Alessandro Fichera

Modern Rectal Cancer Multidisciplinary Treatment: The Role of Radiation and Surgery

IntroductionTreatment of rectal cancer has evolved during the last few decades due to more in-depth knowledge of rectal cancer biology and major advances in the field of preoperative staging, medical management and surgical techniques. Consequently, treatment strategies are shifting moving towards a more personalized approach based on the response to treatment. Currently topics of controversy are centered around the indication for neoadjuvant radiation therapy in locally advanced rectal cancer and the role of surgery in patients with complete clinical response after neoadjuvant combined modality therapy. This manuscript aims to critically evaluate the evolution of treatment of rectal cancer during the last three decades and future directions.MethodsA review of the literature has been performed in PubMed/Medline electronic databases.ResultsTreatment modalities are moving towards a tailored approach to rectal cancer patients based on the response to chemoradiation. A “wait-and-see” approach and local excision by Transanal Endoscopic Microsurgery (TEM) are strategies recently proposed in case of complete clinical response.ConclusionsThe standard of care still requires that locally advanced rectal cancer should be treated by neoadjuvant chemoradiation therapy followed by total mesorectal excision, including patients with a clinical complete response. Further evidence is needed to endorse a “wait-and-see” strategy and to define the role of TEM.

Guidelines for the Multidisciplinary Management of Crohn's Perianal Fistulas: Summary Statement

P erianal fistulas are common manifestations of Crohn’s disease that can result in tremendous morbidity, including scarring, persistent drainage, and fecal incontinence. The typical course for patients with perianal Crohn’s disease includes long time periods of actively draining fistulas and frequent relapses. The risk of developing Crohn’s perianal fistulas increases the more distal the disease involvement. Only 12% of patients with isolated ileal disease develop a perianal fistula compared with 92% of patients with rectal involvement. The frequency of perianal fistulas in patients with Crohn’s disease range from 17% to 43% in reports from referral centers. Three population-based studies have shown similar rates of perianal fistulas between 21% and 23% in patients with Crohn’s disease. Approximately, 5% of individuals will have isolated perianal disease without any evidence of luminal inflammation. In Olmsted County, Minnesota population, perianal disease was present at or before time of diagnosis in 45% of cases; 55% were found at median of 4.8 years (8 d–18.7 yr) after diagnosis. This underscores the difficulty in making the diagnosis of Crohn’s disease in patients who present with only perianal pathology. Natural history studies done before the widespread use of anti-tumor necrosis alpha antibodies (anti-TNF) found that 71% of patients with Crohn’s perianal fistulas required at least 1 operation for their perianal disease. Nearly, one-third of the patients required a major operation such as a proctectomy, proctocolectomy or diverting ileostomy because of refractory disease. It is unclear if the use of anti-TNF agents has decreased these surgical rates. ANATOMY A working knowledge of the perianal anatomy is needed to better understand the etiology and classification schemes for Crohn’s perianal fistulas. The anal canal comprised 2 muscular cylinders (Fig. 1). The internal anal (IAS) sphincter is formed from the continuation of the circular smooth muscle layer of the muscularis propria of the rectum. The external anal sphincter (EAS) is formed from the downward extension of skeletal muscle from the puborectalis muscle. The skeletal muscle above the puborectalis fans out to form the levator ani muscles. This serves to divide the perineum from the abdominal cavity. A potential space called the intersphincteric plane lies between the 2 sphincters. It contains fat and the longitudinal muscle. The dentate line separates the transitional and columnar epithelium of the rectum from the squamous epithelium of the anus. The dentate line is usually located at the middle portion of the IAS. Anal crypts are present at the dentate line. Anal glands exist at the base of many of these crypts and occasionally penetrate into the intersphincteric space and may be one of the sources for the development of perianal fistulas.

Postoperative Portomesenteric Venous Thrombosis: Lessons Learned From 1,069 Consecutive Laparoscopic Colorectal Resections

AbstractBackgroundnPortomesenteric venous thrombosis (PVT) is a known complication after open and laparoscopic colorectal (LCR) surgery. Risk factors and the prognosis of PVT have been poorly described.MethodsThis study is a retrospective analysis of a prospectively collected database. Patients with new-onset postoperative abdominal pain were evaluated with a computed tomography scan of the abdomen. Patients found to have PVT were analyzed. A multivariate analysis was performed to identify predictors of PVT.ResultsA total of 1,069 patients undergoing LCR surgery for inflammatory bowel disease (IBD) or nonmetastatic cancer between June 2002 and June 2012 were included. Altogether, 37 (3.5xa0%) patients experienced symptomatic postoperative PVT. On univariate analysis, IBD (pxa0<xa00.001), ulcerative colitis (pxa0=xa00.016), preoperative therapy with steroids (pxa0=xa00.008), operative timexa0≥220xa0min (pxa0=xa00.004), total proctocolectomy (TPC) (pxa0<xa00.001), ileoanal pouch anastomosis (pxa0=xa00.006), and postoperative intraabdominal septic complications (pxa0<xa00.001) were found to be significant risk factors. By multivariate analysis, TPC (pxa0=xa00.026) and postoperative intraabdominal septic complications (pxa0<xa00.001) were independent predictors of PVT. In the PVT group, postoperative length of stay was longer (14.8 vs. 7.4xa0days, pxa0<xa00.001). Of the patients evaluated with a hematologic workup, 72.7xa0% were found to have a hypercoagulable condition. All patients were managed with oral anticoagulation for at least 6xa0months. No death or complications related to PVT occurred.ConclusionsPVT is a potentially serious complication that is more likely to occur after TPC and in the presence of postoperative intraabdominal septic complications, particularly in patients with a coagulation disorder. Prompt diagnosis and treatment with oral anticoagulation are recommended to avoid long-term sequelae.

Neoadjuvant chemoradiation therapy and pathological complete response in rectal cancer

The management of rectal cancer has evolved significantly in the last few decades. Significant improvements in local disease control were achieved in the 1990s, with the introduction of total mesorectal excision and neoadjuvant radiotherapy. Level 1 evidence has shown that, with neoadjuvant chemoradiation therapy (CRT) the rates of local recurrence can be lower than 6% and, as a result, neoadjuvant CRT currently represents the accepted standard of care. This approach has led to reliable tumor down-staging, with 15–27% patients with a pathological complete response (pCR)—defined as no residual cancer found on histological examination of the specimen. Patients who achieve pCR after CRT have better long-term outcomes, less risk of developing local or distal recurrence and improved survival. For all these reasons, sphincter-preserving procedures or organ-preserving options have been suggested, such as local excision of residual tumor or the omission of surgery altogether. Although local recurrence rate has been stable at 5–6% with this multidisciplinary management method, distal recurrence rates for locally-advanced rectal cancers remain in excess of 25% and represent the main cause of death in these patients. For this reason, more recent trials have been looking at the administration of full-dose systemic chemotherapy in the neoadjuvant setting (in order to offer early treatment of disseminated micrometastases, thus improving control of systemic disease) and selective use of radiotherapy only in non-responders or for low rectal tumors smaller than 5u2009cm.

Paradigm-shifting new evidence for treatment of rectal cancer.

BackgroundTreatment of rectal cancer has dramatically evolved during the last three decades shifting toward a tailored approach based on preoperative staging and response to neoadjuvant combined modality therapy (CMT).MethodsA literature search was performed using PubMed/Medline electronic databases.ResultsSelected patients with T1 N0 rectal cancer are best treated with local excision by transanal endoscopic microsurgery (TEM). Satisfactory results have been reported after CMT and TEM for the treatment of highly selected T2 N0 rectal cancers. CMT followed by rectal resection and total mesorectal excision is considered the standard of care for the treatment of locally advanced rectal cancer. However, a subset of stage II and III patients may not require neoadjuvant radiation treatment. Finally, there are mounting data supporting a “watch and wait” approach or local excision in patients with complete clinical response after neoadjuvant CMT.ConclusionsCurrent evidence shows that selected T1 N0 rectal cancers can be managed by TEM alone, while locally advanced cancers should be treated by CMT followed by radical surgery. Studies are underway to identify patients that do not benefit from neoadjuvant radiation therapy. A non-operative approach in case of complete clinical response must be validated by large prospective studies.

Kono-S Anastomosis for Surgical Prophylaxis of Anastomotic Recurrence in Crohn’s Disease: an International Multicenter Study

IntroductionThe Kono-S (antimesenteric functional end-to-end handsewn) anastomosis has been used for Crohn’s disease in Japan and the USA since 2003 and 2010, respectively. This technique was designed to reduce the risk of anastomotic surgical recurrence. This study reviews the outcomes a decade after the introduction of the Kono-S anastomosis to clinical practice.MethodsThis study was conducted at five hospitals (four in Japan and one in the USA). A total of 187 patients in Japan (144 patients, group J) and the USA (43 patients, group US) who underwent Kono-S anastomosis for Crohn’s disease between September 2003 and September 2011 were included.ResultsWith a median follow-up of 65xa0months, two surgical anastomotic recurrences have occurred in group J. Kaplan–Meier analysis showed that 5 and 10xa0years surgical recurrence-free survival rate was 98.6xa0% in group J. No surgical anastomotic recurrences have been detected in group US with a median follow-up of 32xa0months. The Kono-S anastomosis was technically feasible and performed in all patients.ConclusionThe Kono-S anastomosis appears to be safe and effective in reducing the risk of surgical recurrence in Crohn’s disease.

Biomaterials in the treatment of anal fistula: hope or hype?

Anal fistula (AF) presents a chronic problem for patients and colorectal surgeons alike. Surgical treatment may result in impairment of continence and long-term risk of recurrence. Treatment options for AFs vary according to their location and complexity. The ideal approach should result in low recurrence rates and minimal impact on continence. New technical approaches involving biologically derived products such as biological mesh, fibrin glue, fistula plug, and stem cells have been applied in the treatment of AF to improve outcomes and decrease recurrence rates and the risk of fecal incontinence. In this review, we will highlight the current evidence and describe our personal experience with these novel approaches.

Ligation of Intersphincteric Fistula Tract: a Sphincter-Sparing Option for Complex Fistula-in-Ano

Fistulae-in-ano represent one of the more challenging anorectal diseases faced by surgeons, as appropriate management requires careful balance between the need for local sepsis control and patients’ desire to maintain fecal continence. The ligation of intersphincteric fistula tract (LIFT) procedure, first described by Rojanasakul and colleagues in 2007, represents a sphincter-sparing technique for fistula management which has become our method of choice for transsphincteric fistulas. With this technique, patients frequently enjoy successful fistula healing., or, at worst, conversion to a less complex fistula tract. Here, we describe and illustrate our surgical approach and review success and recurrence rates presented in the published literature.

Postoperative Medical Management of Crohn's Disease: Prevention and Surveillance Strategies.

Postoperative Crohn’s disease recurrence can be defined as histologic, endoscopic, radiographic, clinical, or surgical. Recurrence rates may also vary according to the methodology of the individual study, for example randomized controlled trial versus observational and referral center experience versus a population-based cohort. n nClinical and endoscopic recurrence rates are the most commonly reported postoperative Crohn’s disease measures. Clinical recurrence is defined by symptoms, such as diarrhea, weight loss, and abdominal pain. A variety symptom scores have been adapted to postoperative Crohn’s disease and include, the Inflammatory Bowel Disease Questionnaire or the Crohn’s disease activity index or Harvey-Bradshaw Index. The subjective nature of these symptom-based scores lends to a large variability of clinical recurrence rates across studies. Endoscopic recurrence that is defined at or above the ileocolonic anastomosis by ileocolonoscopy is a more objective measure. n nEndoscopic recurrence, defined by the Rutgeerts score, predicts subsequent clinical and surgical recurrence.5 The Rutgeerts score defines ileal lesions within 10 cm of the ileocolonic anastomosis as follows: n n ni0: no lesions; n n ni1: ≤5 apthous lesions; n n ni2: >5 apthous lesions with normal mucosa between lesions, or skip areas of larger lesions, or lesions confined to the ileocolonic anastomosis <1 cm in length; n n ni3: diffuse apthous ileitis with diffusely inflamed mucosa, and; n n ni4: diffuse inflammation with already larger ulcers, nodules, or narrowing. n n n n n nAt 3 years of follow-up, i0 and i1, i2, i3, and i4 scores are associated with 90 % likelihood of clinical recurrence, respectively.5 n nA recent comprehensive review looked at the incidence of endoscopic and clinical recurrence.6 These authors reported overall 5-year endoscopic recurrence rates of 89 and 58 % in patients from referral centers and population-based cohorts, respectively, and 5-year clinical recurrence rates of 41 and 30 %, respectively. n nSurgical recurrence generally follows clinical recurrence, and the surgical recurrence rates in population-based studies have decreased over time according to a recent review.7 Investigations conducted after 1980 demonstrated a 10-year surgical recurrence rate of 33 % [95 % confidence interval (CI): 31–35 %] compared to earlier studies that reported a rate of 45 % (95 % CI: 38–53 %). The enhancement of medication efficacy, employment of prophylactic medical therapy, and initiation of endoscopy-stimulated treatment likely influenced this reduction. n nThe strongest predictors of postoperative recurrence are active cigarette smoking,6,8 penetrating disease behavior, and recurrent resectional surgery for Crohn’s disease. Other risk factors include perianal disease, extensive (>50 cm) small bowel disease, and early onset, aggressive disease.6

Establishing a Successful Clinical Research Program

Clinical research (CR) is a natural corollary to clinical surgery. It gives an investigator the opportunity to critically review their results and develop new strategies. This article covers the critical factors and the important components of a successful CR program. The first and most important step is to build a dedicated research team to overcome time constraints and enable a surgical practice to make CR a priority. With the research team in place, the next step is to create a program on the basis of an original idea and new clinical hypotheses. This often comes from personal experience supported by a review of the available evidence. Randomized controlled (clinical) trials are the most stringent way of determining whether a cause-effect relationship exists between the intervention and the outcome. In the proper setting, translational research may offer additional avenues allowing clinical application of basic science discoveries.