Desmoid Tumors in Familial Adenomatous Polyposis Patients: Favorable Outcomes with Multidisciplinary Management.

OBJECTIVE: In this study, we aimed to describe the clinical features, management, and outcomes of desmoid tumors (DTs) in familial adenomatous polyposis (FAP) patients at a high-volume sarcoma center. METHODS: Consecutive patients with FAP and DTs were identified from our institutional databases (1985-2021). Patient demographics, treatment, and outcomes were described. Categorical data were compared using Fisher's exact test, and Kaplan-Meier curves were used to estimate progression-free survival (PFS). RESULTS: Forty-five patients with 67 DTs were identified: 39 mesenteric or retroperitoneal (58.2%), 17 abdominal wall (25.4%), 4 extremity (6%), 4 breast (6%) and 3 back (4.4%). Severe DT symptoms were present in 12 patients (26.7%). Initial treatments per tumor were observation in 30 (44.8%) DTs, chemotherapy in 15 (22.4%) DTs, surgery in 10 (14.9%) DTs, and other systemic therapies in 10 (14.9%) DTs. The majority of DTs remained stable with observation or a single intervention (77.8%). Median PFS was 23.4 years (95% confidence interval 7.6-39.2). In the 12 severely symptomatic patients, four patients required more than two interventions for DT control. At a median follow-up of 6.0 years (range 0.7-35.8 years), 33 (73.3%) patients were alive with disease, 7 (15.6%) were alive without disease, and 5 (11.1%) died of other causes. No patients died of DT-related complications. CONCLUSIONS: The majority of DTs in FAP patients remained stable with observation or a single intervention. There were no DT-related deaths; however, 12 of 45 patients (26.7%) experienced significant tumor morbidity and required more interventions for disease control. Further studies on quality of life are required.

[ABDOMINAL WALL BLOCKS FOR POST CESAREAN DELIVERY ANALGESIA].

INTRODUCTION: Intrathecal morphine administration at the time of neuraxial anesthesia performance is the gold standard for post-cesarean delivery (CD) analgesia. When intrathecal morphine administration is inappropriate or contraindicated, the use of systemic analgesic options increase side effects and risks to both the parturient and the breastfeeding neonate. Moreover, systemic analgesia is often inadequate. The increased clinical use of ultrasound has made way for regional analgesia techniques, mostly in the form of local anesthesia injected between muscular planes. The transversus abdominis plane (TAP) block is the most well-known and the most commonly used for Cesarean delivery. It has been shown to be effective in the absence of intrathecal morphine administration. It has however, not been shown to be beneficial when intrathecal morphine has been administered. Other, newer techniques are being increasingly used and investigated. Some may prove to be superior to the TAP block. These techniques include: ilioinguinal/ilio-hypogastric nerve blocks (II-IH), the quadratus lumborum (QL) blocks and the erector spinae plane (ESP) block. In this review, we will discuss and assess these techniques regarding analgesia following CD.

Detection of residual disease after neoadjuvant chemoradiotherapy for oesophageal cancer (preSANO): a prospective multicentre, diagnostic cohort study.

BACKGROUND: After neoadjuvant chemoradiotherapy for oesophageal cancer, roughly half of the patients with squamous cell carcinoma and a quarter of those with adenocarcinoma have a pathological complete response of the primary tumour before surgery. Thus, the necessity of standard oesophagectomy after neoadjuvant chemoradiotherapy should be reconsidered for patients who respond sufficiently to neoadjuvant treatment. In this study, we aimed to establish the accuracy of detection of residual disease after neoadjuvant chemoradiotherapy with different diagnostic approaches, and the optimal combination of diagnostic techniques for clinical response evaluations. METHODS: The preSANO trial was a prospective, multicentre, diagnostic cohort study at six centres in the Netherlands. Eligible patients were aged 18 years or older, had histologically proven, resectable, squamous cell carcinoma or adenocarcinoma of the oesophagus or oesophagogastric junction, and were eligible for potential curative therapy with neoadjuvant chemoradiotherapy (five weekly cycles of carboplatin [area under the curve 2 mg/mL per min] plus paclitaxel [50 mg/m2 of body-surface area] combined with 41·4 Gy radiotherapy in 23 fractions) followed by oesophagectomy. 4-6 weeks after completion of neoadjuvant chemoradiotherapy, patients had oesophagogastroduodenoscopy with biopsies and endoscopic ultrasonography with measurement of maximum tumour thickness. Patients with histologically proven locoregional residual disease or no-pass during endoscopy and without distant metastases underwent immediate surgical resection. In the remaining patients a second clinical response evaluation was done (PET-CT, oesophagogastroduodenoscopy with biopsies, endoscopic ultrasonography with measurement of maximum tumour thickness, and fine-needle aspiration of suspicious lymph nodes), followed by surgery 12-14 weeks after completion of neoadjuvant chemoradiotherapy. The primary endpoint was the correlation between clinical response during clinical response evaluations and the final pathological response in resection specimens, as shown by the proportion of tumour regression grade (TRG) 3 or 4 (>10% residual carcinoma in the resection specimen) residual tumours that was missed during clinical response evaluations. This study was registered with the Netherlands Trial Register (NTR4834), and has been completed. FINDINGS: Between July 22, 2013, and Dec 28, 2016, 219 patients were included, 207 of whom were included in the analyses. Eight of 26 TRG3 or TRG4 tumours (31% [95% CI 17-50]) were missed by endoscopy with regular biopsies and fine-needle aspiration. Four of 41 TRG3 or TRG4 tumours (10% [95% CI 4-23]) were missed with bite-on-bite biopsies and fine-needle aspiration. Endoscopic ultrasonography with maximum tumour thickness measurement missed TRG3 or TRG4 residual tumours in 11 of 39 patients (28% [95% CI 17-44]). PET-CT missed six of 41 TRG3 or TRG4 tumours (15% [95% CI 7-28]). PET-CT detected interval distant histologically proven metastases in 18 (9%) of 190 patients (one squamous cell carcinoma, 17 adenocarcinomas). INTERPRETATION: After neoadjuvant chemoradiotherapy for oesophageal cancer, clinical response evaluation with endoscopic ultrasonography, bite-on-bite biopsies, and fine-needle aspiration of suspicious lymph nodes was adequate for detection of locoregional residual disease, with PET-CT for detection of interval metastases. Active surveillance with this combination of diagnostic modalities is now being assessed in a phase 3 randomised controlled trial (SANO trial; Netherlands Trial Register NTR6803). FUNDING: Dutch Cancer Society.

Analysis of Inpatient Falls After Total Knee Arthroplasty in Patients With Continuous Femoral Nerve Block.

Continuous femoral nerve block (cFNB) is thought to increase the risk of falls after total knee arthroplasty (TKA). Previous studies have failed to consider the timing of cFNB removal in relation to inpatient falls. We investigated all inpatient falls after TKA over a 3-year period using our institutional safety report database. Ninety-five falls were reported from a total of 3745 patients. The frequency of falls after TKA persisted at a similar rate despite removal of cFNB and likely regression of femoral nerve block. Other modifiable risk factors may play a more prominent role in falls risk after TKA.

P53 and SOX2 Protein Expression Predicts Esophageal Adenocarcinoma in Response to Neoadjuvant Chemoradiotherapy.

OBJECTIVE: The aim of the study was to investigate the association between p53, SOX2, and CD44 protein expression and tumor response, and to validate potential predictive biomarker(s) in an independent cohort. BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery has become a standard of care for esophageal adenocarcinoma (EAC). However, the response to nCRT is highly variable among patients. METHODS: EAC patients who underwent nCRT and surgery, between January 2003 and December 2014 at the Erasmus University Medical Center, were included and divided into a primary (n = 77) and a validation cohort (n = 70). P53, SOX2, and CD44 expression was detected by immunohistochemistry in pretreatment tumor biopsies, and scored independently by 2 investigators. Response to nCRT was assessed based on tumor regression grade (TRG) in the resection specimen. RESULTS: Forty-one (53%) patients in the primary cohort and 33 (47%) patients in the validation cohort showed major response (TRG1 or TRG2) in the resection specimen. Aberrant p53 and absence of SOX2 were associated with major response in the primary cohort: adjusted odds ratio (OR) 6.3 [95% confidence interval (CI), 1.3-30.1) and adjusted OR 4.1 (95% CI, 1.4-12.4), respectively. The same was true for the validation cohort (p53: adjusted OR 8.6; 95% CI, 0.93-80.9 and SOX2: adjusted OR 6.1; 95% CI, 1.6-23.4). The highest probability of a major response was seen in patients with concurrent aberrant p53 and absence of SOX2 expression, with an OR of 6.7 (95% CI, 2.1-21.4) and 6.2 (95% CI, 1.8-21.2) in the primary and validation cohort. CONCLUSIONS: Pattern of p53 and particularly SOX2 protein expression in EAC predicts response to nCRT. These biomarkers may help to individualize treatment in EAC patients.

Prognostic Value of Pretreatment Pathological Tumor Extent in Patients Treated With Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal or Junctional Cancer.

OBJECTIVE: We aimed to determine pretreatment pathological tumor extent in the resection specimen after neoadjuvant chemoradiotherapy (nCRT) and to assess its prognostic value in patients with esophageal cancer. METHODS: Patients with esophageal cancer, treated with nCRT plus surgery were included (2003-2011). Pretreatment pathological T-stage (prepT-stage) and N-stage (prepN-stage) were estimated based on the extent of regressional changes and residual tumor cells in the resection specimen. Interobserver agreement was determined between 3 pathologists. The prognostic performance of prepT-stage and prepN-stage was scored using the difference in Akaike information criterion (ΔAIC). PrepN-stage and posttreatment pathological N-stage (ypN-stage) were combined to determine the effect of nodal sterilization on prognosis. RESULTS: Overall concordance for prepT-stage and prepN-stage was 0.69 and 0.84, respectively. Prognostic strength of prepT-stage was similar to clinical T-stage and worse compared with ypT-stage (ΔAIC 1.3 versus 2.0 and 8.9, respectively). In contrast, prognostic strength of prepN-stage was better than cN-stage and similar to ypN-stage (ΔAIC 17.9 versus 6.2 and 17.2, respectively). PrepN+ patients who become ypN0 after nCRT have a worse survival compared with prepN0 patients, with a five year overall survival of 51% versus 68%, P = 0.019, respectively. CONCLUSIONS: PrepT-stage and prepN-stage can be estimated reproducibly. Prognostic strength of prepT-stage is comparable with clinical T-stage, whereas prepN-stage is better than cN-stage. PrepN+ patients who become ypN0 after nCRT have a worse survival compared with prepN0 patients. Pretreatment pathological staging should be considered useful as a new staging parameter for esophageal cancer and could also be of interest for other tumor types.

Sarcopenia/Muscle Mass is not a Prognostic Factor for Short- and Long-Term Outcome After Esophagectomy for Cancer.

BACKGROUND: Recent studies have suggested that sarcopenia is a prognostic risk indicator of postoperative complications and predicts survival in cancer patients. The aim of this study is to investigate whether sarcopenia is associated with postoperative short-term outcome (morbidity and mortality) and long-term survival in patients undergoing esophagectomy for cancer after neoadjuvant chemoradiotherapy. METHODS: All patients who underwent neoadjuvant chemoradiotherapy followed by esophagectomy for cancer, and of whom an adequate CT scan was available, were included in the current study. The presence of sarcopenia was defined by CT imaging using cut-off values of the total cross-sectional muscle tissue measured transversely at the third lumbar level. RESULTS: A total number of 120 patients were eligible for analysis. Almost half of the patients (N = 54, 45 %) were classified as having sarcopenia; 24 sarcopenic patients (44 %) had overweight and 5 sarcopenic patients (9 %) were obese. Overall morbidity and mortality rate did not differ significantly between sarcopenic and non-sarcopenic patients, nor did long-term overall or disease-free survival. Also sarcopenic obesity was not associated with worse outcome. CONCLUSION: The presence of sarcopenia was not associated with a negative short- and long-term outcome in this selected group of esophageal cancer patients after neoadjuvant chemoradiotherapy followed by esophagectomy.

Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial.

BACKGROUND: Initial results of the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) comparing neoadjuvant chemoradiotherapy plus surgery versus surgery alone in patients with squamous cell carcinoma and adenocarcinoma of the oesophagus or oesophagogastric junction showed a significant increase in 5-year overall survival in favour of the neoadjuvant chemoradiotherapy plus surgery group after a median of 45 months' follow-up. In this Article, we report the long-term results after a minimum follow-up of 5 years. METHODS: Patients with clinically resectable, locally advanced cancer of the oesophagus or oesophagogastric junction (clinical stage T1N1M0 or T2-3N0-1M0, according to the TNM cancer staging system, sixth edition) were randomly assigned in a 1:1 ratio with permuted blocks of four or six to receive either weekly administration of five cycles of neoadjuvant chemoradiotherapy (intravenous carboplatin [AUC 2 mg/mL per min] and intravenous paclitaxel [50 mg/m(2) of body-surface area] for 23 days) with concurrent radiotherapy (41·4 Gy, given in 23 fractions of 1·8 Gy on 5 days per week) followed by surgery, or surgery alone. The primary endpoint was overall survival, analysed by intention-to-treat. No adverse event data were collected beyond those noted in the initial report of the trial. This trial is registered with the Netherlands Trial Register, number NTR487, and has been completed. FINDINGS: Between March 30, 2004, and Dec 2, 2008, 368 patients from eight participating centres (five academic centres and three large non-academic teaching hospitals) in the Netherlands were enrolled into this study and randomly assigned to the two treatment groups: 180 to surgery plus neoadjuvant chemoradiotherapy and 188 to surgery alone. Two patients in the neoadjuvant chemoradiotherapy group withdrew consent, so a total of 366 patients were analysed (178 in the neoadjuvant chemoradiotherapy plus surgery group and 188 in the surgery alone group). Of 171 patients who received any neoadjuvant chemoradiotherapy in this group, 162 (95%) were able to complete the entire neoadjuvant chemoradiotherapy regimen. After a median follow-up for surviving patients of 84·1 months (range 61·1-116·8, IQR 70·7-96·6), median overall survival was 48·6 months (95% CI 32·1-65·1) in the neoadjuvant chemoradiotherapy plus surgery group and 24·0 months (14·2-33·7) in the surgery alone group (HR 0·68 [95% CI 0·53-0·88]; log-rank p=0·003). Median overall survival for patients with squamous cell carcinomas was 81·6 months (95% CI 47·2-116·0) in the neoadjuvant chemoradiotherapy plus surgery group and 21·1 months (15·4-26·7) in the surgery alone group (HR 0·48 [95% CI 0·28-0·83]; log-rank p=0·008); for patients with adenocarcinomas, it was 43·2 months (24·9-61·4) in the neoadjuvant chemoradiotherapy plus surgery group and 27·1 months (13·0-41·2) in the surgery alone group (HR 0·73 [95% CI 0·55-0·98]; log-rank p=0·038). INTERPRETATION: Long-term follow-up confirms the overall survival benefits for neoadjuvant chemoradiotherapy when added to surgery in patients with resectable oesophageal or oesophagogastric junctional cancer. This improvement is clinically relevant for both squamous cell carcinoma and adenocarcinoma subtypes. Therefore, neoadjuvant chemoradiotherapy according to the CROSS trial followed by surgical resection should be regarded as a standard of care for patients with resectable locally advanced oesophageal or oesophagogastric junctional cancer. FUNDING: Dutch Cancer Foundation (KWF Kankerbestrijding).

Absence or low IGF-1R-expression in esophageal adenocarcinoma is associated with tumor invasiveness and radicality of surgical resection.

BACKGROUND AND OBJECTIVES: Esophageal adenocarcinoma (EAC) incidence increases, maybe due to increasing prevalences of obesity and diabetes. Concurrent hyperinsulinemia might promote carcinogenesis via the insulin-like growth factor-I receptor (IGF-1R). Expression of the IGF-1R was studied in correlation with diabetes and prognostic parameters. METHODS: Patients with EAC undergoing esophagectomy were prospectively selected. From resected tumors a tissue microarray was constructed. Immunohistochemistry evaluated IGF-1R-expression. Logistic-, cox regression models and survival analyses assessed if diabetes and IGF-1R-expression were associated with prognostic parameters. IGF-1R-expression in normal and Barrett tissues was studied. RESULTS: Absence or low IGF-1R-expression was associated with T3-, grade 3 tumors and R1 resections (P = 0.001, P = 0.025, P < 0.001, respectively). Logistic regression showed that this was associated with R1 resections (HR 0.24, 95%CI 0.11-0.52). Diabetes was not associated with IGF-1R-expression (P = 0.612). Absence or low IGF-1R-expression decreased 5-year overall survival (P = 0.023) univariably, but not multivariably. IGF-1R-expression was present in Barrett tissues, but diminished in high-grade dysplasia. CONCLUSIONS: Absence or low expression of IGF-1R was associated with high grade- and advanced tumors and less radical resections. IGF-1R might be a tumor marker in Barrett's esophagus since a change in expression patterns was found in the course from normal esophageal tissue to adenocarcinoma.

Anesthetic management of prophylactic cervical cerclage: a retrospective multicenter cohort study.

OBJECTIVES: Cervical incompetence complicates approximately 1 in 500 pregnancies and is the most common cause of second-trimester spontaneous abortion and preterm labor. No prospective or large retrospective studies have compared regional and general anesthesia for cervical cerclage. STUDY DESIGN: Following IRB approval, we performed a retrospective study in the two main medical centers over an 8-year period to assess the association of anesthesia choice with anesthetic and obstetric outcomes. Anesthetic and perioperative details were retrospectively collected from fails of all patients undergoing cervical cerclage from 01/01/2005 until 31/12/2012. Details included demographic data, anesthetic technique, PACU data and perioperative complications. RESULTS: We identified 487 cases of cervical cerclage in 327 women during the study period. The most commonly used anesthetic technique was general anesthesia (GA) (402/487; 82.5%) compared with regional anesthesia (RA) (85/487; 17.5%). When GA was performed, facemask was the most commonly used technique (275/402; 68.4%), followed by intravenous deep sedation (61/402; 15.2%); LMA (51/402; 12.7%) and tracheal intubation (13/402; 3.2%). There were no significant differences in demographic characteristics between women receiving general and regional anesthesia. Average duration of suturing the cervix among the GA group was 9.8 ± 1.6 and 10.6 ± 2.1 min in the RA group (p < 0.001). Average length of stay in the operating room in the GA group was 20.5 ± 3.9 and 23 ± 4.6 min in the RA group (p < 0.001). Patients receiving GA received in the PACU more opioids (6.2 versus 1.2%; p < 0.05) and more non-opioids analgesics (36.8 versus 9.4%; p < 0.001). Duration of PACU stay was shorter after GA (49.5 ± 18 min) than after RA (62.4 ± 28 min; p < 0.001). There were no other differences in anesthetic or perioperative outcome between groups. This study was not designed to provide evidence that RA reduces the risk of pulmonary aspiration, airway complications or adverse fetal neurological effects from maternal anesthetic exposure. CONCLUSIONS: Both regional and general anesthesia were safely used for the performance of cerclage. Patients after general anesthesia had a shorter recovery time but a higher demand for opioids and non-opioids analgesia.

Prolonged time to surgery after neoadjuvant chemoradiotherapy increases histopathological response without affecting survival in patients with esophageal or junctional cancer.

OBJECTIVE: To determine the relation between time to surgery (TTS) after neoadjuvant chemoradiotherapy (nCRT) and pathologically complete response (pCR), surgical outcome, and survival in patients with esophageal cancer. BACKGROUND: Standard treatment for potentially curable esophageal cancer is nCRT plus surgery after 4 to 6 weeks. In rectal cancer patients, evidence suggests that prolonged TTS is associated with a higher pCR rate and possibly with better survival. METHODS: We identified patients treated with nCRT plus surgery for esophageal cancer between 2001 and 2011. TTS (last day of radiotherapy to day of surgery) varied mainly for logistical reasons. Minimal follow-up was 24 months. The effect of TTS on pCR rate, postoperative complications, and survival was determined with (ordinal) logistic, linear, and Cox regression, respectively. RESULTS: In total, 325 patients were included. Median TTS was 48 days (p25-p75=40-60). After 45 days, TTS was associated with an increased probability of pCR [odds ratio (OR)=1.35 per additional week of TSS, P=0.0004] and a small increased risk of postoperative complications (OR=1.20, P<0.001). Prolonged TTS had no effect on disease-free and overall survivals (HR=1.00 and HR=1.06 per additional week of TSS, P=0.976 and P=0.139, respectively). CONCLUSIONS: Prolonged TTS after nCRT increases the probability of pCR and is associated with a slightly increased probability of postoperative complications, without affecting disease-free and overall survivals. We conclude that TTS can be safely prolonged from the usual 4 to 6 weeks up to at least 12 weeks, which facilitates a more conservative wait-and-see strategy after neoadjuvant chemoradiotherapy to be tested.

Lymph node retrieval during esophagectomy with and without neoadjuvant chemoradiotherapy: prognostic and therapeutic impact on survival.

OBJECTIVES: We aimed to examine the association between total number of resected nodes and survival in patients after esophagectomy with and without nCRT. BACKGROUND: Most studies concerning the potentially positive effect of extended lymphadenectomy on survival have been performed in patients who underwent surgery alone. As nCRT is known to frequently "sterilize" regional nodes, it is unclear whether extended lymphadenectomy after nCRT is still useful. METHODS: Patients from the randomized CROSS-trial who completed the entire protocol (ie, surgery alone or chemoradiotherapy + surgery) were included. With Cox regression models, we compared the impact of number of resected nodes as well as resected positive nodes on survival in both groups. RESULTS: One hundred sixty-one patients underwent surgery alone, and 159 patients received multimodality treatment. The median (interquartile range) number of resected nodes was 18 (12-27) and 14 (9-21), with 2 (1-6) and 0 (0-1) resected positive nodes, respectively. Persistent lymph node positivity after nCRT had a greater negative prognostic impact on survival as compared with lymph node positivity after surgery alone. The total number of resected nodes was significantly associated with survival for patients in the surgery-alone arm (hazard ratio per 10 additionally resected nodes, 0.76; P=0.007), but not in the multimodality arm (hazard ratio 1.00; P=0.98). CONCLUSIONS: The number of resected nodes had a prognostic impact on survival in patients after surgery alone, but its therapeutic value is still controversial. After nCRT, the number of resected nodes was not associated with survival. These data question the indication for maximization of lymphadenectomy after nCRT.

Inhibition of proliferation and survival of diffuse large B-cell lymphoma cells by a small-molecule inhibitor of the ubiquitin-conjugating enzyme Ubc13-Uev1A.

Diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin lymphoma, remains a partially curable disease. Genetic alterations affecting components of NF-κB signaling pathways occur frequently in DLBCL. Almost all activated B cell-like (ABC) DLBCL, which is the least curable group among the 3 major subtypes of this malignancy, and a substantial fraction of germinal center B cell-like (GCB) DLBCL exhibit constitutive NF-κB pathway activity. It has been demonstrated that ABC-DLBCL cells require such activity for proliferation and survival. Therefore, inhibition of NF-κB activation in DLBCL may provide an efficient and targeted therapy. In screening for small-molecule compounds that may inhibit NF-κB activation in DLBCL cells, we identified a compound, NSC697923, which inhibits the activity of the ubiquitin-conjugating (E2) enzyme Ubc13-Uev1A. NSC697923 impedes the formation of the Ubc13 and ubiquitin thioester conjugate and suppresses constitutive NF-κB activity in ABC-DLBCL cells. Importantly, NSC697923 inhibits the proliferation and survival of ABC-DLBCL cells and GCB-DLBCL cells, suggesting the Ubc13-Uev1A may be crucial for DLBCL growth. Consistently, knockdown of Ubc13 expression also inhibited DLBCL cell survival. The results of the present study indicate that Ubc13-Uev1A may represent a potential therapeutic target in DLBCL. In addition, compound NSC697923 may be exploited for the development of DLBCL therapeutic agents.

Progress in Retroperitoneal Sarcoma Management: Surgical and Radiotherapy Approaches.

Surgical resection is the cornerstone of curative treatment for retroperitoneal sarcomas (RPS), aiming for complete excision, yet the complexity of RPS with its proximity to vital structures continues to lead to high local recurrence rates after surgery alone. Thus, the role of radiotherapy (RT) continues to be refined to improve local control, which remains an important goal to prevent RPS recurrence. The recently completed global randomized trial to evaluate the role of surgery with and without preoperative RT - STRASS1, did not demonstrate a significant overall benefit for neoadjuvant RT based on the pre-specified definition of abdominal recurrence-free survival, however, sensitivity analysis using a standard definition of local recurrence and analysis of outcomes by compliance to the RT protocol suggests histology-specific benefit in well- and some de-differentiated liposarcomas. Ultimately, multidisciplinary collaboration and personalized approaches that consider histological sarcoma types and patient-specific factors are imperative for optimizing the therapeutic strategy in the management of RPS.

Residual esophageal cancer after neoadjuvant chemoradiotherapy frequently involves the mucosa and submucosa.

OBJECTIVES: To gain insight into the exact location of residual esophageal cancer in the esophageal wall and regional lymph nodes after neoadjuvant chemoradiotherapy (nCRT) and to determine the pattern of regression. BACKGROUND: Data from the recently published chemoradiotherapy for oesophageal cancer followed by surgery study trial showed that 49% of squamous cell carcinomas and 23% of adenocarcinomas had a pathologically complete response (pCR) in the resection specimen after nCRT. These results impose the ethical imperative to reconsider the necessity of esophagectomy with its substantial morbidity and mortality in patients with pCR. However, it remains challenging to accurately identify these patients before resection. METHODS: Between January 2003 and July 2011, all patients with esophageal cancer in a tertiary referral center, who underwent nCRT (5 weekly courses of carboplatin and paclitaxel plus 41.4 Gy concurrent radiotherapy) and surgical resection, were analyzed. The resection specimens were carefully re-evaluated by an experienced gastrointestinal pathologist. Tumor regression grade (TRG) was meticulously scored for each specific layer of the esophageal wall and for all removed lymph nodes. RESULTS: One hundred two consecutive patients were included. Seventy-one (70%) of 102 patients were noncomplete responders (≥TRG2) and in 63 of these patients (89%), residual tumor cells were seen in the mucosa and/or submucosa. Five of 8 patients without involvement of the mucosa and the submucosa had isolated remnants in the muscle layer (5/102 = 5%); the other 3 patients had tumor cells only in a single lymph node (3/102 = 3%). The surrounding stroma showed the highest percentage of TRG1 ( = pCR: 47%). In patients with pretreatment lymph node positivity, the percentage of TRG1 in all lymph nodes was also favorable (52%). Overall regression showed a nonrandom mixed pattern of both concentric regression and regression toward the lumen. CONCLUSIONS: After nCRT for esophageal cancer, both the mucosa and the submucosa show frequent residual malignant involvement. The surrounding stroma and the regional lymph nodes show the highest percentage of pCR and the overall regression pattern is most frequently a mixed pattern of both concentric regression and regression toward the lumen. This overall regression pattern lends support to careful testing of a wait-and-see approach in a subgroup of patients with esophageal cancer after nCRT.

Pre-intubation ventilation device for bearded patients: prospective, randomized, crossover trial in anesthetized patients.

Having a beard is an independent predictor of difficult ventilation by face mask. This study evaluates the efficacy of a novel intra-oral Bag-Valve-Guedel Adaptor (BVGA) in anaesthetized bearded patients. Patients with ASA score 1-2, scheduled for elective surgery, were recruited for this prospective, crossover trial. Beard length was categorized as < 0.5 cm, 0.5-1 cm, 1-5 cm, or > 5 cm. Patients were ventilated by attending anesthesiologists using the BVGA and a facemask (both with a Guedel oral airway). End-tidal CO2 (EtCO2) and expiratory tidal volume (TV) were recorded as was the number of hands required for the procedure. The primary outcome was the difference between BVGA and Facemask. Sixty-one patients were enrolled. Of these, 38 had beards, and 23 were without beards or with beards < 0.5 cm length. In bearded patients, ventilation with the BVGA was superior to the face mask by EtCO2 and non-inferior by TV (BVGA-vs-Mask, mean [95% CI]: EtCO2 [mmHg], 33.0 [31.6, 34.3]-vs-27.2 [25.5, 28.8], p < 0.001; TV [ml∙kg-1 IBW], 8.1 [7.4, 8.9]-vs-6.9 [6.0, 7.7], p = 0.11). The BVGA was found to be superior to the face mask by EtCO2 across all beard lengths (p ≤ 0.001), but by TV only for the longest beard group (p = 0.009). After securing the BVGA, ventilation was possible without hands in 74% of the cases - clearly impossible with the facemask (p ≤ 0.001). The BVGA is more effective and more convenient than the facemask in anaesthetized bearded patients. A follow-up study is underway to test whether replacing the face mask with the BVGA will improve effectiveness and ease of pre-intubation field ventilation by less-experienced, first responders.

Individual Participant Data Network Meta-Analysis of Neoadjuvant Chemotherapy or Chemoradiotherapy in Esophageal or Gastroesophageal Junction Carcinoma.

PURPOSE: The optimal neoadjuvant treatment for resectable carcinoma of the thoracic esophagus (TE) or gastroesophageal junction (GEJ) remains a matter of debate. We performed an individual participant data (IPD) network meta-analysis (NMA) of randomized controlled trials (RCTs) to study the effect of chemotherapy or chemoradiotherapy, with a focus on tumor location and histology subgroups. PATIENTS AND METHODS: All, published or unpublished, RCTs closed to accrual before December 31, 2015 and having compared at least two of the following strategies were eligible: upfront surgery (S), chemotherapy followed by surgery (CS), and chemoradiotherapy followed by surgery (CRS). All analyses were conducted on IPD obtained from investigators. The primary end point was overall survival (OS). The IPD-NMA was analyzed by a one-step mixed-effect Cox model adjusted for age, sex, tumor location, and histology. The NMA was registered in PROSPERO (CRD42018107158). RESULTS: IPD were obtained for 26 of 35 RCTs (4,985 of 5,807 patients) corresponding to 12 comparisons for CS-S, 12 for CRS-S, and four for CRS-CS. CS and CRS led to increased OS when compared with S with hazard ratio (HR) = 0.86 (0.75 to 0.99), P = .03 and HR = 0.77 (0.68 to 0.87), P < .001 respectively. The NMA comparison of CRS versus CS for OS gave a HR of 0.90 (0.74 to 1.09), P = .27 (consistency P = .26, heterogeneity P = .0038). For CS versus S, a larger effect on OS was observed for GEJ versus TE tumors (P = .036). For the CRS versus S and CRS versus CS, a larger effect on OS was observed for women (P = .003, .012, respectively). CONCLUSION: Neoadjuvant chemotherapy and chemoradiotherapy were consistently better than S alone across histology, but with some variation in the magnitude of treatment effect by sex for CRS and tumor location for CS. A strong OS difference between CS and CRS was not identified.

Autofluorescent flavoprotein imaging of spinal nociceptive activity.

Pain arises from activation of peripheral nociceptors, and strong noxious stimuli may cause an increase in spinal excitability called central sensitization, which is likely involved in many pathological pain states. So far, it has not been achieved to simultaneously visualize in vivo both the temporal and spatial aspects of spinal activity, including central sensitization. Using autofluorescent flavoprotein imaging (AFI), an optical technique suitable for mapping activity in nervous tissue, we demonstrate a close temporal and spatial correlation of electrically evoked nociceptive input with the spinal AFI signal, representing spinal neuronal activity. The AFI signal increases linearly with stimulation intensity. Furthermore, we found that the AFI signal was much larger in intensity and size when the same electrical stimulation was applied after the induction of central sensitization by a subcutaneous capsaicin injection. Finally, innocuous palpation of the hindpaw did not evoke an AFI response in naive animals, but after capsaicin injection a strong response was obtained. This is the first report demonstrating simultaneously the temporal and spatial propagation of spinal nociceptive activity in vivo.