Impact of lung function changes after induction radiochemotherapy on resected T4 non-small cell lung cancer outcome.

BACKGROUND: Induction radiochemotherapy, followed by resection, for T4 non-small cell lung cancer, has shown promising long-term survival but may be associated with increased postoperative morbidity and death, depending on patient selection. Here, we determined the effect of induction radiochemotherapy on pulmonary function and whether postinduction pulmonary function changes predict hospital morbidity and death and long-term survival. METHODS: A consecutive prospective cohort of 72 patients with T4 N0-2 M0 non-small cell lung cancer managed by radiochemotherapy, followed by resection, is reported. All patients underwent thoracoabdominal computed tomography or fusion positron emission tomography-computed tomography, brain imaging, mediastinoscopy, echocardiography, ventilation-perfusion scintigraphy, and pulmonary function testing before and after induction therapy. Resection was performed if the postoperative forced expiratory volume in 1 second and diffusion capacity of the lung for carbon monoxide exceeded 30% predicted and if the postoperative maximum oxygen consumption exceeded 10 mL/kg/min. RESULTS: The postoperative 90-day mortality rate was 8% (lobectomy, 2%; pneumonectomy, 21%; p=0.01). All deaths after pneumonectomy occurred after right-sided procedures. The 3-year and 5-year survival was 50% (95% confidence interval, 36% to 62%) and 45% (95% confidence interval, 31% to 57%) and was significantly associated with completeness of resection (p=0.004) and resection type (pneumonectomy vs lobectomy, p=0.01). There was no correlation between postinduction pulmonary function changes and postoperative morbidity or death or long-term survival in patients managed by lobectomy or pneumonectomy. CONCLUSIONS: In properly selected patients with T4 N0-2 M0 non-small cell lung cancer, resection after induction radiochemotherapy can be performed with a reasonable postoperative mortality rate and long-term survival, provided the resection is complete and a right-sided pneumonectomy is avoided. Postinduction pulmonary function changes did not correlate with postoperative morbidity or death or with long-term outcome.

Impact of induction therapy on airway complications after sleeve lobectomy for lung cancer.

BACKGROUND: Sleeve lobectomy is a valid alternative to pneumonectomy for the treatment of centrally located operable non-small cell lung cancer (NSCLC), but concern has been evoked regarding a potentially increased risk of bronchial anastomosis complications after induction therapy. This study examined the impact of induction therapy on airway healing after sleeve lobectomy for NSCLC. METHODS: Bronchial anastomosis complications were recorded with respect to the induction regimen applied (neoadjuvant chemotherapy vs chemoradiotherapy) in a consecutive series of patients with sleeve lobectomy for NSCLC. RESULTS: Ninety-nine patients underwent sleeve resection, 28 of them after induction therapy. Twelve patients received chemotherapy alone, and 16 patients had radiochemotherapy. There were no significant differences in postoperative 90-day mortality (3.6% vs 2.8%) and morbidity (54% vs 49%) for patients with and without induction therapy. Bronchial anastomosis complications occurred in 3 patients (10.8%) with neoadjuvant therapy and in 2 (2.8%) without (p = 0.3). In the induction therapy group, two bronchial stenoses occurred after radiochemotherapy and one bronchopleural fistula after chemotherapy alone. In patients without induction therapy, one bronchial stenosis and one bronchopleural fistula were observed. All bronchial stenoses were successfully treated by dilatation, and both bronchopleural fistulas occurring after right lower lobectomy were successfully treated by reoperation and completion sleeve bilobectomy with preservation of the upper lobe. CONCLUSIONS: Sleeve lobectomy for NSCLC can be safely performed after induction chemotherapy and radiochemotherapy with mortality and incidence of airway complications similar to that observed in nonpretreated patients. The treatment of airway complications does not differ for patients with and without induction therapy.

Clinical relevance of L-carnitine-supplemented total parenteral nutrition in postoperative trauma. Metabolic effects of continuous or acute carnitine administration with special reference to fat oxidation and nitrogen utilization.

Carnitine-free total parenteral nutrition (TPN) is claimed to result in a carnitine deficiency with subsequent impairment of fat oxidation. The present study was designed to evaluate the possible benefit of carnitine supplementation on postoperative fat and nitrogen utilization. Sixteen patients undergoing total esophagectomy were evenly randomized and received TPN without or with L-carnitine supplementation (74 mumol.kg-1.d-1) during 11 postoperative days. On day 11, a 4-h infusion of L-carnitine (125 mumol/kg) was performed in both groups. The effect of supplementation was evaluated by indirect calorimetry, N balance, and repeated measurements of plasma lipids and ketone bodies. Irrespective of continuous or acute supplementation, respiratory quotient and fat oxidation were similarly maintained throughout the study in both groups whereas N balance appeared to be more favorable without carnitine. We conclude that carnitine-supplemented TPN does not improve fat oxidation or promote N utilization in the postoperative phase.

Prédiction des complications après duodénopancréatectomie céphalique: validation d'un score de complications postopératoires = Prediction of complications after pancreaticoduodenectomy: validation of a postoperative complication score

Objectifs La chirurgie pancréatique reste associée à une morbidité postopératoire importante. Les efforts sont concentrés la plupart du temps sur la diminution de cette morbidité, mais la détection précoce de patients à risque de complications pourrait être une autre stratégie valable. Un score simple de prédiction des complications après duodénopancréatectomie céphalique a récemment été publié par Braga et al. La présente étude a pour but de valider ce score et de discuter de ses possibles implications cliniques. Méthodes De 2000 à 2015, 245 patients ont bénéficié d'une duodénopancréatectomie céphalique dans notre service. Les complications postopératoires ont été recensées selon la classification de Dindo et Clavien. Le score de Braga se base sur quatre paramètres : le score ASA (American Society of Anesthesiologists), la texture du pancréas, le diamètre du canal de Wirsung (canal pancréatique principal) et les pertes sanguines intra-opératoires. Un score de risque global de 0 à 15 peut être calculé pour chaque patient. La puissance de discrimination du score a été calculée en utilisant une courbe ROC (receiver operating characteristic). Résultats Des complications majeures sont apparues chez 31% des patients, alors que 17% des patients ont eu des complications majeures dans l'article de Braga. La texture du pancréas et les pertes sanguines étaient statistiquement significativement corrélées à une morbidité accrue. Les aires sous la courbe étaient respectivement de 0.95 et 0.99 pour les scores classés en quatre catégories de risques (de 0 à 3, 4 à 7, 8 à 11 et 12 à 15) et pour les scores individuels (de 0 à 15). Conclusions Le score de Braga permet donc une bonne discrimination entre les complications mineures et majeures. Notre étude de validation suggère que ce score peut être utilisé comme un outil pronostique de complications majeures après duodénopancréatectomie céphalique. Les implications cliniques, c'est-à-dire si les stratégies de prise en charge postopératoire doivent être adaptées en fonction du risque individuel du patient, restent cependant à élucider. -- Objectives Pancreatic surgery remains associated with important morbidity. Efforts are most commonly concentrated on decreasing postoperative morbidity, but early detection of patients at risk could be another valuable strategy. A simple prognostic score has recently been published. This study aimed to validate this score and discuss possible clinical implications. Methods From 2000 to 2012, 245 patients underwent pancreaticoduodenectomy. Complications were graded according to the Dindo-Clavien classification. The Braga score is based on American Society of Anesthesiologists score, pancreatic texture, Wirsung duct diameter, and blood loss. An overall risk score (from 0 to 15) can be calculated for each patient. Score discriminant power was calculated using a receiver operating characteristic curve. Results Major complications occurred in 31% of patients compared to 17% in Braga's data. Pancreatic texture and blood loss were independently statistically significant for increased morbidity. The areas under curve were 0.95 and 0.99 for 4-risk categories and for individual scores, respectively. Conclusions The Braga score discriminates well between minor and major complications. Our validation suggests that it can be used as prognostic tool for major complications after pancreaticoduodenectomy. The clinical implications, i.e., whether postoperative treatment strategies should be adapted according to the patient's individual risk, remain to be elucidated.

Serum anticholinergic activity and postoperative cognitive dysfunction in elderly parients

BACKGROUND: Cerebral cholinergic transmission plays a key role in cognitive function, and anticholinergic drugs administered during the perioperative phase are a hypothetical cause of postoperative cognitive dysfunction (POCD). We hypothesized that a perioperative increase in serum anticholinergic activity (SAA) is associated with POCD in elderly patients. METHODS: Seventy-nine patients aged >65 years undergoing elective major surgery under stan- dardized general anesthesia (thiopental, sevoflurane, fentanyl, and atracurium) were investi- gated. Cognitive functions were assessed preoperatively and 7 days postoperatively using the extended version of the CERAD-Neuropsychological Assessment Battery. POCD was defined as a postoperative decline >1 z-score in at least 2 test variables. SAA was measured preop- eratively and 7 days postoperatively at the time of cognitive testing. Hodges-Lehmann median differences and their 95% confidence intervals were calculated for between-group comparisons. RESULTS: Of the patients who completed the study, 46% developed POCD. Patients with POCD were slightly older and less educated than patients without POCD. There were no relevant differences between patients with and without POCD regarding gender, demographically cor- rected baseline cognitive functions, and duration of anesthesia. There were no large differences between patients with and without POCD regarding SAA preoperatively (pmol/mL, median [inter- quartile range]/median difference [95% CI], P; 1.14 [0.72, 2.37] vs 1.13 [0.68, 1.68]/0.12 [−0.31, 0.57], P = 0.56), SAA 7 days postoperatively (1.32 [0.68, 2.59] vs 0.97 [0.65, 1.83]/0.25 [−0.26, 0.81], P = 0.37), or changes in SAA (0.08 [−0.50, 0.70] vs −0.02 [−0.53, 0.41]/0.1 [−0.31, 0.52], P = 0.62). There was no significant relationship between changes in SAA and changes in cognitive function (Spearman rank correlation coefficient preoperatively of 0.03 [95% CI, −0.21, 0.26] and postoperatively of −0.002 [95% CI, −0.24, 0.23]). CONCLUSIONS: In this panel of patients with low baseline SAA and clinically insignificant periopera- tive anticholinergic burden, although a relationship cannot be excluded in some patients, our analysis suggests that POCD is probably not a substantial consequence of anticholinergic medications admin- istered perioperatively but rather due to other mechanisms.

Radiographic volume analysis as a novel tool to determine nasopalatine duct cyst dimensions and its association with presenting symptoms and postoperative complications.

OBJECTIVES: The aims of the study were to use cone beam computed tomography (CBCT) images of nasopalatine duct cysts (NPDC) and to calculate the diameter, surface area, and 3D-volume using a custom-made software program. Furthermore, any associations of dimensions of NPDC with age, gender, presence/absence of maxillary incisors/canines (MI/MC), endodontic treatment of MI/MC, presenting symptoms, and postoperative complications were evaluated. MATERIAL AND METHODS: The study comprised 40 patients with a histopathologically confirmed NPDC. On preoperative CBCT scans, curves delineating the cystic borders were drawn in all planes and the widest diameter (in millimeter), surface area (in square millimeter), and volume (in cubic millimeter) were calculated. RESULTS: The overall mean cyst diameter was 15 mm (range 7-47 mm), the mean cyst surface area 566 mm(2) (84-4,516 mm(2)), and the mean cyst volume 1,735 mm(3) (65-25,350 mm(3)). For 22 randomly allocated cases, a second measurement resulted in a mean absolute aberration of ±4.2 % for the volume, ±2.8 % for the surface, and ±4.9 % for the diameter. A statistically significant association was found for the CBCT determined cyst measurements and the need for preoperative endodontic treatment to MI/MC and for postoperative complications. CONCLUSION: In the hands of a single experienced operator, the novel software exhibited high repeatability for measurements of cyst dimensions. Further studies are needed to assess the application of this tool for dimensional analysis of different jaw cysts and lesions including treatment planning. CLINICAL RELEVANCE: Accurate radiographic information of the bone volume lost (osteolysis) due to expansion of a cystic lesion in three dimensions could help in personalized treatment planning.

Prediction of Complications After Pancreaticoduodenectomy: Validation of a Postoperative Complication Score.

OBJECTIVES: Pancreatic surgery remains associated with important morbidity. Efforts are most commonly concentrated on decreasing postoperative morbidity, but early detection of patients at risk could be another valuable strategy. A simple prognostic score has recently been published. This study aimed to validate this score and discuss possible clinical implications. METHODS: From 2000 to 2012, 245 patients underwent a pancreaticoduodenectomy. Complications were graded according to the Dindo-Clavien Classification. The Braga score is based on American Society of Anesthesiologists score, pancreatic texture, Wirsung duct diameter, and blood loss. An overall risk score (0-15) can be calculated for each patient. Score discriminant power was calculated using a receiver operating characteristic curve. RESULTS: Major complications occurred in 31% of patients compared with 17% in Braga's data. Pancreatic texture and blood loss were independently statistically significant for increased morbidity. Areas under the curve were 0.95 and 0.99 for 4-risk categories and for individual scores, respectively. CONCLUSIONS: The Braga score discriminates well between minor and major complications. Our validation suggests that it can be used as a prognostic tool for major complications after pancreaticoduodenectomy. The clinical implications, that is, whether postoperative treatment strategies should be adapted according to the patient's individual risk, remain to be elucidated.

Final results of the SAKK 16/00 trial: a randomized phase III trial comparing neoadjuvant chemoradiation to chemotherapy alone in stage IIIA/N2 non-small cell lung cancer (NSCLC).

Aim: One standard option in the treatment of stage IIIA/N2 NSCLC is neoadjuvant chemotherapy followed by surgery. We investigated in a randomized trial whether the addition of neoadjuvant radiotherapy would improve the outcome. Here we present the final results of this study. Methods: Patients (pts.) with pathologically proven, resectable stage IIIA/N2 NSCLC, performance status 0-1, and adequate organ function were randomized 1:1 to chemoradiation (CRT) with 3 cycles of neoadjuvant chemotherapy (cisplatin 100 mg/m2 and docetaxel 85 mg/m2 d1, q3weeks) followed by accelerated concomitant boost radiotherapy (RT) with 44 Gy in 22 fractions in 3 weeks, or neoadjuvant chemotherapy alone (CT), with subsequent surgery for all pts. The primary endpoint was event-free survival (EFS). Results: 232 pts. were randomized in 23 centers, the median follow-up was 53 months. Two thirds were men, median age was 60 years (range 37-76). Histology was squamous cell in 33%, adenocarcinoma in 43%. Response rate to CRT was 61% vs. 44% with CT. 85% of all pts. underwent surgery, 30-day postoperative mortality was 1%. The rate of complete resection was 91% (CRT) vs. 81% (CT) and the pathological complete remission (pCR) rate was 16% vs. 12%. The median EFS was 13.1 months (95% CI 9.9 - 23.5) for the CRT group vs. 11.8 months (95% CI 8.4 - 15.2) in the CT arm (p 0.665). The median overall survival (OS) with CRT was 37.1 months (95% CI 22.6 -50), with CT 26.1 months ( 95% CI 26.1 - 52.1, p 0.938). The local failure rate was 23% in both arms. In the CT arm 12 pts. were given postoperative radiotherapy (PORT) for R1 resection, 6 pts. received PORT in violation of the protocol. Pts. with a pCR, mediastinal downstaging to ypN0/1 and complete resection had a better outcome. Toxicity of chemotherapy was substantial, especially febrile neutropenia was common, whereas RT was well tolerated. Conclusions: This is the first completed phase III trial to evaluate the role of induction chemoradiotherapy and surgery, in comparison to neoadjuvant CT alone followed by surgery. RT was active, it increased response, complete resection and pCR rates. However, this failed to translate into an improvement of local control, EFS or OS. Notably, surgery after induction treatment was safe, including pneumonectomy. The overall survival rates of our neoadjuvant regimen are very encouraging, especially for a multicenter setting. Disclosure: M. Pless: Advisory Board for Sanofi; R. Cathomas: Advisory Board Sanofi D.C. Betticher: Advisory Board Sanofi. All other authors have declared no conflicts of interest.

International comparison of the German evidence-based S3-guidelines on the diagnosis and multimodal treatment of early and locally advanced gastric cancer, including adenocarcinoma of the lower esophagus.

BACKGROUND: Clinical guidelines are essential in implementing and maintaining nationwide stage-specific diagnostic and therapeutic standards. In 2011, the first German expert consensus guideline defined the evidence for diagnosis and treatment of early and locally advanced esophagogastric cancers. Here, we compare this guideline with other national guidelines as well as current literature. METHODS: The German S3-guideline used an approved development process with de novo literature research, international guideline adaptation, or good clinical practice. Other recent evidence-based national guidelines and current references were compared with German recommendations. RESULTS: In the German S3 and other Western guidelines, adenocarcinomas of the esophagogastric junction (AEG) are classified according to formerly defined AEG I-III subgroups due to the high surgical impact. To stage local disease, computed tomography of the chest and abdomen and endosonography are reinforced. In contrast, laparoscopy is optional for staging. Mucosal cancers (T1a) should be endoscopically resected "en-bloc" to allow complete histological evaluation of lateral and basal margins. For locally advanced cancers of the stomach or esophagogastric junction (≥T3N+), preferred treatment is preoperative and postoperative chemotherapy. Preoperative radiochemotherapy is an evidence-based alternative for large AEG type I-II tumors (≥T3N+). Additionally, some experts recommend treating T2 tumors with a similar approach, mainly because pretherapeutic staging is often considered to be unreliable. CONCLUSIONS: The German S3 guideline represents an up-to-date European position with regard to diagnosis, staging, and treatment recommendations for patients with locally advanced esophagogastric cancer. Effects of perioperative chemotherapy versus chemoradiotherapy are still to be investigated for adenocarcinoma of the cardia and the lower esophagus.

Magnetic resonance imaging findings of disc-related epidural cysts in nonsurgical and postoperative microdiscectomy patients

OBJECTIVE: To demonstrate five discal cysts with detailed magnetic resonance imaging findings in nonsurgical and following postoperative microdiscectomy. MATERIALS AND METHODS: Five discal cysts in four patients who underwent magnetic resonance imaging were found through a search in our database and referral from a single orthopedic spine surgeon. Computed tomography in two cases and computed tomography discography in one case were also performed. RESULTS: Five discal cysts were present in four patients. Three patients had no history of previous lumbar surgery and the other patient presented with two discal cysts and recurrent symptoms after partial laminectomy and microdiscectomy. All were oval shaped and seated in the anterior epidural space. Four were ventrolateral, and the other one was centrally positioned in the anterior spinal canal. One showed continuity with the central disc following discography. Three were surgically removed. CONCLUSION: Magnetic resonance imaging can easily depict an epidural cyst and the diagnosis of a discal cyst should be raised when an homogeneous ventrolateral epidural cyst contiguous to a mild degenerated disc is identified.

Efficacy of methotrexate to prevent postoperative recurrence of Crohn's disease

BACKGROUND: endoscopic postoperative recurrence (POR) of Crohn’s disease (CD) is the presence of lesions in previously unaffected intestinal segments and occurs in up to 85% of patients one year after bowel resection. Patients at low risk for POR can either remain untreated until lesions recur or receive immediate prevention after surgery with mesalazine, azathioprine (AZA) and/or metronidazole, although with moderate benefit. Out of the postoperative setting, methotrexate (MTX) has been shown to be efficacious for induction and maintenance of remission and has been established as the second-line immunosuppressant for patients with CD unresponsive or intolerant to AZA.AIMS: to determine the efficacy and safety of MTX to prevent endoscopic and clinical POR at 24 weeks after surgery in low risk patientsMETHODS: the study consists on a multicenter, randomized, double-blind and placebo-controlled clinical trial that will enroll 132 patients at low risk for POR (non-smokers, first intestinal resection, non-penetrating behavior). Patients will be randomized to receive subcutaneous MTX at doses of 25 mg/week or an identical placebo, for 24 weeks. Endoscopic and clinical assessment of POR will be performed after 24 weeks (6 months) of treatment. The main outcome is endoscopic POR, defined as a Rutgeerts score of >i2, and secondary outcomes include clinical POR, defined as >i2 lesions plus a Crohn’s Disease Activity Index (CDAI) >150, and description of adverse events

Hypoxia-associated biomarkers in rectal cancer treated by preoperative radiotherapy or chemoradiotherapy

Hypoksiaan liittyvät biologiset merkkiaineet leikkausta edeltävällä sädehoidolla tai kemosädehoidolla hoidetussa peräsuolisyövässä Peräsuolensyöpä on yleinen pahanlaatuinen kasvain. Leikkausta edeltävä sädehoito annetaan yleensä T3-T4-kasvaimille. Tutkimuksella pyrittiin selvittämään, voidaanko kasvaimen hapenpuutteeseen liittyvillä biologisilla merkkiaineilla arvioida peräsuolisyövän ennustetta leikkausta edeltävän sädehoidon tai kemosädehoidon jälkeen. Tällaisia merkkiaineita ovat hapenpuutteen vaikutuksesta aktivoituva HIF-1alfa hiilihappoanhydraasi IX (CA IX), sokerin kuljetukseen solussa osallistuva GLUT-1 sekä solun tukirankaproteiini ezrin. Tutkimukseen otettiin 178 potilasta, jotka olivat saaneet ennen leikkausta lyhyen (n=77) tai pitkän sädehoidon (n=10), pitkän sädehoidon ja solunsalpaajahoidon (n=37) tai ei mitään hoitoa (n=54). Lisäksi osalta leikkausta edeltävää sädehoitoa saaneelta potilaalta tutkittiin hoitoja edeltävät, diagnostiset näytteet (n=80). Tutkimuksessa käytettiin immunehistokemiallisia värjäysmenetelmiä. Kasvaimen regressiota (TRG) arvioitiin pitkän sädehoidon jälkeisistä näytteistä. Leikkausnäytteissä negatiivinen/heikko CA IX intensiteetti liittyi sekä pidempään tautispesifiseen (p=0.034) että tautivapaaseen elinaikaan (p=0.003) ja pitkän sädehoidon jälkeen HIF-1alfa-negatiivisuus pidempään tautispesifiseen (p=0.001) sekä negatiivinen/heikko GLUT-1 pidempään tautivapaaseen elinaikaan (p=0.066). Voimakas ezrin-ilmentymä diagnostisissa näytteissä liittyi lyhyempään tautivapaaseen ja tautispesifiseen (p=0.027 ja p=0.002) ennusteeseen. Monimuuttuja-analyysissä vahva CA IX intensiteetti leikkausnäytteissä ennusti itsenäisesti huonompaa tautivapaata ja tautispesifistä selviytymistä. Erinomainen TRG liittyi negatiiviseen/heikkoon CA IX- (p=0.057), ezrin- (p=0.012) ja GLUT-1 -ilmentymään (p=0.013) leikkausnäytteissä. Kun kaikki neljä merkkiainetta analysoitiin yhdessä monimuuttuja-analyysissä, CA IX intensiteetti leikkausnäytteissä ennusti itsenäisesti tautispesifistä elinaikaa. Voimakas CA IX-ilmentymä leikkausnäytteissä ja positiivinen HIF-1alfa- ja vahva GLUT-1-ilmentymä pitkän sädehoidon jälkeisissä leikkausnäytteissä sekä vahva ezrin-ilmentymä diagnostisissa näytteissä liittyivät epäsuotuisaan ennusteeseen. Monimuuttujaanalyysissä kohtalainen/voimakas CA IX intensiteetti leikkausnäytteissä ennusti itsenäisesti huonompaa tautivapaata ja tautispesifistä elinaikaa. CA IX on vahva biologinen merkkiaine peräsuolisyövässä.