Oncological outcomes of standard versus prolonged time to surgery after neoadjuvant chemoradiotherapy for oesophageal cancer in the multicentre, randomised, controlled NeoRes II trial.

BACKGROUND: The optimal time to surgery (TTS) after neoadjuvant chemoradiotherapy (nCRT) for oesophageal cancer is unknown and has traditionally been 4-6 weeks in clinical practice. Observational studies have suggested better outcomes, especially in terms of histological response, after prolonged delay of up to 3 months after nCRT. The NeoRes II trial is the first randomised trial to compare standard to prolonged TTS after nCRT for oesophageal cancer. PATIENTS AND METHODS: Patients with resectable, locally advanced oesophageal cancer were randomly assigned to standard delay of surgery of 4-6 weeks or prolonged delay of 10-12 weeks after nCRT. The primary endpoint was complete histological response of the primary tumour in patients with adenocarcinoma (AC). Secondary endpoints included histological tumour response, resection margins, overall and progression-free survival in all patients and stratified by histologic type. RESULTS: Between February 2015 and March 2019, 249 patients from 10 participating centres in Sweden, Norway and Germany were randomised: 125 to standard and 124 to prolonged TTS. There was no significant difference in complete histological response between AC patients allocated to standard (21%) compared to prolonged (26%) TTS (P = 0.429). Tumour regression, resection margins and number of resected lymph nodes, total and metastatic, did not differ between the allocated interventions. The first quartile overall survival in patients allocated to standard TTS was 26.5 months compared to 14.2 months after prolonged TTS (P = 0.003) and the overall risk of death during follow-up was 35% higher after prolonged delay (hazard ratio 1.35, 95% confidence interval 0.94-1.95, P = 0.107). CONCLUSION: Prolonged TTS did not improve histological complete response or other pathological endpoints, while there was a strong trend towards worse survival, suggesting caution in routinely delaying surgery for >6 weeks after nCRT.

Neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the esophagus or gastroesophageal junction: long-term results of a randomized clinical trial.

NeoRes I is a randomized phase II trial comparing neoadjuvant chemoradiotherapy with neoadjuvant chemotherapy in the treatment of resectable cancer of the esophagus or gastroesophageal junction. Patients with biopsy-proven adenocarcinoma or squamous cell carcinoma, T1N1 or T2-3N0-1 and M0-M1a (AJCC 6th ed.), were randomized to receive three 3-weekly cycles of cisplatin 100 mg/m2 day 1 and fluorouracil 750 mg/m2/24 hours, days 1-5 with or without the addition of concurrent radiotherapy 40 Gy, 2 Gy/fraction, 5 days a week, followed by esophageal resection with two-field lymphadenectomy. Primary endpoint was complete histopathological response rate in the primary tumor. Survival and recurrence patterns were evaluated as secondary endpoints. Between 2006 and 2013, 181 patients were enrolled in Sweden and Norway. All three chemotherapy cycles were delivered to 73% of the patients allocated to chemoradiotherapy and to 86% of the patients allocated to chemotherapy. 87% of those allocated to chemoradiotherapy received full dose radiotherapy. 87% in the chemoradiotherapy group and 86% in the chemotherapy group underwent tumor resection. Initial results showed that patients allocated to chemoradiotherapy more often responded with complete histopathological response in the primary tumor (28% vs. 9%). Treatment-related complications were similar between the groups although postoperative complications were more severe in the chemoradiotherapy group. This article reports the long-term results. Five-year progression-free survival was 38.9% (95% CI 28.9%-48.8%) in the chemoradiotherapy group versus 33.0% (95% CI 23.6%-42.7%) in the chemotherapy group, P = 0.82. Five-year overall survival was 42.2% (95% CI 31.9%-52.1%) versus 39.6% (95% CI 29.5%-49.4%), P = 0.60. There were no differences in recurrence patterns between the treatment groups. This is to our knowledge that the largest completed randomized trial comparing neoadjuvant chemotherapy with neoadjuvant chemoradiotherapy followed by esophageal resection in patients with cancer in the esophagus or gastroesophageal junction. Despite a higher tumor tissue response in those who received neoadjuvant chemoradiotherapy, no survival advantages were seen. Consequently, the results do not support unselected addition of radiotherapy to neoadjuvant chemotherapy as a standard of care in patients with resectable esophageal cancer.

Disseminated tumour cells as a prognostic biomarker in colorectal cancer.

BACKGROUND: The study was performed to determine detection rate and prognostic relevance of disseminated tumour cells (DTC) in patients receiving curatively intended surgery for colorectal cancer (CRC). METHODS: The study population consisted of 235 patients with CRC prospectively recruited from five hospitals in the Oslo region. Bone marrow (BM) aspirates were collected at the time of surgery and the presence of DTC was determined by two immunological methods; immunomagnetic selection (using an anti-EpCAM antibody) and immunocytochemistry (using a pan-cytokeratin antibody). Associations between the presence of DTC and metastasis-free, disease-specific and overall survival were analysed using univariate and multivariate methods. RESULTS: Disseminated tumour cells were detected in 41 (17%) and 28 (12%) of the 235 examined BM samples by immunomagnetic selection and immunocytochemistry, respectively, with only five samples being positive with both methods. The presence of DTC was associated with adverse outcome (metastasis-free, disease-specific and overall survival) in univariate and multivariate analyses. CONCLUSION: The presence of DTC was associated with adverse prognosis in this cohort of patients curatively resected for CRC, suggesting that DTC detection still holds promise as a biomarker in CRC.

Incarcerated paraesophageal hernia complicated by pancreatic damage and unusual comorbidity: Two retrospective case series.

INTRODUCTION: About 1% of paraesophageal hernias (PEH) require emergency surgery due to obstruction or gangrene. We present two complicated cases of incarcerated PEH. Presentation of cases: A patient aged 18 with trisomy 21 was admitted after four days of vomiting and epigastric pain. CT scan revealed a large PEH. The stomach was massively dilated with compression of adjacent viscera and the celiac trunk. The stomach was repositioned laparoscopically and deflated by endoscopy in an attempt to avoid resection. During second look laparoscopy a gastrectomy was necessary. The patient was reoperated for intestinal obstruction, and treated for dehiscence of the esophagojejunostomy and a pancreatic fistula. A patient aged 65 with hereditary spastic paresis had two days history of emesis and epigastric pain. Upon arrival he was hemodynamically unstable and a CT scan revealed perforation of the herniated stomach. A subtotal gastrectomy without reconstruction was performed with vacuum closure of the abdomen. Later a gastrectomy was completed with a Roux-en-Y reconstruction. Except from reoperation for wound dehiscence after 14 days, the recovery was uneventful. DISCUSSION: Trisomy 21 and hereditary spastic paresis may increase the risk of developing PEH. Challenges in regard to symptom evaluation may delay diagnosis. The pressure of the dilated stomach can give rise to ischemic and mechanical damage from compression of major blood vessels and organs. Urgent diagnosis and gastric deflation is required. CONCLUSIONS: In patients with known PEH or with comorbidity that may increase the risk of PEH, this diagnosis should be considered early on.

Resection rectopexy for external rectal prolapse reduces constipation and anal incontinence.

BACKGROUND AND AIMS: The main aim was to examine constipation and anal incontinence in patients before and after resection for external rectal prolapse. MATERIAL AND METHODS: Twenty patients had ligament preserving suture rectopexy and sigmoid resection (resection rectopexy) for external rectal prolapse by laparoscopic (n = 15) or open (n = 5) technique during 2001-2005. They were prospectively evaluated for constipation and anal incontinence using validated incontinence and KESS-constipation scores. RESULTS AND CONCLUSIONS: Constipation score was significantly reduced from mean 7.7 (5.4-9.9) to 4.5 (2.5-6.4) after median 4 months (1-19) and to 4.3 (2.2-6.3) after median 17 months (4-51). Six and four patients were constipated preoperatively and 17 months postoperatively, respectively. The four symptoms feeling incomplete evacuation of stool, minutes in lavatory per attempt, use of enemas/digitation and painful evacuation effort were significantly reduced, whilst stool consistency increased. Fourteen patients (70%) had anal incontinence. Corresponding and significant reduction in their scores were from mean 12.5 (9.4-15.5) to 5.1 (2.1-8.1) and to 3.6 (1.3-5.9). Incontinence was improved in 13 and unaltered in one patient(s). Two patients with worse outcome had increased stool consistency and constipation scores. Resection rectopexy for rectal prolapse reduced anal incontinence and constipation.

Development of an experimental model for high dose rate endocavitary irradiation of the rat rectum.

Experimental data indicate a greater tolerance for endocavitary than for external beam irradiation of the normal rectal tissue in the rat. Increased tolerance has been attributed to temperature induced rectal hypoxia and a reduction of the dose to the mesentery. The general scarcity of experimental work in the field and the problems concerning hypoxia and dosimetry motivated the development of the current model. An 8 mm diameter endocavitary applicator was used for symmetrical dilatation and central introduction of the 192Ir source into the rectum of male Fischer F344 rats. Pulse oximetry and pO2-electrode readings from the intubated rectum gave no indication of radiobiological hypoxia. In vitro and in vivo thermoluminescence dosimetry (TLD) was supported by MRI based ferrous sulphate gel dosimetry. Using a 25 mm length source configuration the 90% isodose incorporated a 13 mm length segment of the rectum, and a 5.6% maximum deviation from the calculated dose was observed by the TLD and MRI based gel dosimetry. The ureters, the bladder and the skin were the only organs other than the target organ which received doses greater than 10% of the rectal dose. The model seems to be suitable for dose effect studies since endocavitary irradiation of the rat rectum can be performed without induction of local tissue hypoxia.

Sigmoidostomy-related parastomal hernia.

BACKGROUND AND AIMS: The aim was to examine prevalence and treatment of parastomal hernias in patients with sigmoidostomy. MATERIALS AND METHODS: In 2009, the medical records of 447 consecutive patients operated with a sigmoidostomy from January 1999 to December 2008 were retrospectiely reviewed. 119 dead patients (26.6%) were excluded because of short follow up (n = 59) and insufficient clinical data (n = 60). 328 patients (73.4%) were followed-up, of whom 210 (64%) alive patients also were scrutinized for presence of parastomal hernia by phone interview. In 2010, 92 out of 153 alive patients (60.1%) without known parastomal hernia also underwent targeted clinical examination in the ambulatory unit. RESULTS AND CONCLUSION: Follow up from stoma operation in 328 patients was median 20 (range 1-129) months. 319 patients had an end sigmoidostomy and nine patients had a loop sigmoidostomy. Time to parastomal hernia in 66 patients (20.1%) was median 9 (1-54) months. Fourty four patients (66.7%) reported no symptoms, eight (12.1%) had mild discomfort, six (9.1%) leakage, six (9.1%) pain, and two (3%) episodes of intestinal obstruction. Eleven (16.7%) had a hernia operation, eight with onlay mesh repair complicated with bowel perforation and ventral hernia in one patient. Three with mesh repair (37.5%) developed recurrent parastomal hernia, of whom one had tissue repair and a second recurrence 6 months later. The only patient with initial tissue repair had a recurrent hernia successfully treated with mesh repair. Two patients had their stoma uneventfully reversed. Parastomal hernia rate, mainly treated with mesh repair, was fairly low in this heterogenous patient series.