Leif Schiffmann

Tumour regression and mesorectal lymph node changes after intensified neoadjuvant chemoradiation for carcinoma of the rectum

Neoadjuvant radiation or chemoradiation is currently the treatment of choice for patients with locally advanced carcinoma of the rectum. To assess the effects of chemoradiation on tumour regression and on uninvolved mesorectal lymph nodes, a consecutive series of 76 patients receiving neoadjuvant chemoradiation and a stage‐adapted control series of 57 patients without pretreatment were studied. Densities of cells positive for CD4 (T‐helper cells), CD8 (cytotoxic T‐cells), CD83 (mature dendritic cells), and CD57 (natural killer cells) were determined on immunostains. Tumour regression was graded, and presence or absence of extramural tumour was recorded. The densities of CD4+ T‐lymphocytes and CD83+ dendritic cells in the paracortex of mesorectal lymph nodes were observed to be significantly reduced, as were the densities of CD57+ cells in the follicles; densities of CD8+ T‐lymphocytes did not differ. Strong, moderate and poor tumour regression was observed in 29, 25, and 22 cases, respectively. For 12 patients, absence of extramural vital or regressing tumour was recorded, indicating pretherapeutic overstaging. The results bring to mind that neoadjuvant chemoradiation as a side effect may have a negative impact on anti‐tumour immunity. Together with the drawback of overstaging the results argue for a careful selection of patients.

Endoscopic vacuum therapy for various defects of the upper gastrointestinal tract

BackgroundPostoperative, iatrogenic or spontaneous upper gastrointestinal defects result in significant morbidity and mortality of the patients. In the last few years, endoscopic vacuum therapy (EVT) has been recognized as a new promising method for repairing upper gastrointestinal defects of different etiology. However, probably due to insufficient data and no commercially available system for EVT of the upper gastrointestinal tract, until the end of 2014, covering of esophageal defects with self-expanding metal stents (SEMS) were still the mainstay of endoscopic therapy. The aim of this article is to review the data available about EVT for various upper gastrointestinal defects.MethodsA selective literature search was conducted in Medline and PubMed (2007–2016), taking into account all the published case series and case reports reporting on the use of EVT in the management of upper gastrointestinal defects.ResultsEVT works through intracorporal application of negative pressure at the defect zone with an electronic controlled vacuum device along a polyurethane sponge drainage. This results in closure of the esophageal defect and internal drainage of the septic focus, simultaneously. Compared to stenting, EVT enables regular viewing of wound conditions with control of the septic focus and adjustment of therapy. Moreover, endoscopical negative pressure is applicable in all esophageal regions (cricopharygeal, tubular, gastroesophageal junction) and in anastomotic anatomic variants. EVT can be used solely as a definite treatment or as a complimentary therapy combined with operative revision. In total, there are published data of more than 200 patients with upper gastrointestinal defects treated with EVT, showing succes rates from 70–100%.ConclusionThe available data indicate that EVT is feasible, safe and effective with good short-term and long-term clinical outcomes in the damage control of upper GI-tract leaks. Still, a prospective multi-center study has to be conducted to proof the definite benefit of EVT for patients with esophageal defects.

Intensified neoadjuvant radiochemotherapy for rectal cancer enhances surgical complications

BackgroundNeoadjuvant radiochemotherapy has proven superior to adjuvant treatment in reducing the rate of local recurrence without impairing cancer related survival or the incidence of distant metastases. The present study aimed at addressing the effects of an intensified protocol of neoadjuvant treatment on the development of postoperative complications.MethodsA total of 387 patients underwent oncological resection for rectal cancer in our institution between January 2000 and December 2009. 106 patients received an intensified radiochemotherapy. Perioperative morbidity and mortality were analyzed retrospectively with special attention on complication rates after intensified radio-chemotherapy. Therefore, for each patient subjected to neoadjuvant treatment a patient without neoadjuvant treatment was matched in the following order for tumor height, discontinuous resection/exstirpation, T-category of the TNM-system, dividing stoma and UICC stage.ResultsOf all patients operated for rectal cancer, 27.4% received an intensified neoadjuvant treatment. Tumor location in the matched patients were in the lower third (55.2%), middle third (41.0%) and upper third (3.8%) of the rectum. Postoperatively, surgical morbidity was higher after intensified neoadjuvant treatment. In the subgroup with low anterior resection (LAR) the anastomosis leakage rate was higher (26.6% vs. 9.7%) and in the subgroup of patients with rectal exstirpations the perineal wound infection rate was increased (42.2% vs. 18.8%) after intensified radiochemotherapy.ConclusionsIn rectal cancer the decision for an intensified neoadjuvant treatment comes along with an increase of anastomotic leakage and perineal wound infection. Quality of life is often reduced considerably and has to be balanced against the potential benefit of intensifying neoadjuvant radiochemotherapy.

Aggressive colorectal carcinoma phenotypes of invasion can be assessed reproducibly and effectively predict poor survival: interobserver study and multivariate survival analysis of a prospectively collected series of 299 patients after potentially curative resections with long‐term follow‐up

Wöhlke M, Schiffmann L & Prall F 
(2011) Histopathology59, 857–866

Is the lymph node ratio superior to the Union for International Cancer Control (UICC) TNM system in prognosis of colon cancer

BackgroundDecision making for adjuvant chemotherapy in stage III colon cancer is based on the TNM system. It is well known that prognosis worsens with higher pN classification, and several recent studies propose superiority of the lymph node ratio (ln ratio) to the TNM system. Therefore, we compared the prognosis of ln ratio to TNM system in our stage III colon cancer patients.MethodsA total of 939 patients underwent radical surgery for colorectal cancer between January 2000 and December 2009. From this pool of patients, 142 colon cancer stage III patients were identified and taken for this analysis. Using martingale residuals, this cohort could be separated into a group with a low ln ratio and one with a high ln ratio. These groups were compared to pN1 and pN2 of the TNM system.ResultsFor ln ratio, the cutoff was calculated at 0.2. There was a good prognosis of disease-free and cancer-related survival for the N-category of the TNM system as well as for the lymph node ratio. There was no statistical difference between using the N-category of the TNM system and the ln ratio.ConclusionsThere might not be a benefit in using the lymph node ratio rather than the N category of the TNM system as long as the number of subgroups is not increased. In our consideration, there is no need to change the N categorization of the TNM system to the ln ratio.

A novel sialyl Le X expression score as a potential prognostic tool in colorectal cancer

BackgroundTreatment decisions in colorectal cancer subsequent to surgery are based mainly on the TNM system. There is a need to establish novel prognostic markers based on the molecular characterization of tumor cells. Evidence exists that sialyl LeX expression is correlated with an unfavorable outcome in colorectal cancer. The aim of this study was to establish a simple sialyl LeX staining score and to determine a potential correlation with the prognosis in a series of advanced colorectal carcinoma patients.MethodsIn order to implement routine use of sialyl LeX immunohistology, we established a new, easily reproducible score and defined a cutoff which discriminated groups with better or worse outcome, respectively. We then correlated sialyl LeX expression of 215 UICC stage III and IV patients with disease-free and cancer-related survival.ResultsA five-stage score could be established based on automated immunohistochemical stainings. Using a statistical model, we calculated a cutoff to discriminate between weak and strong staining positivity of sialyl LeX. Patients with strong positive specimens had a worse cancer-related survival (P = 0.004) but no difference was observed for disease-free survival (P = 0.352).ConclusionsThese results demonstrate a strong correlation between high sialyl LeX-expression in colorectal carcinomas and cancer-related survival. Our highly standardized and easy-to-use staining score is suitable for routine use and hence it could be recommended to evaluate sialyl LeX-expression as part of the standard histopathological analysis of colorectal carcinomas and to validate the score prospectively based on a larger population.

Tumor regression in rectal cancer after intensified neoadjuvant chemoradiation: a morphometric and clinicopathological study

BackgroundHigh interobserver variation is a well known drawback of conventional tumor regression grading, and reaching consensus among pathologists may require a considerable effort. Therefore, in this study, morphometry was tried to assess tumor regression, and its prognostic role was explored.MethodsTumor regression was quantified by a point counting method to yield tumor area fraction (TAF) as an index of remaining vital tumor.ResultsIn a series of 104 patients with clinically advanced rectal cancer treated with neoadjuvant radiochemotherapy, TAFs were distributed continuously towards complete regression which was observed in 8.7% of the cases. Plotting TAFs grouped by a conventional regression grading (Dworak’s) revealed considerable overlap between groups. In a control series of untreated cancers, only TAFs of cancers with an expansive invasive border were setoff clearly from TAFs obtained for the study cases, but TAFs of control cases with an infiltrative invasive border and mucinous carcinomas extended well into the range of TAFs recorded for regressing tumors. Locoregional recurrence (N = 10) was significantly associated with perineural tumor infiltration and capsule transgressing lymph node metastasis/tumor deposits but not with the degree of tumor regression. Overall survival was better for patients with major regressions (≤20th percentile by morphometry, or Dworak regression grade (DRG) 4/5), although statistical significance was not reached.ConclusionsMorphometry of tumor regression is feasible and explains why conventional regression grading is so difficult to perform. Assessment of tumor regression, by subjective grading or morphometry, does not appear to convey major prognostic information, at least not substantially beyond histopathological tumor staging. This observation discourages expending too much effort on developing this aspect of the pathomorphological workup of the resection specimens.

PEG closure in the second attempt

Background and study aims: This case report demonstrates successful endoscopic treatment of a persistent gastrocutaneous fistula after removal of a percutaneous endoscopic gastrostomy (PEG) in a 21-year-old patient with mucoviscidosis after lung transplantation. Because the initial OTSC clip (gastric) did not close the fistula sufficiently, we had to remove it and replace it with a larger OTSC clip (colon) in a second intervention. That clip finally sufficiently closed the fistula.

478 Surgical Endoscopic Vacuum Therapy for Defects of the Upper GI Tract

S A T A b st ra ct s of esophagogastric junction (EGJ) relaxation. Indeed, the diagnosis of achalasia is established by HRM on the basis of an IRP>15mmHg and absence of normal peristalsis in the esophageal body. Our aim was to assess the effect of Heller myotomy on IRP in achalasia patients. Patients and Methods: We evaluated all consecutive patients who underwent laparoscopic Heller myotomy as first treatment from 2009-2014 and had a HRM evaluation before and after surgery. Patients who had already been treated for achalasia (with Heller myotomy, endoscopic treatment) were excluded from the study. The diagnosis of primary achalasia was established by esophageal manometry on the basis of accepted esophageal motility characteristics (i.e. absence of normal peristalsis in the esophageal body). Symptoms were collected and scored using a detailed questionnaire for dysphagia, regurgitation, and chest pain; barium swallow, endoscopy, HRM were performed, before and 6 months after surgical treatment. Treatment failure was defined as a postoperative symptom score >10th percentile of the preoperative score (i.e. > 10). Results: 139 consecutive achalasia patients (M:F= 72:67) represented the study population. All the patients had 100% simultaneous waves but 11 had a IRP<15 mmHg. According to the HRM classification, patients were classified as having: 58 (42.3%) type I, 63 (46%) type II and 16 (11.7%) type III. At a median follow-up of 24 months, the symptom score was significantly lower after surgery (median preoperative score 18 [IQR 11-20] vs median postoperative score 0 [IQR 0-3]; p<0.0001). The resting LES pressure (median preoperatively 27 [IQR 19-36] vs median postoperatively 11 [IQR 8-14]; p<0.001) and IRP (median preoperatively 27.4 [IQR 20.4-35] vs median postoperatively 7.1 [IQR: 4.4-9.8]; p<0.001). The surgical procedure was completed laparoscopically in all the patients. The failures of surgical treatment were 7 (5%). At univariate analysis IRP was correlated with the gender, LES basal and resting pressure, and the dysphagia score. Conclusion: This is the first study evaluating the role of IRP in achalasia and its modifications after surgery. An increased preoperative IRP directly correlated with dysphagia severity in achalasia patients. Heller myotomy was able to resolve this symptom by reducing the IRP to a value lower than 10 mmHg.