Tertiary lymphoid structures and gastric cancer prognosis.

Tertiary lymphoid structures (TLSs) are part of immune response against cancer. Their high density and high diameter have been shown to be associated with prognosis in different cancer types. The aim of this study was to examine the prognostic significance of TLS density and diameter in gastric cancer and reproducibility of their assessments. TLS densities and maximal TLS diameter were assessed from hematoxylin-eosin (HE) stained slides of 721 surgically treated gastric cancer patients from two hospitals in Finland. Mortality hazard ratios (HRs) for TLS densities and maximal TLS diameter were analyzed. TLS densities and maximal TLS diameter were assessed with moderate interobserver agreement (Cohen's kappa 0.50-0.62). Maximal TLS density was not associated with survival (adjusted HR 0.85, 95% CI 0.70-1.02) and neither was hotspot TLS density (adjusted HR 0.85, 95% CI 0.70-1.02). High maximal TLS diameter was associated with longer survival in overall study population (adjusted HR 0.74, 95% CI 0.61-0.89) and in diffuse type subgroup (adjusted HR 0.65, 95% CI 0.50-0.85). In conclusion, high maximal TLS diameter is associated with improved survival in gastric cancer and can be assessed from HE-stained slides. Its prognostic value might be limited to diffuse histological type.

Routine preoperative MRCP in screening choledocholithiasis in acute cholecystitis compared to selective approach: a population-based study.

Choledocholithiasis is more common in acute cholecystitis than in elective situations. Preoperative diagnosis of choledocholithiasis is essential to facilitate adequate planning of CBD (common bile duct) stone removal, preferably performed as a single-stage procedure. The purpose of this study was to test the feasibility of routine preoperative magnetic resonance cholangiopancreatography (MRCP) in acute cholecystitis followed by consequent cholecystectomy. A total of 180 consecutive patients operated for acute cholecystitis between January 2019 and December 2019 were prospectively enrolled. Preoperative routine MRCP was performed for bile duct evaluation when feasible. The control cohort consisted of 180 consecutive patients undergoing emergency laparoscopic cholecystectomy before the study period. Intraoperative cholangiography was used routinely in both groups when technically achievable. We examined the proportion of patients recruited in preoperative MRCP, possible time delay to MRCP and surgery, and the incidence of CBD stones compared to the control cohort. Routine MRCP in acute cholecystitis was achieved in 114/180 (63%) patients compared to 42/180 (23.3%) patients of the control group. The triage time from emergency to MRCP and the operating theatre was similar in both cohorts. The percentage of patients diagnosed with choledocholithiasis in the study group was notably higher (almost 18% vs 11%), p < 0.05. After a median follow-up time of 2.5 years in the study group and almost 4 years in the control group, recurrent choledocholithiasis was not detected in either group. Routine MRCP in patients with acute cholecystitis can be implemented with a fair execution rate in a population-based setting with minor effects on hospital stay and delays but higher detection of choledocholithiasis. We observed no additional benefit compared to the selective use of MRCP. However, routine preoperative MRCP allows an advantage when considering the appropriate exploration method if choledocholithiasis is detected.

Standard Lymphadenectomy for Esophageal and Lung Cancer: Variability in the Number of Examined Lymph Nodes Among Pathologists and Its Survival Implication.

AIM: We compared variability in number of examined lymph nodes between pathologists and analyzed survival implications in lung and esophageal cancer after standardized lymphadenectomy. METHODS: Outcomes of 294 N2 dissected lung cancer patients and 132 2-field dissected esophageal cancer patients were retrospectively examined. The primary outcome was difference in reported lymph node count among pathologists. Secondary outcomes were overall and disease-specific survival related to this count and survival related to the 50% probability cut-off value of detecting metastasis based on the number of examined lymph nodes. RESULTS: The median number of examined lymph nodes in lung cancer was 13 (IQR 9-17) and in esophageal cancer it was 22 (18-29). The pathologist with the highest median number of examined nodes had > 50% higher lymph node yield compared with the pathologist with the lowest median number of nodes in lung (15 vs. 9.5, p = 0.003), and esophageal cancer (28 vs. 17, p = 0.003). Survival in patients stratified by median reported lymph node count in both lung (adjusted RMST ratio < 14 vs. ≥ 14 lymph nodes 0.99, 95% CI 0.88-1.10; p = 0.810) and esophageal cancer (adjusted RMST ratio < 25 vs. ≥ 25 lymph nodes 0.95, 95% CI 0.79-1.15, p = 0.612) was similar. The cut-off value for 50% probability of detecting metastasis by number of examined lymph nodes in lung cancer was 15.7 and in esophageal cancer 21.8. When stratified by this cut-off, no survival differences were seen. CONCLUSION: The quality of lymphadenectomy based on lymph node yield is susceptible to error due to detected variability between pathologists in the number of examined lymph nodes. This variability in yield did not have any survival effect after standardized lymphadenectomy.

Implementation of Multimodality Therapy and Minimally Invasive Surgery: Short- and Long-term Outcomes of Gastric Cancer Surgery in Medium-Volume Center.

BACKGROUND: Multimodal treatment of gastric cancer includes careful preoperative staging, perioperative oncological treatment, and selective minimally invasive approach. The aim was to evaluate whether this approach improves short- and long-term outcomes in operable gastric cancer. METHODS: This study included 181 gastric cancer patients who underwent curative intent surgery in Central Finland Central Hospital between years 2005 and 2021 for gastric or esophagogastric junction adenocarcinoma. Those 65 patients in group 1 operated between years 2005-2010 had open surgery with possible adjuvant therapy. During the second period including 58 patients (2011-2015), perioperative chemotherapy and minimally invasive surgery were implemented. The period, when these treatments were standard practise, was years 2016-2021 including 58 patients (group 3). Outcomes were lymph node yield, major complications and 1- and 3-year survival rates. RESULTS: Median lymph node yield increased from 17 in group 1 and 20 in group 2 to 23 in group 3 (p < 0.001). Major complication rates in groups 1-3 were 12.3%, 32.8%, and 15.5% (group 1 vs. group 2, p = 0.007; group 2 vs. group 3, p = 0.018), respectively. Overall 1-year survival rates between study groups 1-3 were 78.5% vs. 69.0% vs. 90.2% (p = 0.018) and 3-year rates 44.6% vs. 44.8% vs. 68.1% (p = 0.016), respectively. For overall 3-year mortality, adjusted hazard ratio (HR) was 1.02 (95%CI 0.63-1.66) in group 2 and HR 0.37 (95%CI 0.20-0.68) in group 3 compared to group 1. CONCLUSIONS: In medium-volume center, modern multimodal therapy in operable gastric cancer combined with minimally invasive surgery increased lymph node yield and improved long-term survival without increasing postoperative morbidity.

Increasing Use of PET-CT, Neoadjuvant Treatment, Minimally Invasive Approach and Surgical Radicality in Esophageal Cancer Surgery are Associated with Improved Short- and Long-term Outcomes in Real-World Setting.

BACKGROUND: Guideline adherence has improved outcomes in several cancers. Our aim was to evaluate whether the rate of PET-CT, neoadjuvant treatment, minimally invasive approach, and surgical radicality, suggested also by recent guidelines, would improve short- and long-term operative outcomes in esophageal cancer in real-world setting. METHODS: This retrospective study in two Finnish Hospitals between 2010 and 2020 included 296 esophageal cancer patients. Grouping factors based on four factors with annual cut-offs by center were 90% rate in PET-CT-based staging, 70% in neoadjuvant therapy usage, 80% in minimally invasive approach, and 20 in annual mean lymph node yield. If none of factors were reached, all patients operated in that year were classified into group 1. With one to three cut-offs reached, grouping was into group 2. If all annual cut-offs were reached, patients were classified into group 3. Primary end points were major complication rate and overall 1-, 3-, and 5-year survival. RESULTS: Major complication rate decreased significantly from 38.2% in group 1 (p < 0.001) and 34.2% in group 2 (p < 0.001) to 10.2% in group 3. Overall 1-, 3-, and 5-year survival rates between groups 1-3 were 77.9% vs. 80.3% vs. 94.2% (p = 0.004), 51.5% vs. 51.1% vs. 67.3% (p = 0.022), and 44.1% vs. 47.4% vs. 55.5% (p = 0.065), respectively. Adjusted 5-year overall mortality was reduced significantly in group 3 compared to group 1 (HR 0.46, 95% CI 0.28-0.75). CONCLUSION: This study suggests that increasing rate of PET-CT, neoadjuvant treatment, minimally invasive surgery, and surgical radicality improves short- and long-term outcomes in operated esophageal cancer patients.

Exercise capacity in the stair-climbing test predicts outcomes of operable esophageal cancer in minimally invasive era.

INTRODUCTION: The risk of complications after esophagectomy highlights the need for careful preoperative assessment. Aim was to assess whether stair-climbing test (SCT) could predict outcomes of patients with operable esophageal cancer in minimally invasive era. MATERIALS AND METHODS: Patients with esophageal cancer were evaluated for surgical treatment in Central Finland Central Hospital from 2012 to March 2021. Of evaluated 162 patients, 138 were scheduled to eventually undergo surgery. The exercise capacity was evaluated with symptom limited SCT. Patients were divided into four study groups on intent-to-treat basis: surgery and the SCT >14 m (Group 1), surgery and the SCT <11 m (Group 2), non-surgical therapy and the SCT <11 m (Group 3) and non-surgical therapy and the SCT >14 m (Group 4). Results were adjusted for confounders. RESULTS: Major complication rate was 10.1% vs 40.0% between Group 1 and 2 (p = 0.006), and 90-day mortality 0% vs 20.0% (p < 0.001). Overall survival rates in Groups 1-4 at 1-year were 92.3% vs 72.2% vs 46.8% vs 81.8%, at 3-year 68.5% vs 52.7% vs 15.6% vs 27.3% and at 5-year 58.7% vs 39.5% vs 0% vs 0%, respectively (p < 0.001). In adjusted analysis when compared to Group 1, other groups had increased 5-year mortality hazard (Group 2 HR 2.88 (95% CI 1.25-6.63), Group 3 HR 15.6 (95% CI 5.57-43.5) and Group 4 HR 5.35 (95% CI 2.08-13.7)). CONCLUSION: Exercise capacity measured with SCT in esophageal cancer patients is a strong predictor of complications and survival, and is a potential parameter to be included in any risk or prognostic models.

Minimally invasive esophagectomy learning curves with different types of background experience.

BACKGROUND: Minimally invasive esophagectomy (MIE) is a complex procedure with learning associated morbidity. The aim was to evaluate the learning curve for MIE focusing on short-term outcomes in two settings: (I) experienced MIE surgeon in new hospital (Hospital 1); (II) surgeons experienced with open esophagectomy and minimally invasive surrogate surgery (Hospital 2). METHODS: In Hospital 1 and Hospital 2, on intent-to-treat basis number of MIEs were 132 and 57, respectively. The primary outcomes were major complications and anastomosis leaks. Secondary outcomes were operative time, blood loss, lymph node yield, hospital stay and 1-year mortality. Length of learning curves were analyzed with risk-adjusted cumulative sum (RA-CUSUM) method. RESULTS: In Hospital 1, major complication and anastomosis leak rates were 9.8% and 4.5%, 22.8% and 12.3% in Hospital 2, respectively. In Hospital 1, complication and leak rates remained stable. In Hospital 2, improvement occurred after 34 cases in major complications and 29 cases in leaks. Of secondary outcomes, improvements were seen in Hospital 1 in operative time after 61, blood loss after 86, lymph node yield after 52, hospital stay after 19 and 1-year mortality after 24 cases. In Hospital 2, improvement occurred in operative time after 30, blood loss after 15, lymph node yield after 45, hospital stay after 50 and 1-year mortality after 15 cases. CONCLUSIONS: According to this study, learning phase of the individual surgeon determines the outcomes of MIE, not the institutional learning phase.

Immune Cell Infiltrate and Prognosis in Gastric Cancer.

PURPOSE: To examine and compare the prognostic value of immune cell score (ICS) and Klintrup-Mäkinen (KM) grade in gastric cancer. METHODS: Gastric adenocarcinoma tissues from samples of 741 patients surgically treated in two hospitals in Finland were assessed for ICS and KM grade. Cox regression with adjustment for confounders provided hazard ratios (HRs) and 95% CIs. Subgroup analyses were performed in intestinal and diffuse type subgroups. The primary outcome was 5-year overall survival. RESULTS: High ICS was associated to longer 5-year survival (adjusted HR 0.70, 95% CI 0.52-0.94), compared to low ICS. The difference was significant in intestinal type subgroup (adjusted HR 0.54, 95% CI 0.36-0.81) but not in diffuse type subgroup (adjusted HR 0.92, 95% CI 0.58-1.46). High KM grade was an independent prognostic factor for longer 5-year overall survival (adjusted HR 0.59, 95% CI 0.45-0.77) in both intestinal (adjusted HR 0.61, 95% CI 0.44-0.85) and diffuse subgroups (adjusted HR 0.52, 95% CI 0.31-0.86). ICS and KM grade were moderately correlated (ρ = 0.425). When both immune cell score and KM grade were included in the regression analysis, only KM grade remained prognostic. CONCLUSIONS: Both ICS and KM grade are prognostic factors in gastric adenocarcinoma, but immunohistochemistry-based ICS might not have additional prognostic value over hematoxylin-eosin-based KM grade.

Immunophenotype based on inflammatory cells, PD-1/PD-L1 signalling pathway and M2 macrophages predicts survival in gastric cancer.

BACKGROUND: Immune response against cancer has prognostic impact but its role in gastric cancer is poorly known. The aim of the study was to assess the prognostic significance of immune cell score (CD3+, CD8+), tumour immune escape (PD-L1, PD-1) and immune tolerance (Clever-1). METHODS: After exclusion of Epstein-Barr virus positive (n = 4) and microsatellite instable (n = 6) tumours, the study included 122 patients with GC undergoing D2 gastrectomy. CD3+ and CD8+ based ICS, PD-L1, PD-1 and Clever-1 expressions were evaluated. Differences in survival were examined using Cox regression adjusted for confounders. The primary outcome was 5-year survival. RESULTS: The 5-year overall survival rate was 43.4%. High ICS was associated with improved overall survival (adjusted HR 0.48 (95% CI 0.26-0.87)) compared to low ICS. In the high ICS group, patients with PD-L1 expression (5-year survival 69.2 vs. 53.1%, p = 0.317), high PD-1 (5-year survival 70.6 vs. 55.3% p = 0.312) and high Clever-1 (5-year survival 72.0% vs. 45.5% (p = 0.070) had poor prognosis. CONCLUSIONS: High ICS was associated with improved survival. In the high ICS group, patients with high PD-L1, PD-1 and Clever-1 had poor prognosis highlighting the importance of immune escape and immune tolerance in GC.

Laparoscopic treatment of small bowel strangulation caused by an intramesosigmoid hernia and review of literature.

An internal hernia is defined as a protrusion of an abdominal viscera through the defects of the gastrointestinal mesentery or peritoneum-lined fossa. Sigmoid mesocolic hernias are an uncommon type of internal hernias, accounting for only 6% of all internal hernias. Furthermore, intramesosigmoid hernia is one of the three subtypes of the sigmoid mesocolic hernias. Internal hernias are potentially fatal conditions with diagnostic challenges. Patients presenting with acute obstruction, no surgical history and no external hernia should receive an urgent CT scan to facilitate early surgery and to minimise the risk of strangulation and bowel resection. Here, we report a case of strangulated small bowel obstruction secondary to an intramesosigmoid hernia with a successful laparoscopic repair. We also present a literature review of all reported cases so far and give an up-to-date perspective on intramesosigmoid hernia.

Can We Increase the Resection Rate by Minimally Invasive Approach? Experience from 100 Minimally Invasive Esophagectomies.

BACKGROUND: Whether we can increase the resection rate of esophageal cancer by minimally invasive esophagectomy (MIE) is unknown. The aim was to report the number and results of MIE in high-risk patients considered unsuitable for open surgery and compare these results to other operated patients and to high-risk patients not undergoing surgery. METHODS: At Central Finland Central Hospital, between September 2012 and July 2018, the number of operated MIEs was 100. Of these, 10 patients were prospectively considered unfit for open approach. Nineteen additional high-risk patients with operable disease were ruled out of surgery. The short- and long-term outcomes of these 3 groups were compared. RESULTS: In patients eligible for any approach (n=90), MIE only (n=10), and no surgery (n=19), WHO performance status Grade 0 was observed in 66.7%, 20.0%, and 5.3%, respectively; stair climbing with ≥4 stairs was successfully completed in 77.8%, 50%, and 36.8%, respectively. Between any approach and MIE only groups, rate of major complications (Clavien-Dindo ≥3a) was 6.7% vs. 50.0% (p<0.001) without a difference in median hospital stay (9 vs. 10 days, p=0.542). Readmission rates were 4.4% vs. 30.0% (p=0.003). Survival rates were 100% vs. 80% (p<0.001) at 90-days, 91.5% vs. 66.7% (p=0.005) at 1-year, and 68.9% vs. 53.3% (p=0.024) at 3-years, respectively. In comparison between MIE only and no surgery groups, these survival rates from day of diagnosis were 80% vs. 100%, 68.6% vs. 67.1%, and 45.7% vs. 32.0% (p=0.290), respectively. CONCLUSIONS: By operating patients unsuitable for open approach with MIE, the resection rate increased 11.1%. These high-risk patients had, however, higher early morbidity and reduced long-term survival compared to other operated patients. Though there seems to be long-term benefit of surgery compared to nonsurgical patients, we have to be cautious when offering surgery to those considered unfit for open surgery.

Benchmark values for transthoracic esophagectomy are not set as the defined "best possible"-a validation study.

BACKGROUND: Recently, benchmark values for low-comorbidity patients at high-volume centers were set to define "best achievable results" for transthoracic minimally invasive esophagectomy (MIE). We aimed to validate suggested benchmark values by comparing them to outcomes at a medium-volume center in Finland. METHODS: All MIEs (n=82) performed at Central Finland Central Hospital between September 2012 and November 2017 including 75 totally MIE and 7 hybrid procedures. The aim of the study was to compare the results to previously suggested benchmark parameters for postoperative morbidity measured with the Clavien-Dindo classification and comprehensive complication index. Target benchmark parameters were ≤55.7% for any complications, ≤30.8% for major complications (Clavien-Dindo ≥3a), ≤40.8% for 30-day and ≤42.8% for 90-day comprehensive complication index, ≤20% for anastomosis leak, ≤31.6% for pulmonary complications, ≤1.0% for 30-day mortality and ≤4.6% for 90-day mortality. RESULTS: Compared with benchmark patients, our patients were older (median 68 vs. 58 years), with more comorbidities. All parameters measuring complications showed better results in our study than benchmark values. Median intensive care unit stay of 1 (IQR, 1-1) and hospital stay of 9 (IQR, 9-12) days were also shorter. At least 1 complication developed in 45.1%, and 6.1% faced major morbidity. Median (IQR) comprehensive complication index for both 30 and 90 days was 0 (IQR, 0-20.9 days). Anastomosis leak and pulmonary complications were observed in 3.7% and 22.0%, respectively. The 30- and 90-day mortality was 1.2% (1/82). CONCLUSIONS: Benchmark values assessing postoperative morbidity after MIE do not represent the defined "best achievable" results after completed learning curves.

Cost-analysis and effectiveness of one-stage laparoscopic versus two-stage endolaparoscopic management of cholecystocholedocholithiasis: a retrospective cohort study.

BACKGROUND: One-stage laparoscopic common bile duct (CBD) stone clearance and laparoscopic cholecystectomy (LCBDE+LC) for cholecystocholedocholithiasis ( CCL) can be performed with similar short and long-term outcomes than two-stage endoscopic retrograde cholangiography followed by subsequent LC (ERCP+LC). This study examined retrospectively the outcome and hospital costs of one-stage versus two-stage treatment of CBD stones. METHODS: From January 1999 and December 2014, 217 consecutive, elective patients underwent one-stage (LCBDE + LC ) or two-stage (ERCP + subsequent LC ) treatment for CBD stones. The data from the one-stage management was collected prospectively, and from the two-stage management retrospectively. The main measure of outcome was hospital costs, with the success of one-stage versus two-stage management, postoperative morbidity and postoperative stay as secondary outcome measures. RESULTS: One-stage laparoscopic transcystic management was the least costly option compared to laparoscopic one-stage transductal approach (TC 5455€ versus TD 9364, p < 0.001) or two-stage management (6913 €, p = 0.02). Overall success rate of primary intervention (including conversions to open surgery) for CBD stone clearance was 96.9%, 97.0% and 98.3% after transcystic one-stage, transductal one-stage and two-stage approach, p = 0.79. Postoperative morbidity was 15.5% versus 7.5%, p = 0.64, and postoperative hospital stay median 2 days (IQR 2-5) versus 4.5 days ( IQR 3-7), p < 0.001 in the one-stage and two-stage management groups. CONCLUSIONS: Our study shows that laparoscopic one-stage transcystic management of CCL results in high rate of CBD clearance, fewer procedures per patient, shorter hospital and lower costs than the two-stage management. Therefore the one-stage transcystic management seems to be an attractive strategy for the treatment of CCL depending on local resources and surgical expertise .

Expectant management of gallbladder stones after endoscopic removal of common bile duct stones.

BACKGROUND: Wait-and-see policy after endoscopic sphincterotomy (ES) for common bile duct (CBD) stones in patients with concomitant gallbladder stones may lead to recurrent biliary complications. The aim of this study was to assess the short and long-term results of wait-and-see policy in patients with intact gallbladder after endoscopic clearance of CBD stones. MATERIALS AND METHODS: From January 1999 to December 2014 a total of 181 consecutive patients with intact gallbladder underwent ES for CBD stones. The main measures of outcome were long-term biliary complications, biliary related mortality, CBD stone recurrence and need for surgical interventions. Secondary outcomes were 30-day mortality and 30-day morbidity. Clinical data were retrospectively collected from hospital records and from the National Registry of Death. RESULTS: During the median follow-up of 3.9 years (IQR 1.6-6.6) late biliary complications were observed in 24 (13.8%) patients. Cumulative biliary related morbidity at 3 and 5 years was 7.6% and 10.8%, respectively. CBD stone recurrence was observed in 9 (5.2%) patients. On-demand cholecystectomy was performed in 6 (3.3%) patients. 30-day mortality was 3.9% and 30-day morbidity 9.4%. Overall cumulative mortality rate at 3 and 5 years after ES was 31.4% and 49.7%, respectively. Long-term biliary related mortality was 1.7%. No significant difference in long term complications or biliary mortality was observed between patients< 75 or ≥75 years of age. CONCLUSION: Prophylactic cholecystectomy after ES has been shown to reduce mortality even in high-risk patients. In our series late biliary related mortality and morbidity were relatively low, because a considerable number of patients died from non-biliary related causes.However, most biliary-related events seem to occur evenly during the follow-up after ES. A prompt risk assesment and consideration of surgical treatment during index admission may prevent late biliary -related complications.

Near-infrared image-guided lymphatic mapping in minimally invasive oesophagectomy of distal oesophageal cancer.

OBJECTIVES: We aimed to assess the potential of near-infrared (NIR) imaging during minimally invasive oesophagectomy in patients with distal oesophageal cancer for detection of nodal metastases inside and outside the standard en bloc surgical field. METHODS: We enrolled 6 patients diagnosed with distal oesophageal cancer for intraoperative lymphatic mapping with NIR imaging. Indocyanine green dye was injected endoscopically in 8 corners of the primary tumour at the start of the operation. The minimally invasive oesophagectomy with en bloc lymphadenectomy was performed using 3D optics. A separate endoscopic fluorescence imaging system was used to systematically detect the NIR signal of 23 lymphatic stations. The NIR-positive stations outside the en bloc resection area were also removed for histological analysis. RESULTS: Lymphatic mapping was successful in all patients. The NIR-positive areas were most commonly detected in the lower mediastinum (100% of patients), cardia (83%), region of the left gastric artery (67%), celiac axis (50%) and pericardial-diaphragmatic groove (50%). We detected NIR-positive areas outside the traditional en bloc field above the azygous arch in 50% of the patients. A total of 182 lymph nodes were resected from 6 patients. In 3 patients, a total of 19 lymph node metastases were detected, 4 of which were outside the en bloc field. CONCLUSIONS: NIR imaging can be useful for detecting lymphatic stations that most likely present with metastatic disease and to guide the tailored extension of the traditional lymphadenectomy.