Does neoadjuvant treatment in resectable pancreatic cancer improve overall survival? A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Neoadjuvant chemotherapy may improve overall survival (OS) in 'borderline' resectable pancreatic cancer (RPC). Whether the results are the same in upfront RPC is unknown. MATERIALS AND METHODS: To evaluate the association of neoadjuvant treatment and survival outcomes in RPC, a systematic literature review was carried out including prospective randomized trials of neoadjuvant treatment versus upfront surgery. Articles indexed in PubMed, Embase and Scopus were evaluated. Data regarding systemic treatment regimens, R0 resection rates, disease-free survival (DFS) and OS were extracted. The outcomes were compared using a random-effects model. The index I2 and the graphs of funnel plot were used for the interpretation of the data. RESULTS: Of 3229 abstracts, 6 randomized controlled trials were considered eligible with a combined sample size of 805 RPC patients. Among the trials, PACT-15, PREP-02/JSAP-05 and updated long-term results from PREOPANC and NEONAX trials were included. Combining the studies with meta-analysis, we could see that neoadjuvant treatment in RPC does not improve DFS [hazard ratio (HR) 0.71 (0.46-1.09)] or OS [HR 0.76 (0.52-1.11)], without significant heterogeneity. Interestingly, R0 rates improved ∼20% with the neoadjuvant approach [HR 1.2 (1.04-1.37)]. It is important to note that most studies evaluated gemcitabine-based regimens in the neoadjuvant setting. CONCLUSIONS: Neoadjuvant chemotherapy or chemoradiation does not improve DFS or OS in RPC compared to upfront surgery followed by adjuvant treatment. Neoadjuvant treatment improves R0 rates by ∼20%. Randomized ongoing trials are eagerly awaited with more active combined regimens including modified FOLFIRINOX.

Magnetic resonance imaging following neoadjuvant chemoradiation and transanal endoscopic microsurgery for rectal cancer.

AIM: Full-thickness local excision after neoadjuvant chemoradiotherapy (CRT) for patients with rectal cancer and incomplete clinical response has been a treatment strategy for organ preservation. Follow-up of these patients is challenging since anatomic distortion and postoperative changes may be clinically indistinguishable from tumour recurrence. MRI may have a role in detecting recurrence. The aim of this study was to describe the MRI findings during follow-up in patients having local excision following CRT with and without local recurrence. METHOD: The data were collected retrospectively from a single centre. Fifty-three patients with rectal cancer who had full-thickness local excision after neoadjuvant CRT and near-complete response were eligible for the study. Patients with local recurrence were treated by radical salvage surgery. The main outcome was local MRI assessment findings during follow-up. RESULTS: Fifteen patients (five who developed local recurrence and 10 with no evidence of local recurrence) had MR images available for review and were included in the study. High signal intensity and thickening of the rectal wall were present in all patients with recurrent disease within the rectal wall. Overall, 80% of the patients with recurrence showed diffusion restriction. MRI mesorectal fascia status and circumferential resection margin showed agreement in all cases. A low signal intensity scar was seen in all patients without recurrent disease. CONCLUSION: MRI shows high signal intensity and thickening of the rectal wall in recurrent disease in comparison to a low signal intensity fibrotic scar in non-recurrent disease. These findings may be useful in surveillance of these patients.

Functional outcome of autologous anorectal transplantation in an experimental model.

BACKGROUND: Although anorectal transplantation is a challenging procedure, it is a promising option for patients who have completely lost anorectal function or in whom it failed to develop, as in congenital malformations. The paucity of animal models with which to test functional outcomes was addressed in this study of anorectal manometry in rats. METHODS: Wistar rats were assigned randomly to four groups: orthotopic anorectal transplantation, heterotopic transplantation, sham operation, or normal control. Bodyweight and anal pressure were measured immediately before and after operation, and on postoperative days 7 and 14. ANOVA and Tukey's test were used to compare results for bodyweight, anal manometry and length of procedure. RESULTS: Immediately after the procedure, mean(s.d.) anal pressure in the orthotopic group (n = 13) dropped from 31·4(13·1) to 1·6(13·1) cmH2 O (P < 0·001 versus both sham operation (n = 13) and normal control (n = 15)), with partial recovery on postoperative day 7 (14·9(13·9) cmH2 O) (P = 0·009 versus normal control) and complete recovery on day 14 (23·7(12·2) cmH2 O). Heterotopic rats (n = 14) demonstrated partial functional recovery: mean(s.d.) anal pressure was 26·9(10·9) cmH2 O before operation and 8·6(6·8) cmH2 O on postoperative day 14 (P < 0·001 versus both sham and normal control). CONCLUSION: Orthotopic anorectal transplantation may result in better functional outcomes than heterotopic procedures. Surgical relevance Patients with a permanent colostomy have limited continence. Treatment options are available, but anorectal transplantation may offer hope. Some experimental studies have been conducted, but available data are currently insufficient to translate into a clinical option. This paper details functional outcomes in a rat model of anorectal autotransplantation. It represents a step in the translational research that may lead to restoration of anorectal function in patients who have lost or have failed to develop it.

Transanal total mesorectal excision: a systematic review of the experimental and clinical evidence.

Achieving a clear distal or circumferential resection margins with laparoscopic total mesorectal excision (TME) may be laborious, especially in obese males and when operating on advanced distal rectal tumors with a poor response to neoadjuvant treatment. Transanal (TaTME) is a new natural orifice translumenal endoscopic surgery modality in which the rectum is mobilized transanally using endoscopic techniques with or without laparoscopic assistance. We conducted a comprehensive systematic review of publications on this new technique in PubMed and Embase databases from January, 2008, to July, 2014. Experimental and clinical studies written in English were included. Experimental research with TaTME was done on pigs with and without survival models and on human cadavers. In these studies, laparoscopic or transgastric assistance was frequently used resulting in an easier upper rectal dissection and in a longer rectal specimen. To date, 150 patients in 16 clinical studies have undergone TaTME. In all but 15 cases, transabdominal assistance was used. A rigid transanal endoscopic operations/transanal endoscopic microsurgery (TEO/TEM) platform was used in 37 patients. Rectal adenocarcinoma was the indication in all except for nine cases of benign diseases. Operative times ranged from 90 to 460 min. TME quality was deemed intact, satisfactory, or complete. Involvement in circumferential resection margins was detected in 16 (11.8 %) patients. The mean lymph node harvest was equal or greater than 12 in all studies. Regarding morbidity, pneumoretroperitoneum, damage to the urethra, and air embolism were reported intraoperatively. Mean hospital stay varied from 4 to 14 days. Postoperative complications occurred in 34 (22.7 %) patients. TaTME with TEM is feasible in selected cases. Oncologic safety parameters seem to be adequate although the evidence relies on small retrospective series conducted by highly trained surgeons. Further studies are expected.

Long-term follow up of abdominal rectosigmoidectomy with posterior end-to-side stapled anastomosis for Chagas megacolon.

AIM: Chagas' disease is an endemic parasitosis found in Latin America. The disease affects different organs, such as heart, oesophagus, colon and rectum. Megacolon is the most frequent long-term complication, caused by damage to the myoenteric and submucous plexus, ultimately leading to a functional barrier to the faeces. Patients with severe constipation are managed surgically. The study aimed to analyse the 10-year minimum functional outcome after rectosigmoidectomy with posterior end-to-side anastomosis (RPESA). METHOD: A total of 21 of 46 patients were available for follow up. Patients underwent clinical, radiological and manometric evaluation, and the results were compared with preoperative parameters. RESULTS: Of the 21 patients evaluated, 81% (17) were female, with a mean age of 60.6 years. Good function was achieved in all patients, with significant improvement in defaecatory frequency (P < 0.0001), usage of enemas (P < 0.0001) and patient satisfaction. Barium enema also showed resolution of the colonic and rectal dilatation in 19 cases evaluated postoperatively. CONCLUSION: Minimal 10-year follow up of RPESA showed excellent functional results, with no recurrence of constipation.

Laparoscopic total mesorectal excision: early and late results.

BACKGROUND: Laparoscopic colectomy is superior to open colectomy in terms of short-term surgical outcomes. There is solid evidence indicating that laparoscopic and open surgery are equally effective for colon cancer, but for rectal cancer, the issues of neoadjuvant treatment, the need for total mesorectal excision and autonomic nerve preservation, and the technical demands of a well-constructed low colorectal or coloanal anastomosis challenge even the most specialized surgeons. This review discusses the available evidence on short-term and long-term outcomes after laparoscopic total mesorectal excision for rectal cancer. DATA SOURCES: Systematic MEDLINE and Embase searches of outcomes on laparoscopic total mesorectal excision were conducted and data were retrieved. CONCLUSIONS: Information on short-term and long-term outcomes after laparoscopic total mesorectal excision remains limited. Data are mainly retrospective and from randomized studies based on few cases that had minimal follow-up. Early non-oncologic surgical outcomes seem improved after laparoscopy, but an increased rate of positive circumferential resection margins has been detected. Though scarce, the available evidence on recurrence and survival does not indicates disadvantages to the laparoscopic approach.

Role of colonoscopy in colorectal cancer.

Colorectal cancer (CRC) represents the third most common malignancy throughout the world. Little or no improvement in survival has been effectively achieved in the last 50 years. Extensive epidemiological and genetic data are able to identify more precisely definite risk-groups so screening and early diagnosis can be more frequently accomplished. CRC is best detected by colonoscopy, which allows sampling for histologic diagnosis. Colonoscopy is the gold standard for detection of small and premalignant lesions, although it is not cost-effective for screening average-risk population. Colonoscopic polypectomy and mucosal resection constitute curative treatment for selective cases of invasive CRC. Similarly, alternative trans-colonoscopic treatment can be offered for adequate palliation, thus avoiding surgery.

Colorectal cancer screening.

Colorectal cancer (CRC) is the third most common cancer in the world, and mortality has remained the same for the past 50 years, despite advances in diagnosis and treatment. Because significant numbers of patients present with advanced or incurable stages, patients with pre-malignant lesions (adenomatous polyps) that occur as result of genetic inheritance or age should be screened, and patients with long-standing inflammatory bowel disease should undergo surveillance. There are different risk groups for CRC, as well as different screening strategies. It remains to be determined which screening protocol is the most cost-effective for each risk catagory. The objective of screening is to reduce morbidity and mortality in a target population. The purpose of this review is to analyze the results of the published CRC screening studies, with regard to the measured reduction of morbidity and mortality, due to CRC in the studied populations, following various screening procedures. The main screening techniques, used in combination or alone, include fecal occult blood tests, flexible sigmoidoscopy, and colonoscopy. Evidence from the published literature on screening methods for specific risk groups is scanty and frequently does not arise from controlled studies. Nevertheless, data from these studies, combined with recent advances in molecular genetics, certainly lead the way to greater efficacy and lower cost of CRC screening.

Diagnostic colonoscopy.

Colonoscopy is employed in prevention, diagnosis, follow-up and treatment of colorectal diseases. The technological advancement of colonoscopes and supplementary equipment, has broadened indications for colonoscopy. However, since it is an invasive method with potential complications and hazards it should be performed by specialists capable of preventing, recognizing and treating them. The authors report their personal experience with 1,234 colonoscopies. The most frequent indications were changes in bowel habits and rectal bleeding in 35.1% and 30.5% cases respectively. The patients were given 10% mannitol for bowel cleansing and inadequate bowel cleansing in only 15 (1.2%) so that the colonoscopy could not be completed. The overall incidence of perforation was 0.16%. Three hundred and one polypectomies were performed and two cases (0.75%) of bleeding were noted.

Bowel preparation for colonoscopy: comparison of mannitol and sodium phosphate. Results of a prospective randomized study.

METHOD: Eighty patients were prospectively randomized for precolonoscopic cleansing either with 750ml of 10% mannitol (Group M) or 180ml of a sodium phosphate preparation (Group NaP). Laboratory examinations before and after preparation on all patients included hemoglobin, hematocrit, sodium, potassium, phosphorous, calcium and serum osmolarity. A questionnaire was used to assess undesirable side effects and patient tolerance to the solution. The quality of preparation was assessed by the endoscopist who was unaware of the solution employed. RESULTS: Statistically significant changes were verified in serum sodium, phosphorous, potassium and calcium between the two groups, but no clinical symptoms were observed. There were no significant differences in the frequency of side effects studied. Six of the eight patients in Group NaP who had taken mannitol for a previous colonoscopy claimed better acceptance of the sodium phosphate solution. The endoscopic-blinded trial reported excellent or good bowel preparation in 85% prepared with sodium phosphate versus 82.5% for mannitol (p=0.37). CONCLUSIONS: Quality of preparation and frequency of side effects was similar in the two solutions. The smaller volume of sodium phosphate necessary for preparation seems to be related to its favorable acceptance. Nevertheless, the retention of sodium and phosphate ions contraindicates the use of sodium phosphate in patients with renal failure, cirrhosis, ascites, and heart failure.

Polypectomies: colonic endoscopic resections.

The authors present their experience with 924 colonoscopic polypectomies in 549 patients. Postpolypectomy bleeding was 0.36% without perforations. Complications associated with the procedure are analyzed; evaluating the risk, diagnosis and treatment based on a survey of the literature and personal experience.

[Colonoscopy: indications, contraindications and complications]. / Colonoscopia: indicações, contra-indicações e complicações.

The bioengeneering technological development associated with new medical information transformed colonscopy today in one of the most complete method of investigation on colorrectal diseases. The authors aim to describe the use of colonoscopy as a diagnostic and therapeutic method, its main indications and limitations. The wide utilization of colonoscopy as therapy is emphasized in the polipectomy, the identification of bleeding areas and the hemostasy. Some intervening facts are discussed as copious bleeding, perfuration and post polipectomy syndrome. Finally, the authors report the low morbidity and mortality rates in their personal experience with colonoscopy during the last decade.

[Villous and tubulovillous adenomas of the colon and rectum. Results in 30 patients]. / Adenomas vilosos e túbulo-vilosos do cólon e reto. Resultados observados em 30 casos.

UNLABELLED: Colorectal adenomas precede carcinomas as much as they become larger and present villous histology. Since colonoscopic polypectomy cannot remove all polyps, surgical options include local resection as well as segmental colectomy. Significant morbidity and high recurrence rates may occur following individual and polyp-related characteristics. This paper focuses the clinical aspects of colorectal tubulo-villous adenomas and the results of the surgical treatment. PATIENTS AND METHODS: Hospital charts from 30 patients who underwent surgical treatment of colorectal tubulovillous adenomas between 1980 and 1997 were retrospectively reviewed. RESULTS: Rectal bleeding, urgency and mucus discharge were the most frequent clinical findings. Proctologic examination (digital and rigid rectosigmoidoscopy) diagnosed the lesion for the majority of cases. Seventy per cent of the polyps were in the distal rectum and 60% were larger than 4 cm. Transanal resection was the surgical option for one half of the patients and segmental colectomy for the other. Fourty-two per cent of the polyps that were considered benign as result of preoperative biopsy showed malignant transformation when the whole polyp was examined. Recurrence rate was 26.7% and 6.7% for patients who underwent local resection and segmental colectomy respectively. Postoperative complication rate was similar for the two surgical groups. CONCLUSIONS: Recurrence may occur frequently after standard local resection. Preoperative biopsy examination has no role for the diagnosis of malignant transformation. Office proctologic examination diagnoses majority of colorectal polyps that may be elected for surgical resection.

[Laparoscopic abdominoperineal resection of rectum. Analysis of 18 cases]. / Amputação abdominoperineal do reto por acesso videolaparoscópico. Análise de 18 casos.

Laparoscopic abdominoperineal resection (APR-L) represents a truly laparoscopic operation which feasibility has been demonstrated by several authors. The wish to offer a minimally invasive procedure to patients that will deal with permanent colostomy was responsible for the authors' initial experience with the method which began in 1992. Hospital charts of patients who underwent APR-L to this date were reviewed and data regarding duration of the operation, intraoperative complications, need for conversion and characteristics of the postoperative period were assessed. Seventeen patients with the diagnosis of adenocarcinoma of the low rectum and one with squamous carcinoma of the anal canal underwent APR-L in a selective basis. The duration of the procedure was between two and six hours. There were no intraoperative complications. There was one conversion due to a large uterus that impaired pelvic dissection. One patient underwent laparotomy in the postoperative course as result of abdominal distension and incipient pelvic herniation of a small bowel wall through perineal wound. There were no septic complications and mean hospital stay was seven days. Perineal hernia occurring in the late postoperative period was seen in two patients. One of these underwent surgical correction through a conventional approach. Authors conclude that APR-L is feasible with low morbidity. Rectal oncologic dissection through video-laparoscopic access seems to be preserved and the method seems to be superior to the conventional access when considering that there is no need for abdominal incision.

[Colonoscopy as a diagnostic and therapeutic method in large intestine diseases. Results of 1715 exams]. / Emprego da colonoscopia como método diagnóstico e terapêutico das doenças do intestino grosso. Resultados observados em 1.715 exames.

Widespread use of colonoscopy in clinical practice results from the continuous progress of the techniques developed for exam completion and from the therapeutic perspective for several colorectal conditions. This paper analyses in a retrospective basis the results associated to the employment of fibrocolonoscopy between 1984 and 1995 at Discipline of Coloproctology from the University of São Paulo School of Medicine. For this period, 1,715 exams were realized. More than 50% of the patients were between the 50th and 70th decade. Habit change of hemorrhage were indications for the exam in more than 35%. Inflammatory bowel disease and cancer follow-up were indications, respectively, in 18% and 16%. "Express mannitol" bowel prep resulted satisfactory in more than 97% but precluded complete exam for seven (0.4%) patients. In 42.5%, colonoscopic examination was normal. Polyps were found in 248 (14.5%) patients for whom 376 polypectomy procedures were done successfully. Endoscopists could not reach the cecum in 68 (3.9%) patients. Incidence of hemorrhage and perforation was nill for this series. Authors conclude that fibrocolonoscopy remains as a safe and efficient method for the diagnosis and treatment (polypectomy) of common colorectal conditions.

[Surgical treatment outcome of hemorrhoidal in 475 patients]. / Resultados do tratamentro cirúrgico da doença hemorroidária em 475 doentes.

Despite feared by patients and reserved for the minority of patients suffering from hemorrohoids, hemorrhoidectomy remains as the most effective approach to this condition. To analyse results from 475 hemorrhoidectomies performed at University of São Paulo Hospital das Clínicas between 1984 and 1995, a retrospective chart review regarding gender, age, associated anorectal conditions, surgical technique, complications and their management and follow-up was addressed. Two hundred and seven (43.6%) were male. Age between fourth and sixth decades were observed for 70.8%. Associated anorectal conditions were diagnosed in 18.9%. Chronic anal fissure was the commonest one. Milligan-Morgan operation was performed in the majority of patients (91.2%) and Ferguson technique in 6.7%. There were no intraoperative complications postoperative complications occurred in 38 (8%) patients regardless of employed surgical technique. Urinary retention was the commonest postoperative complication. Mean follow-up was 5.8 years for 70% of patients. Surgical hemorrhoidectomy remains as a treatment with excellent results in the management of hemorrhoid disease for selected patients. Produces erradications of the disease in all cases in spite of low morbidity.