major role. During operative closure of high intrathoracic or cervical fistulas, intraoperative neuromonitoring can be useful to prevent nerve damage.

[Updated German S3 guidelines on esophageal cancer and supplements from a surgical perspective]. / Aktualisierte S3-Leitlinie zum Ösophaguskarzinom und Ergänzungen aus chirurgischer Sicht.

The updated German S3 guidelines recommend transthoracic subtotal esophagectomy with 2­field lymphadenectomy for surgical treatment of esophageal cancer in patients with squamous cell carcinoma and adenocarcinoma of the esophagogastric (AEG type I) junction of the middle and lower third. For AEG type III transhiatal extended total gastrectomy with distal esophageal resection is favored. Patients with AEG type II can be treated by both procedures under the prerequisite that an R0 resection can be achieved. A limited resection of the distal esophagus and the proximal stomach can only be considered in cT1 N0 M0 possibly cT2 AEG junction without an oncological risk constellation, i.e. grade G1/G2, intestinal type and no poorly cohesive carcinoma, because the rate of lymph node metastasis at the distal stomach is less than 2%. Minimally invasive procedures provide advantages compared to open esophagectomy due to the lower rate of postoperative total and especially pulmonary complications. This is true for hybrid esophagectomy (laparoscopy and thoracotomy) versus open access in cases of intrathoracic anastomoses and for total minimally invasive esophagectomy including robotic techniques versus open access in cervical esophagogastrostomy.

Determination of the transection margin during colorectal resection with hyperspectral imaging (HSI).

PURPOSE: This study evaluated the use of hyperspectral imaging for the determination of the resection margin during colorectal resections instead of clinical macroscopic assessment. METHODS: The used hyperspectral camera is able to record light spectra from 500 to 1000 nm and provides information about physiologic parameters of the recorded tissue area intraoperatively (e.g., tissue oxygenation and perfusion). We performed an open-label, single-arm, and non-randomized intervention clinical trial to compare clinical assessment and hyperspectral measurement to define the resection margin in 24 patients before and after separation of the marginal artery over 15 min; HSI was performed each minute to assess the parameters mentioned above. RESULTS: The false color images calculated from the hyperspectral data visualized the margin of perfusion in 20 out of 24 patients precisely. In the other four patients, the perfusion difference could be displayed with additional evaluation software. In all cases, there was a deviation between the transection line planed by the surgeon and the border line visualized by HSI (median 1 mm; range - 13 to 13 mm). Tissue perfusion dropped up to 12% within the first 10 mm distal to the border line. Therefore, the resection area was corrected proximally in five cases due to HSI record. The biggest drop in perfusion took place in less than 2 min after devascularization. CONCLUSION: Determination of the resection margin by HSI provides the surgeon with an objective decision aid for assessment of the best possible perfusion and ideal anastomotic area in colorectal surgery.

Metamizole inhibits arachidonic acid-induced platelet aggregation after surgery and impairs the effect of aspirin in hospitalized patients.

PURPOSE: The inhibitory effect of metamizole on platelet aggregation is known for several years, but most studies were conducted in healthy volunteers with contradictory results. Recent studies have shown an inhibitory effect of metamizole on acetylsalicylic acid (ASA)-induced platelet aggregation. We aimed to investigate the effect of metamizole on platelet aggregation after an elective surgery and the effect of metamizole on ASA-induced platelet aggregation in hospitalized patients. METHODS: We performed platelet aggregation analysis after induction with ADP, arachidonic acid (AA), epinephrine, and collagen in 37 patients prior to an elective visceral or thoracic surgery and on postoperative day (POD) 1 and POD 3 1-2 h and 5-6 h after metamizole. In another cohort of 10 hospitalized patients receiving the combination of metamizole and ASA for more than 7 days, AA-induced platelet aggregation was analyzed in the morning prior to the intake of both drugs. RESULTS: Metamizole induced a strong inhibitory effect on AA-induced platelet aggregation at all time points being detectable up to 41 h in some patients. Besides a less pronounced effect on collagen-induced platelet aggregation on POD 3 1-2 h after metamizole, all other inductors showed no effect. In 4 out of 10 hospitalized patients, no ASA-induced inhibition of platelet aggregation was detectable without correlation to sequence of administration. CONCLUSIONS: The reason why some patients have a long-lasting inhibitory effect of metamizole on COX-induced platelet aggregation that might interfere with ASA should be investigated in a larger cohort of patients.