Evaluation of National Surgical Practice for Lateral Lymph Nodes in Rectal Cancer in an Untrained Setting.

BACKGROUND: Involved lateral lymph nodes (LLNs) have been associated with increased local recurrence (LR) and ipsi-lateral LR (LLR) rates. However, consensus regarding the indication and type of surgical treatment for suspicious LLNs is lacking. This study evaluated the surgical treatment of LLNs in an untrained setting at a national level. METHODS: Patients who underwent additional LLN surgery were selected from a national cross-sectional cohort study regarding patients undergoing rectal cancer surgery in 69 Dutch hospitals in 2016. LLN surgery consisted of either 'node-picking' (the removal of an individual LLN) or 'partial regional node dissection' (PRND; an incomplete resection of the LLN area). For all patients with primarily enlarged (≥7 mm) LLNs, those undergoing rectal surgery with an additional LLN procedure were compared to those  undergoing only rectal resection. RESULTS: Out of 3057 patients, 64 underwent additional LLN surgery, with 4-year LR and LLR rates of 26% and 15%, respectively. Forty-eight patients (75%) had enlarged LLNs, with corresponding recurrence rates of 26% and 19%, respectively. Node-picking (n = 40) resulted in a 20% 4-year LLR, and a 14% LLR after PRND (n = 8; p = 0.677). Multivariable analysis of 158 patients with enlarged LLNs undergoing additional LLN surgery (n = 48) or rectal resection alone (n = 110) showed no significant association of LLN surgery with 4-year LR or LLR, but suggested higher recurrence risks after LLN surgery (LR: hazard ratio [HR] 1.5, 95% confidence interval [CI] 0.7-3.2, p = 0.264; LLR: HR 1.9, 95% CI 0.2-2.5, p = 0.874). CONCLUSION: Evaluation of Dutch practice in 2016 revealed that approximately one-third of patients with primarily enlarged LLNs underwent surgical treatment, mostly consisting of node-picking. Recurrence rates were not significantly affected by LLN surgery, but did suggest worse outcomes. Outcomes of LLN surgery after adequate training requires further research.

Short- and Long-term Outcomes After Laparoscopic Emergency Resection of Left-Sided Obstructive Colon Cancer: A Nationwide Propensity Score-Matched Analysis.

BACKGROUND: The role of laparoscopy for emergency resection of left-sided obstructive colon cancer remains unclear, especially regarding impact on survival. OBJECTIVE: This study aimed to determine short- and long-term outcomes after laparoscopic versus open emergency resection of left-sided obstructive colon cancer. DESIGN: This observational cohort study compared patients who underwent laparoscopic emergency resection to those who underwent open emergency resection between 2009 and 2016 by using 1:3 propensity-score matching. Matching variables included sex, age, BMI, ASA score, previous abdominal surgery, tumor location, cT4, cM1, multivisceral resection, small-bowel distention on CT, and subtotal colectomy. SETTING: This was a nationwide, population-based study. PATIENTS: Of 2002 eligible patients with left-sided obstructive colon cancer, 158 patients who underwent laparoscopic emergency resection were matched with 474 patients who underwent open emergency resection. INTERVENTIONS: The intervention was laparoscopic versus open emergency resection. MAIN OUTCOME MEASURES: The main outcome measures were 90-day mortality, 90-day complications, permanent stoma, disease recurrence, overall survival, and disease-free survival. RESULTS: Intentional laparoscopy resulted in significantly fewer 90-day complications (26.6% vs 38.4%; conditional OR, 0.59; 95% CI, 0.39-0.87) and similar 90-day mortality. Laparoscopy resulted in better 3-year overall survival (81.0% vs 69.4%; HR, 0.54; 95% CI, 0.37-0.79) and disease-free survival (68.3% vs 52.3%; HR, 0.64; 95% CI, 0.47-0.87). Multivariable regression analyses of the unmatched 2002 patients confirmed an independent association of laparoscopy with fewer 90-day complications and better 3-year survival. LIMITATIONS: Selection bias was the limitation that cannot be completely ruled out because of the retrospective nature of this study. CONCLUSIONS: This population-based study with propensity score-matched analysis suggests that intentional laparoscopic emergency resection might improve outcomes in patients with left-sided obstructive colon cancer compared to open emergency resection. Management of those patients in the emergency setting requires proper selection for intentional laparoscopic resection if relevant expertise is available, thereby considering other alternatives to avoid open emergency resection (ie, decompressing stoma). See Video Abstract at http://links.lww.com/DCR/B972 . RESULTADOS A CORTO Y LARGO PLAZO DESPUS DE LA RESECCIN LAPAROSCPICA DE EMERGENCIA EN CNCER DE COLON IZQUIERDO OBSTRUCTIVO UN ANLISIS EMPAREJADO POR PUNTAJE DE PROPENSIN A NIVEL NACIONAL: ANTECEDENTES:El papel de la laparoscopia en la resección de emergencia en cáncer de colon izquierdo obstructivo sigue sin estar claro, especialmente con respecto al impacto en la supervivencia.OBJETIVO:El objetivo de este estudio fue determinar los resultados a corto y largo plazo después de la resección de emergencia laparoscópica versus abierta en cáncer de colon izquierdo obstructivo.DISEÑO:Estudio observacional de cohortes comparó pacientes que se sometieron a resección de laparoscópica de emergencia versus resección abierta de emergencia entre 2009 y 2016, mediante el uso de emparejamineto por puntaje de propensión 1: 3. Las variables emparejadas incluyeron sexo, edad, IMC, puntaje ASA, cirugía abdominal previa, ubicación del tumor, cT4, cM1, resección multivisceral, distensión del intestino delgado en la TAC y colectomía subtotal.ENTORNO CLINICO:A nivel nacional, basado en la población.PACIENTES:De 2002 pacientes elegibles con cáncer de colon izquierdo obstructivo, 158 pacientes con resección laparoscópica s de emergencia e emparejaron con 474 pacientes con resección abierta de emergencia.INTERVENCIONES:Resección laparoscópica de emergencia versus abierta.PRINCIPALES MEDIDAS DE RESULTADO:Las medidas primarias fueron la mortalidad a 90 días, complicaciones a 90 días, estoma permanente, recurrencia de la enfermedad, supervivencia general y supervivencia libre de enfermedad.RESULTADOS:La laparoscopia intencional dió como resultado significativamente menos complicaciones a los 90 días (26,6 % vs 38,4 %, cOR 0,59, IC del 95 %: 0,39-0,87) y una mortalidad similar a los 90 días. La laparoscopia resultó en una mejor supervivencia general a los 3 años (81,0 % vs 69,4 %, HR 0,54, IC del 95 % 0,37-0,79) y supervivencia libre de enfermedad (68,3 % vs 52,3 %, HR 0,64, IC del 95 % 0,47-0,87). Los análisis de regresión multivariable de los 2002 pacientes no emparejados confirmaron una asociación independiente de la laparoscopia con menos complicaciones a los 90 días y una mejor supervivencia a los 3 años.LIMITACIONES:El sesgo de selección no se puede descartar por completo debido a la naturaleza retrospectiva de este estudio.CONCLUSIONES:Estudio poblacional con análisis emparejado por puntaje de propensión sugiere que la resección laparoscópica de emergencia intencional podría mejorar los resultados a corto y largo plazo en pacientes con cáncer de colon izquierdo obstructivo en comparación con resección abierta de emergencia, lo que justifica la confirmación en estudios futuros. El manejo de esos pacientes en el entorno de emergencia requiere una selección adecuada para la resección laparoscópica intencional si se dispone de experiencia relevante, considerando así otras alternativas para evitar la resección abierta de emergencia (es decir, ostomia descompresiva). Consulte Video Resumen en http://links.lww.com/DCR/B972 . (Traducción- Dr. Francisco M. Abarca-Rendon & Dr. Fidel Ruiz Healy).

Transanal minimally invasive surgery (TAMIS) versus endoscopic submucosal dissection (ESD) for resection of non-pedunculated rectal lesions (TRIASSIC study): study protocol of a European multicenter randomised controlled trial.

BACKGROUND: In the recent years two innovative approaches have become available for minimally invasive en bloc resections of large non-pedunculated rectal lesions (polyps and early cancers). One is Transanal Minimally Invasive Surgery (TAMIS), the other is Endoscopic Submucosal Dissection (ESD). Both techniques are standard of care, but a direct randomised comparison is lacking. The choice between either of these procedures is dependent on local expertise or availability rather than evidence-based. The European Society for Endoscopy has recommended that a comparison between ESD and local surgical resection is needed to guide decision making for the optimal approach for the removal of large rectal lesions in Western countries. The aim of this study is to directly compare both procedures in a randomised setting with regard to effectiveness, safety and perceived patient burden. METHODS: Multicenter randomised trial in 15 hospitals in the Netherlands. Patients with non-pedunculated lesions > 2 cm, where the bulk of the lesion is below 15 cm from the anal verge, will be randomised between either a TAMIS or an ESD procedure. Lesions judged to be deeply invasive by an expert panel will be excluded. The primary endpoint is the cumulative local recurrence rate at follow-up rectoscopy at 12 months. Secondary endpoints are: 1) Radical (R0-) resection rate; 2) Perceived burden and quality of life; 3) Cost effectiveness at 12 months; 4) Surgical referral rate at 12 months; 5) Complication rate; 6) Local recurrence rate at 6 months. For this non-inferiority trial, the total sample size of 198 is based on an expected local recurrence rate of 3% in the ESD group, 6% in the TAMIS group and considering a difference of less than 6% to be non-inferior. DISCUSSION: This is the first European randomised controlled trial comparing the effectiveness and safety of TAMIS and ESD for the en bloc resection of large non-pedunculated rectal lesions. This is important as the detection rate of these adenomas is expected to further increase with the introduction of colorectal screening programs throughout Europe. This study will therefore support an optimal use of healthcare resources in the future. TRIAL REGISTRATION: Netherlands Trial Register, NL7083 , 06 July 2018.

Low Hartmann's procedure or intersphincteric abdominoperineal resection in the primary treatment of low rectal cancer; a survey among surgeons evaluating current practice.

BACKGROUND: Low Hartmann's procedure (LHP) and intersphincteric abdominoperineal resection (iAPR) are both surgical options in the treatment of distal rectal cancer when there is no intention to restore bowel continuity. This study aimed to evaluate current practice among members of the Dutch Association of Coloproctology (WCP). METHODS: An online survey among members of the WCP who represent 66 Dutch hospitals was conducted. The survey consisted of 15 questions addressing indications for surgical procedures and complications. RESULTS: Surgeons from 37 hospitals (56%) responded. Thirty-six percent does not distinguish low from high Hartmann's procedures based on estimated length of the rectal remnant. Overall, iAPR was the preferred technique in 86%. If asking whether operative approach would be different in tumours at 1 cm from the pelvic floor compared to 5 cm distance, 62% stated that they would consider a different technique. The incidence of pelvic abscess after LHP was thought to be higher, equal or lower than iAPR in 36%, 36% and 21%, respectively, with the remaining respondents not answering this question. CONCLUSIONS: The vast majority of the respondents considers iAPR as the preferred non-restorative procedure for rectal cancer not invading the sphincter complex, which contradicts with population based data from 2011.

Outcome After Redo Surgery for Complicated Colorectal and Coloanal Anastomosis: A Systematic Review.

BACKGROUND: When a colorectal or coloanal anastomosis fails because of persistent leakage or stenosis, or the anastomosis has to be resected for recurrent cancer, constructing a new anastomosis might be an option in selected patients. This is a rare and complex type of redo surgery. OBJECTIVE: The aim of this review was to evaluate the current literature on redo anastomosis for complicated colorectal or coloanal anastomosis. DATA SOURCES: A systematic literature search of MEDLINE, EMBASE, the Cochrane Library, the PROSPERO register, clinicaltrials.gov, and the World Health Organization International Clinical Trials Registry Platform database was performed. STUDY SELECTION: Two reviewers independently screened the available literature. All studies reporting on redo surgery and aiming at reconstruction of a prior low colorectal or coloanal anastomosis for any indication were included. MAIN OUTCOME MEASURES: Primary outcome was successful restoration of continuity. Secondary outcomes were postoperative morbidity, pelvic sepsis, incontinence, and mortality. RESULTS: Nine studies were included, comprising 291 patients, of whom 76% had index surgery for colorectal cancer. Pooled proportions showed an overall success rate of 79% (95% CI, 69-86), with a pooled incidence of major postoperative morbidity of 16% (95% CI, 10-24). The pooled pelvic sepsis rate was 16% (95% CI, 9-27), and the pooled surgical reintervention and readmission rates were 11% (95% CI, 8-17) and 7% (95% CI, 3-15). Five studies reported on incontinence, with a pooled proportion of 17% (95% CI, 10-26). LIMITATIONS: The limitations of this review are the lack of randomized controlled trials and high-quality studies, and the small sample sizes and heterogeneous patient populations in the included studies. CONCLUSIONS: Redo surgery is a valuable treatment option for the complicated colorectal or coloanal anastomosis with 79% successful restoration of bowel continuity in the published literature from experienced tertiary centers.

Low Hartmann's procedure or intersphincteric proctectomy for distal rectal cancer: a retrospective comparative cohort study.

PURPOSE: Two non-restorative options for low rectal cancer not invading the sphincter are the low Hartmann's procedure (LH) or intersphincteric proctectomy (IP). The aim of this study was to compare postoperative morbidity with emphasis on pelvic abscesses after LH and IP. METHODS: All patients that had LH or IP for low rectal cancer were included in three centres between 2008 and 2014 in this retrospective cohort study. Follow-up was performed for at least 12 months. RESULTS: A total of 52 patients were included: 40 LH and 12 IP. Median follow-up was 29 months (IQR 23). There were no differences between groups in gender, age and ASA classification. Seven patients in the LH group (18%) and four patients in the IP group (33%) developed a complication within 30-day postoperative with a Clavien-Dindo classification grade III or higher (P = 0.253). Four out of 40 patients (10%) in the LH group and two out of 12 patients (17%) in the IP group developed a pelvic abscess (P = 0.612). Reinterventions were performed in 11 (28%) patients in the LH group and five (42%) patients in the IP group (P = 0.478), with a total number of reinterventions of 13 and 20, respectively. Six and 15 interventions were related to pelvic abscesses, respectively. CONCLUSION: Pelvic abscesses seem to occur in a similar rate after both LH and IP. Previous reports from the literature suggesting that IP might be associated with less infectious pelvic complications compared to LH are not supported by this study, although numbers are small.

Outcome of Completion Surgery after Endoscopic Submucosal Dissection in Early-Stage Colorectal Cancer Patients.

T1 colorectal cancers (T1CRC) are increasingly being treated by endoscopic submucosal dissection (ESD). After ESD of a T1CRC, completion surgery is indicated in a subgroup of patients. Currently, the influence of ESD on surgical morbidity and mortality is unknown. The aim of this study was to compare 90-day morbidity and mortality of completion surgery after ESD to primary surgery. The completion surgery group consisted of suspected T1CRC patients from a multicenter prospective ESD database (2014-2020). The primary surgery group consisted of pT1CRC patients from a nationwide surgical registry (2017-2019). Patients with rectal or sigmoidal cancers were selected. Patients receiving neoadjuvant therapy were excluded. Propensity score adjustment was used to correct for confounders. In total, 411 patients were included: 54 in the completion surgery group (39 pT1, 15 pT2) and 357 in the primary surgery group with pT1CRC. Adverse event rate was 24.1% after completion surgery and 21.3% after primary surgery. After completion surgery 90-day mortality did not occur, though one patient died in the primary surgery group. After propensity score adjustment, lymph node yield did not differ significantly between the groups. Among other morbidity-related outcomes, stoma rate (OR 1.298 95%-CI 0.587-2.872, p = 0.519) and adverse event rate (OR 1.162; 95%-CI 0.570-2.370, p = 0.679) also did not differ significantly. A subgroup analysis was performed in patients undergoing rectal surgery. In this subgroup (37 completion and 136 primary surgery), these morbidity outcomes also did not differ significantly. In conclusion, this study suggests that ESD does not compromise morbidity or 90-day mortality of completion surgery.

Ferric carboxymaltose infusion versus oral iron supplementation for preoperative iron deficiency anaemia in patients with colorectal cancer (FIT): a multicentre, open-label, randomised, controlled trial.

BACKGROUND: A third of patients with colorectal cancer who are eligible for surgery in high-income countries have concomitant anaemia associated with adverse outcomes. We aimed to compare the efficacy of preoperative intravenous and oral iron supplementation in patients with colorectal cancer and iron deficiency anaemia. METHODS: In the FIT multicentre, open-label, randomised, controlled trial, adult patients (aged 18 years or older) with M0 stage colorectal cancer scheduled for elective curative resection and iron deficiency anaemia (defined as haemoglobin level of less than 7·5 mmol/L (12 g/dL) for women and less than 8 mmol/L (13 g/dL) for men, and a transferrin saturation of less than 20%) were randomly assigned to either 1-2 g of ferric carboxymaltose intravenously or three tablets of 200 mg of oral ferrous fumarate daily. The primary endpoint was the proportion of patients with normalised haemoglobin levels before surgery (≥12 g/dL for women and ≥13 g/dL for men). An intention-to-treat analysis was done for the primary analysis. Safety was analysed in all patients who received treatment. The trial was registered at ClincalTrials.gov, NCT02243735, and has completed recruitment. FINDINGS: Between Oct 31, 2014, and Feb 23, 2021, 202 patients were included and assigned to intravenous (n=96) or oral (n=106) iron treatment. Treatment began a median of 14 days (IQR 11-22) before surgery for intravenous iron and 19 days (IQR 13-27) for oral iron. Normalisation of haemoglobin at day of admission was reached in 14 (17%) of 84 patients treated intravenously and 15 (16%) of 97 patients treated orally (relative risk [RR] 1·08 [95% CI 0·55-2·10]; p=0·83), but the proportion of patients with normalised haemoglobin significantly increased for the intravenous treatment group at later timepoints (49 [60%] of 82 vs 18 [21%] of 88 at 30 days; RR 2·92 [95% CI 1·87-4·58]; p<0·0001). The most prevalent treatment-related adverse event was discoloured faeces (grade 1) after oral iron treatment (14 [13%] of 105), and no treatment-related serious adverse events or deaths were observed in either group. No differences in other safety outcomes were seen, and the most common serious adverse events were anastomotic leakage (11 [5%] of 202), aspiration pneumonia (5 [2%] of 202), and intra-abdominal abscess (5 [2%] 202). INTERPRETATION: Normalisation of haemoglobin before surgery was infrequent with both treatment regimens, but significantly improved at all other timepoints following intravenous iron treatment. Restoration of iron stores was feasible only with intravenous iron. In selected patients, surgery might be delayed to augment the effect of intravenous iron on haemoglobin normalisation. FUNDING: Vifor Pharma.

Predicting the outcome of closed-loop small bowel obstruction by preoperative characteristics.

BACKGROUND: Closed-loop small bowel obstruction (CL-SBO) can threaten the viability of the intestine by obstructing a bowel segment at two adjacent points. Prompt recognition and surgery are crucial. AIM: To analyze the outcomes of patients who underwent surgery for CL-SBO and to evaluate clinical predictors. METHODS: Patients who underwent surgery for suspected CL-BSO on computed tomography (CT) at a single center between 2013 and 2019 were evaluated retrospectively. Patients were divided into three groups by perioperative outcome, including viable bowel, reversible ischemia, and irreversible ischemia. Clinical and laboratorial variables at presentation were compared and postoperative outcomes were analyzed. RESULTS: Of 148 patients with CL-SBO, 28 (19%) had a perioperative viable small bowel, 86 (58%) had reversible ischemia, and 34 (23%) had irreversible ischemia. Patients with a higher age had higher risk for perioperative irreversible ischemia [odds ratio (OR): 1.03, 95% confidence interval (CI): 0.99-1.06]. Patients with American Society of Anaesthesiologists (ASA) classification ≥ 3 had higher risk of perioperative irreversible ischemia compared to lower ASA classifications (OR: 3.76, 95%CI: 1.31-10.81). Eighty-six patients (58%) did not have elevated C-reactive protein (> 10 mg/L), and between-group differences were insignificant. Postoperative in-hospital stay was significantly longer for patients with irreversible ischemia (median 8 d, P = 0.001) than for those with reversible ischemia (median 6 d) or a viable bowel (median 5 d). Postoperative morbidity was significantly higher in patients with perioperative irreversible ischemia (45%, P = 0.043) compared with reversible ischemia (20%) and viable bowel (4%). CONCLUSION: Older patients or those with higher ASA classification had an increased risk of irreversible ischemia in case of CL-SBO. After irreversible ischemia, postoperative morbidity was increased.

Recurrent vaginal cuff dehiscence after surgery for endometriosis: a technique for laparoscopic repair with an omental flap.

Vaginal evisceration is a rare but severe complication after hysterectomy or colpotomy and is generally successfully repaired by reapproximating healthy tissue edges of the vagina. Recurrent vaginal cuff dehiscence is problematic especially in sexually active women. We describe two cases of recurrent vaginal cuff dehiscence. The first patient had a hysterectomy for endometriosis. The second patient underwent laparoscopic excision of an endometriotic nodule at the vaginal vault. The vaginal cuff dehiscence was repaired by a laparoscopic approach employing an omental flap to enhance tissue healing. This closure technique turned out to be successful at follow-up in both cases. In case of recurrent vaginal cuff dehiscence, management options are limited. Our case report offers a laparoscopic treatment option by using an omental flap. This procedure can be used when conventional repair fails.

Correlation of CT findings with intra-operative outcome in closed-loop small bowel obstruction (CL-SBO).

PURPOSE: To correlate CT-findings in patients with closed-loop small bowel obstruction (CL-SBO) with perioperative findings, to identify patients who require immediate surgical intervention. Secondary purpose was to substantiate the role of radiologists in predicting perioperative outcome. METHODS: Data were retrospectively obtained from patients with surgically confirmed CL-SBO, between September 2013 and September 2019. Three radiologists reviewed CTs to assess defined CT features and predict patient outcome for bowel wall ischemia and necrosis using a likelihood score. Univariate statistical analyses were performed and diagnostic performance parameters and interobserver agreement were assessed for each feature. RESULTS: Of 148 included patients, 28 (19%) intraoperatively had viable bowel and 120 (81%) had bowel wall ischemia or necrosis. Most CT characteristics, as well as the likelihood of ischemia and necrosis, found fair or moderate multirater agreement. Increased attenuation of bowel wall and mesenteric vessels on non-contrast-enhanced CT had a specificity for bowel ischemia or necrosis of 100% (sensitivity respectively 48% (p < 0.001) and 21% (p = 0.09)). Mesenteric edema had high sensitivity for ischemia or necrosis (90%), but specificity of only 26% (p < 0.001). For mesenteric fluid, sensitivity was 60% and specificity 57% (p = 0.004). Decreased enhancement of bowel wall in both arterial and PV-phase showed significant correlation, respectively a sensitivity of 58% and 42%, and specificity of 88% and 79% (both p < 0.001). Likelihood of both ischemia and necrosis were significantly correlated with perioperative outcome (p < 0.001). CONCLUSION: CT findings concerning mesenteric and bowel wall changes, as well as radiologists' judgement of likelihood of ischemia and necrosis are significantly correlated with perioperative outcome of bowel wall ischemia and necrosis in patients with CL-SBO.

Identifying best performing hospitals in colorectal cancer care; is it possible?

BACKGROUND: Comparing outcomes across hospitals to learn from best performing hospitals can be valuable. However, reliably identifying best performance is challenging. This study assesses the possibility to distinguish best performing hospitals on single outcomes and consistency of performance on different outcomes. METHODS: Data were derived from the Dutch ColoRectal Audit 2013-2015. Outcomes considered were textbook outcome (colon), (circumferential) resection margins, (serious) complications, mortality, and 'failure to rescue'. To include uncertainty in rankings, random effect logistic regression models were used to calculate expected ranks (ERs), for each hospital and outcome. Rankability was calculated for each outcome, as a measure of reliability of ranking. Furthermore, correlation between ERs on different outcomes was assessed. Correlation was considered weak <0.40, moderate between 0.40 - 0.59 and strong >0.60. RESULTS: The study included 32 143 patients; of whom 11 373 were treated in 2015 across 84 hospitals, 8181 colon and 3192 rectal cancer patients. In this one-year period 'Postoperative complications' had the highest rankability for colon (57%) and rectal (41%) surgery. No (group of) hospital(s) had the highest ER(s) on all outcomes. Correlation between ERs of outcomes was moderate in 2 (of 25) and strong in 4 (of 25) combinations. Rankability of colorectal mortality increased from 14% in 2015 to 35% when data over 2013-2015 were used. CONCLUSION: The highest reliability of identifying best performance based on an outcome was 57%. However, the balance between reliability and relevance of outcomes is vulnerable. No (group of) hospital(s) could be identified as best performer on all outcomes. Performance was not consistent on outcomes.

Role of positron emission tomography in the (re-)staging of oesophageal cancer.

BACKGROUND: Various studies have demonstrated that 18F-Fluorodeoxyglucose-positron emission tomography (FDG-PET), measuring altered tissue glucose metabolism, is a promising non-invasive method for detecting both distant nodal and haematogenous metastases in patients with oesophageal carcinoma (OC) and might thus prevent futile esophagectomy. Moreover, FDG-PET is a promising tool in assessing response to non-surgical treatment, and might therefore be used for an early decision on whether treatment should be stopped or continued. MATERIAL AND METHODS: Review of the recent literature regarding the diagnostic performance of FDG-PET in the preoperative staging of patients with OC and regarding diagnostic accuracy of FDG-PET in assessing response to neoadjuvant therapy in patients with OC compared to conventional techniques (especially computed tomography (CT) and endoscopic ultrasonography (EUS)). RESULTS: A search of the literature resulted in the inclusion of 16 studies on the diagnostic value of FDG-PET. Sensitivity and specificity for the detection of locoregional metastases were moderate. Sensitivity and specificity were reasonable for distant metastases. The diagnostic accuracy of FDG-PET in assessing response to treatment was similar to the accuracy of EUS, but significantly higher than that of CT. CONCLUSIONS: The staging value of FDG-PET in OC patients is limited in the detection of locoregional metastases; however; its value is higher in the detection of distant lymphatic and haematogenous metastases. Moreover, FDG-PET is a valuable tool for the non-invasive assessment of histopathologic tumour response after neoadjuvant therapy..

Synchronous primary neoplasms detected on 18F-FDG PET in staging of patients with esophageal cancer.

UNLABELLED: Because of improvements in diagnostic technology, the incidental detection of synchronous primary tumors during the preoperative work-up of patients with esophageal cancer has increased. The aim of this study was to determine the rate and clinical relevance of synchronous neoplasms seen on (18)F-FDG PET in staging of esophageal cancer. METHODS: From January 1996 to July 2004, 366 patients with biopsy-proven malignancy of the esophagus underwent (18)F-FDG PET for initial staging. This series of patients was retrospectively reviewed for the detection of synchronous primary neoplasms. RESULTS: Twenty synchronous primary neoplasms (5.5%) were identified in 366 patients. Eleven neoplasms were in the colorectum, 5 in the kidney, 2 in the thyroid gland, 1 in the lung, and 1 in the gingiva. One of the thyroid lesions and the lung lesion were erroneously interpreted as metastases, leading to incorrect upstaging of the esophageal tumor. CONCLUSION: (18)F-FDG PET detected unexpected synchronous primary neoplasms in 5.5% of patients with esophageal cancer. Sites of pathologic (18)F-FDG uptake should be confirmed by dedicated additional investigations before treatment, because synchronous neoplasms may mimic metastases.

Outcome of surgical treatment for early adenocarcinoma of the esophagus or gastro-esophageal junction.

Adenocarcinoma of the esophagus, or GEJ, has a poor prognosis. Early lesions [i.e. high grade dysplasia (HGD) or T1-carcinoma] are potentially curable. Local endoscopic therapies are promising treatment options for superficial lesions; however, for deeper lesions, surgical resection is considered to be the treatment of choice. To contribute to therapeutic decision-making, we retrospectively analysed the outcome of transhiatal esophagectomy in 120 patients with pathologically proven HGD (n=13) or T1-adenocarcinoma (n=107) of the distal esophagus or gastro-esophageal junction (GEJ). Tumors were subdivided into six different depths of invasion ('T1-mucosal' m1-m3, 'T1-submucosal' sm1-sm3), and the frequency of lymphatic dissemination and time to locoregional and/or distant recurrence were analysed. Only one of the 79 T1m1-3/sm1 tumors (1%) showed lymph node metastases as compared with 18 out of 41 T1sm2-3 tumors (44%). There was a significant difference in recurrence-free period between T1m1-m3/sm1 versus T1sm2-sm3 tumor patients (P log rank <0.0001), with 5-year recurrence-free percentages of 97% and 57%, respectively. In multivariate analysis including age, gender, tumor differentiation grade, N-stage and depth of invasion, only N-stage was an independent prognostic factor for recurrence-free period (hazard rate=5.9, 95% CI 1.7-20.7). However, if N-stage was excluded from analysis, only depth of invasion (T1sm2-3 versus T1m1-m3/sm1) was an independent prognostic factor for recurrence-free period (hazard rate=7.5, 95% CI 2.0-27.7). These data indicate that T1m1-m3/sm1 adenocarcinomas of esophagus or GEJ show a very low risk of lymphatic dissemination and are therefore eligible for local endoscopic therapy. After transhiatal surgical resection, almost half of the patients with T1sm2-sm3 lesions develop recurrent disease within 5 years, and therefore need additional therapy to improve survival.

Low serum cortisol in combination with high adrenocorticotrophic hormone concentrations are associated with poor outcome in children with severe meningococcal disease.

OBJECTIVES: To study the correlation between serum concentrations of adrenocorticotrophic hormone (ACTH) and cortisol in relation to severity of disease in children with meningococcal sepsis. METHODS: Subjects were children with meningococcal sepsis, admitted to the pediatric intensive care unit. Clinical data, laboratory values and blood samples were selected. Arterial cortisol, ACTH, interleukin 6 and tumor necrosis factor alpha concentrations were measured on admission and studied for their relation to severity of disease (sepsis, septic shock/survivors, septic shock/nonsurvivors). RESULTS: Seventy-two patients fulfilled the criteria for meningococcal sepsis. Sixty-two of these children with positive blood cultures of Neisseria meningitidis, who were not treated with corticosteroids before admission, were included. Fifty of the 62 patients had septic shock. Twelve of those children (24%) died. The median age of the subjects was 2.6 years (range, 0.3 to 16.1 years). Cortisol values were significantly lower in non-survivors (median, 654 nmol/l) than in survivors (median, 2184 nmol/l) (P < 0.01). ACTH values were significantly higher in children who died (median, 1271 ng/l) than in survivors (85 ng/l) (P < 0.01). The median cortisol:ACTH ratio decreased significantly depending on the disease severity categories. CONCLUSIONS: Low serum cortisol concentrations in combination with high ACTH concentrations are associated with poor outcome in children with severe meningococcal disease.

Patients' perception of diagnostic tests in the preoperative assessment of esophageal cancer.

OBJECTIVE: Defining an optimal staging strategy requires an evaluation of the effectiveness and costs of diagnostic tests and may include the burden of these tests for patients. This study evaluated the burden of cervical ultrasonography (US), endoscopic ultrasonography (EUS), computed tomography (CT) and positron emission tomography (PET) in patients with esophageal carcinoma (EC). METHODS: Consenting consecutive patients underwent a standard preoperative work-up. Burden of testing was evaluated with a self-report questionnaire addressing anxiety, embarrassment, and discomfort, each measured on a 1(none) to 5 (extreme) point-scale. An overall burden score was calculated by summing the three item scores. In addition, patients were asked to rank the four tests from least to most inconvenient. Statistical analysis was performed with nonparametric tests. RESULTS: 82 patients (67 , 15 ; mean age 64.3 yrs) participated. For most tests and most dimensions of burden, the large majority of subjects was in categories 1 and 2.With respect to anxiety, the rank order (from highest burden to lowest burden) was EUS, US, PET, and CT (average scores 1.7, 1.5, 1.4, and 1.2, respectively). For embarrassment, the rank order was EUS, PET, US, and CT (1.9, 1.5, 1.4, and 1.3 respectively). For discomfort, the rank order was EUS, PET, US and CT (2.0, 1.6, 1.4, and 1.2, respectively). And for total burden, the rank order was EUS, PET, US and CT (5.6, 4.6, 4.2, and 3.7). PET was ranked as least inconvenient by 35% of patients and as most inconvenient by 16% compared with the other tests. CONCLUSION: Significant but small differences were observed in patient burden for imaging tests to evaluate EC. The perceived burden of PET was lower than that of EUS, but higher than the burden of CT. However absolute values were low for all tests and therefore patient burden will not be a key feature for the construction of an optimal staging algorithm for EC.

Differential responses of cellular immunity in patients undergoing neoadjuvant therapy followed by surgery for carcinoma of the oesophagus.

BACKGROUND: To compare immune responses following neoadjuvant chemoradiation therapy in combination with hyperthermia plus surgery to those induced by surgery alone in patients with oesophageal cancer. METHODS: Thirty-two patients with histopathologically proven oesophageal cancer, scheduled for potentially curative transhiatal or transthoracic oesophagectomy with (neo, n = 20) or without (control, n = 12) neoadjuvant thermochemoradiation therapy (ThCR) were included. Peripheral blood samples were obtained before ThCR, after 2 weeks of ThCR, 1 day before surgery, on postoperative days 1, 3, 7, and 6 weeks after surgery, for white blood cell counts, lymphocyte subsets and T helper type 1 (Th1) and type 2 (Th2) lymphocyte responses. RESULTS: Neo patients showed a significant decrease in granulocytes and lymphocyte subsets, and T cell cytokines after 2 weeks of ThCR. Only CD8+ (cytotoxic) T cells recovered after ThCR to reach normal levels prior to surgery. In contrast, CD4+ T (helper) cells, and NK- and B cells in neo patients did not recover prior to surgery (all P < 0.05). Oesophagectomy induced a significant increase in granulocytes and a decrease in lymphocytes (and subsets). Only those subsets that had not recovered after ThCR (CD4+ T cells, NK and B cells but not CD8+ T cells), were significantly lower (all P < 0.05) during the entire postoperative study period. Postoperatively, the stimulated cytokine production capacity of Th1 and Th2 cells, corrected for number of T cells, was not significantly different between the groups. CONCLUSION: Neoadjuvant thermochemoradiation for oesophageal cancer caused significant disturbances of host cellular immunity with reduced T, NK and B cell counts, and differential recovery of cytotoxic and helper T cells leading to prolonged T cell imbalance that extends beyond the time of surgery. The functional and anti-tumour consequences of this immunodisturbance need further investigation, as recovery of T helper cytokine production towards surgery was less impaired than T helper cell counts.

18FDG uptake in oesophageal adenocarcinoma: linking biology and outcome.

PURPOSE: Variable uptake of 18FDG has been noticed in positron emission tomography (PET) studies of patients with oesophageal adenocarcinoma. The aim of the present study was to investigate biological parameters involved in 18FDG uptake in oesophageal adenocarcinoma for selection of patients with increased 18FDG uptake and prediction of prognostic value of 18FDG PET. PATIENTS AND METHODS: Preoperative PET scans were performed in 26 patients with histologically proven oesophageal adenocarcinoma. 18FDG uptake was semiquantitatively measured by SUV(BSAg. )Tumour sections were stained by immunohistochemistry for angiogenic markers (VEGF, CD31), glucose transporter-1 (Glut-1), hexokinase (HK) isoforms, for proliferation marker (Ki67), for macrophage marker (CD68) and for apoptosis marker (cleaved caspase-3). Cell densities, differentiation grade, degree of necrosis and mucus, T-stage and tumour size were assessed. In addition follow-up was analysed. RESULTS: No association was found between 18FDG uptake and angiogenic markers. In contrast, a significant correlation was found between 18FDG uptake and Glut-1 expression. No correlations were found between 18FDG uptake and HK isoforms, Ki67 or cleaved caspase-3. Also, no correlations were found between 18FDG uptake and cell density, differentiation grade, CD68, mucus and necrosis. However, there was a significant correlation between 18FDG uptake and tumour size and between 18FDG uptake and tumour recurrence. CONCLUSIONS: Glut-1 expression and tumour size seem parameters associated with 18FDG uptake in patients with biopsy proven oesophageal adenocarcinoma, and may be used to select oesophageal cancer patients in whom 18FDG-PET is of diagnostic value and may predict disease outcome.