Combined positron emission tomography and contrast enhanced CT (PET/CeCT) is a feasible single investigation in the staging of oesophagogastric cancers: single-centre pilot study experience during the COVID-19 pandemic.

INTRODUCTION: Staging of oesophagogastric (OG) cancers usually involves endoscopy (OGD), and separate visits for contrast enhanced computed tomography (CeCT) and positron emission tomography (PET/CT). At the height of the COVID-19 pandemic, some of our patients underwent single-visit combined staging with PET/CeCT. We compare this novel pathway with standard separate imaging in time to completion of staging, to start of treatment, and cost. METHODS: We identified all patients discussed at our OG multidisciplinary team (MDT) meeting in 2020. Clinical records revealed dates of investigations and treatments. Data were tabulated in Excel, with statistical analysis in SPSS. All patients followed the same MDT process and image reviewing criteria. Costs were compared using prices supplied by finance departments. RESULTS: A total of 211 new patients were discussed at our MDT in 2020. Of these, 48 patients had combined PET/CeCT staging, and 68 had separate scans. Median time (interquartile range) in days from OGD to final imaging was 9 (6-23) for the combined group versus 21 (16-28) for the separate group (p≤0.001). Median time (days) from OGD to treatment start was 37 (29-52) for combined versus 55 (40-71) for separate (p≤0.001). No combined scans were of insufficient diagnostic quality for the MDT. PET/CeCT had a potential cost saving of £113 per patient. CONCLUSIONS: PET/CeCT allows accurate radiological staging of OG cancers with a single scan. Patients completed staging and started treatment faster, with a potential saving of £10,509 in one year. PET/CeCT has become standard staging at our trust, and we aim to incorporate radiotherapy planning images too.

Peri-operative chemotherapy versus preoperative chemoradiotherapy in treatment of gastro-oesophageal junctional adenocarcinomas: A 10-year cohort study.

BACKGROUND: Gastro-oesophageal junctional (GOJ) cancers have been, more latterly, considered a distinct tumor entity with characteristic genetic profiles. The optimal multimodal therapy of advanced GOJ cancers remains debatable. In this comparative study, we analyzed the outcomes of peri-operative chemotherapy (CT) versus pre-operative chemoradiotherapy (CRT) in treatment of advanced GOJ adenocarcinomas. METHODS: This study included patients with locally advanced but resectable GOJ adenocarcinomas who underwent surgical resection after oncological therapy between 2010 till 2019 at our institution. Follow up to May 2021 was completed. The outcomes between CT and CRT groups were retrospectively analyzed. The long-term follow up data was obtained via direct contact with the patients during oncological clinics, cross-checked with hospital/national patients' electronic databases. RESULTS: 107 patients had GOJ cancers; 90 (84%) patients met our inclusion criteria. Perioperative chemotherapy was administrated in 65 (72%) patients. Overall median survival rate was 2.2 years in CRT-group compared to 2.4 years in CT-group (p-value 0.29), with comparable recurrence rates (48% vs 36% respectively). R0-resections were higher in CRT-group (84%) compared to CT-group (71%), yet insignificant p-value 0.197. Preoperative chemoradiotherapy achieved higher complete pathological response (28% vs 6%, p-value 0.009) and negative lymph nodes rates (64% vs 37%, p-value 0.014) compared to CT-group. Short-term outcomes (postoperative complications, morbidity rates and length of hospital stay) were similar across both groups. CONCLUSION: Preoperative chemoradiotherapy was associated with higher complete pathological response and negative lymph nodes rates for GOJ adenocarcinomas compared to peri-operative chemotherapy, without an increase in postoperative complications or morbidity rates. However, it wasn't associated with improved overall or disease-free survival rates.

Gastric schwannoma: a benign tumour often mistaken clinically, radiologically and histopathologically for a gastrointestinal stromal tumour--a case series.

INTRODUCTION: Gastric schwannomas are rare mesenchymal tumours that arise from the nerve plexus of the gut wall. They present with non-specific symptoms and are often detected incidentally. Pre-operative investigation is not pathognomonic and many are therefore diagnosed as gastrointestinal stromal tumours (GISTs). Operative resection is usually curative as they are almost always benign, underpinning the importance of differentiating them from GISTs. METHODS: Three cases of gastric schwannomas were identified over a seven-year period. The clinical details and management were reviewed retrospectively. RESULTS: There were two women and one man with a mean age of 62 years (range: 51-69 years). Two patients presented with bleeding and one with abdominal pain. The mean tumour size was 5.2 cm (range: 2-10 cm) and the tumours were resected completely following total or wedge gastrectomies. Histology in all cases showed spindle cells with a cuff of lymphoid tissue. Immunohistochemistry confirmed positive S100 staining and negative CD117 and DOG-1 staining in all cases. CONCLUSIONS: We report our experience with these unusual primary stromal tumours of the gut and their presentations, pre-operative investigations, operative findings and pathological findings are discussed. Operative resection in all cases has been considered curative, which is supported by previous series confirming the excellent prognosis of gastric schwannomas.

Histopathological and molecular analysis of gastrectomy specimens from hereditary diffuse gastric cancer patients has implications for endoscopic surveillance of individuals at risk.

Hereditary diffuse gastric cancer (HDGC) is caused by germline E-cadherin (CDH1) mutations in 25-40% of tested families. Management options for asymptomatic mutation carriers are fraught, since endoscopic surveillance can miss cancer foci and prophylactic gastrectomy has profound clinical sequelae. The aims of this study were to evaluate the impact of current surveillance practices on pre-operative diagnosis and to characterize the microscopic lesions in gastrectomy specimens to better inform clinical practice. Histological assessment and mapping of endoscopic surveillance and gastrectomy specimens were performed for eight asymptomatic CDH1 mutation carriers. E-cadherin expression and proliferation were analysed and evidence of epithelial-mesenchymal transition (EMT) was sought by immunohistochemistry for vimentin and cytokeratin 8/18. Four of eight patients had lesions detected at endoscopic surveillance. A median of 20.5 (range 0-66) signet ring foci were identified per gastrectomy (including in situ lesions and pagetoid spread). Foci were predominantly identified in the fundus and body (90% endoscopic biopsies and 85% in gastrectomy). The likelihood of detecting foci pre-operatively was positively correlated with the number of biopsies taken and the number of lesions in the gastrectomy specimen. E-cadherin expression in gastrectomy specimens was reduced or absent in all of the foci compared with the intervening gastric tissue, suggesting that these lesions are polyclonal. The foci had a low proliferative index (<2%) and there was no evidence for EMT. Multiple endoscopic biopsy sampling of the gastric mucosa increases the yield of microscopic cancer foci. The low proliferative index and lack of EMT suggests that these foci may represent an indolent stage of HDGC.

Mechanisms and sequelae of E-cadherin silencing in hereditary diffuse gastric cancer.

Around 25-40% of cases of hereditary diffuse gastric cancer (HDGC) are caused by heterozygous E-cadherin (CDH1) germline mutations. The mechanisms for loss of the second allele still remain unclear. The aims of this study were to elucidate mechanisms for somatic inactivation of the wild-type CDH1 allele and to seek evidence for cadherin switching. Archival tumour material was analysed from 16 patients with CDH1 germline mutations and seven patients fulfilling HDGC criteria without CDH1 germline mutations. The 16 CDH1 exons were sequenced. E-cadherin promoter methylation was analysed by bisulphite sequencing and pyrosequencing and allele specificity was determined using polymorphic loci. Loss of heterozygosity was analysed using microsatellite markers. Cadherin expression levels were determined by real-time RT-PCR and immunohistochemistry. Six of 16 individuals with germline mutations had at least one second hit mechanism. Two exonic mutations (exon 9 truncating, exon 3 missense) and four intronic mutations which may affect splicing were identified. Tumours from 4/16 individuals had promoter hypermethylation that was restricted to the A allele haplotype in three cases. E-cadherin loss (mRNA and protein) generally correlated with identification of a second hit. In cases without germline E-cadherin mutations there was no evidence for somatic mutation or significant promoter methylation. P-cadherin (>25% cells) was expressed in 7/13 (54%) and 4/5 (80%) with and without germline CDH1 mutations, respectively, independent of complete E-cadherin loss. Overall, inactivation of the second CDH1 allele occurs by mutation and methylation events. Methylation is commonly allele-specific and is uncommon without germline mutations. P-cadherin over-expression commonly occurs in individuals with diffuse type gastric cancer.

Salvage oesophagectomy after local failure of definitive chemoradiotherapy.

BACKGROUND: Definitive chemoradiotherapy (CRT) is one treatment option for locally advanced oesophageal carcinoma. CRT typically consists of high-dose (50-66 Gy) external beam radiotherapy concurrent with 5-fluorouracil and cisplatin. When definitive CRT fails to achieve local control, salvage oesophagectomy is frequently the only treatment available that can offer a chance of long-term survival. METHODS: Online databases were searched for publications relating to salvage oesophagectomy and definitive CRT. Nine series containing a total of 105 patients were reviewed. Demographics, indications for surgery, type of resection, complications and outcome data were extracted. RESULTS: Each centre performed one to three salvage resections per year comprising 1.7-4.1 per cent of the oesophagectomy workload. The overall anastomotic leak rate was 17.1 per cent. The in-hospital mortality rate was 11.4 per cent. Five-year survival rates of 25-35 per cent were achieved. Prognostic factors for increased survival were R0 resection (P = 0.006) and longer interval between CRT and recurrence (P = 0.002). CONCLUSION: Salvage resection after CRT is feasible for selected patients but is a formidable undertaking. Restaging investigations after CRT for potentially resectable tumours in fit candidates should include endoscopy and positron emission tomography-computed tomography. Salvage oesophagectomy is carried out with the goal of cure and it should be attempted only if an R0 resection is technically possible.

Randomized trial of preoperative cimetidine in patients with colorectal carcinoma with quantitative assessment of tumor-associated lymphocytes.

BACKGROUND: Previous studies have suggested that cimetidine, a histamine-2 receptor antagonist with immunostimulatory effects, may improve survival in patients with colorectal carcinoma. This effect may be apparent by an increase in the number of peritumoral lymphocytes. A prospective, double blind, randomized, placebo-controlled trial of a short course of preoperative treatment with cimetidine in patients with colorectal carcinoma was performed to assess the effect of cimetidine on survival and on the number of peritumoral lymphocytes. METHODS: One hundred and twenty-five patients who were scheduled to undergo elective colon or rectal excision for carcinoma were randomized to receive either placebo or cimetidine preoperatively for 5 days. In addition to standard histopathology, immunohistochemistry and computer video image analysis were used to assess the number of peritumoral lymphocytes in an objective manner. Interim survival analysis according to the Kaplan-Meier method was performed. RESULTS: A trend toward a survival advantage in the group of patients receiving cimetidine (800 mg twice daily) compared with the placebo group was observed (P = 0.20, log rank test) that was most marked in patients with replication error negative tumors (P = 0.04). Similarly, in these two groups there was a trend toward an increase in the number of patients with a conspicuous lymphocytic infiltration (P = 0.10, chi-square test). However, there was no difference in the number of peritumoral lymphocytes as measured by image analysis. CONCLUSIONS: Based on the results of the current study, a short course of preoperative treatment with cimetidine does appear to have an effect on patient survival; however, the exact mechanism is unknown. The failure of this study to demonstrate a clear increase in the local lymphocyte response does not exclude an immunologic mechanism of action.

Stripping the long saphenous vein reduces the rate of reoperation for recurrent varicose veins: five-year results of a randomized trial.

OBJECTIVE: The purpose of this study was to investigate the possible long-term clinical advantages of stripping the long saphenous vein during routine primary varicose vein surgery. METHODS: The study was designed as a 5-year, clinical and duplex scan follow-up examination of a group of patients who were randomized to stripping of the long saphenous vein during varicose vein surgery versus saphenofemoral ligation alone. The study was conducted in the vascular unit of a district general hospital. One hundred patients (133 legs) with uncomplicated primary long saphenous varicose veins originally were randomized. After invitation 5 years later, 78 patients (110 legs) underwent clinical review and duplex scan imaging. RESULTS: Sixty-five patients remained pleased with the results of their surgery (35 of 39 stripped vs 30 of 39 ligated; P = .13). Reoperation, either done or awaited, for recurrent long saphenous veins was necessary for three of 52 of the legs that underwent stripping versus 12 of 58 ligated legs. The relative risk was 0.28, with a 95% confidence interval of 0.13 to 0.59 (P = .02). Neovascularization at the saphenofemoral junction was responsible for 10 of 12 recurrent veins that underwent reoperation and also was the cause of recurrent saphenofemoral incompetence in 12 of 52 stripped veins versus 30 of 58 ligated legs. The relative risk was 0.45, with a 95% confidence interval of 0.26 to 0.78 (P = .002). CONCLUSION: Stripping reduced the risk of reoperation by two thirds after 5 years and should be routine for primary long saphenous varicose veins.

Cimetidine does not influence TIL in breast cancer.

Cimetidine is known to have immunomodulatory effects and this study aimed to examine the effect of pre-operative cimetidine treatment on lymphocytic infiltration in n = 72 women with breast cancer randomised to 400 mg bd or placebo for five days presurgery. A combined index was devised by adding infiltrating lymphocyte percentage and lymphoid score. There were no significant differences in circumferential infiltrate and lymphoid follicles in cimetidine treated patients and control patients with breast cancer.

Prospective evaluation of magnetic resonance cholangiography to detect common bile duct stones before laparoscopic cholecystectomy.

BACKGROUND: With the advent of laparoscopic cholecystectomy, endoscopic retrograde cholangiography (ERC) is frequently employed before operation to detect common bile duct stones. However, this is an invasive technique with recognized complications. This study evaluated the accuracy of magnetic resonance cholangiography (MRC) to detect choledocholithiasis in selected patients before laparoscopic cholecystectomy. METHODS: Patients scheduled for elective laparoscopic cholecystectomy, with risk factors for common bile duct stones, underwent MRC followed by ERC or peroperative cholangiography. RESULTS: Over a 2-year period 40 patients were studied. MRC had a sensitivity of 88 per cent, specificity of 93 per cent, positive predictive value of 78 per cent and negative predictive value of 97 per cent for the detection of common bile duct stones. CONCLUSION: MRC is a simple non-invasive method for preoperative screening for common bile duct stones in at-risk patients. In this study it would have reduced the need for ERC by three-quarters.

Multiple bilobar liver metastases: cryotherapy for residual lesions after liver resection.

BACKGROUND AND OBJECTIVES: Most patients with colorectal liver metastases are not eligible for resection because they have multiple lesions or because of anatomical constraints. We report the use of cryotherapy to destroy residual metastases following liver resection in patients with disease too widespread for treatment by resection alone. METHODS: Twenty patients with bilobar disease confined to the liver (median 3; range 2-8 lesions) were treated in this way. Seventeen patients also received regional chemotherapy postoperatively. RESULTS: Morbidity was high, but there were no procedure-related deaths and only one patient's hospital stay exceeded 24 days. Significant destruction of tumor, as evidenced by a decline in CEA levels, occurred within 3 months of surgery in all patients (P < 0.001). Median duration of follow-up was 15 (6-53) months. Survival rates at 1 and 2 years were 88% and 60%, respectively, and median survival was 32 months. Seven patients remain well and seven are alive with recurrent liver and/or other metastases. CONCLUSIONS: Although this is not a control study, it would appear that some patients with irresectable liver metastases benefit from this multimodality approach.

Hepatic resection with cryotherapy to involved or inadequate resection margin (edge freeze) for metastases from colorectal cancer.

BACKGROUND: In patients undergoing liver resection for colorectal liver metastases, a resection edge either involved by tumour or with the tumour extending to within 1 cm is associated with a high risk of liver recurrence and survival is reduced markedly. METHODS: Twenty-six patients underwent cryotherapy of the resection edge following liver resection for metastases from colorectal carcinoma with an involved or inadequate (less than 1 cm) resection margin. RESULTS: At a median follow-up of 23 (range 1-47) months four patients were alive and disease free, and 21 had developed recurrence, of whom 13 had died. One patient died following surgery. Sixteen patients developed recurrences involving the liver, only five of which were at the resection margin. CONCLUSION: Cryotherapy to involved or inadequate resection margins improves local disease control considerably. The use of resection edge cryotherapy might allow a greater proportion of patients with liver metastases to be usefully treated and help to avoid high-risk resections.

Cryosurgery.

The in situ destruction of malignant tissue by freezing is a relatively new addition to the list of treatment options for patients with cancer in solid organs. Although skin cancers have long been treated by cryosurgery, the lack of suitable equipment for both delivering and monitoring the freezing process hindered further development of the treatment of more inaccessible lesions until the 1960s. At this time, Cooperz developed cryosurgical machines which enabled the destruction of CNS lesions in patients with Parkinson's disease and stimulated renewed interest in the application of cryosurgery to the treatment of cancer.

Rectus sheath haematoma mimicking splenic enlargement.

Rectus sheath haematoma is uncommon and frequently misdiagnosed. In this paper an incorrect diagnosis of splenic enlargement was made. Ultrasound and computerized tomography revealed a large rectus sheath haematoma.

Strangulated iatrogenic diaphragmatic hernia: a late diagnosed complication.

Three cases of iatrogenic diaphragmatic herniation are reported following thoracic and high abdominal surgery. Each case presented at least 6 months after the original surgery with symptoms of acute upper gastrointestinal obstruction. Diaphragmatic herniation was not considered in the initial differential diagnosis which lead to a delay in their referral. We emphasise the importance of checking the diaphragm following upper abdominal surgery and care when closing a defect.