Endoscopic ultrasonography-related diagnostic accuracy and clinical significance on small rectal neuroendocrine neoplasms

This research aimed to examine the diagnostic accuracy and clinical significance of endoscopic ultrasonography(EUS)in the context of small rectal neuroendocrine neoplasms(NENs).A total of 108 patients with rectal subepithelial lesions(SELs)with a diameter of<20 mm were included in the analysis.The diagnosis and depth assessment of EUS was compared to the histology findings.The prevalence of NENs in rectal SELs was 78.7%(85/108).The sensitivity of EUS in detecting rectal NENs was 98.9%(84/85),while the specificity was 52.2%(12/23).Overall,the diagnostic accuracy of EUS in identifying rectal NENs was 88.9%(96/108).The overall accuracy rate for EUS in assessing the depth of invasion in rectal NENs was 92.9%(78/84).Therefore,EUS demonstrates reasonable diagnostic accuracy in detecting small rectal NENs,with good sensitivity but inferior specificity.EUS may also assist physicians in assessing the depth of invasion in small rectal NENs before endoscopic excision.

Evaluating the clinical application and effect of acupuncture therapy in anal function rehabilitation after low-tension rectal cancer surgery

BACKGROUND According to the indexes of serum and anal function,acupuncture therapy was applied to patients with low rectal cancer in order to avoid the occurrence of anal incontinence and reduce complications.AIM To explore the clinical application and evaluate the effect of acupuncture therapy for anal function rehabilitation after low-tension rectal cancer surgery.METHODS From the anorectal surgery cases,we selected 120 patients who underwent colorectal cancer surgery between January 2020 and December 2022 and randomly divided them into a control group(n=60),observation group(n=60),and control group after surgery for lifestyle intervention(including smoking cessation and exercise),dietary factor adjustment,anal movement,and oral loperamide treatment.The serum levels of motilin,5-hydroxytryptamine,and vasoactive intestinal peptide(VIP),Wexner score for anal incontinence,and incidence of complications were compared between groups.RESULTS After treatment,the VIP and 5-hydroxytryptamine levels in the observation group were lower than those in the control group(P<0.05).The motilin level was higher than that in the control group(P<0.05).Postoperative anal incontinence was better in the observation group than in the control group(P<0.05).The incidence of complications in the observation group was 6.67%,which was significantly lower than that in the control group(21.67%;P<0.05).CONCLUSION Acupuncture therapy has a positive effect on the rehabilitation of anal function after low-tension rectal cancer surgery;it can effectively help to improve the serum indices of patients,avoid the occurrence of anal incontinence,and reduce the incidence of complications.Popularizing and applying it will be valuable.

Azacitidine maintenance therapy for blastic plasmacytoid dendritic cell neoplasm allograft: A case report

BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant neoplasm.There is no universally accepted standard of care because of its rarity and the dearth of prospective research.It is still challenging for some patients to achieve persistent clinical remission or cure,despite the success of allogeneic hematopoietic stem cell transplantation(allo-HSCT),indicating that there is still a significant recurrence rate.We report a case of prevention of BPDCN allograft recurrence by azacitidine maintenance therapy and review the relevant literature.CASE SUMMARY We report a 41-year-old man with BPDCN who was admitted to hospital due to skin sclerosis for>5 mo’duration.BPDCN was diagnosed by combined clinical assessment and laboratory examinations.Following diagnosis,the patients underwent induction consolidation chemotherapy to achieve the first complete remission,followed by bridging allo-HSCT.Post-transplantation,azacitidine(75 mg/m2 for 7 d)was administered as maintenance therapy,with repeat administration every 4–6 wk and appropriate extension of the chemotherapy cycle.After 10 cycles,the patient has been disease free for 26 mo after transplantation.Regular assessments of bone marrow morphology,minimal residual disease,full donor chimerism,Epstein–Barr virus,and cytomegalovirus all yielded normal results with no abnormalities detected.CONCLUSION Azacitidine may be a safe and effective maintenance treatment for BPDCN following transplantation because there were no overt adverse events during the course of treatment.

Implications of recent neoadjuvant clinical trials on the future practice of radiotherapy in locally advanced rectal cancer

Over the last two decades, the standard treatment for locally advanced rectal cancer(LARC) has been neoadjuvant chemoradiotherapy plus total mesorectal excision followed by adjuvant chemotherapy. Total neoadjuvant treatment(TNT) and immunotherapy are two major issues in the treatment of LARC. In the two latest phase Ⅲ randomized controlled trials(RAPIDO and PRODIGE23), the TNT approach achieved higher rates of pathologic complete response and distant metastasis-free survival than conventional chemoradiotherapy. Phase I/II clinical trials have reported promising response rates to neoadjuvant(chemo)-radiotherapy combined with immunotherapy. Accordingly, the treatment paradigm for LARC is shifting toward methods that increase the oncologic outcomes and organ preservation rate. However, despite the progress of these combined modality treatment strategies for LARC, the radiotherapy details in clinical trials have not changed significantly. To guide future radiotherapy for LARC with clinical and radiobiological evidence, this study reviewed recent neoadjuvant clinical trials evaluating TNT and immunotherapy from a radiation oncologist’s perspective.

Genetic polymorphisms in genes regulating cell death and prognosis of patients with rectal cancer receiving postoperative chemoradiotherapy

Objective:The identification of biomarkers for predicting chemoradiotherapy efficacy is essential to optimize personalized treatment.This study determined the effects of genetic variations in genes involved in apoptosis,pyroptosis,and ferroptosis on the prognosis of patients with locally advanced rectal cancer receiving postoperative chemoradiotherapy(CRT).Methods:The Sequenom MassARRAY was used to detect 217 genetic variations in 40 genes from 300 patients with rectal cancer who received postoperative CRT.The associations between genetic variations and overall survival(OS)were evaluated using hazard ratios(HRs)and 95%confidence intervals(CIs)computed using a Cox proportional regression model.Functional experiments were performed to determine the functions of the arachidonate 5-lipoxygenase(ALOX5)gene and the ALOX5 rs702365 variant.Results:We detected 16 genetic polymorphisms in CASP3,CASP7,TRAILR2,GSDME,CASP4,HO-1,ALOX5,GPX4,and NRF2 that were significantly associated with OS in the additive model(P<0.05).There was a substantial cumulative effect of three genetic polymorphisms(CASP4 rs571407,ALOX5 rs2242332,and HO-1 rs17883419)on OS.Genetic variations in the CASP4 and ALOX5 gene haplotypes were associated with a higher OS.We demonstrated,for the first time,that rs702365[G]>[C]represses ALOX5 transcription and corollary experiments suggested that ALOX5 may promote colon cancer cell growth by mediating an inflammatory response.Conclusions:Polymorphisms in genes regulating cell death may play essential roles in the prognosis of patients with rectal cancer who are treated with postoperative CRT and may serve as potential genetic biomarkers for individualized treatment.

Neoadjuvant intermediate-course versus long-course chemoradiotherapy in T3-4/N0+rectal cancer:Istanbul R-02 phase II randomized study

Radiation therapy(RT)is typically applied using one of two standard approaches for preoperative treatment of resectable locally advanced rectal cancer(LARC):short-course RT(SC-RT)alone or long-course RT(LC-RT)with concurrent fluorouracil(5-FU)chemotherapy.The Phase II single-arm KROG 11-02 study using intermediate-course(IC)(33 Gy(Gray)/10 fr(fraction)with concurrent capecitabine)preoperative chemoradiotherapy(CRT)demonstrated a pathologically complete response rate and a sphincter-sparing rate that were close to those of LC-CRT.The current trial aim to compare the pathological/oncological outcomes,toxicity,and quality of life results of LC-CRT and IC-CRT in cases of LARC.The prescribed dose was 33 Gy/10 fr for the IC-CRT group and 50.4 Gy/28 fr for the LC-CRT group.Concurrent chronomodulated capecitabine(Brunch regimen)1650 mg/m2/daily chemotherapy treatment was applied in both groups.The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal Cancer Module(EORTC QLQ-CR29)was administered at baseline and at three and six months after CRT.A total of 60 patients with LARC randomized to receive IC-CRT(n=30)or LC-CRT(n=30)were included in this phase II randomized trial.No significant difference was noted between groups in terms of pathological outcomes,including pathological response rates(ypT0N0-complete response:23.3%vs.16.7%,respectively,and ypT0-2N0-downstaging:50%for each;p=0.809)and Dworak score-based pathological tumor regression grade(Grade 4-complete response:23.3 vs.16.7%,p=0.839).The 5-year overall survival(73.3 vs.86.7%,p=0.173)rate was also similar.The acute radiation dermatitis(p<0.001)and any hematological toxicity(p=0.004)rates were significantly higher in the LC-CRT group,while no significant difference was noted between treatment groups in terms of baseline,third month,and sixth month EORTC QLQ-CR29 scores.

Systematic review of ablative therapy for the treatment of renal allograft neoplasms

BACKGROUND To date,there are no guidelines on the treatment of solid neoplasms in the transplanted kidney.Historically,allograft nephrectomy has been considered the only reasonable option.More recently,nephron-sparing surgery (NSS) and ablative therapy (AT) have been proposed as alternative procedures in selected cases.AIM To review outcomes of AT for the treatment of renal allograft tumours.METHODS We conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 Checklist.PubMed was searched in March 2019 without time restrictions for all papers reporting on radiofrequency ablation (RFA),cryoablation (CA),microwave ablation (MWA),high-intensity focused ultrasound (HIFU),and irreversible electroporation (IRE) of solid tumours of the kidney allograft.Only original manuscripts describing actual cases and edited in English were considered.All relevant articles were accessed in full text.Additional searches included all pertinent references.Selected studies were also assessed for methodological quality using a tool based on a modification of the Newcastle Ottawa scale.Data on recipient characteristics,transplant characteristics,disease characteristics,treatment protocols,and treatment outcomes were extracted and analysed.Given the nature and the quality of the studies available (mostly retrospective case reports and small retrospective uncontrolled case series),a descriptive summary was provided.RESULTS Twenty-eight relevant studies were selected describing a total of 100 AT procedures in 92 patients.Recipient age at diagnosis ranged from 21 to 71 years whereas time from transplant to diagnosis ranged from 0.1 to 312 mo.Most of the neoplasms were asymptomatic and diagnosed incidentally during imaging carried out for screening purposes or for other clinical reasons.Preferred diagnostic modality was Doppler-ultrasound scan followed by computed tomography scan,and magnetic resonance imaging.Main tumour types were: papillary renal cell carcinoma (RCC) and clear cell RCC.Maximal tumour diameter ranged from 5 to 55 mm.The vast majority of neoplasms were T1a N0 M0 with only 2 lesions staged T1b N0 M0.Neoplasms were managed by RFA (n = 78),CA (n = 15),MWA (n = 3),HIFU (n = 3),and IRE (n = 1).Overall,3 episodes of primary treatment failure were reported.A single case of recurrence was identified.Follow-up ranged from 1 to 81 mo.No cancer-related deaths were observed.Complication rate was extremely low (mostly < 10%).Graft function remained stable in the majority of recipients.Due to the limited sample size,no clear benefit of a single procedure over the other ones could be demonstrated.CONCLUSION AT for renal allograft neoplasms represents a promising alternative to radical nephrectomy and NSS in carefully selected patients.Properly designed clinical trials are needed to validate this therapeutic approach.

Transanal Endoscopic Microsurgery (TEM) for Rectal Neoplasms

Introduction: The abdominal approach for the treatment of rectal tumors is associated with a considerable rate of morbidity. Transanal Endoscopic Microsurgery (TEM) is an alternative technique that is less invasive than radical surgery, and therefore has a lower associated morbidity. Moreover, with proper patient selection, TEM presents oncological outcomes comparable to radical surgery. The aim of this study is to review our results obtained with TEM and discuss its role in the treatment of malignant rectal lesions. Patients and Methods: A prospective descriptive study from June 2008 until February 2011. The indications for TEM were: early rectal neoplastic lesions (T1N0M0) with good prognostic factors;neoplastic lesions in more advanced stages in selected patients (high surgical risk, refusal of radical surgery or stoma, and palliative intention). Results: Resection by TEM was performed on 19 patients. The average hospital stay was 5.7 days with an associated morbidity of 16.7%. R0 resection was 88.8%. During the follow-up of 15 (3 - 31) months, no recurrence has been shown. Conclusions: TEM is a safe and effective procedure for the treatment of selected early malignant rectal lesions and is associated with low morbidity. It is a therapeutic strategy based on a multidisciplinary team, careful patient selection, an audited surgical technique and a strict follow-up protocol.

Liver-directed therapies for liver metastases from neuroendocrine neoplasms:Can laser ablation play any role?

Aggressive cytoreduction can prolong survival in patients with unresectable liver metastases(LM)from neuroendocrine neoplasms(NEN),and minimally invasive,liver-directed therapies are gaining increasing interest.Catheter-based treatments are used in disseminated disease,whereas ablation techniques are usually indicated when the number of LM is limited.Although radiofrequency ablation(RFA)is by far the most used ablative technique,the goal of this opinion review is to explore the potential role of laser ablation(LA)in the treatment of LM from NEN.LA uses thinner needles than RFA,and this is an advantage when the tumors are in at-risk locations.Moreover,the multi-fiber technique enables the use of one to four laser fibers at once,and each fiber provides an almost spherical thermal lesion of 12-15 mm in diameter.Such a characteristic enables to tailor the size of each thermal lesion to the size of each tumor,sparing the liver parenchyma more than any other liver-directed therapy,and allowing for repeated treatments with low risk of liver failure.A recent retrospective study reporting the largest series of LM treated with LA documents both safety and effectiveness of LA,that can play a useful role in the multimodality approach to LM from NEN.

Advances in radiotherapy and targeted therapies for rectal cancer

The last decade witnessed a significant progress in understanding the biology and immunology of colorectal cancer alongside with the technical innovations in radiotherapy.The stepwise implementation of intensitymodulated and image-guided radiation therapy by means of megavolt computed tomography and helical tomotherapy enabled us to anatomically sculpt dose delivery,reducing treatment related toxicity.In addition,the administration of a simultaneous integrated boost offers excellent local control rates.The novel challenge is the development of treatment strategies for medically inoperable patient and organ preserving approaches.However,distant control remains unsatisfactory and indicates an urgent need for biomarkers that predict the risk of tumor spread.The expected benefit of target?ed therapies that exploit the tumor genome alone is so far hindered by high cost techniques and pharmaceuticals,hence hardly justifying rather modest improvements in patient outcomes.On the other hand,the immune landscape of colorectal cancer is now better clarified with regard to the immunosuppressive network that promotes immune escape.Both N2 neutrophils and myeloid-derived suppressor cells(MDSC)emerge as useful clinical biomarkers of poor prognosis,while the growing list of anti-MDSC agents shows promising ability to boost antitumor T-cell immunity in preclinical settings.Therefore,integration of genetic and immune biomarkers is the next logical step towards effective targeted therapies in the context of personalized cancer treatment.

Feasibility and safety of minimally invasive multivisceral resection for T4b rectal cancer:A 9-year review

BACKGROUND Colorectal cancer is the third most common cancer and the second highest cause of cancer-related mortality worldwide.About 5%-10%of patients are diagnosed with locally advanced rectal cancer(LARC)on presentation.For LARC invading into other structures(i.e.T4b),multivisceral resection(MVR)and/or pelvic ex-enteration(PE)remains the only potential curative surgical treatment.MVR and/or PE is a major and complex surgery with high post-operative morbidity.Minimally invasive surgery(MIS)has been shown to improve short-term post-operative outcomes in other gastrointestinal malignancies,but there is little evi-dence on its use in MVR,especially so for robotic MVR.This is a single-center retrospective cohort study from 1st January 2015 to 31st March 2023.Inclusion criteria were patients diagnosed with cT4b rectal cancer and underwent MVR,or stage 4 disease with resectable systemic metastases.Pa-tients who underwent curative MVR for locally recurrent rectal cancer,or me-tachronous rectal cancer were also included.Exclusion criteria were patients with systemic metastases with non-resectable disease.All patients planned for elective surgery were enrolled into the standard enhanced recovery after surgery pathway with standard peri-operative management for colorectal surgery.Complex sur-gery was defined based on technical difficulty of surgery(i.e.total PE,bladder-sparing prostatectomy,pelvic lymph node dissection or need for flap creation).Our primary outcomes were the margin status,and complication rates.Cate-gorical values were described as percentages and analysed by the chi-square test.Continuous variables were expressed as median(range)and analysed by Mann-Whitney U test.Cumulative overall survival(OS)and recurrence-free survival(RFS)were analysed using Kaplan-Meier estimates with life table analysis.Log-rank test was performed to determine statistical significance between cumulative estimates.Statistical significance was defined as P<0.05.Meier estimates with life table analysis.Log-rank test was performed to determine statistical significance between cumulative estimates.Statistical significance was defined as P<0.05.RESULTS A total of 46 patients were included in this study[open MVR(oMVR):12(26.1%),miMVR:36(73.9%)].Patients’American Society of Anesthesiologists score,body mass index and co-morbidities were comparable between oMVR and miMVR.There is an increasing trend towards robotic MVR from 2015 to 2023.MiMVR was associated with lower estimated blood loss(EBL)(median 450 vs 1200 mL,P=0.008),major morbidity(14.7%vs 50.0%,P=0.014),post-operative intra-abdominal collections(11.8%vs 50.0%,P=0.006),post-operative ileus(32.4%vs 66.7%,P=0.04)and surgical site infection(11.8%vs 50.0%,P=0.006)compared with oMVR.Length of stay was also shorter for miMVR compared with oMVR(median 10 vs 30 d,P=0.001).Oncological outcomes-R0 resection,recurrence,OS and RFS were comparable between miMVR and oMVR.There was no 30-d mortality.More patients underwent robotic compared with laparoscopic MVR for complex cases(robotic 57.1%vs laparoscopic 7.7%,P=0.004).The operating time was longer for robotic compared with laparoscopic MVR[robotic:602(400-900)min,laparoscopic:Median 455(275-675)min,P<0.001].Incidence of R0 resection was similar(laparoscopic:84.6%vs robotic:76.2%,P=0.555).Overall complication rates,major morbidity rates and 30-d readmission rates were similar between la-paroscopic and robotic MVR.Interestingly,3-year OS(robotic 83.1%vs 58.6%,P=0.008)and RFS(robotic 72.9%vs 34.3%,P=0.002)was superior for robotic compared with laparoscopic MVR.CONCLUSION MiMVR had lower post-operative complications compared to oMVR.Robotic MVR was also safe,with acceptable post-operative complication rates.Prospective studies should be conducted to compare short-term and long-term outcomes between robotic vs laparoscopic MVR.

Re-evaluating the role of pelvic radiation in the age of modern precision medicine and systemic therapy

The efficacy of pelvic radiation in the management of locally advanced stage rectal cancer has come under scrutiny in the context of modern precision medicine and systemic therapy as evidenced by recent clinical trials such as FOWARC(J Clin Oncol 2019;37:3223-3233),NCT04165772(N Engl J Med 2022;386:2363-2376),and PROSPECT(N Engl J Med 2023;389:322-334).In this review,we comprehensively assess these pivotal trials and offer additional insights into the evolving role of pelvic radiation in contemporary oncology.

Experimental study on effect of recombinant human growth hormone combined with chemotherapy on stomach neoplasms implanted in nude mice

Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stom- ach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P<0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P<0.05), but it was no significant difference between rhGH/5-FU groups and control group (P>0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P>0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P<0.05). They were no significant difference between rhGH/5- FU groups and 5-FU group (P>0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index (PI) were not significantly changed in rhGH groups compared with control group (P>0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P>0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.

Favorable response after radiation therapy for intraductal papillary mucinous neoplasms manifesting as acute recurrent pancreatitis:A case report

BACKGROUND There has been an increasing number of elderly patients with intraductal papillary mucinous neoplasm(IPMN),who are surgically intolerant and require less invasive treatment options,which are limited.In the present study,we report a case of IPMN presenting with acute recurrent pancreatitis(ARP),in which radiation therapy effectively prevented further attacks of ARP and reduced tumor volume.CASE SUMMARY An 83-year-old man was referred to our hospital with an asymptomatic incidental pancreatic cyst.Endoscopic ultrasound imaging and magnetic resonance cholangiopancreatography revealed a multiloculated tumor in the head of the pancreas,with dilated pancreatic ducts and mural nodules.The patient was diagnosed with mixed-type IPMN,and five years later,he developed ARP.Several endoscopic pancreatic ductal balloon dilatations failed to prevent further ARP attacks.Surgery was considered clinically inappropriate because of his old age and comorbidities.He was referred to our department for radiation therapy targeted at those lesions causing intraductal hypertension and radiation was administered at a dose of 50 Gy.An magnetic resonance imaging scan taken ten weeks after treatment revealed a decrease in tumor size and improvement of pancreatic duct dilatation.Fourteen months later,he remains symptom-free from ARP.CONCLUSION This case highlights the important role of radiation therapy in mitigating the signs and symptoms of ARP in patients with inoperable IPMN.

Management of lateral pelvic lymph nodes in rectal cancer:Is it time to reach an Agreement?

In this editorial,we proceed to comment on the article by Chua et al,addressing the management of metastatic lateral pelvic lymph nodes(mLLN)in stage II/III rectal cancer patients below the peritoneal reflection.The treatment of this nodal area sparks significant controversy due to the strategic differences followed by Eastern and Western physicians,albeit with a higher degree of convergence in recent years.The dissection of lateral pelvic lymph nodes without neoadjuvant therapy is a standard practice in Eastern countries.In contrast,in the West,preference leans towards opting for neoadjuvant therapy with chemoradiotherapy or radiotherapy,that would cover the treatment of this area without the need to add the dissection of these nodes to the total mesorectal excision.In the presence of high-risk nodal characteristics for mLLN related to radiological imaging and lack of response to neoadjuvant therapy,the risk of lateral local recurrence increases,suggesting the appropriate selection of strategies to reduce the risk of recurrence in each patient profile.Despite the heterogeneous and retrospective nature of studies addressing this area,an international consensus is necessary to approach this clinical scenario uniformly.

Impact of technology on indications and limitations for transanal surgical removal of rectal neoplasms

Transanal surgery has and continues to be well accepted for local excision of benign rectal disease not amenable to endoscopic resection. More recently, there has been increasing interest in applying transanal surgery to local resection of early malignant disease. In addition, some groups have started utilizing a transanal route in order to accomplish total mesorectal excision(TME) for more advanced rectal malignancies. We aim to review the role of various transanal and endoscopic techniquesin the local resection of benign and malignant rectal disease based on published trial data. Preliminary data on the use of transanal platforms to accomplish TME will also be highlighted. For endoscopically unresectable rectal adenomas, transanal surgery remains a widely accepted method with minimal morbidity that avoids the downsides of a major abdomino-pelvic operation. Transanal endoscopic microsurgery and transanal minimally invasive surgery offer improved visualization and magnification, allowing for finer and more precise dissection of more proximal and larger rectal lesions without compromising patient outcome. Some studies have demonstrated efficacy in utilizing transanal platforms in the surgical management of early rectal malignancies in selected patients. There is an overall higher recurrence rate with transanal surgery with the concern that neither chemoradiation nor salvage surgery may compensate for previous approach and correct the inferior outcome. Application of transanal platforms to accomplish transanal TME in a natural orifice fashion are still in their infancy and currently should be considered experimental. The current data demonstrate that transanal surgery remains an excellent option in the surgical management of benign rectal disease. However, care should be used when selecting patients with malignant disease. The application of transanal platforms continues to evolve. While the new uses of transanal platforms in TME for more advanced rectal malignancy are exciting, it is important to remain cognizant and not sacrifice long term survival for short term decrease in morbidity and improved cosmesis.

Therapy-related myeloid neoplasms - what have we learned so far?

Therapy-related myeloid neoplasms are neoplastic processes arising as a result of chemotherapy, radiation therapy, or a combination of these modalities given for a primary condition. The disease biology varies based on the etiology and treatment modalities patients receive for their primary condition. Topoisomerase Ⅱ inhibitor therapy results in balanced translocations. Alkylating agents, characteristically, give rise to more complex karyotypes and mutations in p53. Other etiologies include radiation therapy, high-dose chemotherapy with autologous stem cell transplantation and telomere dysfunction. Poor-risk cytogenetic abnormalities are more prevalent than they are in de novo leukemias and the prognosis of these patients is uniformly dismal. Outcome varies according to cytogenetic risk group. Treatment recommendations should be based on performance status and karyotype. An in-depth understanding of risk factors that lead to the development of therapyrelated myeloid neoplasms would help developing riskadapted treatment protocols and monitoring patients after treatment for the primary condition, translating into reduced incidence, early detection and timely treatment.

How reliable is current imaging in restaging rectal cancer after neoadjuvant therapy?

In patients with advanced rectal cancer,neoadjuvant chemo radiotherapy provides tumor downstaging and downsizing and complete pathological response in up to 30%of cases.After proctectomy complete pathological response is associated with low rates of local recurrence and excellent long term survival.Several authors claim a less invasive surgery or a non operative policy in patients with partial or clinical complete response respectively,however to identify patients with true complete pathological response before surgical resection remains a challenge.Current imaging techniques have been reported to be highly accurate in the primary staging of rectal cancer,however neoadjuvant therapy course produces deep modifications on cancer tissue and on surrounding structures such as overgrowth fibrosis,deep stroma alteration,wall thickness,muscle disarrangement,tumor necrosis,calcification,and inflammatory infiltration.As a result,the same imaging techniques,when used for restaging,are far less accurate.Local tumor extent may be overestimated or underestimated.The diagnostic accuracy of clinical examination,rectal ultrasound,computed tomography,magnetic resonance imaging,and positron emission tomography using 18F-fluoro-2’-deoxy-Dglucose ranges between 25%and 75%being less than 60%in most studies,both for rectal wall invasion and for lymph nodes involvement.In particular the ability to predict complete pathological response,in order to tailor the surgical approach,remains low.Due to the radio-induced tissue modifications,combined with imaging technical aspects,low rate accuracy is achieved,making modern imaging techniques still unreliable in restaging rectal cancer after chemo-radiotherapy.

Neoadjuvant radiotherapy for rectal cancer management

Thirty per cent of all colorectal tumours develop in the rectum.The location of the rectum within the bony pelvis and its proximity to vital structures presents significant therapeutic challenges when considering neoadjuvant options and surgical interventions.Most patients with early rectal cancer can be adequately managed by surgery alone.However,a significant proportion of patients with rectal cancer present with locally advanced disease and will potentially benefit from down staging prior to surgery.Neoadjuvant therapy involves a variety of options including radiotherapy,chemotherapy used alone or in combination.Neoadjuvant radiotherapy in rectal cancer has been shown to be effective in reducing tumour burden in advance of curative surgery.The gold standard surgical rectal cancer management aims to achieve surgical removal of the tumour and all draining lymph nodes,within an intact mesorectal package,in order to minimise local recurrence.It is critically important that all rectal cancer cases are discussed at a multidisciplinary meeting represented by all relevant specialties.Pre-operative staging including CT thorax,abdomen,pelvis to assess for distal disease and magnetic resonance imaging to assess local involvement is essential.Staging radiology and MDT discussion are integral in identifying patients who require neoadjuvant radiotherapy.While Neoadjuvant radiotherapy is potentially beneficial it may also result in morbidity and thus should be reserved for those patients who are at a high risk of local failure,which includes patients with nodal involvement,extramural venous invasion and threatened circumferential margin.The aim of this review is to discuss the role of neoadjuvant radiotherapy in the management of rectal cancer.

Gene therapy for human colorectal carcinoma using human CEA promoter controlled bacterial ADP-ribosylating toxin genes:PEA and DTA gene transfer

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