Expression levels of circulating miRNAs as biomarkers during multimodal treatment of rectal cancer - TiMiSNAR-mirna: a substudy of the TiMiSNAR Trial (NCT03962088).

BACKGROUND: Neoadjuvant chemoradiotherapy followed by surgery is the mainstay treatment for locally advanced rectal cancer, leading to significant decrease in tumor size (downsizing) and a shift towards earlier disease stage (downstaging). Extensive histopathological work-up of the tumor specimen after surgery including tumor regression grading and lymph node status helped to visualize individual tumor sensitivity to chemoradiotherapy, retrospectively. As the response to neoadjuvant chemoradiotherapy is heterogeneous, however, valid biomarkers are needed to monitor tumor response. A relevant number of studies aimed to identify molecular markers retrieved from tumor tissue while the relevance of blood-based biomarkers is less stringent assessed. MicroRNAs are currently under investigation to serve as blood-based biomarkers. To date, no screening approach to identify relevant miRNAs as biomarkers in blood of patients with rectal cancer was undertaken. The aim of the study is to investigate the role of circulating miRNAs as biomarkers in those patients included in the TiMiSNAR Trial (NCT03465982). This is a biomolecular substudy of TiMiSNAR Trial (NCT03962088). METHODS: All included patients in the TiMiSNAR Trial are supposed to undergo blood collection at the time of diagnosis, after neoadjuvant treatment, after 1 month from surgery, and after adjuvant chemotherapy whenever indicated. DISCUSSION: TiMiSNAR-MIRNA will evaluate the association of variation between preneoadjuvant and postneoadjuvant expression levels of miRNA with pathological complete response. Moreover, the study will evaluate the role of liquid biopsies in the monitoring of treatment, correlate changes in expression levels of miRNA following complete surgical resection with disease-free survival, and evaluate the relation between changes in miRNA during surveillance and tumor relapse. TRIAL REGISTRATION: Clinicaltrials.gov NCT03962088 . Registered on 23 May 2019.

Correction to: Standard (8 weeks) vs long (12 weeks) timing to minimally-invasive surgery after NeoAdjuvant Chemoradiotherapy for rectal cancer: a multicenter randomized controlled parallel group trial (TiMiSNAR).

Following publication of the original article [1], the authors reported that the family name of the author, Ludovica Baldari, was misspelled.

Standard (8 weeks) vs long (12 weeks) timing to minimally-invasive surgery after NeoAdjuvant Chemoradiotherapy for rectal cancer: a multicenter randomized controlled parallel group trial (TiMiSNAR).

BACKGROUND: The optimal timing of surgery in relation to chemoradiation is still controversial. Retrospective analysis has demonstrated in the recent decades that the regression of adenocarcinoma can be slow and not complete until after several months. More recently, increasing pathologic Complete Response rates have been demonstrated to be correlated with longer time interval. The purpose of the trial is to demonstrate if delayed timing of surgery after neoadjuvant chemoradiotherapy actually affects pathologic Complete Response and reflects on disease-free survival and overall survival rather than standard timing. METHODS: The trial is a multicenter, prospective, randomized controlled, unblinded, parallel-group trial comparing standard and delayed surgery after neoadjuvant chemoradiotherapy for the curative treatment of rectal cancer. Three-hundred and forty patients will be randomized on an equal basis to either robotic-assisted/standard laparoscopic rectal cancer surgery after 8 weeks or robotic-assisted/standard laparoscopic rectal cancer surgery after 12 weeks. DISCUSSION: To date, it is well-know that pathologic Complete Response is associated with excellent prognosis and an overall survival of 90%. In the Lyon trial the rate of pCR or near pathologic Complete Response increased from 10.3 to 26% and in retrospective studies the increase rate was about 23-30%. These results may be explained on the relationship between radiation therapy and tumor regression: DNA damage occurs during irradiation, but cellular lysis occurs within the next weeks. Study results, whether confirmed that performing surgery after 12 weeks from neoadjuvant treatment is advantageous from a technical and oncological point of view, may change the current pathway of the treatment in those patient suffering from rectal cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT3465982.

Robotic-assisted approach to Median Arcuate Ligament Syndrome with left gastric artery originating directly from the aorta. Report of a case and review of the current mini-invasive treatment modalities.

BACKGROUND: Median Arcuate Ligament Syndrome (MALS) is a rare clinical condition. METHODS: Through the analysis of a case report and a review of the international literature, we examined whether robotic and laparoscopic MAL release are safe and feasible. RESULTS: Of 354 and 19 patients who underwent laparoscopic MAL release (LMALr) and robotic-assisted MAL release (RMALr), respectively, conversion to open surgery occurred in 6.8% of cases following LMALr, whereas no case of conversion was reported following RMALr. Immediate symptomatic improvement was reported in 92.1% of cases following LMALr and in 84.2% of cases following RMALr. In the LMALr group 9% of patients presented with recurrence of symptoms, whereas the percentage in the RMALr group was 5.3%. LMALr was related to a higher overall complication rate when compared with RMALr (7.3% vs 5.3%). CONCLUSIONS: Both laparoscopic and robotic-assisted MAL lysis with celiac ganglionectomy can be safely performed with minimal patient morbidity.

Prophylactic central neck lymphadenectomy in high risk patients with T1 or T2 papillary thyroid carcinoma: is it useful?

INTRODUCTION: The aim of this study was to evaluate the role of prophylactic central neck lymph node dissection in high risk patients with T1 or T2 papillary thyroid cancer. MATERIALS AND METHODS: Seventy-three patients who had undergone total thyroidectomy for papillary thyroid cancer smaller than 4cm, without cervical lymphadenopathy and prophylactic central neck lymph node dissection were included. Patients were divided in two groups: low risk patients (group A) and high risk patients (group B). High risk patients were considered those with at least one of the followings: male sex, age ≥ 45 years, and extracapsular or extrathyroid disease. Statistical significant differences in persistent disease, recurrence and complications rates between the two groups were studied. RESULTS: Persistence of the disease was observed in one case in group A (5.9%) and in three cases in group B (5.4%), while thyroid cancer recurrence was registered in zero and two (3.6%) cases respectively. One single case (5.9%) of transitory recurrent laryngeal nerve damage was reported in group A and none in group B, while transitory hypoparathyroidism was observed in 2 (3.6%) patients in group A, and 1 (1.8%) patient in group B. Permanent recurrent laryngeal nerve damage was observed in one patient in group A, while permanent hypoparathyroidism was registered in one case in group B. Logistic regression evidenced that multifocality was the only risk factor significantly related to persistence of disease and recurrence. CONCLUSIONS: Our results suggests that prophylactic central neck lymph node dissection can be safely avoided in patients with T1 or T2 papillary thyroid cancer, except in those with multifocal disease. KEY WORDS: Cancer, Central neck, Cervical, Lymphadenectomy, Lymph nodes, Papillary carcinoma, Thyroid.

Impact of transthoracic endoscopic sympathectomy on plantar hyperhidrosis.

INTRODUCTION: The aim of this study is to evaluate the impact of transthoracic endoscopic sympathectomy on plantar hyperhidrosis in patients operated on for upper limb hyperhidrosis. MATERIALS AND METHODS: From 2003 to 2011, 41 consecutive patients underwent videothoracoscopic T3-T4 sympathicotomy or T3-T4 ganglion block at our Unit for upper limb hyperhidrosis. Twenty-one (51%) were affected by palmar hyperhidrosis and 20 (49%) by palmar and axillary hyperhidrosis combined. The patients affected by the plantar form were 26 (63%). Clinical follow-up was performed at 3, 6 and 12 months after surgery. Phone interviews and/or clinical assessment were made after a variable period of time (range 6 months to 8 years) to asses long term results. RESULTS: Plantar hyperhidrosis improved in 14 patients, which represents the 54% of the sufferers and the 34% of all patients. It was partially regressed in 11 patients (79%) and resolved in 3 cases (21%). There were not significant differences between patients treated with sympathicotomy and those treated with ganglion block. CONCLUSIONS: Transthoracic endoscopic sympathectomy performed through T3-T4 sympathicotomy or ganglion block improves plantar hyperhidrosis in approximately 54% of the affected patients, with a partial and complete resolution rate of 79% and 21% respectively.

Molecular analysis of appendiceal mucinous cystadenoma and rectal adenocarcinoma in a patient with urothelial carcinoma: a case report.

INTRODUCTION: In this report, we present the case of a patient affected by appendiceal cystadenoma, a colorectal adenocarcinoma, and a concomitant bladder carcinoma, as well as the results of the molecular study of the most relevant mutational pathways involved in these tumors. CASE PRESENTATION: A 68-year-old Italian man was admitted to our unit complaining of macrohematuria, rectorrhagia, and rectal tenesmus for about 2 months. A colonoscopy showed the presence of a rectal lesion at 11cm from the anal margin; multiple biopsies were performed and a diagnosis of moderately differentiated adenocarcinoma was made. Abdominal ultrasonography and total body computed tomography performed subsequently to stage the rectal cancer showed the presence of two round nodules, interpreted as swollen lymph nodes of neoplastic origin, at the anterior aspect of the iliopsoas muscle and a budding lesion affecting the bladder. The patient underwent transurethral biopsy of the lesion in the right retrotrigonal region; the diagnosis was grade II urothelial carcinoma. The patient underwent an open anterior rectal resection with loco-regional lymphadenectomy. An enlarged appendix and a voluminous whitish soft-tissue lesion requiring an appendicectomy were detected perioperatively. Transurethral resection of the bladder lesion was also performed. The histological examination revealed that the nodular lesions in the appendix were due to a cystadenoma. For mutation analysis, genomic deoxyribonucleic acid was isolated from tumor tissue samples; for PIK3CA mutations, screening revealed that all three samples analyzed carried mutations in exon 9. CONCLUSIONS: Appendiceal mucoceles are rare but require adequate surgical treatment, given their malignant potential and the possibility of causing peritoneal pseudomyxoma. It is essential to make a correct preoperative evaluation based on a colonoscopy rather than ultrasound and computed tomography to exclude synchronous neoplasias often associated with mucoceles and to plan the optimum surgical strategy. The association between appendiceal mucoceles and other neoplasias is relatively frequent, especially with colorectal cancer. Oncogenic activation in the PIK3CA-depending pathway may contribute substantially to the pathogenesis of the different solid tumors in the same patient.

Impact of age on the quality of lymphadenectomy for colorectal cancer.

The aim of this study was to evaluate the impact of patient age on the number of lymph nodes dissected during surgery for colorectal cancer. Clinical and histopathological data of 231 consecutive patients who underwent elective surgery for colorectal cancer were reviewed retrospectively. Patients were divided into those aged ≤70 years and >70 years. Our findings suggest that patient's age influences the number of lymph nodes detected in surgical specimens; this number was lower in patients aged >70 years and decreased with further aging.

Conservative management of minor anastomotic leakage after open elective colorectal surgery.

INTRODUCTION: The utility of prophylactic drainage in colorectal surgery is controversial. The aim of the present article is to study the role of drainage tubes on the management of minor anastomotic dehiscences. PATIENTS AND METHODS: We retrospectively review clinical reports of 18 consecutive patients with anastomotic dehiscence after open elective colorectal surgery. The mean age was 63 years and the male - female ratio was 5:1. Nine (50%) patients underwent re-operation for fecal peritonitis (group A) while the remaining nine (50%) were managed conservatively (group B). The parameters evaluated in both groups were: time of the anastomotic breakdown, clinical findings, amount of fluid drained the day of the dehiscence, diagnostic means used, length of stay and mortality. RESULTS: Anastomotic leakages were observed medially after 3, 6 days from surgery in group A and after 5.6 days in group B. The most frequent clinical manifestations were: fecal material through the tubes (88.9%), pelvic pain (88.9%) and fever (77.8%). Patients in group A had a median faecal fluid flow of 235cc the day of the dehiscence and 130cc those in group B. Imaging was employed only in three cases in group A and in all cases in group B. The length of hospital stay was longer in patients treated surgically: 37 days versus 29 in those treated conservatively. CONCLUSIONS: Minor anastomotic leakages generally occur later than greater ones, they have a milder clinical presentation and can be managed conservatively with the use of drain tubes.