Completion total mesorectal excision after neoadjuvant radiochemotherapy and local excision for rectal cancer.

AIM: Local excision (LE) in selected cases after neoadjuvant radiochemotherapy (RCT) for locally advanced rectal cancer in clinically complete or major responders has been recently reported as an alternative to standard radical resection. Completion total mesorectal excision (cTME) is generally performed when high-risk pathological features are found in LE surgical specimens. The aim of this study was to evaluate the incidence of residual tumour and lymph node metastases after cTME in patients previously treated by RCT + LE. The secondary aims were to quantify the rate of postoperative morbidity and mortality and to evaluate the long-term oncological outcome of this group of patients. METHODS: All patients treated from 2007 to 2020 by LE for locally advanced rectal cancer with a clinically complete or major response to RCT who had a subsequent cTME for high-risk pathological factors (ypT >1 and/or TRG >2 and/or positive margins) were included in this multicentre retrospective study. Pathological data, postoperative short-term morbidity (classified according to Clavien-Dindo) and mortality and oncological long-term outcome after cTME were recorded in a database. Statistical analysis was performed using Wizard for iOS version 1.9.31. RESULTS: A total of 47 patients were included in the study. The rate of R0 resection was 95.7%, and a sphincter-saving procedure was performed in 37 patients (78.7%), with a protective stoma rate of 78.4%. In 28 cases (59.6%), it was possible to perform a minimally invasive approach. A residual tumour (pT and/or pN) on cTME specimens was found in 21 cases (44.7%). The rate of lymph node metastases was 12.8%. The overall short-term (within 30 days) postoperative morbidity was 34%, but grade >2 postoperative complications occurred in only nine patients (19.1%), with a reoperation rate of 6.4%. No short-term postoperative deaths occurred. At a median follow-up of 57 months (range: 21-174), the long-term stoma-free rate was 70.2%, and the actuarial 5-year overall survival (OS), disease-free survival (DFS) and local control (LC) were 86.7%, 88.9% and 95.7%, respectively. CONCLUSION: When patients exhibit high-risk pathological factors after RCT + LE, cTME should be suggested due to the high risk of residual tumour or lymph node involvement (44.7%). The results after cTME in terms of the rate of R0 resection, sphincter-saving procedure, postoperative morbidity and mortality and long-term oncological outcome seem to be acceptable and do not represent a contraindication to use LE as a first-step treatment in patients with major or complete clinical response after RCT.

Minimally invasive vs. open segmental resection of the splenic flexure for cancer: a nationwide study of the Italian Society of Surgical Oncology-Colorectal Cancer Network (SICO-CNN).

BACKGROUND: Evidence on the efficacy of minimally invasive (MI) segmental resection of splenic flexure cancer (SFC) is not available, mostly due to the rarity of this tumor. This study aimed to determine the survival outcomes of MI and open treatment, and to investigate whether MI is noninferior to open procedure regarding short-term outcomes. METHODS: This nationwide retrospective cohort study included all consecutive SFC segmental resections performed in 30 referral centers between 2006 and 2016. The primary endpoint assessing efficacy was the overall survival (OS). The secondary endpoints included cancer-specific mortality (CSM), recurrence rate (RR), short-term clinical outcomes (a composite of Clavien-Dindo > 2 complications and 30-day mortality), and pathological outcomes (a composite of lymph nodes removed ≧12, and proximal and distal free resection margins length ≧ 5 cm). For these composites, a 6% noninferiority margin was chosen based on clinical relevance estimate. RESULTS: A total of 606 patients underwent either an open (208, 34.3%) or a MI (398, 65.7%) SFC segmental resection. At univariable analysis, OS and CSM were improved in the MI group (log-rank test p = 0.004 and Gray's tests p = 0.004, respectively), while recurrences were comparable (Gray's tests p = 0.434). Cox multivariable analysis did not support that OS and CSM were better in the MI group (p = 0.109 and p = 0.163, respectively). Successful pathological outcome, observed in 53.2% of open and 58.3% of MI resections, supported noninferiority (difference 5.1%; 1-sided 95%CI - 4.7% to ∞). Successful short-term clinical outcome was documented in 93.3% of Open and 93.0% of MI procedures, and supported noninferiority as well (difference - 0.3%; 1-sided 95%CI - 5.0% to ∞). CONCLUSIONS: Among patients with SFC, the minimally invasive approach met the criterion for noninferiority for postoperative complications and pathological outcomes, and was found to provide results of OS, CSM, and RR comparable to those of open resection.

Transanal Endoscopic Microsurgery Versus Total Mesorectal Excision in ypT0-1 Rectal Cancer After Preoperative Radiochemotherapy: Postoperative Morbidity, Functional Results, and Long-term Oncologic Outcome.

BACKGROUND: In patients with locally advanced extraperitoneal rectal cancer, a multidisciplinary approach represents the standard treatment. However, considering the favorable prognosis in patients with major or complete response, radical surgery might represent overtreatment. OBJECTIVE: This study aimed to evaluate postoperative short-term morbidity, functional outcome, and oncologic long-term outcome in patients with rectal cancer treated with local excision by transanal endoscopic microsurgery or radical surgery and to determine who achieved a complete or major pathological response (ypT0-1) after neoadjuvant treatment. DESIGN: This was a retrospective study. SETTING: The study was conducted at a single center. PATIENTS: Patients who had received neoadjuvant treatment by local excision with a major or complete pathological response at histological examination (transanal endoscopic microsurgery group) were compared to patients treated by radical surgery with the same pathological response (total mesorectal excision group). INTERVENTIONS: The interventions included local excision by transanal endoscopic microsurgery and radical surgery with total mesorectal excision. MAIN OUTCOME MEASURES: Postoperative short-term morbidity, functional outcome 1 year after surgery, and oncologic long-term outcome were measured. RESULTS: Ninety-three patients were included in the study (35 in the transanal endoscopic microsurgery group and 58 in the mesorectal excision group). In the total mesorectal excision group, a sphincter-saving approach was possible in 89.7% (vs 100%; p = 0.049); a protective temporary stoma was necessary in 74.1% of radical procedures (vs 0%; p < 0.001), and 13.8% of these became permanent. Short-term postoperative morbidity was lower after local excision (14.3% vs 46.6%; p = 0.002). One year after surgery, the transanal endoscopic microsurgery group recorded better evacuation and continence function than the total mesorectal excision group. Oncologic outcome was similar between the groups. LIMITATIONS: This study had a retrospective design. CONCLUSION: If a major or complete pathological response occurs after neoadjuvant treatment, an organ-sparing approach by local excision seems to offer the same oncologic results as radical surgery, but it has a better postoperative morbidity rate and better functional results. See Video Abstract at http://links.lww.com/DCR/B901 .Microcirugía endoscópica transanal versus escisión total del mesorrecto en cáncer de recto ypT0-1 después de radioquimioterapia preoperatoria: morbilidad posoperatoria, resultados funcionales y resultado oncológico a largo plazo. ANTECEDENTES: En pacientes con cáncer rectal extraperitoneal localmente avanzado, un abordaje multidisciplinario con radioquimioterapia preoperatoria y cirugía con escisión total del mesorrecto representa el tratamiento estándar. En pacientes que obtienen una respuesta mayor o completa, la cirugía radical puede representar un sobretratamiento, considerando el pronóstico favorable de estos casos. OBJETIVO: Evaluar la morbilidad posoperatoria a corto plazo, el resultado funcional y el resultado oncológico a largo plazo en pacientes con cáncer de recto tratados con escisión local mediante microcirugía endoscópica transanal o mediante cirugía radical y que obtuvieron una respuesta patológica completa o mayor (ypT0-1) después del tratamiento neoadyuvante. DISEO: Este fue un estudio retrospectivo. AJUSTE: El estudio se realizó en un solo centro. ESCENARIO: El estudio se realizó en un solo centro. PACIENTES: Se comparó a los pacientes tratados, tras tratamiento neoadyuvante (1996-2016), mediante escisión local con respuesta patológica mayor o completa al examen histológico (grupo de microcirugía endoscópica transanal), con los pacientes tratados mediante cirugía radical con la misma respuesta patológica (grupo de escisión mesorrectal total). INTERVENCIONES: Extirpación local mediante microcirugía endoscópica transanal y cirugía radical con escisión mesorrectal total. PRINCIPALES MEDIDAS DE RESULTADO: Morbilidad posoperatoria a corto plazo, resultado funcional a un año después de la cirugía (evaluado con una puntuación de evacuación y continencia) y resultado oncológico a largo plazo. LIMITACIONES: Las limitaciones de este estudio incluyen su diseño retrospectivo. CONCLUSIN: Si se produce una respuesta patológica mayor o completa después del tratamiento neoadyuvante, un abordaje con preservación de órganos mediante escisión local parece ofrecer los mismos resultados oncológicos que la cirugía radical, pero tiene una menor tasa de morbilidad postoperatoria y mejores resultados funcionales un año después de la cirugía. Consulte Video Resumen en http://links.lww.com/DCR/B901 . (Traducción-Dr. Felipe Bellolio ).

Risk factors for anastomotic leakage after anterior resection for rectal cancer (RALAR study): A nationwide retrospective study of the Italian Society of Surgical Oncology Colorectal Cancer Network Collaborative Group.

AIM: Anastomotic leakage after restorative surgery for rectal cancer shows high morbidity and related mortality. Identification of risk factors could change operative planning, with indications for stoma construction. This retrospective multicentre study aims to assess the anastomotic leak rate, identify the independent risk factors and develop a clinical prediction model to calculate the probability of leakage. METHODS: The study used data from 24 Italian referral centres of the Colorectal Cancer Network of the Italian Society of Surgical Oncology. Patients were classified into two groups, AL (anastomotic leak) or NoAL (no anastomotic leak). The effect of patient-, disease-, treatment- and postoperative outcome-related factors on anastomotic leak after univariable and multivariable analysis was measured. RESULTS: A total of 5398 patients were included, 552 in group AL and 4846 in group NoAL. The overall incidence of leaks was 10.2%, with a mean time interval of 6.8 days. The 30-day leak-related mortality was 2.6%. Sex, body mass index, tumour location, type of approach, number of cartridges employed, weight loss, clinical T stage and combined multiorgan resection were identified as independent risk factors. The stoma did not reduce the leak rate but significantly decreased leak severity and reoperation rate. A nomogram with a risk score (RALAR score) was developed to predict anastomotic leak risk at the end of resection. CONCLUSIONS: While a defunctioning stoma did not affect the leak risk, it significantly reduced its severity. Surgeons should recognize independent risk factors for leaks at the end of rectal resection and could calculate a risk score to select high-risk patients eligible for protective stoma construction.

Italian Guidelines for the Nursing Management of Enteral and Urinary Stomas in Adults: An Executive Summary.

PURPOSE: This article is an executive summary of Italian guidelines for nursing management of enteral and urinary ostomies in adults. METHODS: Scoping review and generation of evidence and consensus-based clinical guidelines. SEARCH STRATEGY: The Multidisciplinary Italian Study group for STOmas (MISSTO) was founded in 2018. This group created guidelines for management of enteral and urinary ostomies in adults based on a scoping review of the literature. The research included previous guidelines, systematic reviews, meta-analyses, randomized clinical trials, cohort studies, and case reports. Five main topics were identified: "stoma preparation," "stoma creation," "stoma complications," "stoma care," and "stoma reversal" (for enteral stomas)." All the studies were evaluated according to the GRADE system and AGREE II tool. Recommendations were elaborated in the form of statements, with an established grade of recommendation for each statement. For low levels of scientific evidence statements, a consensus conference composed of expert members of the major Italian scientific societies in the field of stoma management and care discussed, corrected, validated, or eliminated the statements. A final version of the guidelines with definitive recommendations was elaborated and prepared for publication. FINDINGS/CONCLUSIONS: This document represents the first Italian guidelines on enteral and urinary stoma management to assist nurses caring for persons with an enteral or urinary ostomy.

Vitamin D, reproductive disorders and assisted reproduction: evidences and perspectives.

Vitamin D is an important nutrient involved in many fundamental health outcomes. However, its influence on female reproductive function remains ambiguous. Cholecalciferol seems to have a role in the reproductive processes and in the patients affected by polycystic ovary syndrome, endometriosis, uterine myomas and premature ovarian failure. Moreover, it may play an important role in the assisted reproductive techniques, given that it is capable of influencing oocyte quality, but also an adequate preparation of the endometrium for embryonic implantation. Although promising, available evidence is based on a limited number of in vitro, in vivo and clinical studies. We provide an overview of the association between vitamin D and female infertility reporting the most recent data published in the literature. Nevertheless, properly randomised clinical trials are mandatory to achieve more conclusive results about the promising role of vitamin D in the management of female assisted reproduction.

Pleiotropic Actions of Peroxisome Proliferator-Activated Receptors (PPARs) in Dysregulated Metabolic Homeostasis, Inflammation and Cancer: Current Evidence and Future Perspectives.

BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) have demonstrated a lot of important effects in the regulation of glucose and lipid metabolism and in the correct functioning of adipose tissue. Recently, many studies have evaluated a possible effect of PPARs on tumor cells. The purpose of this review is to describe the effects of PPARs, their action and their future prospective; METHODS: Narrative review aimed to synthesize cutting-edge evidence retrieved from searches of computerized databases; RESULTS: PPARs play a key role in metabolic diseases, which include several cardiovascular diseases, insulin resistance, type 2 diabetes, metabolic syndrome, impaired immunity and the increasing risk of cancer; in particular, PPARα and PPARß/δ mainly enable energy combustion, while PPARγ contributes to energy storage by enhancing adipogenesis; CONCLUSION: PPAR agonists could represent interesting types of molecules that can treat not only metabolic diseases, but also inflammation and cancer. Additional research is needed for the identification of high-affinity, high-specificity agonists for the treatment of obesity, type 2 diabetes (T2DM) and other metabolic diseases. Further studies are needed also to elucidate the role of PPARs in cancer.

Risk factors for wound complications in patients undergoing primary closure of the perineal defect after total proctectomy.

PURPOSE: Perineal wounds after complete proctectomy are at risk for failure, with dramatic consequences on patients' health and quality of life. This study is aimed at identifying risk factors for wound complications in patients undergoing primary closure of the perineal defect after total proctectomy. METHODS: Data from 284 patients undergoing total proctectomy from 2002 to 2012 either at the University of Chicago Medical Center or the Catholic University of Rome Hospital were collected and analyzed. RESULTS: Overall, the perineal wound complication rate was 21.8%. Successful conservative management was accomplished in 45.2% of cases. Complications occurred significantly more often in patients with a higher Charlson score index, with the diagnosis of rectal cancer, who had received preoperative radiation and who had a surgical drain placed at the time of initial surgery. Neoadjuvant radiation was the only significant risk factor at multivariate analysis (OR 4.40). In the rectal cancer subgroup, younger age, female gender, and preoperative radiation were predictors of wound complications. Based on that, a 3-point score (radiation, age, and gender (RAG)) was developed. Patients with a score of 3 had a 50% risk of developing a perineal wound complication. CONCLUSIONS: Perineal wound complications are a common and burdensome problem after total proctectomy. Preoperative radiation is the single most significant and controllable risk factor predicting perineal wound failure. In the presence of multiple, non-modifiable risk factors, alternative approaches to primary closure should be considered in managing complex perineal defects.

Soy-Based Tempeh as a Functional Food: Evidence for Human Health and Future Perspective.

Tempeh is an Indonesian traditional food made from fermented soybeans, which offers wide culinary use in East Asian countries. Similar to all fermented foods, its preparation offers the purpose of food preservation. However, preclinical studies have highlighted that microbial action leads to a modification in the nutritional composition of the food's matrix. Although there is a wide availability of data on the beneficial effect of soy, tempeh remains relatively unexplored, perhaps due to its limited diffusion in the world, which limits its research availability. However, available data suggest that tempeh may confer beneficial health effects due to the high bioavailability of nutrients and phytochemicals, showing ameliorative action on oxidative stress, glycaemic control, and blood lipid levels. Furthermore, the high biological value of tempeh means it can be used to optimize protein and caloric intake in athletes, vegetarians, and children. Moreover, the microbial fermentation used in the production of tempeh, in addition to improving the bioavailability of minerals, proteins, fibre, vitamins, and isoflavones, produces biopeptides whose biological effect is currently of great interest. Tempeh can be employed in traditional preparations as well as second-generation foods, such as plant-based meat substitutes, to provide functional and nutritional properties and a higher eco-friendly option compared to animal foods. This review aims to provide an overview of tempeh's properties, regarding human data and future research perspectives.

Bone mineral density parameters and related nutritional factors in vegans, lacto-ovo-vegetarians, and omnivores: a cross-sectional study.

Introduction: The growing prevalence of vegetarianism determines the need for comprehensive study of the impact of these diets on health and particularly on bone metabolism. We hypothesized that significant dietary differences between vegans, lacto-ovo-vegetarians, and omnivores also cause significant differences in their nutrient status, which may affect bone health. Methods: The study assessed dual-energy X-ray absorptiometry parameters in lumbar spine and femoral neck, average nutrient intake, serum nutrient concentrations, serum PTH levels, and urinary pH among 46 vegans, 38 lacto-ovo-vegetarians, and 44 omnivores. Results: There were no differences in bone mineral density (BMD) between the groups. However, the parathyroid hormone (PTH) levels were still higher in vegans compared to omnivores, despite the same prevalence of hyperparathyroidism in all groups. These findings may probably be explained by the fact that each group had its own "strengths and weaknesses." Thus, vegans and, to a lesser extent, lacto-ovo-vegetarians consumed much more potassium, magnesium, copper, manganese, and vitamins B6, B9, and C. At the same time, the diet of omnivores contained more protein and vitamins D and B12. All the subjects consumed less vitamin D than recommended. More than half of vegans and omnivores had insufficiency or even deficiency of vitamin D in the blood. Low serum concentrations of manganese with its quite adequate intake are also noteworthy: its deficiency was observed in 57% of vegans, 79% of lacto-ovo-vegetarians, and 63% of omnivores. Discussion: Currently, it is no longer possible to conclude that lacto-ovo-vegetarians have lower BMD than omnivores, as our research supported. Vegans in our study also did not demonstrate lower BMD values, only higher PTH blood concentrations, compared to omnivores, however, a large number of studies, including recent, show the opposite view. In this regard, further large-scale research is required. Vegans and lacto-ovo-vegetarians now have a variety of foods fortified with vitamins D and B12, as well as calcium. There is also a great diversity of ethically sourced dietary supplements. The found low concentrations of manganese require further investigation.

Serum copper status of patients with colorectal cancer: A systematic review and meta-analysis.

BACKGROUND: Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide and a public health problem. Several clinical studies have shown that copper (Cu) is involved in carcinogenesis, possibly via cuproptosis, a new form of programmed cell death, but the conclusions from published reports are inconsistent. This study aimed at evaluating the potential of Cu dysregulation as a CRC susceptibility factor. METHODS: In this systematic review and meta-analysis, we searched Cochrane Library, EBSCOhost, EMBASE, ProQuest, PubMed/MEDLINE, Scopus, and Web of Science for studies reporting serum Cu concentrations in CRC patients and controls from articles published till June 2023. The studies included reported measurements of serum/plasma/blood Cu levels. Meta-analyses were performed as well as study quality, heterogeneity, and small study effects were assessed. Based on a random effects model, summary standardized mean differences (SMDs) and the corresponding 95% confidence intervals (95% CIs) were applied to compare the levels of Cu between CRC patients and controls. RESULTS: 26 studies with a pooled total of9628 participants and 2578 CRC cases were included. The pooled SMD was equal to 0.85 (95% CIs -0.44; 2.14) showing that the CRC patients had higher mean Cu levels than the control subjects, but the difference was not significant (p = 0.185) and the heterogeneity was very high, I2 = 97.9% (95% CIs: 97.5-98.3%; p < 0.001). CONCLUSION: The pooled results were inconclusive, likely due to discordant results and inaccuracy in reporting data of some studies; further research is needed to establish whether Cu dysregulation might contribute to the CRC risk and whether it might reflect different CRC grades.

Promising Sources of Plant-Derived Polyunsaturated Fatty Acids: A Narrative Review.

(1) Background: Polyunsaturated fatty acids (PUFAs) are known for their ability to protect against numerous metabolic disorders. The consumption of oily fish is the main source of PUFAs in human nutrition and is commonly used for supplement production. However, seafood is an overexploited source that cannot be guaranteed to cover the global demands. Furthermore, it is not consumed by everyone for ecological, economic, ethical, geographical and taste reasons. The growing demand for natural dietary sources of PUFAs suggests that current nutritional sources are insufficient to meet global needs, and less and less will be. Therefore, it is crucial to find sustainable sources that are acceptable to all, meeting the world population's needs. (2) Scope: This review aims to evaluate the recent evidence about alternative plant sources of essential fatty acids, focusing on long-chain omega-3 (n-3) PUFAs. (3) Method: A structured search was performed on the PubMed search engine to select available human data from interventional studies using omega-3 fatty acids of non-animal origin. (4) Results: Several promising sources have emerged from the literature, such as algae, microorganisms, plants rich in stearidonic acid and GM plants. However, the costs, acceptance and adequate formulation deserve further investigation.

Environmental Impact of Two Plant-Based, Isocaloric and Isoproteic Diets: The Vegan Diet vs. the Mediterranean Diet.

Food consumption is one of the major causes of climate change, resource depletion, loss of biodiversity, and other kinds of environmental impact by modern households. According to evidence, a global change in dietary habits could be the single most effective and rapid intervention to reduce anthropic pressure on the planet, especially with respect to climate change. Our study applied Life Cycle Assessment (LCA) to investigate the total environmental impact of two plant-based diets: the Mediterranean and the Vegan diets, according to relevant Italian nutritional recommendations. The two diets share the same macronutrient rates and cover all the nutritional recommendations. Calculations were made on the basis of a theoretical one-week 2000 kcal/day diet. According to our calculations, the Vegan diet showed about 44% less total environmental impact when compared to the Mediterranean diet, despite the fact that the content of animal products of the latter was low (with 10.6% of the total diet calories). This result clearly supports the concept that meat and dairy consumption plays a critical role, above all, in terms of damage to human health and ecosystems. Our study supports the thesis that even a minimal-to-moderate content of animal foods has a consistent impact on the environmental footprint of a diet, and their reduction can elicit significant ecological benefits.

The Role of Hemp (Cannabis sativa L.) as a Functional Food in Vegetarian Nutrition.

Recently, there has been a renewed interest in Cannabis sativa and its uses. The recreational use of inflorescences as a source of THC has led to the legal restriction of C. sativa cultivation to limit the detrimental effects of psychotropic substance abuse on health. However, this has also limited the cultivation of textile/industrial varieties with a low content of THC used for textile and nutritional purposes. While previously the bans had significantly penalized the cultivation of C. sativa, today many countries discriminate between recreational use (marijuana) and industrial and food use (hemp). The stalks of industrial hemp (low in psychotropic substances) have been used extensively for textile purposes while the seeds are nutritionally versatile. From hemp seeds, it is possible to obtain flours applicable in the bakery sector, oils rich in essential fatty acids, proteins with a high biological value and derivatives for fortification, supplementation and nutraceutical purposes. Hemp seed properties seem relevant for vegetarian diets, due to their high nutritional value and underestimated employment in the food sector. Hemp seed and their derivatives are a valuable source of protein, essential fatty acids and minerals that could provide additional benefit to vegetarian nutrition. This document aims to explore the information available in the literature about hemp seeds from a nutritional point of view, highlighting possible beneficial effects for humans with particular attention to vegetarian nutrition as a supplemental option for a well-planned diet.

Soy Milk Consumption in the United States of America: An NHANES Data Report.

With the increasing adoption of plant-based diets in the United States, more and more individuals replace cow milk with plant-based milk alternatives. Soy milk is a commonly used cow milk substitute, which is characterized by a higher content of polyunsaturated fatty acids and fibers. Despite these favorable characteristics, little is known about the current prevalence of soy milk consumption the United States. We used data from the National Health and Nutrition Examination Surveys (NHANES) to assess soy milk usage in the United States and identified potential predictors for its consumption in the US general population. The proportion of individuals reporting soy milk consumption in the NHANES 2015-2016 cycle was 2%, and 1.54% in the NHANES 2017-2020 cycle. Non-Hispanic Asian and Black ethnicities (as well as other Hispanic and Mexican American ethnicities in the 2017-2020 cycle) significantly increased the odds for soy milk consumption. While a college degree and weekly moderate physical activity were associated with significantly higher odds for consuming soy milk (OR: 2.21 and 2.36, respectively), sex was not an important predictor. In light of the putative health benefits of soy milk and its more favorable environmental impact as compared to cow milk, future investigations should attempt to identify strategies that may help promote its consumption in selected populations.