Prognostic value of hepatocyte growth factor for muscle-invasive bladder cancer

Purpose The HGF/MET pathway is involved in cell motility, angiogenesis, proliferation, and cancer invasion. We assessed the clinical utility of plasma HGF level as a prognostic biomarker in patients with MIBC. Methods We retrospectively analyzed 565 patients with MIBC who underwent radical cystectomy. Logistic regression and Cox regression models were used, and predictive accuracies were estimated using the area under the curve and concordance index. To estimate the clinical utility of HGF, DCA and MCID were applied. Results Plasma HGF level was significantly higher in patients with advanced pathologic stage and LN metastasis (p = 0.01 and p < 0.001, respectively). Higher HGF levels were associated with an increased risk of harboring LN metastasis and non-organ-confined disease (OR1.21, 95%CI 1.12–1.32, p < 0.001, and OR1.35, 95%CI 1.23–1.48, p < 0.001, respectively) on multivariable analyses; the addition of HGF improved the predictive accuracies of a standard preoperative model (+ 7%, p < 0.001 and + 8%, p < 0.001, respectively). According to the DCA and MCID, half of the patients had a net benefit by including HGF, but the absolute magnitude remained limited. In pre- and postoperative predictive models, a higher HGF level was significant prognosticator of worse RFS, OS, and CSS; in the preoperative model, the addition of HGF improved accuracies by 6% and 5% for RFS and CSS, respectively. Conclusion Preoperative HGF identified MIBC patients who harbored features of clinically and biologically aggressive disease. Plasma HGF could serve, as part of a panel, as a biomarker to aid in preoperative treatment planning regarding intensity of treatment in patients with clinical MIBC.

DIAGNOSTIC BRONCHOSCOPY FOR EVALUATION OF CONGENITAL STRIDOR:A CASE SERIES

Introduction: Stridor is a noise mechanically produced through partially occluded airway. Airway obstruction may be extrathoracic or intrathoracic. Stridor may be congenital or acquired. Timing in respiratory cycle determines anatomic location of lesion – inspiratory, biphasic, or expiratory. Gold standard for diagnosis is bronchoscopy which requires general anaesthesia in infants and small children. Major anaesthetic concerns are – possible difficult airway, sharing of an already compromised airway, airway oedema. Case Description: 40 infants, 0 - 6 months age, with history of noisy breathing suggestive of congenital stridor, planned for diagnostic rigid bronchoscopy with or without therapeutic procedure, over one year period. Preoperative treatment – humidified oxygen, nebulization, dexamethasone, antibiotics, anti-reflux medication. Not premedicated, standard monitors applied. Induction of anaesthesia with inhalational oxygen and sevoflurane or intravenous propofol, fentanyl 1 mcg/kg, dexamethasone 0.5 mg/kg. Topical lidocaine 2% sprayed at vocal cords. 100% oxygen with propofol infusion for maintenance with spontaneous ventilation via nasopharyngeal airway. Patients requiring surgical intervention intubated using microcuffed endotracheal tube. Patients observed post-operatively. If ventilation was inadequate, intubated to control airway during recovery, extubated on restoration of spontaneous ventilation. After surgical intervention, babies shifted to ICU for elective ventilation for 48 hours. Discussion: On bronchoscopy, laryngomalacia was the finding in majority of cases. Others had subglottic stenosis, tracheomalacia, vocal-cord paresis, laryngeal cyst. Out of 40 patients, 9 underwent therapeutic procedure and were electively ventilated, 26 resumed spontaneous breathing, 2 patients had delayed recovery and 2 had severe chest retractions and desaturations and they were managed accordingly. One baby aged 6 months diagnosed with grade III subglottic stenosis desaturatedand tracheostomy had to be done. Conclusion:Anaesthesia for rigid diagnostic bronchoscopy is a significant challenge. Rigid bronchoscopy under general anaesthesia requires multidisciplinary approach and close cooperation between all team members.

Stratified Prognostic Value of Pathological Response to Preoperative Treatment in yp II/III Rectal Cancer

AimAccumulated studies have verified that tumor regression is associated with the prognosis of rectal cancer. However, stratified analysis within a certain stage is still unknown. The purpose of our study was to assess the impact of pathologic response on the survival of stageII and III rectal cancer patients after neoadjuvant chemoradiotherapy (nCRT).MethodsClinicopathologic characteristics and tumor regression scores (TRS) were assessed in 236 rectal cancer patients who treated with nCRT followed by surgery. Survival analysis was performed using Cox proportional hazards models.ResultsAmong these patients, the stage of 88 patients was ypII, and 91 patients were with the stage of ypIII. The median follow-up time was 59.8 months. TRS was not an independent prognostic factor in ypII patients while it was significantly associated with the prognosis of ypIII patients (5-year survival rate 67.2% vs. 42.5%, P &lt; 0.001). Furthermore, ypIII patients with the response to nCRT had similar survival to that of ypII patients (5-year survival rate 67.2% vs. 70.5%, P = 0.56). For ypIII patients, multivariable analysis showed that well differentiation, negative surgical margin, and the administration of adjuvant chemotherapy were associated with better survival. The surgical margin and differentiation were prognostic factors for ypII patients.ConclusionsypIII rectal cancer patients with poor response to preoperative treatment are at high risk of worse oncological outcomes.

Modifiable Individual Risks of Perioperative Blood Transfusions and Acute Postoperative Complications in Total Hip and Knee Arthroplasty

Background: The primary aim of this study was to identify modifiable patient-related predictors of blood transfusions and perioperative complications in total hip and knee arthroplasty. Individual predictor-adjusted risks can be used to define preoperative treatment thresholds. Methods: We performed this retrospective monocentric study in orthopaedic patients who underwent primary total knee or hip arthroplasty. Multivariate logistic regression models were used to assess the predictive value of patient-related characteristics. Predictor-adjusted individual risks of blood transfusions and the occurrence of any perioperative adverse event were calculated for potentially modifiable risk factors. Results: 3754 patients were included in this study. The overall blood transfusion and complication rates were 4.8% and 6.4%, respectively. Haemoglobin concentration (Hb, p < 0.001), low body mass index (BMI, p < 0.001) and estimated glomerular filtration rate (eGFR, p = 0.004) were the strongest potentially modifiable predictors of a blood transfusion. EGFR (p = 0.001) was the strongest potentially modifiable predictor of a complication. Predictor-adjusted risks of blood transfusions and acute postoperative complications were calculated for Hb and eGFR. Hb = 12.5 g/dL, BMI = 17.6 kg/m2, and eGFR = 54 min/mL were associated, respectively, with a 10% risk of a blood transfusion, eGFR = 59 mL/min was associated with a 10% risk of a complication. Conclusion: The individual risks for blood transfusions and acute postoperative complications are strongly increased in patients with a low preoperative Hb, low BMI or low eGFR. We recommend aiming at a preoperative Hb ≥ 13g/dL, an eGFR ≥ 60 mL/min and to avoid a low BMI. Future studies must show if a preoperative increase of eGFR and BMI is feasible and truly beneficial.

Neoadjuvant Chemotherapy Switch in Borderline Resectable/Locally Advanced Pancreatic Cancer

Background Neoadjuvant chemotherapy (NAC) is an integral part of preoperative treatment for patients with borderline resectable/locally advanced (BR/LA) pancreatic ductal adenocarcinoma (PDAC). The identification of a chemotherapeutic regimen that is both effective and tolerable is critical for NAC to be of oncologic benefit. After initial first-line (FL) NAC, some patients have lack of response or therapeutic toxicities precluding further treatment with the same regimen; optimal decision making regarding this patient population is unclear. Chemotherapy switch (CS) may allow for a larger proportion of patients to undergo curative-intent resection after NAC. Methods We reviewed our surgical database for patients undergoing combinatorial NAC for BR/LA PDAC. Variant histologic exocrine carcinomas, intraductal papillary mucinous neoplasm-associated PDAC, and patients without research consent were excluded. Results Overall, 468 patients with BR/LA PDAC receiving FL chemotherapy were reviewed, of whom 70% (329/468) continued with FL chemotherapy followed by surgical resection. The remaining 30% (139/468) underwent CS, with 72% (100/139) of CS patients going on to curative-intent surgical resection. Recurrence-free survival (RFS) and overall survival (OS) were not significantly different between the resected FL and CS cohorts (30.0 vs. 19.1 months, p = 0.13, and 41.4 vs. 36.4 months, p = 0.94, respectively) and OS was significantly worse in those undergoing CS without subsequent resection (19 months, p < 0.0001). On multivariable analysis, carbohydrate antigen (CA) 19-9 and pathologic treatment responses were predictors of RFS and OS. Conclusion CS in patients undergoing NAC for BR/LA pancreatic cancer does not incur oncologic detriment. The incorporation of CS into NAC treatment sequencing may allow a greater proportion of patients to proceed to curative-intent surgery.

Pathological Complete Response of Clinical T4b Ascending Colon Cancer after Preoperative Chemotherapy Using Pembrolizumab

Preoperative chemotherapy is efficacious in several cancers. However, it is not an established treatment for locally advanced colon cancer, particularly cases with microsatellite instability-high (MSI-H)/deficient mismatch repair. Herein, we report a case of pathological complete response of MSI-H clinical T4b ascending colon cancer to preoperative treatment with pembrolizumab. A 78-year-old man was diagnosed with ascending colon cancer that invaded into the iliacus muscle and enlarged regional lymph nodes. The tumor was classified as T4bN1bM0 stage IIIC according to the 8th Union for International Cancer Control guidelines, with MSI-H status. Based on our initial diagnosis, this tumor could not be resected completely. Thus, the patient underwent preoperative therapy with CAPOX (capecitabine and oxaliplatin combination) plus bevacizumab. After 4 cycles of preoperative CAPOX/bevacizumab, we observed tumor reduction corresponding to a partial response based on the Response Evaluation Criteria in Solid Tumors criteria. Nevertheless, tumor invasion of the iliacus muscle persisted. Since oxaliplatin-induced peripheral sensory neuropathy was observed, we discontinued treatment with oxaliplatin and changed the regimen to pembrolizumab in anticipation of the therapeutic effect of this immune checkpoint inhibitor against MSI-H tumors. After 2 cycles of therapy with pembrolizumab (200 mg/body on day 1 every 3 weeks), there was drastic tumor regression. In addition, computed tomography indicated that all lymph node metastases had disappeared. Therefore, the patient underwent laparoscopic right hemicolectomy with D3 lymph node dissection. Analysis of the resected specimen showed pathological complete response.