What is the outcome for patients undergoing more than two ileocolonic resections for recurrent Crohn's disease? A comparative study of 569 consecutive procedures.

AIM: To assess the outcome for patients undergoing repeated ileocolonic resection for recurrent Crohn's disease (CD). METHOD: All patients undergoing ileocolonic resection for terminal ileal CD between 1998 and 2016 in our tertiary care centre were retrospectively reviewed. RESULTS: Between 1998 and 2016, 569 ileocolonic resections were performed for CD: 403 of these were primary resections (1R, 71%), 107 second resections (2R, 19%) and 59 were third (or more) resections (> 2R, 10%). The laparoscopic approach rate was significantly less in the > 2R group (20/59, 34%) compared with the 2R (71/107, 66%; P = 0.002) and 1R (366/403, 91%) groups. However, conversion to an open approach did not show any difference between the three groups [1R group 46/366 (13%) vs 2R group 14/71 (20%) vs > 2R group 3/20 (15%); 1R vs > 2R P = 0.750; 2R vs > 2R P = 0.633]. Postoperative morbidity was significantly increased in the > 2R (28/59, 52%) group compared with the 1R group (115/403, 29%; P < 0.001) but showed no difference compared with the 2R group (43/107, 40%; P = 0.365). There was no difference between the groups in the incidence of severe postoperative morbidity (Clavien-Dindo ≥ 3) [1R group n = 24 (6%); 2R group n = 6 (6%); > 2R group n = 4, 7%; 1R vs > 2R P = 0.865, 2R vs > 2R P = 0.761]. CONCLUSION: Although the overall morbidity rate was higher, repeated surgery for recurrent CD in patients undergoing three or more ileocolonic resections was not associated with an increased risk of severe postoperative morbidity in our series.

Hospital stay for temporary stoma closure is shortened by C-reactive protein monitoring: a prospective case-matched study.

BACKGROUND: C-reactive protein (CRP) has been suggested as a satisfactory early marker of postoperative complications after colorectal surgery. The aim of this study was to assess the impact of a CRP monitoring-driven discharge strategy, after stoma reversal following laparoscopic sphincter-saving surgery for rectal cancer. METHODS: Eighty-eight patients who had stoma reversal between June 2016 and April 2018 had CRP serum level monitoring on postoperative day (POD) 3 and, if necessary, on POD5. Patients were discharged on POD4 if the CRP level was < 100 mg/L. Patients were matched [according to age, gender, body mass index, neoadjuvant pelvic irradiation, type of anastomosis (stapled or manual), and adjuvant chemotherapy] to 109 identical control patients who had stoma reversal between 2012 and 2016 with the same postoperative care but without CRP monitoring. RESULTS: Postoperative 30-day overall morbidity [CRP group: 12/88 (14%) vs controls: 11/109, (10%), p = 0.441] and severe morbidity rates (i.e. Dindo 3-4) [CRP group: 2/88 (2%) vs controls: 2/109 (2%), p = 0.838] were similar between groups. Mean length of stay was significantly shorter in the CRP group (CRP group: 4.6 ± 1.3 vs controls: 5.8 ± 1.8 days; p < 0.001). Discharge occurred before POD5 in 59/88 (67%) CRP patients vs 15/109 (14%) controls (p < 0.001). The unplanned rehospitalization rate [CRP group: 6/88 (7%) vs controls: 4/109 (4%), p = 0.347] was similar between groups. CONCLUSIONS: In patients having temporary stoma closure after laparoscopic surgery for rectal cancer, postoperative CRP monitoring is associated with a significant shortening of hospital stay without increasing morbidity or rehospitalization rates.

Transversus abdominis plane (TAP) block in laparoscopic colorectal surgery improves postoperative pain management: a meta-analysis.

AIM: Transversus abdominis plane (TAP) block is a locoregional anaesthesia technique of growing interest in abdominal surgery. However, its efficacy following laparoscopic colorectal surgery is still debated. This meta-analysis aimed to assess the efficacy of TAP block after laparoscopic colorectal surgery. METHOD: All comparative studies focusing on TAP block after laparoscopic colorectal surgery have been systematically identified through the MEDLINE database, reviewed and included. Meta-analysis was performed according to the Mantel-Haenszel method for random effects. End-points included postoperative opioid consumption, morbidity, time to first bowel movement and length of hospital stay. RESULTS: A total of 13 studies, including 7 randomized controlled trials, were included, comprising a total of 600 patients who underwent laparoscopic colorectal surgery with TAP block, compared with 762 patients without TAP block. Meta-analysis of these studies showed that TAP block was associated with a significantly reduced postoperative opioid consumption on the first day after surgery [weighted mean difference (WMD) -14.54 (-25.14; -3.94); P = 0.007] and a significantly shorter time to first bowel movement [WMD -0.53 (-0.61; -0.44); P < 0.001] but failed to show any impact on length of hospital stay [WMD -0.32 (-0.83; 0.20); P = 0.23] although no study considered length of stay as its primary outcome. Finally, TAP block was not associated with a significant increase in the postoperative overall complication rate [OR = 0.84 (0.62-1.14); P = 0.27]. CONCLUSION: Transversus abdominis plane (TAP) block in laparoscopic colorectal surgery improves postoperative opioid consumption and recovery of postoperative digestive function without any significant drawback.

Is trans-anal total mesorectal excision really safe and better than laparoscopic total mesorectal excision with a perineal approach first in patients with low rectal cancer? A learning curve with case-matched study in 68 patients.

AIM: To compare the learning curve for trans-anal total mesorectal excision (TATME) with laparoscopic TME started by a perineal approach (LTME). METHOD: The first 34 consecutive patients who underwent TATME for low rectal cancer were matched with LTME (performed by the same surgeon) for gender, body mass index and chemoradiation. RESULTS: Thirty-four patients undergoing TATME (23 men; 58 ± 14 years) were matched with 34 undergoing LTME (23 men; 59 ± 13 years). Intra-operative complications occurred more frequently during TATME (21%) than LTME (6%), but this difference was not significant (P = 0.07). The complications of TATME included rectal (n = 4), bladder (n = 1) and vaginal (n = 1) injury and bleeding (n = 1). Length of stay and postoperative overall and major morbidities were similar between groups. Early symptomatic anastomotic leakage (AL) occurred in 1/34 TATME and 5/34 LTME (15%; P = 0.02) procedures. Asymptomatic AL occurred in four TATME (12%) and four LTME (12%, P = 1). Thus, the overall rate of AL was 5/34 (15%) for TATME vs 9/34 (26%) for LTME (P = 0.4). No significant difference between the two groups was noted with regard to tumour, number of harvested and positive lymph nodes, R1 resection rate or completeness of the mesorectum. Metastatic recurrence was similar between groups (15% vs 18%, P = 0.7), but follow-up was shorter after TATME (13 ± 6 months) than after LTME (25 ± 14 months; P < 0.0001). CONCLUSION: The TATME learning curve seems to be associated with a significant rate of intra-operative complications. Because no significant benefit has been reported to date, more evidence is needed before TATME can be considered as a better approach than laparoscopic TME with a perineal approach first in patients with low rectal cancer.

Oncological impact of anastomotic leakage after laparoscopic mesorectal excision.

BACKGROUND: The effect of anastomotic leakage on oncological outcomes after total mesorectal excision (TME) is controversial. This study aimed to assess the influence of symptomatic and asymptomatic anastomotic leakage on oncological outcomes after laparoscopic TME. METHODS: All patients who underwent restorative laparoscopic TME for rectal adenocarcinoma with curative intent from 2005 to 2014 were identified from an institutional database. Asymptomatic anastomotic leakage was defined by CT performed systematically 4-8 weeks after rectal surgery, with no relevant clinical symptoms or laboratory examination findings during the postoperative course. RESULTS: Of a total of 428 patients, anastomotic leakage was observed in 120 (28·0 per cent) (50 asymptomatic, 70 symptomatic). After a mean follow-up of 40 months, local recurrence was observed in 36 patients (8·4 per cent). Multivariable Cox regression identified three independent risk factors for reduced local recurrence-free survival (LRFS): symptomatic anastomotic leakage (odds ratio (OR) 2·13, 95 per cent c.i. 1·29 to 3·50; P = 0·003), positive resection margin (R1) (OR 2·41, 1·40 to 4·16; P = 0·001) and pT3-4 category (OR 1·77, 1·08 to 2·90; P = 0·022). Patients with no risk factor for reduced LRFS had an estimated 5-year LRFS rate of 87·7(s.d. 3·2) per cent, whereas the rate dropped to 75·3(4·3) per cent with one risk factor, 67(7) per cent with two risk factors, and 14(13) per cent with three risk factors (P < 0·001). Asymptomatic anastomotic leakage was not significantly associated with LRFS in multivariable analysis. CONCLUSION: Symptomatic anastomotic leakage is a risk factor for disease recurrence in patients with rectal adenocarcinoma.

Colorectal surgery for functional bowel disorders.

Surgery is a last-resort treatment for the management of severe constipation, an alternative after failure of medical treatment. We can distinguish two types of management: "conservative" colon-sparing surgery, i.e. the Malone procedure (MP), or sacral neuromodulation (SNM), and "radical" surgery such as colorectal resection. While the place of SNM remains to be defined, the MP is well codified and has shown very satisfactory results. For radical treatment, total colectomy with ileo-rectal anastomosis is the reference procedure because it is the best documented. The place of more limited segmental colectomies is poorly defined and needs a more precise identification of the colonic segment involved. Finally, it is imperative that any severe constipation be managed within a multidisciplinary radiology-medico-surgical consultative program. Indeed, a multidisciplinary strategy allows rigorous selection of patients, the only guarantee of better long-term functional results, even though they unfortunately remain uncertain.

Clinical and molecular characterisation of hereditary and sporadic metastatic colorectal cancers harbouring microsatellite instability/DNA mismatch repair deficiency.

BACKGROUND: Patients treated with chemotherapy for microsatellite unstable (MSI) and/or mismatch repair deficient (dMMR) cancer metastatic colorectal cancer (mCRC) exhibit poor prognosis. We aimed to evaluate the relevance of distinguishing sporadic from Lynch syndrome (LS)-like mCRCs. PATIENTS AND METHODS: MSI/dMMR mCRC patients were retrospectively identified in six French hospitals. Tumour samples were screened for MSI, dMMR, RAS/RAF mutations and MLH1 methylation. Sporadic cases were molecularly defined as those displaying MLH1/PMS2 loss of expression with BRAFV600E and/or MLH1 hypermethylation and no MMR germline mutation. RESULTS: Among 129 MSI/dMMR mCRC patients, 81 (63%) were LS-like and 48 (37%) had sporadic tumours; 22% of MLH1/PMS2-negative mCRCs would have been misclassified using an algorithm based on local medical records (age, Amsterdam II criteria, BRAF and MMR statuses when locally tested), compared to a systematical assessment of MMR, BRAF and MLH1 methylation statuses. In univariate analysis, parameters associated with better overall survival were age (P < 0.0001), metastatic resection (P = 0.001) and LS-like mCRC (P = 0.01), but not BRAFV600E. In multivariate analysis, age (hazard ratio (HR) = 3.19, P = 0.01) and metastatic resection (HR = 4.2, P = 0.001) were associated with overall survival, but not LS. LS-like patients were associated with more frequent liver involvement, metastatic resection and better disease-free survival after metastasectomy (HR = 0.28, P = 0.01). Median progression-free survival of first-line chemotherapy was similar between the two groups (4.2 and 4.2 months; P = 0.44). CONCLUSIONS: LS-like and sporadic MSI/dMMR mCRCs display distinct natural histories. MMR, BRAF mutation and MLH1 methylation testing should be mandatory to differentiate LS-like and sporadic MSI/dMMR mCRC, to determine in particular whether immune checkpoint inhibitors efficacy differs in these two populations.

Physical exercise counteracts MPTP-induced changes in neural precursor cell proliferation in the hippocampus and restores spatial learning but not memory performance in the water maze.

Parkinson's disease (PD) is characterized by a continuous loss of dopaminergic neurons in the substantia nigra, which not only leads to characteristic motor symptoms but also to cognitive impairments. Physical exercise has been shown to improve hippocampus-dependent cognitive functions in PD patients. Animal studies have demonstrated the involvement of adult hippocampal neurogenesis in exercise-induced improvements of visuo-spatial learning and memory. Here, we investigated the direct impact of voluntary wheel running on hippocampal neurogenesis and spatial learning and memory in the Morris water maze (MWM) using the1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. We also analyzed striatal and hippocampal dopamine transmission and mRNA expression levels of dopamine receptors. We show that MPTP-induced spatial learning deficits were alleviated by short-term physical exercise but not MPTP-induced spatial memory impairments in either exercise intervention group. Neural precursor proliferation was transiently altered in MPTP-treated mice, while the cell survival was increased by exercise. Dopamine was progressively depleted by MPTP and its turnover altered by exercise. In addition, gene expression of dopamine receptor D1/D5 was transiently upregulated following MPTP treatment but not affected by physical exercise. Our findings suggest that physical exercise benefits spatial learning but not memory performance in the MWM after MPTP-induced dopamine depletion by restoring precursor cell proliferation in the hippocampus and influencing dopamine transmission. This adds to the understanding of cognitive decline and mechanisms for potential improvements by physical exercise in PD patients.

Enhanced benzo(a)pyrene metabolism and formation of DNA adducts in monocytes of patients with lung cancer.

The conversion of G[3H]benzo(a)pyrene to water-soluble material and to DNA adducts was determined in peripheral blood monocytes of 52 healthy male and female volunteers and 27 patients with lung cancer. Active smokers converted more benzpyrene to DNA-bound material than nonsmokers, but did not form significantly more water soluble material. Monocytes of lung cancer patients clearly formed more water soluble material than cells of the control group, and slightly more DNA adducts when only males are compared. This enhanced BP conversion of lung cancer patients is independent of smoking habits.

[Computed tomographic findings in diffuse malignant pleural mesothelioma]. / Computertomographische Befunde bei diffusem malignen Pleuramesotheliom.

Malignant pleural mesothelioma is a rare tumour and often difficult to diagnose. In this report, the CT findings of 50 patients with proven malignant pleural mesothelioma are described and tabulated. In 31 cases the CT findings could be compared with the results of thoracotomy and thoracoscopy. CT proved reliable in evaluating the exact extent of the disease. Additionally, a combination of findings can be detected by CT, suggesting the diagnosis of malignant pleural mesothelioma. The limitations of CT in malignant pleural mesothelioma are discussed.

Clinical and radiological observations on asbestos-related pathology.

The papers in this session, which are summarized briefly, do not cover the wide range of radiological and clinical problems resulting from inhalation of asbestos dust. Pleural effusions are found in persons exposed occupationally to asbestos, even in the absence of asbestosis, but they are difficult to attribute to such exposure. Asbestosis of the lung shows no striking symptoms and can also be diagnosed only after all other possibilities have been excluded. There are no convincing or striking morphological peculiarities that suggest that an 'asbestos lung cancer' exists. Mesotheliomas of the pleura and of the peritoneum are usually resistant to therapy of any kind, although several possibilities are discussed. Radiological surveillance is presented as being still the most effective and reliable method for medical surveillance of asbestos workers. Circumscribed pleural thickening is benign but a good indicator of exposure to mineral dusts. Diffuse pleural thickening occurs frequently in nonexposed groups and cannot, therefore, be used as an indication of exposure; however, it cannot yet be ruled out as being significant epidemiologically.

[Chemotherapy of non-small cell bronchial cancer with mitomycin C, vindesine and cisplatin. Results of a phase II study]. / Chemotherapie des nicht-kleinzelligen Bronchialkarzinoms mit Mitomycin C, Vindesin und Cisplatin. Ergebnisse einer Phase-II-Studie.

Forty-five patients (39 male, 6 female) with inoperable non-small-cell lung cancer were treated with combined mitomycin C, vindesine and cisplatin. All patients had measurable disease and had no previously received chemotherapy. The performance status of all patients was over 60%. Twenty-one patients had limited, 24 extensive disease. The overall remission rate was 53.3% (3 complete and 21 partial remissions) with a median remission duration of 9 months. Adeno- and squamous cell carcinoma responded to the chemotherapy with a remission rate of 63% (7 out of 11 patients) and 58% (14 out of 24 patients), but there were only 30% responders in large cell carcinoma (3 out of 10 patients). The median survival time for responders was 12 months, for those with no change and for patients with progressive disease 6 months. Myelosuppression and renal toxicity of the combination was generally not a treatment problem; subjective tolerance, however, (gastrointestinal upset) was poor.

[Malignant diffuse pleural mesothelioma: a comparison between computed tomography and the conventional chest x-ray]. / Malignes diffuses Pleuramesotheliom: Vergleich zwischen Computertomographie und konventioneller Thoraxübersicht.

The rate of incidence of malignant pleural mesothelioma is increasing although diagnosis of this disease may be very difficult. Computed tomography examinations and conventional chest x-rays of 30 patients with malignant pleural mesothelioma were reviewed independently, to evaluate the role of both modalities. CT offered the following advantages over conventional chest x-ray examinations: CT was more sensitive in detecting the smooth and nodular changes of malignant pleural mesothelioma, especially at the diaphragm and lower parts of the thorax, tumours could be better demonstrated at the pericardium and in the greater fissure, in some cases, where chest films showed just abnormal widening of the mediastinum, CT could differentiate between tumour involvement of the mediastinal pleura and local invasion of the mediastinum by the tumour, CT was more effective in detecting pleural calcifications and thickening of the contralateral pleura. CT proves more accurate in assessing the extent of the disease, and gives additional diagnostic help.

Malignant mesothelioma of the pleura. A prospective therapeutic study of 132 patients from 1981-1985.

Between March 1981 and February 1985, 93 out of 132 patients with a histologically confirmed diagnosis of malignant pleural mesothelioma were eligible for therapy and were prospectively assigned to receive either combined therapy or best supportive care, according to their personal preferences. Fifty-seven patients underwent multimodal therapy including surgical resection where possible, polychemotherapy, and radiation therapy in case of partial remission. Thirty-six patients received maximal supportive care only, as did 39 patients who were not eligible for treatment. The median survival was 13 months for treated patients compared to 7 for those receiving best supportive care and 5 for patients not amenable to treatment. Median progress-free survival was 6, 2, and 1 month respectively. Surgical resection did not prolong life expectancy within the treated group. In view of significant differences in the distribution of various cofactors over the two study groups, stepwise Cox model analyses were performed. Prognostic nontreatment variables related to prolonged survival were: good performance status, stage I and II, absence of chest pain, age below 50 years, and epithelial histology. Although in the Cox model analyses the survival improvement of patients being treated could be greatly attributed to other cofactors, multimodal treatment showed some prolongation of life expectancy.

[Combined chemotherapy-radiotherapy study of small cell bronchial carcinoma: chemo-/radiotherapy vs radio-/chemotherapy]. / Kombinierte Chemotherapie-Radiotherapie-Studie des kleinzelligen Bronchuskarzinoms (CCR-Studie): Chemo-/Radiotherapie gegen Radio-/Chemotherapie.

The authors studied the effect of a chemo-/radiotherapy or radio-/chemotherapy on 52 cases of microcellular bronchial carcinoma, classification "limited disease". The survival curves were slightly better for the patients submitted to primary chemotherapy, but the difference was not statistically significant, and the curves coincided again after 18 months. 60 to 80% of the patients had no complaints or only unimportant complaints during more than half of their survival time. In 23 patients with "extensive disease" who received only a symptomatic therapy or a combined palliative chemotherapy, chemotherapy had a slightly better effect, but this was not statistically significant.