Machine Learning-Based Prediction of Responsiveness to Neoadjuvant Chemoradiotheapy in Locally Advanced Rectal Cancer Patients from Endomicroscopy.

The protocol for treating locally advanced rectal cancer consists of the application of chemoradiotherapy (neoCRT) followed by surgical intervention. One issue for clinical oncologists is predicting the efficacy of neoCRT in order to adjust the dosage and avoid treatment toxicity in cases when surgery should be conducted promptly. Biomarkers may be used for this purpose along with in vivo cell-level images of the colorectal mucosa obtained by probe-based confocal laser endomicroscopy (pCLE) during colonoscopy. The aim of this article is to report our experience with Motiro, a computational framework that we developed for machine learning (ML) based analysis of pCLE videos for predicting neoCRT response in locally advanced rectal cancer patients. pCLE videos were collected from 47 patients who were diagnosed with locally advanced rectal cancer (T3/T4, or N+). The patients received neoCRT. Response to treatment by all patients was assessed by endoscopy along with biopsy and magnetic resonance imaging (MRI). Thirty-seven patients were classified as non-responsive to neoCRT because they presented a visible macroscopic neoplastic lesion, as confirmed by pCLE examination. Ten remaining patients were considered responsive to neoCRT because they presented lesions as a scar or small ulcer with negative biopsy, at post-treatment follow-up. Motiro was used for batch mode analysis of pCLE videos. It automatically characterized the tumoral region and its surroundings. That enabled classifying a patient as responsive or non-responsive to neoCRT based on pre-neoCRT pCLE videos. Motiro classified patients as responsive or non-responsive to neoCRT with an accuracy of ~ 0.62 when using images of the tumor. When using images of regions surrounding the tumor, it reached an accuracy of ~ 0.70. Feature analysis showed that spatial heterogeneity in fluorescence distribution within regions surrounding the tumor was the main contributor to predicting response to neoCRT. We developed a computational framework to predict response to neoCRT by locally advanced rectal cancer patients based on pCLE images acquired pre-neoCRT. We demonstrate that the analysis of the mucosa of the region surrounding the tumor provides stronger predictive power.

Pretreatment colostomy in patients with anal squamous cell carcinoma: Risk factors for a permanent stoma.

BACKGROUND: The current standard of care for anal squamous cell carcinoma (SCC) is concurrent chemoradiation (CRT), which enables tumor eradication while preserving the anal sphincter. Patients with locally advanced tumors, however, may experience complications that preclude treatment before stoma creation. OBJECTIVE: To evaluate the reversal rate of pretreatment stomas and the risk factors associated with nonreversal. METHODS: This single-institution retrospective cohort study using a prospective database included patients diagnosed with anal SCC from January 2008 to December 2020 who required a stoma before curative CRT. RESULTS: In total, 651 patients were identified; 65 required a stoma before chemoradiation due to obstruction (43.1%), rectovaginal fistula (20%), and perianal sepsis (36.9%). The stoma was reversed in nine patients after a mean follow-up of 35.8 months. Risk factors associated with a permanent stoma were perianal sepsis (p = 0.010), interruptions during radiotherapy for more than 7 days (p = 0.010), male sex (p = 0.013), poor performance status (Eastern Cooperative Oncology Group [ECOG] ≥ 2) (p = 0.023), large tumors (p = 0.045), and cisplatin-based chemotherapy (p = 0.047). CONCLUSIONS: Pretreatment stomas are unlikely to be reversed, and risk factors for a permanent stoma are perianal sepsis, interruptions during radiotherapy for more than 7 days, male sex, poor performance status (ECOG ≥ 2), large tumors, and cisplatin-based chemotherapy.

Two-step ESD: an option for en-bloc resection of extensive colorectal laterally spreading tumors.

Background and study aims Endoscopic submucosal dissection (ESD) is considered feasible and safe for treatment of colorectal laterally spreading tumors (LST), However it remains a challenge in case of extensive lesions even for experts. This study aimed to describe a new method to facilitate ESD of extensive colorectal LSTs. Between July 2010 and January 2018, 140 patients underwent ESD for colorectal LSTs. Four of them were submitted to two-step ESD and were included in this retrospective study. The submucosal dissection of lesions larger than 12 cm started and continued until the medical team decided to pause the procedure and continue it in a second step. The second procedure was performed 2 days after to finish the en-bloc resection.Three patients were male, with mean age of 67.2y (±â€Š2.2). All lesions were located in the rectum, with a mean size of 153.7 mm (±â€Š33.8). En-bloc and curative resection were successfully achieved in all cases. Mean duration of the first step of the procedure was 255 minutes (±â€Š61.8), and mean duration of the second step was 205 minutes (±â€Š205). Overall mean duration of both steps was 460 minutes (±â€Š168). Mean dissected area in the first step of the procedure was approximately 55 % of the lesion. No adverse events were observed. In conclusion, our results suggest that performing ESD in two steps could be a feasible and safe option for exceptional cases in which is not possible to finish the procedure in one step, avoiding the morbidity of surgical treatment.

Role of Magnification Chromoendoscopy in the Management of Colorectal Neoplastic Lesions Suspicious for Submucosal Invasion.

BACKGROUND: Correctly predicting the depth of tumor invasion in the colorectal wall is crucial for successful endoscopic resection of superficial colorectal neoplasms. OBJECTIVE: The aim of this study was to assess the accuracy of magnifying chromoendoscopy in a Western medical center to predict the depth of invasion by the pit pattern classification in patients with colorectal neoplasms with a high risk of submucosal invasion. DESIGN: This single-center retrospective study, from a prospectively collected database, was conducted between April 2009 and June 2015. SETTINGS: The study was conducted at a single academic center. PATIENTS: Consecutive patients with colorectal neoplasms with high risk of submucosal invasion were included. These tumors were defined by large (≥20 mm) sessile polyps (nonpedunculated), laterally spreading tumors, or depressed lesions of any size. INTERVENTIONS: Patients underwent magnifying chromoendoscopy and were classified according to the Kudo pit pattern. The therapeutic decision, endoscopic or surgery, was defined by the magnification assessment. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive values of magnifying chromoendoscopy for assessment of these lesions were determined. RESULTS: A total of 123 lesions were included, with a mean size of 54.0 ± 37.1 mm. Preoperative magnifying chromoendoscopy with pit pattern classification had 73.3% sensitivity, 100% specificity, 100% positive predictive value, 96.4% negative predictive value, and 96.7% accuracy to predict depth of invasion and consequently to guide the appropriate treatment. Thirty-three rectal lesions were also examined by MRI, and 31 were diagnosed as T2 lesions. Twenty two (70.1%) of these lesions were diagnosed as noninvasive by magnifying colonoscopy, were treated by endoscopic resection, and met the curative criteria. LIMITATIONS: This was a single-center retrospective study with a single expert endoscopist experience. CONCLUSIONS: Magnifying chromoendoscopy is highly accurate for assessing colorectal neoplasms suspicious for submucosal invasion and can help to select the most appropriate treatment. See Video Abstract at http://links.lww.com/DCR/A920.

Outcomes of Immediate Internal Pudendal Artery Perforator Flap Reconstruction for Irradiated Abdominoperineal Resection Defects.

BACKGROUND: There are many previous reports for using the internal pudendal artery perforator flap in vulvovaginal reconstruction; however, reports of this flap for perineal reconstruction after abdominoperineal excision of the rectum are scarce. OBJECTIVE: The purpose of this study was to evaluate the outcomes of immediate internal pudendal artery perforator flap reconstruction for irradiated abdominoperineal resection defects. DESIGN: This was a prospective case series. SETTINGS: This flap could represent a step forward over other perineal flap approaches or primary closure. PATIENTS: A total of 73 consecutive patients with anorectal tumors were included. INTERVENTIONS: The study included immediate perineal reconstruction using 122 internal pudendal artery perforator flaps after abdominoperineal excision of the rectum. MAIN OUTCOME MEASURES: Dimensions of the perineal defect (in centimeters squared), hospital stay (days), healing time (days), and postoperative complications (Clavien-Dindo grades) were measured. RESULTS: The means of the perineal defect, hospital stay, and healing time were 51.62 cm, 15.94 days, and 38.52 days. The higher the patient BMI, the longer healing time (p = 0.02); Clavien-Dindo complications grades III to IV were greater in patients with perineal defect ≥60 cm (p = 0.03; OR = 10.56); postoperative complications were higher both in patients with anal squamous cell carcinoma (p = 0.005; OR = 6.09) and in patients with comorbidities (p = 0.04; OR = 2.78); hospital stay (p= 0.001) and healing time (p < 0.001) were higher in patients who had postoperative complications. The complete perineal wound healing at 12 weeks was achieved by 95% of patients, and our 30-day mortality rate was 4%. LIMITATIONS: As a nonrandomized study, our results have to be interpreted with caution. CONCLUSIONS: Multiple previously described advantages associated with internal pudendal artery perforator flap were also observed here, reinforcing the idea that it is reliable, versatile, and a useful option for perineal reconstruction after abdominoperineal excision of the rectum. Therefore, we propose that this flap could be considered as the first choice for perineal reconstruction in selected patients with moderate and some large defects after abdominoperineal excision of the rectum. See Video Abstract at http://links.lww.com/DCR/A367.

Evaluation of cutaneous sensibility of the internal pudendal artery perforator (IPAP) flap after perineal reconstructions.

BACKGROUND: In oncological perineal reconstructions, the internal pudendal artery perforator (IPAP) flap is our flap of choice, supplied by perforator vessels from the internal pudendal artery and innervated by branches from the pudendal nerve and the posterior femoral cutaneous nerve. Data related to the evaluation of its cutaneous sensibility are scarce, discrepant, and subject to methodological criticism. OBJECTIVE: The objective of this study was to evaluate the cutaneous sensibility of the IPAP flap 12 months after perineal reconstruction and compare it with the preoperative cutaneous sensibility of the gluteal fold (flap donor area). METHODS: A prospective study of 25 patients undergoing abdominoperineal excision of rectum (APER) and reconstruction with bilateral VY advancement IPAP flap was conducted. The tactile, pain, thermal, and vibration sensibilities were analyzed in four areas of the gluteal fold preoperatively and in the four corresponding areas of the flap 12 months after surgery. Tactile sensibility was assessed using the Pressure Specified Sensory Device™ (PSSD™), which measures the pressure applied to the skin. The other types of sensibility were analyzed using a needle for pain, hot/cold contact for thermal, and a tuning fork for vibration sensibility. RESULTS: A comparison between tactile sensibility thresholds on the gluteal fold preoperatively and on the flap 12 months after surgery showed no statistically significant difference, with p values>0.05 in all four areas evaluated. All patients had preserved pain, thermal, and vibration sensibility in all four areas, postoperatively. CONCLUSION: In oncological perineal reconstructions after APER, it is expected that the cutaneous sensibility on the IPAP flap be maintained.

Composition and structural effects on the adsorption of ionic liquids onto activated carbon.

The applications and variety of ionic liquids (ILs) have increased during the last few years, and their use at a large scale will require their removal/recovery from wastewater streams. Adsorption on activated carbons (ACs) has been recently proposed for this aim and this work presents a systematic analysis of the influence of the IL chemical structures (cation side chain, head group, anion type and the presence of functional groups) on their adsorption onto commercial AC from water solution. Here, the adsorption of 21 new ILs, which include imidazolium-, pyridinium-, pyrrolidinium-, piperidinium-, phosphonium- and ammonium-based cations and different hydrophobic and hydrophilic anions, has been experimentally measured. This contribution allows an expansion of the range of IL compounds studied in previous works, and permits a better understanding of the influence of the IL structures through the adsorption on AC. In addition, the COSMO-RS method was used to analyze the measured adsorption isotherms, allowing the understanding of the role of the cationic and anionic structures in the adsorption process, in terms of the different interactions between the IL compound and AC surface/water solvent. The results of this work provide new insights for the development of adsorption as an effective operation to remove/recover ILs with very different chemical nature from water solution.

Aqueous biphasic systems composed of ionic liquids and sodium carbonate as enhanced routes for the extraction of tetracycline.

Aqueous biphasic systems (ABS) using ionic liquids (ILs) offer an alternative approach for the extraction, recovery, and purification of biomolecules through their partitioning between two aqueous liquid phases. In this work, the ability of a wide range of ILs to form ABS with aqueous solutions of Na2 CO3 was evaluated. The ABS formed by IL + water + Na2 CO3 were determined at 25°C, and the respective solubility curves, tie-lines, and tie-line lengths are reported. The studied ILs share the common chloride anion, allowing the IL cation core, the cation isomerism, the presence of functionalized groups, and alkyl side chain length effects to be evaluated. An increase in the cation side alkyl chain length leads to a higher ability for liquid-liquid demixing whereas different positional isomers and the presence of an allyl group have no major influence in the phase diagrams behavior. Quaternary phosphonium- and ammonium-based fluids are more able to form an ABS when compared with imidazolium-, pyridinium-, pyrrolidinium-, and piperidium-based ILs. Moreover, the presence of an aromatic cation core has no major contribution to the formation of ABS when compared to the respective nonaromatic counterparts. Finally, to appraise on the systems applicability in downstream processing, selected systems were used for the partitioning of tetracyclines (neutral and salt forms) - a class of antibiotics produced by bacteria fermentation. Single-step extraction efficiencies for the IL-rich phase were always higher than 99% and confirm the great potential of ILs to be applied in the biotechnological field.

Screening anal dysplasia in HIV-infected patients: is there an agreement between anal pap smear and high-resolution anoscopy-guided biopsy?

PURPOSE: The purpose of this study was to analyze the agreement between anal Pap smear and high-resolution anoscopy-guided biopsy in diagnosing anal dysplasia in HIV-infected patients. METHODS: We conducted cross-sectional analysis of HIV-infected patients receiving anal dysplasia screening as part of routine care. Agreement between measures was estimated by weighted kappa statistics, using a three-tiered cytologic and histologic grading system (normal, low-grade dysplasia, and high-grade dysplasia). Estimates of sensitivity, specificity, and predictive values were calculated using a two-tiered cytologic and histologic grading system ("without dysplasia" and "with dysplasia of any grade"). Estimates were also calculated for the detection of high-grade dysplasia. RESULTS: During a one-year period, 222 patients underwent 330 anal Pap smears followed by high-resolution anoscopy-guided biopsies. There were 311 satisfactory Pap smears with concurrent biopsies. Considering histology the standard, the frequency of anal dysplasia was 46%. Kappa agreement between anal Pap smear and biopsy was 0.20. For detection of anal dysplasia of any grade, anal Pap smear showed sensitivity of 61%, specificity of 60%, positive predictive value of 56%, and negative predictive value of 64%. For high-grade dysplasia, anal Pap smear showed sensitivity of 16% and specificity of 97%. CONCLUSION: Anal Pap smears alone were not sensitive enough to rule out anal dysplasia. We recommend that high-resolution anoscopy-guided biopsy be incorporated as a complementary screening test for anal dysplasia in high-risk patients. Following baseline high-resolution anoscopy, these individuals could be followed with serial anal cytology to dictate the need for future high-resolution anoscopy-guided biopsies.

Early rectal cancer: local excision or radical surgery?

BACKGROUND: Sphincter preservation, disease control, and long-term survival are the main goals in the treatment of rectal cancer. Although transanal local excision is attractive because it is a sphincter sparing procedure, some contradictory data exist in the literature about its ability to locally control disease and provide overall survival comparable with radical procedures, even for patients with early stage tumor. PURPOSE: To compare transanal local excision and radical surgery treatment results based on the appropriate data in literature. METHODS: We reviewed the literature to identify the current recurrence and survival rates of both techniques as well as the salvage surgery success. A PubMed search of the last 10 years was performed, and a total of 10 nonrandomized studies were identified; only 1 study was prospective, 5 were comparative, and 5 were case reports. RESULTS: Five-year overall survival rate varied from 69% to 83% in the local excision group versus 82% to 90% for the radical excision group. Local recurrence rates ranged from 9% to 20% for local excision and from 2% to 9% for radical surgery. Systemic recurrence rates ranged from 6% to 21% for local excision and from 2% to 9% for radical surgery. CONCLUSION: Radical surgery is the more definitive cancer treatment; however, it does not eliminate local excision as a reasonable choice for many patients, who will have lesser procedure-related morbidity and will accept an increased risk of tumor recurrence, a prolonged period of postoperative cancer surveillance, and a decreased success rate by salvage surgery.

Surgical treatment of Chagasic megacolon by abdominal rectosigmoidectomy with immediate posterior end-to-side stapling (Habr-Gama technique).

PURPOSE: Various techniques have been used in the surgical treatment of Chagasic megacolon, including sympathectomy, sphincterotomy, anterior abdominal resection with high or low anastomosis, pull-through procedures, and Duhamel technique. However, results have not been consistently satisfactory, with reportedly high morbidity and mortality rates. The purpose of this study was to assess the technique and results of anterior rectosigmoidectomy with immediate posterior colorectal end-to-side stapled anastomosis for the treatment of Chagasic megacolon. METHODS: A prospective, noncontrolled study between 1989 and 2000 analyzed 49 patients with Chagasic megacolon. Preoperative barium enema confirmed Chagasic megacolon in all patients and preoperative anorectal manometry in 33 patients (67 percent). Rectal stump closure was undertaken by surgical stapling in 41 patients (84 percent); mechanical colorectal anastomosis was accomplished with a circular stapler in all patients. RESULTS: Symptoms of intestinal constipation ranged from 6 months to 40 years, Chagas' serology was positive in 98 percent of patients, 41 percent used bowel enemas for evacuation, and 71 percent had a history of fecaloma. The overall postoperative complication rate was 20 percent. Surgical complications occurred in 18 percent, 2 percent had nonsurgical complications, and there was no mortality. Postoperative barium enema was performed in 82 percent of cases, confirming the absence of disease. Postoperative anorectal manometry demonstrated normal resting pressure and rectal capacity; the inhibitory reflex remained absent and rectal sensitivity was increased. Ninety-three percent of patients were followed for more than 48 months, and all patients reported daily stool elimination without recurrence of constipation. CONCLUSIONS: The current study indicates that our technique is effective for surgical treatment of patients with Chagasic megacolon.

Fatal pulmonary thromboembolism in gastrectomy intraoperative procedures by gastric adenocarcinoma: case report

Relata-se um caso de paciente com adenocarcinoma gastrico com indicacao de gastrectomia. O ato operatorio transcorreu sem anormalidades. Foi realizada gastrectomia subtotal paliativa, pois encontrou-se linfonodos para-aorticos comprometidos pela neoplasia, confirmado pelo exame anatomo-patologico de congelacao realizado no decorrer da intervencao. Ao fim da confeccao da gastroentero-anastomose o paciente passou a apresentar bradicardia intensa: 38 batimentos por minuto (bpm), hipotensao arterial, alteracoes do tracado do eletrocardiograma (Supra-desnivelamento do segmento ST) e parada cardiaca. Realizadas as manobras de ressucitacao com sucesso temporario, ja que a seguir o paciente apresentou novo colapso circulatorio, sendo novamente recuperado, finalmente a terceira parada cardiaca foi irreversivel e constatou-se o obito intra-operatorio