The yield of diagnostic laparoscopy with peritoneal lavage in gastric adenocarcinoma: A retrospective cohort study.

INTRODUCTION: Diagnostic laparoscopy (DL) with peritoneal lavage has been adopted as a standard staging procedure for patients with gastric cancer (GC). Evaluation of the value of DL is important given ongoing improvements in diagnostic imaging and treatment. As contemporary data from European centres are sparse, this retrospective cohort study aimed to assess the yield of DL in patients with potentially curable gastric cancer, and to identify predictive factors for peritoneal metastases. METHODS: Patients with adenocarcinoma of the stomach, treated between January 2016 and December 2018, were identified from institutional databases of two high volume European Upper-GI centres. Patients who underwent a DL with peritoneal lavage for potentially curable disease after clinical staging with imaging (cT1-4N0-3M0) were included. The primary outcome was the proportion of patients with a positive DL, defined as macroscopic metastatic disease, positive peritoneal cytology washings (PC+) or locally irresectable disease. RESULTS: Some 80 of 327 included patients (24.5%) had a positive DL, excluding these patients from neoadjuvant treatment (66 of 327; 20.2%) and/or surgical resection (76 of 327; 23.2%). In 34 of 327 patients (10.3%), macroscopic metastatic disease was seen, with peritoneal deposits in 30 of these patients. Only 16 of 30 patients with peritoneal disease had positive cytology. Some 41 of 327 patients (12.5%) that underwent DL had PC+ in the absence of macroscopic metastases and five patients (1.5%) had an irresectable primary tumour. Diffuse type carcinoma had the highest risk of peritoneal dissemination, irrespective of cT and cN categories. CONCLUSION: The diagnostic yield of staging laparoscopy is high, changing the management in approximately one quarter of patients. DL should be considered in patients with diffuse type carcinoma irrespective of cT and cN categories.

COVID-19 vaccines and adverse events of special interest: A multinational Global Vaccine Data Network (GVDN) cohort study of 99 million vaccinated individuals.

BACKGROUND: The Global COVID Vaccine Safety (GCoVS) Project, established in 2021 under the multinational Global Vaccine Data Network™ (GVDN®), facilitates comprehensive assessment of vaccine safety. This study aimed to evaluate the risk of adverse events of special interest (AESI) following COVID-19 vaccination from 10 sites across eight countries. METHODS: Using a common protocol, this observational cohort study compared observed with expected rates of 13 selected AESI across neurological, haematological, and cardiac outcomes. Expected rates were obtained by participating sites using pre-COVID-19 vaccination healthcare data stratified by age and sex. Observed rates were reported from the same healthcare datasets since COVID-19 vaccination program rollout. AESI occurring up to 42 days following vaccination with mRNA (BNT162b2 and mRNA-1273) and adenovirus-vector (ChAdOx1) vaccines were included in the primary analysis. Risks were assessed using observed versus expected (OE) ratios with 95 % confidence intervals. Prioritised potential safety signals were those with lower bound of the 95 % confidence interval (LBCI) greater than 1.5. RESULTS: Participants included 99,068,901 vaccinated individuals. In total, 183,559,462 doses of BNT162b2, 36,178,442 doses of mRNA-1273, and 23,093,399 doses of ChAdOx1 were administered across participating sites in the study period. Risk periods following homologous vaccination schedules contributed 23,168,335 person-years of follow-up. OE ratios with LBCI > 1.5 were observed for Guillain-Barré syndrome (2.49, 95 % CI: 2.15, 2.87) and cerebral venous sinus thrombosis (3.23, 95 % CI: 2.51, 4.09) following the first dose of ChAdOx1 vaccine. Acute disseminated encephalomyelitis showed an OE ratio of 3.78 (95 % CI: 1.52, 7.78) following the first dose of mRNA-1273 vaccine. The OE ratios for myocarditis and pericarditis following BNT162b2, mRNA-1273, and ChAdOx1 were significantly increased with LBCIs > 1.5. CONCLUSION: This multi-country analysis confirmed pre-established safety signals for myocarditis, pericarditis, Guillain-Barré syndrome, and cerebral venous sinus thrombosis. Other potential safety signals that require further investigation were identified.

The Potential Antidepressant Compound Org 34167 Modulates HCN Channels Via a Novel Mode of Action.

Org 34167 is a small molecule hyperpolarization-activated cyclic nucleotide-gated (HCN) channel modulator that has been trialed in humans for its potential antidepressant activity. The precise action of Org 34167 is not fully understood. Here we use two-electrode voltage clamp recordings and an allosteric model to explore the interaction of Org 34167 with human HCN1 channels. The impact of Org 34167 on channel function included a hyperpolarizing shift in activation voltage dependence and a slowing of activation kinetics. Furthermore, a reduction in the maximum open probability at extreme hyperpolarization argued for an additional voltage-independent mechanism. Org 34167 had a similar impact on a truncated HCN1 channel lacking the C-terminal nucleotide binding domain, thus ruling out an interaction with this domain. Fitting a gating model, derived from a 10-state allosteric scheme, predicted that Org 34167 strongly reduced the equilibrium constant for the voltage-independent pore domain to favor a closed pore, as well as reducing the voltage sensing domain-pore domain coupling and shifting the zero voltage equilibrium constant of the voltage sensing domain to favor the inactive state. SIGNIFICANCE STATEMENT: The brain penetrant small molecule Org 34167 has been reported to have an antidepressant action by targeting HCN channels; however, its mode of action is unknown. We used heterologously expressed human HCN1 channels to show that Org 34167 inhibits channel activity by modulating kinetic parameters associated with the channel pore domain, voltage sensing domain, and interdomain coupling.

Accelerated rehabilitation following thumb ulnar collateral ligament repair with suture tape augmentation: A case series of professional basketball players.

STUDY DESIGN: Case series. INTRODUCTION: Rehabilitation protocols following thumb metacarpophalangeal (MCP) ulnar collateral ligament (UCL) repair typically do not allow for return to sport until 12 weeks post-surgery. The potential for accelerated rehabilitation following thumb MCP UCL repair with suture tape augmentation has yet to be explored. PURPOSE OF THE STUDY: To describe the accelerated rehabilitation following thumb MCP UCL repair with the suture tape augmentation in professional basketball players. METHODS: Three professional basketball players underwent thumb MCP UCL repair with suture tape augmentation. The athletes followed an accelerated rehabilitation program post-surgery that began with range-of-motion exercises at 2-3 days, proximal strengthening at 7-10 days, grip/pinch strengthening at 1-2 weeks, followed by progressive sport specific intervention with a custom orthosis. RESULTS: At 5-6 weeks post-surgery, active thumb MCP range of motion returned to 83%-100%, grip strength to 81%-100%, and tripod pinch strength to 73%-78% of the contralateral side. All athletes successfully returned to sport within 5-6 weeks post-surgery. DISCUSSION/CONCLUSION: This is the first clinical application of an accelerated rehabilitation protocol in athletes following thumb MCP UCL repair. In this series, professional basketball players were able to return to sport in half the routine recovery time. Further prospective studies re-thinking current rehabilitation protocols are warranted.

The impact of age on long-term survival following gastrectomy for gastric cancer.

INTRODUCTION: Gastrectomy remains the primary curative treatment modality for patients with gastric cancer. Concerns exist about offering surgery with a high associated morbidity and mortality to elderly patients. The study aimed to evaluate the long-term survival of patients with gastric cancer who underwent gastrectomy comparing patients aged <70 years with patients aged ≥70 years. METHODS: Consecutive patients who underwent gastrectomy for adenocarcinoma with curative intent between January 2000 and December 2017 at a single centre were included. Patients were stratified by age with a cut-off of 70 years used to create two cohorts. Log rank test was used to compare overall survival and Cox multivariable regression used to identify predictors of long-term survival. RESULTS: During the study period, 959 patients underwent gastrectomy, 520 of whom (54%) were aged ≥70 years. Those aged <70 years had significantly lower American Society of Anesthesiologists grades (p<0.001) and were more likely to receive neoadjuvant chemotherapy (39% vs 21%; p<0.001). Overall complication rate (p=0.001) and 30-day postoperative mortality (p=0.007) were lower in those aged <70 years. Long-term survival (median 54 vs 73 months; p<0.001) was also favourable in the younger cohort. Following adjustment for confounding variables, age ≥70 years remained a predictor of poorer long-term survival following gastrectomy (hazard ratio 1.35, 95% confidence interval 1.09, 1.67; p=0.006). CONCLUSIONS: Low postoperative mortality and good long-term survival were demonstrated for both age groups following gastrectomy. Age ≥70 years was, however, associated with poorer outcomes. This should be regarded as important factor when counselling patients regarding treatment options.

Therapeutic thoracic duct drainage: A systematic review of the Eastern European experience and future potential.

Thoracic duct drainage (TDD) is gaining renewed interest, largely due to accumulation of evidence supporting the gut-lymph model, where toxic mesenteric lymph from the intestine contributes to development of multi-organ failure in acute and critical illness (ACI). Advances in minimally invasive TDD have added to this growing interest. The English TDD literature has been previously reviewed, but the more extensive Eastern European literature has not been available to English readers. Therefore, we undertook a systematic search of Eastern European human TDD studies using Scopus and PubMed databases and Russian language websites. Indications for TDD, clinical outcomes, and complications were reviewed. 113 studies, published between 1965 and 2015, were reviewed. The most common indications for TDD were hepatic failure, acute pancreatitis, and peritonitis. It was often used late and when other treatment options had been exhausted. Human TDD appeared safe and probably effective, especially when combined with lymphosorption. The benefit appeared to correlate with the volume of lymph drained. A randomized controlled trial (and some case-control studies) showed reduced mortality in patients with ACI with TDD. Other benefits included rapid normalization of blood parameters and decreased organ edema. This review provides further support for the gut-lymph model and justification for high quality randomized controlled trials of TDD in ACI. It also highlights other potential indications for TDD, such as bridging patients with liver failure to surgery or transplant.

Changing patterns of referral into a family history clinic and detection of ovarian cancer: a retrospective 10-year review.

This study examines whether a change in the criteria for genetic testing for ovarian cancer risk changed the nature of referrals into our Familial Cancer service. This is a retrospective review of 273 women who underwent risk reducing surgery (RRS). The primary outcome was to establish whether there was an increase in women having RRS with a confirmed genetic mutation. Secondary outcomes included the incidence of occult cancer and of subsequent primary peritoneal cancer. The results showed an increase in women being offered RRS based on genetic diagnosis; 91% versus 32% before the criteria change. Four occult malignancies (1.5%) and two peritoneal cancers (0.7%) were noted.We have demonstrated a change in the nature of referrals to the familial cancer service from perceived risk to genetic diagnosis. We can now counsel women more accurately. With a defined risk we are enabling them to make an informed decision regarding risk reduction.

Good mid- to long-term results of the cemented oxford phase 3 unicompartmental knee arthroplasty in a non-designer centre.

PURPOSE: Unicompartmental knee arthroplasty (UKA) provides patients with an alternative treatment to TKA in isolated medial compartment osteoarthritis providing better functional outcomes and faster recovery in the short term. Our aim was to quantify revision rates, predictors of revision, mortality rate and functionality of the Oxford Phase 3 UKA in a non-designer institution. METHODS: This was a retrospective review of prospectively collected regional registry data. All Oxford Phase 3 UKAs performed for medial tibio-femoral osteoarthritis of the knee joint were included from a single academic institution between the period of January 1st 2006 and December 30th 2009. Kaplan-Meier survivorship curves adjusting for loss to follow-up and deceased patients were generated. Primary outcome variables included all-cause and aseptic revision. Secondary outcome variables included functional outcome scores. Patients were reviewed at 6 months, 2 years, 5 years, 10 years and 15 years. RESULTS: A total of 64 cemented Oxford phase 3 UKAs were performed between January 2006 and November 2009. Fifteen-year follow-up data were available for 51 patients, of these 12 required revision. Survival rates, adjusting for patients that were either lost to follow-up or deceased, were 87.5% at 5 years, 81.4% at 10 years and 76.4% at 15 years. The overall aseptic revision rate at the time of review was 18.75% (n = 12). The only significant predictor of postoperative WOMAC score at 15 years was the preoperative WOMAC score (p = 0.03). CONCLUSION: The Oxford Phase 3 UKA for medial tibio-femoral arthritis has promising outcomes at 15-year follow-up with a survival rate of 76.4% in a non-designer centre. LEVEL OF EVIDENCE: III.

Prehabilitation, improving postoperative outcomes.

Cardiopulmonary fitness impacts upon post-operative outcomes. Improved fitness may lead to a reduction in postoperative morbidity, mortality, reduced length of stay and improvements in patients quality of life. Prehabilitation can be defined as a group of interventions undertaken prior to a surgical procedure, with the aim of reducing peri-operative risk, improving post-operative recovery and outcomes. This is an evolving field which is generating significant scientific and clinical interest. There is growing evidence demonstrating the effectiveness of this approach. It has been proven that prehabilitation could lead to improvement in cardiopulmonary fitness and reduction of postoperative morbidity. Physical exercise composed of aerobic and strengthening exercise is a mainstay of prehabilitation. Multimodal interventions are preferred nowadays and therefore these programmes are commonly enhanced by nutritional and psychological support. Prehabilitation has its place in elective surgery and should be commenced immediately after diagnosis is made. It can be home-based or within hospitals under supervision. Prehabilitation programmes should be individualised, based on patients diagnosis, age, comorbidities, background physical activity and social circumstances in order to achieve the highest possible effectivity of the programmes. It remains unclear as to what the optimal programme looks like in terms of frequency, length and intensity of exercise. High-intensity interval training has been shown to be highly effective. There is a need to answer many questions and bring more substantial evidence of prehabilitation effectivity before this can become part of a routine clinical care. There are several ongoing large randomised clinical in prehabilitation that can help address this knowledge gap.

Safety of hormone replacement therapy in women with a history of cervical adenocarcinoma.

OBJECTIVES: Studies investigating the safety of hormone replacement therapy in cervical cancer have predominantly included patients with squamous disease. Pathological studies have identified estrogen receptor positivity in cervical adenocarcinomas. A recent small case-control study suggested a trend towards reduced survival with hormone replacement therapy in cervical adenocarcinomas. Our objective was to determine if hormone replacement therapy use in patients treated for cervical adenocarcinomas is detrimental to survival. STUDY DESIGN: A retrospective review of all women under the age of 50 with stage 1B-2B cervical adenocarcinomas diagnosed between 1 November 2000 and 24 September 2019. Women were categorised into three groups: ovaries conserved (OVCON); or iatrogenic menopause with (IM-HRT) or without (IM-NOHRT) hormone replacement therapy. Hormone replacement therapy use was defined on an intention to treat basis. Statistical analysis was performed using Kaplan-Meier and Cox proportional hazards methods. MAIN OUTCOME MEASURES: Overall (OS), disease specific (DSS) and progression free (PFS) survival. RESULTS: A total of 58 women (mean age 38.5 ± 6.6) were included in the study of whom 25 (43.1%) had OVCON, 20 (34.4%) had IM-HRT and 13 (22.4%) had IM-NOHRT. No menopause-associated deaths occurred. Although five-year DSS was 73% in IM-NOHRT compared to 95% in IM-HRT and 95% in OVCON, these differences were not statistically significant. Five-year PFS was 68% in IM-NOHRT compared to 90% in IM-HRT and 81% in OVCON but again, these differences were not statistically significant. CONCLUSION: In this small study, hormone replacement therapy does not appear to be detrimental to survival in cervical adenocarcinomas. There is a trend towards improved survival with hormone replacement therapy. Larger studies are required to substantiate these findings.

Neoadjuvant chemoradiotherapy or chemotherapy alone for oesophageal cancer: population-based cohort study.

BACKGROUND: Although both neoadjuvant chemoradiotherapy (nCRT) and chemotherapy (nCT) are used as neoadjuvant treatment for oesophageal cancer, it is unknown whether one provides a survival advantage over the other, particularly with respect to histological subtype. This study aimed to compare prognosis after nCRT and nCT in patients undergoing oesophagectomy for oesophageal adenocarcinoma (OAC) or squamous cell carcinoma (OSCC). METHODS: Data from the National Cancer Database (2006-2015) were used to identify patients with OAC and OSCC. Propensity score matching and Cox multivariable analyses were used to account for treatment selection biases. RESULTS: The study included 11 167 patients with OAC (nCRT 9972, 89.3 per cent; nCT 1195, 10.7 per cent) and 2367 with OSCC (nCRT 2155, 91.0 per cent; nCT 212, 9.0 per cent). In the matched OAC cohort, nCRT provided higher rates of complete pathological response (35.1 versus 21.0 per cent; P < 0.001) and margin-negative resections (90.1 versus 85.9 per cent; P < 0.001). However, patients who had nCRT had similar survival to those who received nCT (hazard ratio (HR) 1.04, 95 per cent c.i. 0.95 to 1.14). Five-year survival rates for patients who had nCRT and nCT were 36 and 37 per cent respectively (P = 0.123). For OSCC, nCRT had higher rates of complete pathological response (50.9 versus 30.4 per cent; P < 0.001) and margin-negative resections (92.8 versus 82.4 per cent; P < 0.001). A statistically significant overall survival benefit was evident for nCRT (HR 0.78, 0.62 to 0.97). Five-year survival rates for patients who had nCRT and nCT were 45.0 and 38.0 per cent respectively (P = 0.026). CONCLUSION: Despite pathological benefits, including primary tumour response to nCRT, there was no prognostic benefit of nCRT compared with nCT for OAC suggesting that these two modalities are equally acceptable. However, for OSCC, nCRT followed by surgery appears to remain the optimal treatment approach.

Comparison of multimodal analgesia with thoracic epidural after transthoracic oesophagectomy.

BACKGROUND: Thoracic epidural analgesia (TEA) has been regarded as the standard of care after oesophagectomy for pain control, but has several side-effects. Multimodal (intrathecal diamorphine, paravertebral and rectus sheath catheters) analgesia (MA) may facilitate postoperative mobilization by reducing hypotensive episodes and the need for vasopressors, but uncertainty exists about whether it provides comparable analgesia. This study aimed to determine whether MA provides comparable analgesia to TEA following transthoracic oesophagectomy. METHODS: Consecutive patients undergoing oesophagectomy for cancer between January 2015 and December 2018 were grouped according to postoperative analgesia regimen. Propensity score matching (PSM) was used to account for treatment selection bias. Pain scores at rest and on movement, graded from 0 to 10, were used. The incidence of hypotensive episodes and the requirement for vasopressors were evaluated. RESULTS: The study included 293 patients; 142 (48.5 per cent) received TEA and 151 (51.5 per cent) MA. After PSM, 100 patients remained in each group. Mean pain scores were significantly higher at rest in the MA group (day 1: 1.5 versus 0.8 in the TEA group, P = 0.017; day 2: 1.7 versus 0.9 respectively, P = 0.014; day 3: 1.2 versus 0.6, P = 0.047). Fewer patients receiving MA had a hypotensive episode (25 per cent versus 45 per cent in the TEA group; P = 0.003) and fewer required vasopressors (36 versus 53 per cent respectively; P = 0.016). There was no significant difference in the overall complication rate (71.0 versus 61.0 per cent; P = 0.136). CONCLUSION: MA is less effective than TEA at controlling pain, but this difference may not be clinically significant. However, fewer patients experienced hypotension or required vasopressor support with MA; this may be beneficial within an enhanced recovery programme.

Bleeding gastric ulcer from a pulmonary artery 20 years post-oesophagectomy: a common presentation with a rare cause.

This case presents an unusually late complication of oesophagectomy 20-years post-surgery, with upper gastrointestinal bleeding. Further investigation revealed a gastric conduit ulcer eroding into the lower lobe of the right lung, forming a fistula with a basal branch of the right pulmonary artery. Upon successful embolisation, the HydroCoil® was visible on endoscopy. This case highlights the need for lifetime proton pump inhibitor cover post-oesophagectomy and demonstrates that when approaching uncommon presentations of common problems, careful consideration to treatment technique is essential.