Outcomes and Side Effects of Preoperative Chemoradiotherapy for Locally Advanced Upper Rectal Cancer.

BACKGROUND/AIM: The benefit of neoadjuvant (chemo) radiotherapy for locally advanced upper rectal tumors remains controversial. Thus, we aimed to evaluate the outcome of patients with stage II or-III upper rectal cancer undergoing neoadjuvant (chemo) radiotherapy followed by total mesorectal excision in our institution. PATIENTS AND METHODS: From April 2004 to October 2019, all patients with stage II or III upper rectal cancer treated with neoadjuvant (chemo) radiotherapy followed by total mesorectal excision were identified from our database. Overall survival, progression-free survival, and local recurrence were assessed using the Kaplan-Meier method. Acute and late treatment-related toxicities were recorded according to the CTCAE-5 version. RESULTS: The study group consisted of 106 patients. Respectively, 36% and 61% of patients had stage II and stage III upper rectal cancer. The median follow-up period was 4.4 ± 3.4 years. Five-year overall survival and progression-free survival were respectively 78% [95% confidence interval (CI)=69.2-88] and 76.8% (95%CI=68.4-86.2). The rate of local recurrence at 5 years was 3.78% (95%CI=0-7.98). Forty-two percent of patients presented early toxicities and 27.4% of patients experienced early surgical complications. Late toxicities and surgical complications occurred in 24.5% and 9.4% of patients, respectively. CONCLUSION: Neoadjuvant (chemo) radiotherapy followed by total mesorectal excision of stage II-III upper rectal cancer is effective and safe.

Simultaneous or staged resection for synchronous liver metastasis and primary rectal cancer: a propensity score matching analysis.

BACKGROUND: Colorectal cancer is the third most common cancer in France and by the time of the diagnosis, 15-25% of patients will suffer from synchronous liver metastases. Surgery associated to neoadjuvant treatment can cure these patients, but few studies focus only on rectal cancer. This study was meant to compare the outcomes of patients who underwent a simultaneous resection to those who underwent a staged resection (rectum first or liver first) in the University Hospital of Tours, France. METHODS: We assessed retrospectively a prospective maintained data base about the clinical, pathological and survival outcomes of patients who underwent a simultaneous or a staged resection in our center between 2010 and 2018. A propensity score matching was used, considering the initial characteristics of our groups. RESULTS: There were 70 patients (55/15 males, female respectively) with median age 60 (54-68) years. After matching 48 (69%) of them underwent a staged approach and 22 (31%) a simultaneous approach were compared. After PSM, there were 22 patients in each group. No differences were found in terms of morbidity (p = 0.210), overall survival (p = 0.517) and disease-free survival (p = 0.691) at 3 years after matching. There were significantly less recurrences in the simultaneous group (50% vs 81.8%, p = 0.026). CONCLUSIONS: Simultaneous resection of the rectal primary cancer and synchronous liver metastases is safe and feasible with no difference in terms of survival.

Impact of Modern Management Strategies on the Clinical Outcome of Patients With Low Rectal Cancer - A Retrospective, Monocentric Cohort Study.

BACKGROUND: The aim of this study was to retrospectively investigate the impact of intersphincteric resection (ISR) and Enhanced Recovery After Surgery (ERAS) protocols for rectal cancer. PATIENTS AND METHODS: Since we implemented rectal ERAS protocol and ISR in 2016, we retrospectively assessed and compared clinical, pathological and survival outcomes of two groups of patients: group 1, treated 2000-2015 (n=242); and group 2, treated 2016-2020 (n=108). Propensity score matching using nearest-neighbor method was used to match each patient of group 1 to a patient of group 2. RESULTS: Before and after matching, the American Society of Anesthesiology score for patients in group 1 was significantly lower than in group 2 (score of 3: 9.9% vs. 25.9%, p<0.0001) as were grade I-II complications (27.7% vs. 45.4% p<0.001). Before and after matching, the quality of the mesorectum excision was significantly lower in group 1 (complete in 31% vs. 59.2% p<0.0001). After matching, 3-year overall survival for groups 1 and 2 were similar (88.2% vs. 92.6%; p=0.988). CONCLUSION: ERAS and ISR had no negative impact on the oncological outcome of our patients and increased the preservation of bowel continuity.

Simultaneous Versus Delayed Resection for Initially Resectable Synchronous Colorectal Cancer Liver Metastases: A Prospective, Open-label, Randomized, Controlled Trial.

OBJECTIVE: To answer whether synchronous colorectal cancer liver metastases (SLM) should be resected simultaneously with primary cancer or should be delayed. SUMMARY BACKGROUND DATA: Numerous studies have compared both strategies. All were retrospective and conclusions were contradictory. METHODS: Adults with colorectal cancer and resectable SLM were randomly assigned to either simultaneous or delayed resection of the metastases. The primary outcome was the rate of major complications within 60 days following surgery. Secondary outcomes included overall and disease-free survival. RESULTS: A total of 105 patients were recruited. Eighty-five patients (39 and 46 in the simultaneous- and delayed-resection groups, respectively) were analyzed. The percentage of major perioperative complications did not differ between groups (49% and 46% in the simultaneous- and delayed-resection groups, respectively, adjusted OR 0.84, 95% CI 0.35-2.01; P = 0.70, logistic regression). Complications rates were 28% and 13% (P = 0.08, χ2 test) at colorectal site and 15% and 17% (P = 0.80, χ2 test) at liver site, in simultaneous- and delayed-resection groups, respectively. In the delayed-resection group, 8 patients did not reach the liver resection stage, and this was due to disease progression in 6 cases. After 2 years, overall and disease-free survival tended to be improved in simultaneous as compared with delayed-resection groups (P = 0.05), a tendency which persisted for OS after a median follow-up of 47 months. CONCLUSIONS: Complication rates did not appear to differ when colorectal cancer and synchronous liver metastases are resected simultaneously. Delayed resection tended to impair overall survival.

Long term outcome of anastomotic leakage in patients undergoing low anterior resection for rectal cancer.

BACKGROUND: The influence of anastomotic leakage (AL) on local recurrence rates and survival in rectal cancer remains controversial. The aim of this study was to analyze the effect of asymptomatic anastomotic leakage (AAL) and symptomatic anastomotic leakage (SAL) on short- and long-term outcome after curative rectal cancer resection. METHODS: All patients who underwent surgical resection of non-metastatic rectal cancer with curative intent from January 2005 to December 2017 were retrospectively analyzed. Short-term morbidity, long-term functional and oncological outcomes were compared between patients with SAL, AAL and without AL (WAL). RESULTS: Overall, 200 patients were included and AL was observed in 39 (19.5%) patients (10 AAL and 29 SAL) with a median follow-up of 38.5 months. Rectal cancer location and preoperative neoadjuvant treatment was similar between the three groups. Postoperative 30-day mortality rate was nil. The permanent stoma rate was higher in patients with SAL or AAL compared to WAL patients (44.8 and 30% vs 9.3%, p < 0.001). The mean wexner continence grading scale was significantly different between AAL (11,4 ± 3,8), SAL (10,3 ± 0,6) and WAL (6,4 ± 4,7) groups (p = 0.049). The 3 and 5-year overall and disease-free survival rates were similar between the 3 groups (86.6% /84% vs 100%/100% vs 76%/70 and 82.9%/77% vs 100%/100% vs 94.7%/88.3% for patients with SAL, AAL, and WAL, p = 0.480 and p = 0.527). CONCLUSION: The permanent stoma rate was significant higher in patients with SAL or AAL compared to WAL patients. AL did not impair long-term oncological outcome.

Complete Pathological Response Following Radiochemotherapy for Locally Advanced Rectal Cancer: Short and Long-term Outcome.

BACKGROUND/AIM: Preoperative radiochemotherapy (RCT) followed by total mesorectum excision has become the gold standard for locally advanced carcinoma of the low and middle rectum. The aim of the study is to evaluate the short and long-term outcomes of patients in complete pathological response (PR) following this treatment sequence. PATIENTS AND METHODS: One hundred and thirty patients were retrospectively included between 2005 and 2017 in an expert centre, with 3 groups formed, according to the PR: i) complete PR (absence of tumour cells on the surgical specimen ypT0N0), ii) partial PR (T or N downsizing) and iii) without PR. RESULTS: The complete PR rate was 13.1%. The complete PR group tended to develop less symptomatic fistulas compared to partial PR and without PR groups (5.8% versus 13.5% versus 18.7, respectively; p=0.607). The 5-year disease-free survival was increased for complete-PR patients (93% versus 79% versus 47%, respectively; p=0.0003) without an improvement in overall survival. CONCLUSION: Complete PR is associated with an improvement in survival without recurrence and without an improvement in the overall survival at 5 years.

Low Tie Compared to High Tie Vascular Ligation of the Inferior Mesenteric Artery in Rectal Cancer Surgery Decreases Postoperative Complications Without Affecting Overall Survival.

BACKGROUND/AIM: The aim of this study was to determine the clinical impact of low tie ligation (LT) of the inferior mesenteric artery (IMA) below the left colic artery versus high tie ligation (HT) at the origin of the IMA in patients undergoing rectal cancer surgery. PATIENTS AND METHODS: Between January 2005 and December 2017, all consecutive patients who underwent rectal resection for non-metastatic cancer were retrospectively included. Patients who had LT were compared to those who had HT. RESULTS: Overall, 200 patients were identified (101 HT and 99 LT). Postoperative 30-day mortality rate was nil in both groups. There were significantly higher severe postoperative complications in HT versus LT patients (Clavien-Dindo III-IV) (18.8% vs. 9.1%, p=0.048). Median follow-up was 38.5 months and overall survival at 5 years was 91.5% and there was no difference between the two groups (90.1% vs. 92.9%; HT vs. LT p=0.640). CONCLUSION: LT ligation of IMA significantly decreased the severe postoperative complication rate without affecting recurrence-free or overall survival.

Natural history of liver adenomatosis: A long-term observational study.

BACKGROUND & AIMS: Liver adenomatosis (LA) is characterized by the presence of at least 10 hepatocellular adenomas (HCAs), but the natural history of this rare liver disorder remains unclear. Thus, we aimed to reappraise the natural history and the risk of complications in a cohort of patients with at least 10 HCAs. METHODS: We analyzed the natural history of 40 patients with LA, excluding glycogen storage disorders, in a monocentric cohort. Pathological examination was performed, with immunostaining and molecular biology carried out on surgical specimens or liver biopsies. RESULTS: Forty patients (36 female) were included with a median follow-up of 10.6 (1.9-26.1) years. Six (15%) patients had familial LA, all with germline HNF1A mutations. Median age at diagnosis was 39 (9-55) years. Thirty-three (94%) women had a history of oral contraception, and 29 (81%) women had a pregnancy before LA diagnosis. Overall, thirty-seven (93%) patients underwent surgery at diagnosis. Classification of HCAs showed 46% of patients with HNF1A-mutated HCA, 31% with inflammatory HCA, 3% with sonic hedgehog HCA, 8% with unclassified HCA. Only 15% of the patients demonstrated a "mixed LA" with different HCA subtypes. Hepatic complications were identified in 7 patients: 1 patient (3%) died from recurrent hepatocellular carcinoma after liver transplantation; 6 (15%) had hemorrhages, of which 5 occurred at diagnosis, with 1 fatal case during pregnancy, and 2 occurred in male patients with familial LA. Four patients (10%) had repeated liver resections. Finally, 4 (10%) patients developed extrahepatic malignancies during follow-up. CONCLUSIONS: The diversity in HCA subtypes, as well as the occurrence of bleeding and malignant transformation during long-term follow-up, underline the heterogeneous nature of LA, justifying close and specific management. In patients with germline HNF1A mutation, familial LA occurred equally frequently in males and females, with a higher rate of bleeding in male patients. LAY SUMMARY: Liver adenomatosis is a rare disease characterized by the presence of 10 or more hepatocellular adenomas that may rarely be of genetic origin. Patients with liver adenomatosis have multiple adenomas of different subtypes, with a risk of bleeding and malignant transformation that justify a specific management and follow-up.

Only Surgical Treatment to Be Considered for Adhesive Small Bowel Obstruction: A New Paradigm.

BACKGROUND: Adhesive small bowel obstruction (SBO) represents a heavy burden in healthcare systems worldwide and is associated with significant morbidity and mortality. Although conservative treatment alone can lead to SBO resolution in most cases, its optimal duration is still a matter of debate. The aim of this study was to analyze different SBO evolution patterns in order to further determine when to switch to surgical treatment. STUDY DESIGN: All patients who were admitted for adhesive SBO between 2011 and 2016 were reviewed. Patients who had immediate surgery (IS), a successful medical treatment (SMT), and a failed medical treatment (FMT) were compared in terms of overall morbidity, mortality, and SBO recurrence. RESULTS: Overall 154 patients were identified, including 23 (14.9%) in IS, 27 (17.5%) in FMT, and 104 (67.6%) in SMT groups. In terms of comorbidities, patients were similar in all groups. Overall morbidity rates were highest in IS and FMT groups (30% and 33%, respectively, vs. 4% in the SMT group, p < 0.001) whereas mortality rate was highest in the FMT group (22% vs. 0% and 0% in IS and SMT groups, respectively, p < 0.001). SBO recurrence rate was highest in the SMT group (22% vs. 4% and 7% in IS and FMT groups, respectively, p = 0.042). CONCLUSION: FMT seems to be associated with similar overall morbidity compared with IS but with increased postoperative mortality. Patient frailty seems to be worsened by prolonged inefficient medical treatment.

Interest of variations in microRNA-152 and -122 in a series of hepatocellular carcinomas related to hepatitis C virus infection.

AIM: Hepatocellular carcinoma (HCC) is a common outcome of chronic hepatitis C virus (HCV) infection and constitutes the main burden of this disease. The molecular mechanisms underlying the development of HCC are multiple and might involve certain microRNA (miR). As discordant results have been reported concerning the detection of expression of miR-152 and miR-122 in HCC, our aim was to measure the levels of both miRs in serum and liver samples. METHODS: We analyzed miR-152 and miR-122 expression by reverse transcription-quantitative polymerase chain reaction in a serum cohort from 14 HCV-infected patients who developed HCC, 20 HCV+ patients without HCC, and 19 control patients. We also studied miR-152 and miR-122 in an independent tissue cohort from 11 normal livers, and from paired HCC and non-tumor adjacent livers of 11 HCV-infected patients and 12 non-infected patients. RESULTS: In serum samples, higher levels of miR-122 were found in non-HCC HCV+ compared to HCC HCV+ and control groups, whereas miR-152 was detectable in a lower range in HCC HCV+ compared to non-HCC HCV+ and control groups. We found higher signals for miR-122 and miR-152 in non-tumor liver and HCC tissues compared to control tissues. Hepatocellular carcinoma etiology had no detectable influence on miR-122 expression, whereas miR-152 was increased in HCV+ tissue samples. CONCLUSIONS: Detection of low values of circulating miR-152 is a potentially interesting marker of hepatocarcinogenesis in HCV+ patients, in contrast to miR-122, which varies according to hepatocyte damage.

Parathyroid hormone decline 4 hours after total thyroidectomy accurately predicts hypocalcemia.

BACKGROUND: The level of parathyroid hormone (iPTH) serum has been controversial in the prediction of postthyroidectomy hypocalcemia. Analysis of the decrease between preoperative and postoperative iPTH levels should be more accurate. Therefore, the aim of our study was to prospectively establish the reliability of the iPTH decrease for early diagnosis of postoperative hypocalcemia and to identify the patients who are not at risk for hypocalcemia. METHODS: A prospective study of 137 consecutive patients who underwent total thyroidectomy was performed. Serum iPTH level was measured preoperatively and 4 hours postoperatively (iPTH(H4)). The sensitivity, specificity, and positive and negative predictive values for the iPTH(H4) and for the iPTH decline were estimated by confidence interval from thresholds determined by ROC curve analysis. RESULTS: Thirty-nine patients developed hypocalcemia (28.5%). Patients who developed hypocalcemia had a significantly lower iPTH(H4) and a significantly greater iPTH decrease (P < .001). The thresholds enabling prediction of hypocalcemia were 19.4 ng/L for iPTH(H4) and 68.5% for iPTH decline. Sensitivity, specificity, and positive and negative predictive values for iPTH(H4) were 84.6%, 92.9%, 82.5%, and 93.8% (overall accuracy, 90.5%). iPTH decline was more accurate to predict hypocalcemia (sensitivity, 97.4%; specificity, 95.9%; positive predictive values 90.5%; negative predictive values, 98.6%; and overall accuracy, 96.4%). CONCLUSION: The decrease in iPTH is more precise than the iPTH(H4) alone and can accurately predict hypocalcemia after total thyroidectomy. Patients with a decrease in iPTH less than 68.5% can be discharged at postoperative day one without any supplementation. Patients with iPTH decline more than 68.5% should be administered calcium and vitamin D supplementation before symptoms appear.

[Correcting the critical reading test of the national ranking examination]. / Epreuve de lecture critique d'article scientifique des épreuves classantes nationales: pertinence de la correction.

INTRODUCTION: In 2008 the national ranking examination (NRE) will include a test on critical reading of scientific articles. This decision has provoked controversy about whether reproducible correction is possible. The aim of our study was to assess the consistency of grading between this two-part test (critical analysis and summarizing, analyzed separately), and the more classic tests. METHODS: Eight graders, all instructors at the Tours Medical School, corrected papers for each of the 3 tests. Papers for the critical reading test came from medical school final examinations and for the standard test from a practice examination. The instructors worked in pairs: each pair read 30 papers for each test, and both members separately graded each paper. The final grade was the mean of the two grades. The consistency of grading between the 4 pairs was estimated by Kendall's coefficient of concordance. RESULTS: Kendall's coefficients of concordance were estimated at 0.94 (95% CI=[0.86; 0.97]) for the standard test, at 0.92 (95% CI=[0.81;0.97]) for the critical analysis test, and at 0.75 (95% CI=[0.62; 0.84]) for the summaries. Pairwise comparisons estimated the difference in concordance between the standard test and the summary at 0.18 (95% CI=[0.08; 0.32]) and that between the standard and critical reading test at 0.01 (95% CI= [-0.07; 0.12]). Finally the difference in concordance between the 2 new tests - summary and critical reading - was estimated at -0.17 (95% CI=[-0.32; -0.04]). CONCLUSION: The focus should be on the difficulty of reproducible correction of the summaries, to set up methods for appropriate correction and adequate grading. The elaboration of detailed scoring templates, including numerous items and specifying in which part of the summary each item must be placed, should help to improve the reproducibility of this test's correction.

Differential diagnosis of focal nodular hyperplasia with quantitative parametric analysis in contrast-enhanced sonography.

OBJECTIVES: We investigated the potential of quantitative parametric analysis in the differential diagnosis of focal nodular hyperplasia (FNH) from other hypervascularized liver focal lesions. MATERIALS AND METHODS: Eighty-five focal liver lesions (in 83 patients) were explored using contrast-enhanced ultrasound (SonoVue and Cadence Contrast Pulse Sequencing) consisting of typical FNH (n=52), hepatocellular carcinoma (n=11), hemangioma with high flow (n=8), hypervascular metastases (n=10), and hepatocellular adenoma (n=4). QontraXt software (AMID, Italy) was used here to estimate the following parameters: maximum peak value, Tr (time corresponding to time for obtaining 63% of the plateau), beta parameter corresponding to the exponential factor, and slope corresponding to the tangent value of the first phase of enhancement. These parameters were obtained from the time-intensity curves derived from the enhancement observed in 2 regions of interest corresponding, respectively, to the whole lesion and the central region only. RESULTS: A significant statistical difference (P<0.05) was found in the values of Tr, beta, and slope between FNH and other hypervascularized lesions on both the whole lesion and central region. Among these parameters, slope appeared as the most valuable whatever the region of interest, ie, central or whole lesion (P<0.01). Central region was more accurate in the differentiation of FNH and concordant with visual characterization. CONCLUSION: Quantitative parametric curve analysis of the different hypervascularized lesions confirms the depiction of the central artery in FNH and thus could help in differentiating this specific focal liver lesion from the others.

Familial liver adenomatosis associated with hepatocyte nuclear factor 1alpha inactivation.

BACKGROUND & AIMS: Germline mutations in hepatocyte nuclear factor 1alpha (TCF1/HNF-1alpha) are associated with maturity-onset diabetes of the young type 3 (MODY3), and somatic biallelic inactivations of the gene are found in hepatocellular adenomas and liver adenomatosis. This study investigated cosegregation of HNF-1alpha germline mutations with diabetes and liver adenomatosis in 2 families. METHODS: Two unrelated patients with liver adenomatosis and harboring HNF-1alpha germline and somatic mutations were studied. Subsequently, we screened 9 relatives in the 2 independent families for diabetes, hepatocellular adenomas, and HNF-1alpha germline mutations. RESULTS: In family A, a father and his son presented with an intraperitoneal hemorrhagic rupture of a liver adenomatosis without diabetes. A heterozygous R229X germline mutation was identified in HNF-1alpha in the father and his son and also in his second 27-year-old son without hepatocellular adenomas. In family B, a diagnosis of liver adenomatosis was made fortuitously in a 14-year-old girl. A heterozygous G55fsX57 germline mutation in HNF-1alpha was identified in this patient, her diabetic father, and her 2 sisters. Systematic exploration showed liver adenomatosis in the 2 sisters. Somatic inactivation of the second HNF-1alpha allele was found in liver tumors in both families. CONCLUSIONS: This study describes familial liver adenomatosis and shows the association with germline HNF-1alpha mutations in adults and children. It also highlights the importance of screening for hepatocellular adenomas, diabetes, and HNF-1alpha germline mutations in relatives of patients with liver adenomatosis. Finally, prevalence of liver adenomatosis remains to be evaluated in MODY3 subjects.

Enteral nutrition during acute pancreatitis: feasibility study of a self-propeeling spiral distal end jejunal tube.

OBJECTIVE: The aim of our study was to evaluate the feasibility of enteral jejunal nutrition for acute pancreatitis using a self-propelling spiral distal end jejunal tube. METHODS: Sixteen consecutive patients with acute pancreatitis in whom Flocare tubes were placed for enteral nutrition were included in this open prospective study. All of them had pancreatic and/or peripancreatic necrosis (Balthazar >=D). The median computed topography index was 5 (range 3-10) and the median Ranson score was 2 (range 0-5). The nasoenteric Flocare tube (spiral distal end) was inserted in the stomach at the bedside. Self progression into the jejunum was assessed by X-ray at 1, 7 and 12 hours and then every 24 hours for 4 days. The rate of successful tube self-placement in the jejunum and the time to successful placement were noted. RESULTS: Insertion was successful in 12 of 16 patients (75%). Treitz's ligament was reached in a median of 12 hours (range 1-96 hours). For the remaining patients, the tube was successfully repositioned under fluoroscopic guidance in 2 and withdrawn in 2, one for oral renutrition and one to change to a weighted jejunal tube. No tube dysfunction or recurrence of pancreatitis occurred during the entire period of enteral nutrition. CONCLUSIONS: This study suggests that the nasoenteric Flocare tube can be used effectively and safely in early enteral jejunal nutrition for severe acute pancreatitis, without endoscopic or radiological manipulation.