ILEOSTIM trial: a study protocol to evaluate the effectiveness of efferent loop stimulation before ileostomy reversal.

PURPOSE: A protective loop ileostomy is the most useful method to reduce sequelae in the event of an anastomotic leakage (AL) after rectal cancer surgery. However, it requires an additional stoma reversal surgery with its own potential complications. Postoperative ileus (POI) remains the most common complication after ileostomy reversal, which leads to an increase in morbidity, length of hospital stay (LOS) and overall healthcare costs. Several retrospective studies carried out in this field have concluded that there are insufficient evidence-based recommendations about the routine application of preoperative bowel stimulation in clinical practice. Here we discuss whether stimulation of the efferent limb before ileostomy reversal might reduce POI and improve postoperative outcomes. METHODS: This is a multicentre randomised controlled trial to determine whether mechanical stimulation of the efferent limb during the 2 weeks before the ileostomy reversal would help to reduce the development of POI after surgery. This study was registered on Clinicaltrials.gov (NCT05302557). Stimulation will consist of infusing a solution of 500 ml of saline chloride solution mixed with a thickening agent (Resource©, Nestlé Health Science; 6.4 g sachet) into the distal limb of the ileostomy loop. This will be performed within the 2 weeks before ileostomy reversal, in an outpatient clinic under the supervision of a trained stoma nurse. CONCLUSION: The results of this study could provide some insights into the preoperative management of these patients.

Mid-term oncologic outcome of a novel approach for locally advanced colon cancer with neoadjuvant chemotherapy and surgery

Purpose. Neoadjuvant chemotherapy is being actively tested as an emerging alternative for the treatment of locally advanced colon cancer (LACC) patients, resembling its use in other gastrointestinal tumors. This study assesses the mid-term oncologic outcome of LACC patients treated with oxaliplatin and fluoropyrimidines-based preoperative chemotherapy followed by surgery. Methods and patients. Patients with radiologically resectable LACC treated with neoadjuvant therapy between 2009 and 2014 were retrospectively analyzed. Radiological, metabolic, and pathological tumor response was assessed. Both postoperative complications, relapse-free survival (RFS), and overall survival (OS) were studied. Results. Sixty-five LACC patients who received treatment were included. Planned treatment was completed by 93.8 % of patients. All patients underwent surgery without delay. The median time between the start of chemotherapy and surgery was 71 days (65-82). No progressive disease was observed during preoperative treatment. A statistically significant tumor volume reduction of 62.5 % was achieved by CT scan (39.8-79.8) (p < 0.001). It was also observed a median reduction of 40.5 % (24.2-63.7 %) (p < 0.005) of SUVmax (Standard Uptake Value) by PET-CT scan. Complete pathologic response was achieved in 4.6 % of patients. Postoperative complications were observed in 15.4 % of patients, with no cases of mortality. After a median follow-up of 40.1 months, (p25-p75: 27.3-57.8) 3-5 year actuarial RFS was 88.9-85.6 %, respectively. Five-year actuarial OS was 95.3 %. Conclusion. Preoperative chemotherapy in LACC patients is safe and able to induce major tumor regression. Survival times are encouraging, and further research seems warranted (AU)

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Perineural Invasion is a Major Prognostic and Predictive Factor of Response to Adjuvant Chemotherapy in Stage I-II Colon Cancer.

BACKGROUND: Perineural invasion (PNI) in colon cancer (CC) has been associated with poorer prognosis even in stage II disease (T3-4 N0 M0). The aim of this study is to analyze prognostic histopathologic factors in stage II colon cancer in patients treated with curative surgery as established in National Comprehensive Cancer Network guidelines. METHODS: From a prospective database of CC cases, 507 patients with stage I-II disease who had undergone curative resection from January 2000 and December 2012 were identified. Of these patients, 17 % received 5-flurouracil-based adjuvant chemotherapy. Together with demographic and anatomic variables, we also studied perineural and lymphovascular invasion, degree of differentiation, and their correlation with disease-free survival. RESULTS: Perineural invasion was identified in 57 patients (11.2 %) and lymphovascular invasion (LVI) in 82 (16.2 %) of the 507 patients. Perineural invasion was associated with LVI, the depth of invasion of the wall of the colon, and location of the tumor. Overall and disease-free survival of the complete series at 5 and 10 years was 89.5, 85.2, 83.2 and 81.6 %, respectively. In the PNI positive patients, disease-free survival at 5 years was significantly lower than in those without PNI (73.5 vs 88.6 %; p = 0.02). Multivariate analysis showed the presence of PNI to be a significant independent prognostic factor for disease-free survival (p = 0.025). Adjuvant chemotherapy reversed the impact of PNI on 5- to 10-year disease-free survival. CONCLUSIONS: PNI a major prognostic and predictive factor in stage II colon cancer, and our results support the use of adjuvant chemotherapy in patients with PNI.

Mid-term oncologic outcome of a novel approach for locally advanced colon cancer with neoadjuvant chemotherapy and surgery.

PURPOSE: Neoadjuvant chemotherapy is being actively tested as an emerging alternative for the treatment of locally advanced colon cancer (LACC) patients, resembling its use in other gastrointestinal tumors. This study assesses the mid-term oncologic outcome of LACC patients treated with oxaliplatin and fluoropyrimidines-based preoperative chemotherapy followed by surgery. METHODS AND PATIENTS: Patients with radiologically resectable LACC treated with neoadjuvant therapy between 2009 and 2014 were retrospectively analyzed. Radiological, metabolic, and pathological tumor response was assessed. Both postoperative complications, relapse-free survival (RFS), and overall survival (OS) were studied. RESULTS: Sixty-five LACC patients who received treatment were included. Planned treatment was completed by 93.8 % of patients. All patients underwent surgery without delay. The median time between the start of chemotherapy and surgery was 71 days (65-82). No progressive disease was observed during preoperative treatment. A statistically significant tumor volume reduction of 62.5 % was achieved by CT scan (39.8-79.8) (p < 0.001). It was also observed a median reduction of 40.5 % (24.2-63.7 %) (p < 0.005) of SUVmax (Standard Uptake Value) by PET-CT scan. Complete pathologic response was achieved in 4.6 % of patients. Postoperative complications were observed in 15.4 % of patients, with no cases of mortality. After a median follow-up of 40.1 months, (p 25-p 75: 27.3-57.8) 3-5 year actuarial RFS was 88.9-85.6 %, respectively. Five-year actuarial OS was 95.3 %. CONCLUSION: Preoperative chemotherapy in LACC patients is safe and able to induce major tumor regression. Survival times are encouraging, and further research seems warranted.

Patterns and management of distant failure in locally advanced rectal cancer: a cohort study

PURPOSE: To determine the long-term outcomes of locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation (CRT) and surgery, and to analyze the management and survival once distant failure has developed. METHODS: Data from LARC patients treated from 2000 to 2010 were retrospectively reviewed. CRT protocols were based on fluoropirimidines ± oxaliplatin. Follow-up consisted of physical examination, carcinoembryonic antigen levels, and chest-abdominal-pelvic CT scan. RESULTS: The study included 228 patients with a mean age of 59 years. Forty-eight (21.1 %) patients had distant recurrence and 6 patients (2.6 %) had local recurrence. Median follow-up was 49 months. The 5- and 10-year actuarial disease free survival was 75.3 and 65.0 %, respectively. The 5- and 10-year actuarial overall survival (OS) was 89.6 and 71.2 %, respectively. Patients were classified as having liver (14 patients) or lung (27 patients) relapse according to the organ firstly metastasized. The variables significantly associated by univariate Cox analysis to survival were the achievement of an R0 metastases resection and the Köhne risk index, while the metastatic site showed a statistical trend. By multivariate Cox analysis, the only variable associated with survival was a R0 resection (HR = 16.3, p\0.001). Median OS for patients undergoing a R0 resection was 73 months (95 % CI 67.8-78.2) compared to 25 months (95 % CI 5.47-44.5) in those non-operated patients (p\0.001). CONCLUSIONS: Combined treatment for LARC obtains a 5-year OS rounding 90 %. Follow-up based on thoracic abdominal CT scan allows an early diagnosis of metastatic lesions. Surgical resection of metastases, regardless of their location, greatly increases the patient's survival rate

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Clinical significance of cellular and acellular mucin pools in rectal carcinoma following preoperative chemoradiotherapy

Background and objectives: The standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (CRT) followed by surgery. Pathological findings remain the most significant prognostic factor. The presence of mucin pools and their prognostic significance is a controversial issue. The aim of this study was to analyze the incidence of cellular and acellular mucin pools and their clinical significance. Methods: Four-hundred and forty-six consecutive prospectively collected specimens from patients with LARC treated with long-course preoperative CRT and surgery were analyzed. Kaplan-Meier analysis was performed. Results: Mucin pools were present in 182 specimens (40.8 %); 66 (14.7 %) were acellular, and viable tumor cells were identified in 116 (26 %). The complete pathological response rate was 13.5 % (60 of 446). With a median follow-up of 79.0 months, the 5- and 10-year disease-free survivals for patients with acellular and cellular mucin pools were 81.5, 78.1, 63.7 and 61.2 %, respectively (p B 0.026). The presence of cells in the colloid response to treatment was associated with a 17.8 and 16.9 % decrease in 5- and 10-year disease survival vs. acellular colloid response. Conclusions: Our results suggest that cellular mucin pools are an indicator of an aggressive phenotype and harbingers of a worse prognosis (AU)

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Clinical significance of cellular and acellular mucin pools in rectal carcinoma following preoperative chemoradiotherapy.

BACKGROUND AND OBJECTIVES: The standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (CRT) followed by surgery. Pathological findings remain the most significant prognostic factor. The presence of mucin pools and their prognostic significance is a controversial issue. The aim of this study was to analyze the incidence of cellular and acellular mucin pools and their clinical significance. METHODS: Four-hundred and forty-six consecutive prospectively collected specimens from patients with LARC treated with long-course preoperative CRT and surgery were analyzed. Kaplan-Meier analysis was performed. RESULTS: Mucin pools were present in 182 specimens (40.8 %); 66 (14.7 %) were acellular, and viable tumor cells were identified in 116 (26 %). The complete pathological response rate was 13.5 % (60 of 446). With a median follow-up of 79.0 months, the 5- and 10-year disease-free survivals for patients with acellular and cellular mucin pools were 81.5, 78.1, 63.7 and 61.2 %, respectively (p ≤ 0.026). The presence of cells in the colloid response to treatment was associated with a 17.8 and 16.9 % decrease in 5- and 10-year disease survival vs. acellular colloid response. CONCLUSIONS: Our results suggest that cellular mucin pools are an indicator of an aggressive phenotype and harbingers of a worse prognosis.

Patterns and management of distant failure in locally advanced rectal cancer: a cohort study.

PURPOSE: To determine the long-term outcomes of locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation (CRT) and surgery, and to analyze the management and survival once distant failure has developed. METHODS: Data from LARC patients treated from 2000 to 2010 were retrospectively reviewed. CRT protocols were based on fluoropirimidines ± oxaliplatin. Follow-up consisted of physical examination, carcinoembryonic antigen levels, and chest-abdominal-pelvic CT scan. RESULTS: The study included 228 patients with a mean age of 59 years. Forty-eight (21.1 %) patients had distant recurrence and 6 patients (2.6 %) had local recurrence. Median follow-up was 49 months. The 5- and 10-year actuarial disease free survival was 75.3 and 65.0 %, respectively. The 5- and 10-year actuarial overall survival (OS) was 89.6 and 71.2 %, respectively. Patients were classified as having liver (14 patients) or lung (27 patients) relapse according to the organ firstly metastasized. The variables significantly associated by univariate Cox analysis to survival were the achievement of an R0 metastases resection and the Köhne risk index, while the metastatic site showed a statistical trend. By multivariate Cox analysis, the only variable associated with survival was a R0 resection (HR = 16.3, p < 0.001). Median OS for patients undergoing a R0 resection was 73 months (95 % CI 67.8-78.2) compared to 25 months (95 % CI 5.47-44.5) in those non-operated patients (p < 0.001). CONCLUSIONS: Combined treatment for LARC obtains a 5-year OS rounding 90 %. Follow-up based on thoracic-abdominal CT scan allows an early diagnosis of metastatic lesions. Surgical resection of metastases, regardless of their location, greatly increases the patient's survival rate.

Impact of perineural and lymphovascular invasion on oncological outcomes in rectal cancer treated with neoadjuvant chemoradiotherapy and surgery.

BACKGROUND: The prognostic significance of perineural and/or lymphovascular invasion (PLVI) and its relationship with tumor regression grade (TRG) in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (CRT) and surgery. METHODS: A total of 324 patients with LARC were treated with CRT and operated on between January 1992 and June 2007. Tumors were graded using a quantitative 5-grade TRG classification and the presence of PLVI was histologically studied. RESULTS: At a median follow-up of 79.0 months (range 3-250 months), a total of 80 patients (24.7%) relapsed. The observed 5- and 10-year overall survival (OS) was 83.2 and 74.9 %, respectively. The 5- and 10-year disease-free survival (DFS) was 75.1 and 71.4%, respectively. A significant correlation was found between the TRG and survival (log rank, p < 0.001). The 10-year OS was 32.7% for grade 1, 63.8% for grade 2, 75.0% for grade 3, 90.4% for grade 3+, and 96.0%,for grade 4. The 10-year DFS was 31.8% for grade 1, 58.6% for grade 2, 70.4% for grade 3, 88.4% for grade 3+, and 97.1% for grade 4. In patients with PLVI, the TRG had no impact on survival. When excluding patients with PLVI, the TRG was an independent prognostic factor for OS and DFS. CONCLUSIONS: The presence of PLVI is a more powerful prognostic factor than TRG in LARC patients treated with neoadjuvant CRT followed by surgery. PLVI denotes an aggressive phenotype, suggesting that these patients may benefit from adjuvant systemic therapy.

Is the cleft lift procedure for non-acute sacrococcygeal pilonidal disease a definitive treatment? Long-term outcomes in 74 patients.

PURPOSE: No definitive surgical treatment for non-acute pilonidal disease has been established thus far. We herein report the short-term and long-term outcomes of 74 consecutive patients who underwent the cleft lift procedure for non-acute pilonidal disease. METHODS: A total of 74 consecutive patients who underwent the cleft lift procedure for the treatment of non-acute pilonidal disease were evaluated. RESULTS: Complete healing was achieved in 54 patients (73%). Wound seroma was observed in 12 patients (15%) in the first week, and this persisted until the second week in 10 patients (13%). Partial dehiscence was found in eight patients (11%). One patient presented with complete wound dehiscence (1%), and another experienced early postoperative bleeding (1%). Wound infection was observed in one patient (1%). The median follow-up period was 51.5 months (range 15-88 months). Three cases of recurrences were observed, which occurred after 51, 42 and 12 months of follow-up. CONCLUSIONS: If longer-term follow-up is achieved, definitive conclusions may be obtained. However, the present results suggest that the cleft lift procedure may become the gold standard technique for the surgical management of non-acute pilonidal disease.

Terapia celular en los errores congénitos del metabolismo / Cell therapy in inborn errors of metabolism

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Preliminary outcome of a treatment strategy based on perioperative chemotherapy and surgery in patients with locally advanced colon cancer.

AIM: Preoperative chemotherapy followed by radical surgery is an attractive treatment for locally advanced colon cancer (LACC) given the promising results of this approach in other locally advanced tumours. The study evaluates the outcome and treatment-related complications of perioperative oxaliplatin- and capecitabine-based chemotherapy and surgery for clinical Stage III colon cancer. METHOD: Twenty-two consecutive patients with a CT-staged LACC were included. All were staged at baseline and before surgery. Surgery-related complications and oncological outcome were determined. RESULTS: Toxicity was manageable, with 19/22 patients completing the planned chemotherapy protocol. The median time from initial diagnosis to surgery was 65.5 days. The median time from the end of chemotherapy to surgery was 22 days. After neoadjuvant treatment, tumour reduction of 69.5% was observed by CT scan and a 59.9% decrease of SUVmax (standard uptake value) was achieved on positron emission tomography/CT. No progressive disease was reported during preoperative chemotherapy and surgery was performed in all 22 patients. Four patients developed postoperative complications. After a median postoperative follow-up of 14.4 months, the actuarial overall and disease-free survival rates were 100 and 90%. CONCLUSION: Neoadjuvant chemotherapy followed by surgery and chemotherapy for LACC is safe without apparent increase of early and medium-term complications.

Peutz-Jeghers syndrome and duodeno-jejunal adenocarcinoma – therapeutic implications

The Peutz-Jeghers syndrome (PJS) is an autosomal dominant hamartomatous poliposis describred in 1921. Hemminki in 1997 described the presence of LKB-1 mutation tumor-suppressor gen. The patients with PJS develop a higher cumulative incidence of gastrointestinal, pancreas and extraintestinal tumors, being occasion of a renew interest on hamartomatous polyposis syndromes regarding the clinical care, cancer surveillance treatment and long term follow-up. We report the case of a 38 years old male, diagnosed of PJS who developed a multiple adenocarcinoma in duodenum and yeyunum. Surgically treated and with a long-term free disease survival of 11 years represents the sixth case reported in the spanish literature of PJS associated with a gastrointestinal tumor. A critical review, molecular alterations and the established criteria of tumor screening and surveillance are reviewed(AU)

[Cutaneous granular cell tumor: a clinical and pathologic analysis of 34 cases]. / Tumor de células granulares cutáneo: análisis clínico-patológico de treinta y cuatro casos.

BACKGROUND: Granular cell tumor (GCT), also known as Abrikossoff tumor, is an uncommon benign neoplasm, probably of neural origin derived from Schwann cells. It presents clinically as a solitary asymptomatic nodule and its pathogenesis has been the subject of much debate in the literature. OBJECTIVES: We aimed to analyze the clinical, histologic, and immunohistochemical characteristics associated with this tumor and to determine whether these findings correspond to those reported to date in the literature. METHODS: In this retrospective study of 34 patients with histologic diagnosis of GCT, we analyzed clinical characteristics (site, age, sex, duration, and suspected diagnosis), histological findings (border, cell atypia and mitoses, involvement of adnexal structures, pseudoepitheliomatous hyperplasia, and presence of the recently described pustulo-ovoid bodies), and immunohistochemical findings (S-100 staining in 16 randomly selected cases). RESULTS: In total, 58.82 % were men and 41.18 % were women, and the mean age was 31.74 years. The most common site was the oral cavity (61.76 %). The most frequently suspected clinical diagnosis was fibroma (17.65 %). The lesion was poorly defined and diffuse in 85.29 %. Pseudoepitheliomatous hyperplasia was present in 58.82 %. Nuclear atypia was found in 29.41 % and mitoses in 20.59 %. One case was considered malignant (2.94 %) and 2 atypical (5.88 %). Pustulo-ovoid bodies were present in 47.06 % of the cases and S-100 staining was positive in all cases analyzed. CONCLUSIONS: Our series confirms the characteristics described previously for GCT, except for certain peculiarities, and supports the presence of pustulo-ovoid bodies as an additional histologic finding for diagnosis of this tumor.

Peutz-Jeghers syndrome and duodeno-jejunal adenocarcinoma--therapeutic implications.

The Peutz-Jeghers syndrome (PJS) is an autosomal dominant hamartomatous poliposis describred in 1921. Hemminki in 1997 described the presence of LKB-1 mutation tumor-suppressor gen.The patients with PJS develop a higher cumulative incidence of gastrointestinal, pancreas and extraintestinal tumors, being occasion of a renew interest on hamartomatous polyposis syndromes regarding the clinical care, cancer surveillance treatment and long term follow-up.We report the case of a 38 years old male, diagnosed of PJS who developed a multiple adenocarcinoma in duodenum and yeyunum. Surgically treated and with a long-term free disease survival of 11 years represents the sixth case reported in the spanish literature of PJS associated with a gastrointestinal tumor.A critical review, molecular alterations and the established criteria of tumor screening and surveillance are reviewed.

Analysis of POSSUM score and postoperative morbidity in patients with rectal cancer undergoing surgery.

BACKGROUND: The Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) and later modifications (P-POSSUM y CR-POSSUM) have been used to predict morbidity and mortality rates among patients with rectal cancer undergoing surgery. These calculations need some adjustment, however. The aim of this study was to assess the applicability of POSSUM to a group of patients with rectal cancer undergoing surgery, analysing surgical morbidity by means of several variables. METHODS: between January 1995 and December 2004, 273 consecutive patients underwent surgery for rectal cancer. Information was gathered about the patients, tumour and therapy. To assess the prediction capacity of POSSUM, subgroups for analysis were created according to variables related to operative morbidity and mortality. RESULTS: The global morbidity rate was 23.6% (31.2% predicted by POSSUM). The mortality rate was 0.7% (6.64, 1.95 and 2.08 predicted by POSSUM, P-POSSUM and CR-POSSUM respectively). POSSUM predictions may be more accurate for patients younger than 51 years, older than 70 years, with low anaesthetic risk (ASA I/II), DUKES stage C and D, surgery duration of less than 180 minutes and for those receiving neoadjuvant therapy. CONCLUSION: POSSUM is a good instrument to make results between different institutions and publication comparable. We found prediction errors for some variables related to morbidity. Modifications of surgical variables and specifications for neoadjuvant therapy as well as physiological variables including life style may improve future prediction of surgical risk. More research is needed to identify further potential risk factors for surgical complications.