Is there an optimal neoadjuvant therapy for locally advanced pancreatic cancer?

Treatment of locally advanced pancreatic cancer is challenging. Despite continuing research, effective treatments continue to be elusive with median survival of only 8-12 months. Treatment options for locally advanced pancreatic cancer include radiation therapy, concurrent chemoradiation or chemotherapy. It is felt that radiation therapy is a suboptimal treatment as most of patients will die of systemic disease. In the past, radiation with 5-FU was the standard treatment for locally advanced pancreatic cancer. But now radiation has been used with combination other chemo agents such as paclitaxel or gemcitabine in order to increase the efficacy. Chemotherapy such as gemcitabine alone or gemcitabine doublet also has been studied in patients with locally advanced pancreatic cancer as well with overall survival being approximately the same magnitude as chemoradiation. The exact role of chemoradiation or chemotherapy in treatment of locally advanced pancreatic cancer is yet to be defined. Hence, this review summarizes and compares of role of radiation, chemoradiation and chemotherapy in treating this disease.     

Is adjuvant chemotherapy necessary for patients with pathological complete response after neoadjuvant chemoradiotherapy and radical surgery in locally advanced rectal cancer? Long-term analysis of 40 ypCR patients at a single center

Objectives

According to practice guidelines, adjuvant chemotherapy (ACT) is required for all patients with locally advanced rectal cancer who have received neoadjuvant chemoradiotherapy (NCRT) and total mesorectal excision (TME). The objective of this study was to determine whether ACT is necessary for patients achieving pathological complete response (pCR) after NCRT followed by surgery.

Methods

By retrospectively reviewing a prospectively collected database in our single tertiary care center, 210 patients with locally advanced rectal cancer who underwent NCRT followed by TME were identified between February 2005 and August 2013. All patients achieving ypCR were enrolled in this study, in which who underwent ACT (chemo group) and who did not (non-chemo group) were compared in terms of local recurrence (LR) rate, 5-year disease-free survival (DFS) rate and overall survival (OS) rate.

Results

Forty consecutive patients with ypCR were enrolled, 19 (47.5 %) in chemo group and 21 (52.5 %) in non-chemo group. After a median follow-up of 57 months, five patients developed systemic recurrences, with the 5y-DFS rate of 83.5 %. No LR occurred in the two groups. The 5y-DFS rates for patients in chemo group and non-chemo group was 90.9 and 76.0 %, respectively, showing no statistically significant difference (p?=?0.142). Multivariate analysis showed that tumor grade was the only independent prognostic factor for 5y-DFS and 5y-OS.

Conclusions

Results of this study suggested that it may not be necessary for all rectal cancer patients with ypCR after NCRT and radical surgery to receive ACT. Prospective randomized trials are warranted to further determine the value of ACT for ypCR patients.

     

Zolpidem improves patients’ sleep quality after surgical treatment for infective endocarditis: a prospective observational study

Sleep and Breathing - The objective of this study was to investigate the efficacy of zolpidem for improving post-operative sleep quality among patients with infective endocarditis (IE) and to...     

The effect of smoking after surgery for Crohn’s disease: a meta-analysis of observational studies

Objective  The aim of the study was to quantify the risk of disease recurrence associated with cigarette smoking for individuals with Crohn’s disease after disease-modifying surgery. Design  Meta-analysis of observational studies. Data sources  Medline, Embase, Ovid and the Cochrane database. Materials and methods  A literature search was performed to identify studies published between 1966 and 2007 comparing outcomes of smokers, ex-smokers and non-smokers with Crohn’s disease. Random-effect meta-analytical techniques were employed to assess the risk of medical or surgical recurrence. Results  Sixteen studies encompassing 2,962 patients including 1,425 non-smokers (48.1%), 1,393 smokers (47.0%) and 137 ex-smokers (4.6%) were included. Smokers had significantly higher clinical post-operative recurrence than non-smokers (odds ratio [OR] = 2.15; 95%CI = 1.42, 3.27; p < 0.001). Smokers were also more likely to experience surgical recurrence by 5 (OR = 1.06; 95%CI = 0.32; 3.53, p = 0.04) and 10 years of follow-up (OR = 2.56; 95%CI = 1.79, 3.67; p < 0.001) compared to non-smokers, although the crude re-operation rate was not statistically significant. When matched for operation and disease site, smokers had significantly higher re-operation rates to non-smokers (OR = 2.3; 95%CI = 1.29, 4.08; p = 0.005). There was no significant difference between ex-smokers and non-smokers in re-operation rate at 10 years (OR = 0.30; 95%CI = 0.09, 1.07; p = 0.10) or in post-operative acute relapses (OR = 1.54; 95%CI = 0.78, 3.02; p = 0.21). Conclusions  Patients with Crohn’s disease who smoke have a 2.5-fold increased risk of surgical recurrence and a twofold risk of clinical recurrence compared to non-smokers. Patients with Crohn’s disease should be encouraged to stop smoking since the risk of disease relapse is minimised upon its cessation. George E. Reese and Theodore Nanidis with equal contribution.     

Chemotherapy as initial treatment of locally advanced unresectable pancreatic cancer: a valid option?

INTRODUCTION: Radio-chemotherapy is the standard treatment for locally advanced unresectable pancreatic cancer (LAPC). Chemotherapy has been shown to be effective in the treatment of metastatic disease and we therefore evaluated its use as a first-line treatment for LAPC. PATIENTS AND METHODS: We carried out a retrospective analysis of all consecutive patients treated for LAPC (N=33) between July 1997 and April 2005, analysing the results of first-line chemotherapy (CT group) and radio-chemotherapy (RCT group) in this setting. RESULTS: The first-line treatment was RCT in six patients (18.3%) and CT in 26 patients (78.8%). Secondary treatment was administered to nine patients of CT group with well-controlled disease: "closure" radio-chemotherapy for seven patients (26.9%) and secondary resection for three (12%). After a median follow-up of 27 months, 23 patients died (69.7%). Overall survival was 13.8 months [95% CI: 10.1-19.4] for the whole population, 9.5 months [95% CI: 4.6-] for the RCT and 18.0 months [95% CI: 12.4-25.5] for the CT. Overall survival for the CT patients undergoing secondary surgery or "consolidation" radio-chemotherapy was 28.8 months [95% CI: 13.8-]. CONCLUSION: First-line chemotherapy is a valid option for LAPC treatment, making it possible to identify the patients who may benefit from secondary resection or radio-chemotherapy.     

Stenting for colorectal cancer obstruction compared to surgery—a study of consecutive patients in a single institution

Background  

Colonic obstruction is a common complication to colorectal cancer and surgical treatment is associated with high morbidity and mortality. Stenting has emerged as an alternative to surgery. The aim of this study was to compare short-term morbidity, mortality and hospital stay between treatment with self-expandable metallic stent and emergency surgery performed at our department during a 5-year period in a non-randomized setting.     

Conventional treatment regimens for ulcerative colitis alleviate fatigue – an observational cohort study

Objective: The aim of the study was to investigate the course of fatigue in a conventional inflammatory bowel disease treatment setting.

Materials and methods: Eighty-two patients with newly diagnosed ulcerative colitis were included in an observational cohort study and received conventional non-biological drug treatment for 3 months. Colonoscopy was performed at diagnosis and after 3 months, disease activity was assessed by Mayo score and measurements of serum C-reactive protein (CRP) and fecal calprotectin levels. Fatigue was evaluated using the fatigue visual analog scale (fVAS). Mood was assessed with the hospital anxiety and depression scale (HADS). Associations between fVAS scores and time; age; CRP, fecal calprotectin, hemoglobin, and ferritin levels; and Mayo scores, Mayo endoscopic scores, and HADS depression subscale (HADS-D) scores were explored.

Results: Median fVAS scores decreased, as did Mayo scores and CRP and fecal calprotectin concentrations. HADS-D scores remained unchanged, whereas hemoglobin levels increased after 3 months. Increased fVAS scores were associated with higher ferritin, Mayo and HADS-D scores. There were no associations between fVAS scores and CRP, fecal calprotectin, or Mayo endoscopic scores. Colonic disease distribution did not influence fatigue significantly.

Conclusions: Disease activity and fatigue improved after 3 months of conventional ulcerative colitis treatment. Over time, more severe fatigue was associated with more ulcerative colitis symptoms, but not with objective disease activity markers or colonic disease distribution. A clinical setting of standard treatment regimens and medical attention may alleviate fatigue in IBD patients.     

No prognostic impact of isolated lymphovascular invasion after radical resection of rectal cancer—results of a multicenter observational study

Background The prognostic impact of isolated lymphovascular invasion (LVI) after radical resection of rectal cancer is controversially discussed. However, it could be relevant to decide for an adjuvant treatment. Aim The aim of the analysis was, based on the data of an observational study, to determine the prognostic relevance of the isolated LVI. Materials and methods Patients after radical resection of rectal cancer with no hemangioinvasion were subdivided in three groups: I—no LVI, no lymph node metastases (LNM); II—positive LVI, no LNM; III—positive LNM. Five-year local recurrence rate, distant metastases-free and disease-free survival were determined uni- and multivariate. Results Patients, n = 846, were studied (I, n = 471; II, n = 75; III, n = 300). The univariate comparison between the groups revealed the following 5-year results: local recurrence rate: 9.4 vs 10.0 vs 14.0%; distant metastases-free survival: 84.1 vs 82.5 vs 49.3%; disease-free survival: 83.2 vs 80.7 vs 45.5%. The differences between groups I and III were significant, but not between groups I and II. The determined higher disease-free survival rate in group II vs group III was significant (P = 0.041), but the differences in local recurrence rate and rate of distant metastases did not reach statistical significance. The multivariate analysis revealed no impact of the isolated LVI on the oncological outcome. Conclusion The isolated LVI has no independent prognostic impact on the local recurrence rate and long-term survival after radical resection of rectal cancer. Based on this finding, no indication for an adjuvant treatment in these patients can be derived.     

Can Hemoccult-IIℳ replace colonoscopy in surveillance after radical surgery for colorectal cancer and after polypectomy?

Surveillance after colorectal carcinoma and adenoma includes colonoscopy, which is a demanding procedure for the patient, doctor, and society. Therefore, it was investigated whether a simple fecal occult blood test could replace colonoscopy. Hemoccult-II (H-II) was performed before 1,244 colonoscopies in patients with previous cancer and before 328 colonoscopies in an adenoma surveillance program. The H-II test was positive in 3 of 9 patients with local recurrence, in 2 of 13 with metachronous cancer, and in 31 of 186 with adenomas. The test was positive more often in patients with large and multiple adenomas, sigmoid adenomas, and adenomas with villous elements and moderate-to-severe dysplasia, but the sensitivity did not reach more than 25 to 40 percent. It was concluded that markers more sensitive than H-II are needed to detect metachronous cancers and new adenomas. In the meantime, colonoscopy has to be used with intervals of several years, but not for detection of local recurrent cancer, which in most cases may be found by simpler means.Supported by grants from the Danish Cancer Society.     

Surgical treatment for gallbladder cancer – a systematic literature review

Objective: To evaluate existing evidence regarding surgical treatments for gallbladder cancer in a Health Technology Assessment. A specific aim was to evaluate whether extended surgery regarding liver, lymph nodes, bile duct, and adjacent organs compared with cholecystectomy alone in the adult patient with gallbladder cancer in early and late stages implies improved survival.

Methods: In April 2015 and updated in June 2016, a systematic literature search was conducted in PubMed, Embase, and the Cochrane Library. Two authors independently screened titles, abstracts, and full-text articles. The certainty of evidence was evaluated according to GRADE.

Main results: Forty-four observational studies (non-randomised, controlled studies) and seven case series were included. Radical resection, including liver and lymph node resection, compared with cholecystectomy alone showed significantly better survival for patients with stages T1b and above. All studies had serious study limitations and the certainty of evidence was very low (GRADE ⊕○○○). A survival benefit seen in patients with stage T1b or higher with lymph node resection, was most evident in stage T2, but the certainty of evidence was low (GRADE ⊕⊕○○). It is uncertain whether routine bile duct resections improve overall survival in patients with gallbladder cancer stage T2–T4 (GRADE ⊕○○○).

Conclusion: Data indicate that prognosis can be improved if liver resection and lymph node resection is performed in patients with tumour stage T1b or higher. There is no evidence supporting resection of the bile duct or adjacent organs if it is not necessary in order to achieve radicality.     

Neoadjuvant treatment for resectable pancreatic cancer: Time for phase Ⅲ testing?

This paper discusses the rationale for phaseⅢtesting of neoadjuvant therapy in patients affected by resectable pancreatic adenocarcinoma.The therapeutic management of patients affected by resectable pancreatic cancer is particularly troublesome due to the aggressiveness of the disease and to the limited efficacy and sometimes unfavourable risk-benefit ratio of the available therapeutic tools.Conflicting data on the role of adjuvant chemoradiation have been reported,while adjuvant single-agent chemotherapy significantly improved overall survival(OS)when compared to surgery alone. However,the OS figures for adjuvant chemotherapy remain disappointing.In effect,pancreatic cancer exhibits a prominent tendency to recur after a brief median time interval from surgery and extra-pancreatic dissemination represents the predominant pattern of disease failure.Neoadjuvant treatment has a strong rationale in this disease but limited information on the efficacy of this approach is available from single arm trials with low levels of evidence.Thus,in spite of two decades of investigation there is currently no evidence to support the routine use of pre-surgical therapy in clinical practice. To foster knowledge on the optimal management of this disease,and to produce evidence-based treatment guidelines,there is no alternative to well designed randomized trials.Systemic chemotherapy is a candidate for testing because it is supported by a more robust rationale than chemoradiation.Combination chemotherapy regimens with elevated activity in advanced disease warrant investigation.Caution would suggest the running of an exploratory phaseⅡrandomized trial before embarking on a large phase Ⅲ study.     

Robotic versus laparoscopic surgery for mid–low rectal cancer after neoadjuvant chemoradiation therapy: comparison of oncologic outcomes

Purpose

Minimal invasive surgery for mid and low rectal cancer after neoadjuvant long-course chemoradiotherapy (LCRT) can be challenging. The aim of our study was to compare outcomes of laparoscopic and robotic resections in mid and low rectal cancers after LCRT.

Methods

Between Jan 2006 and Dec 2010, all patients who underwent robotic or laparoscopic resections for mid and low rectal cancers after LCRT were identified from a prospective database. These patients received treatment (5FU-based chemotherapy, 50.4 Gy radiotherapy), as they were T3 or T4 and/or node?+?ve. Patients in the two groups were compared with respect to demographics, clinical safety, and oncological outcomes.

Results

One hundred thirty-eight patients underwent rectal cancer resection after LCRT, either robotic (n?=?74) or laparoscopic (n?=?64). The patients in both groups were comparable in terms of demographics, distance of tumor from anal verge, and type of procedures. There were four (6.3 %) conversions in laparoscopic group and one (1.4 %) in the robotic group (p?=?0.183). The morbidity rates in the laparoscopic and robotic group were 26.6 % and 16.2 %, respectively (p?=?0.137). With a median follow up of 3 years, the local recurrence in the laparoscopic and robotic group was four (6.3 %) and two (2.7 %), respectively (p?=?0.420). The 3-year overall survival rate for laparoscopic and robotic group was 92.1 and 90.0 %, respectively (p?=?0.803). The 3-year disease-free survival was also comparable, 78.8 % (laparoscopic) versus 77.7 % (robotic) (p?=?0.390).

Conclusion

With a median follow up of 3 years, robotic surgery for mid and low rectal cancer was associated with oncological outcomes comparable to laparoscopic surgery.     

The burning question: Why is smoking a risk factor for pancreatic cancer?

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease. The prognosis is poor; less than 5% of those diagnosed are still alive five years after diagnosis, and complete remission is still rare. Tobacco smoking is a major risk factor of pancreatic cancer. However, the mechanism(s) through which it causes the disease remains unknown. Accumulating evidence indicates that carcinogenic compounds in cigarette smoke stimulate pancreatic cancer progression through induction of inflammation and fibrosis which act in concert with genetic factors leading to the inhibition of cell death and stimulation of proliferation resulting in the promotion of the PDAC.     

Intensity modulated radiation therapy and chemotherapy for locally advanced pancreatic cancer： Results of feasibility study

AIM: To explore whether intensity modulated radiation therapy (IMRT) in combination with chemotherapy could increase radiation dose to gross tumor volume without severe acute radiation related toxicity by decreasing the dose to the surrounding normal tissue in patients with locally advanced pancreatic cancer. METHODS: Twenty-one patients with locally advanced pancreatic cancer were evaluated in this clinical trial. Patients would receive the dose of IMRT from 21Gy to 30Gy in 7 to 10 fractions within two weeks after conventional radiotherapy of 30Gy in 15 fractions over 3 weeks. The total escalation tumor dose would be 51, 54, 57, 60Gy, respectively. 5-fluororacil (5-FU) or gemcitabine was given concurrently with radiotherapy during the treatment course. RESULTS: Sixteen patients who had completed the radiotherapy plan with doses of 51Gy (3 cases), 54Gy (3 cases), 57Gy (3 cases) and 60Gy (7 cases) were included for evaluation. The median levels of CA19-9 prior to and after radiotherapy were 716 U/ml and 255 U/ml respectively (P<0.001) in 13 patients who demonstrated high levels of CA19-9 before radiotherapy. Fourteen patients who suffered from pain could reduce at least 1/3-1/2 amount of analgesic intake and 5 among these patients got complete relief of pain. Ten patients improved in Karnofsky performance status (KPS). The median follow-up period was 8 months and one-year survival rate was 35%. No patient suffered more than grade III acute toxicities induced by radiotherapy. CONCLUSION: Sixty Gy in 25 fractions over 5 weeks with late course IMRT technique combined with concurrent 5-FU chemotherapy can provide a definitely palliative benefit with tolerable acute radiation related toxicity for patients with advanced pancreatic cancer.     

Complete pathological response after FOLFIRINOX for locally advanced pancreatic cancer. The beginning of a new era? Case report and review of the literature

Neoadjuvant treatments (chemo or chemoradiation therapy) are used for patients with locally advanced Pancreatic Ductal Adeno-Carcinoma (PDAC). FOLFIRINOX is now considered an effective treatment modality for patients with metastatic pancreatic cancer and a promising option for patients with locally advanced PDAC. Complete pathologic response after neoadjuvant therapies is anecdotic and its prognostic impact is completely unclear. We report the case of a complete pathological response after treatment with FOLFIRINOX in a patient affected by a locally advanced PDAC with a review of the literature regarding the use of FOLFIRINOX for locally advanced PDAC.