A preoperative predictive tool to assess the need for staging laparoscopy in oesophagogastric cancer patients.

INTRODUCTION: Staging laparoscopy (SL) has become commonplace in the preoperative staging pathway for oesophagogastric (OG) cancer. SL is often performed before curative treatment to examine for macroscopic peritoneal metastases (PM) or positive peritoneal cytology (PPC). The aim of this study was to develop an objective risk scoring system to predict both PM and PPC at SL. METHODS: A prospectively collected and maintained database of all OG cancer patients treated between 2006 and 2020 was reviewed. Univariate and multivariate analyses were performed to identify risk factors for both PM and PPC at SL. A risk score was produced for both PM and PPC, and then validated internally. RESULTS: Among 968 patients who underwent SL, 96 (9.9%) had PM and 81 (8.4%) had PPC at SL. Tumour site (p < 0.001), computed tomography (CT) T stage (p < 0.001) and N stage (p = 0.029) were significantly associated with PM at SL (p < 0.001). Tumour site (p < 0.001), biopsy histology (p = 0.041), CT T stage (p < 0.001) and N stage (p < 0.001) were significantly associated with PPC. The risk scoring model for PM included cancer site and CT T stage. This was successfully tested on the validation set (area under the receiver operating characteristic [AUROC] = 0.730). The risk scoring model for PPC included cancer site, CT T and N stage. This was successfully tested on the validation set (AUROC = 0.773). CONCLUSIONS: The current risk scores are valid tools with which to predict the risk PM and PPC in patients undergoing SL for OG cancer and may help to avoid subjecting patients to unnecessary SL.

Impact of postoperative complications on survival after oesophagectomy for oesophageal cancer.

BACKGROUND: Recent evidence suggests that complications after oesophagectomy may decrease short- and long-term survival of patients with oesophageal cancer. This study aimed to analyse the impact of complications on survival in a Western cohort. METHODS: Complications after oesophagectomy were recorded for all patients operated on between January 2006 and February 2017, with severity defined using the Clavien-Dindo classification. Associations between complications and overall and recurrence-free survival were assessed using univariable and multivariable Cox regression models. RESULTS: Of 430 patients, 292 (67·9 per cent) developed postoperative complications, with 128 (39·8 per cent) classified as Clavien-Dindo grade III or IV. No significant associations were detected between Clavien-Dindo grade and either tumour (T) (P = 0·071) or nodal (N) status (P = 0·882). There was a significant correlation between Clavien-Dindo grade and ASA fitness grade (P = 0·032). In multivariable analysis, overall survival in patients with Clavien-Dindo grade I complications was similar to that in patients with no complications (hazard ratio (HR) 0·97, P = 0·915). However, patients with grade II and IV complications had significantly shorter overall survival than those with no complications: HR 1·64 (P = 0·007) and 1·74 (P = 0·013) respectively. CONCLUSION: Increasing severity of complications after oesophagectomy was associated with decreased overall survival. Prevention of complications should improve survival.

The long term results of endoscopic surveillance of premalignant gastric lesions.

BACKGROUND: A large proportion of patients attending open access endoscopy have histological and gross pathological findings that are potentially premalignant. The proportion of these patients who go on to develop malignancies and the timescale over which this occurs are uncertain. AIMS: This study aims to discover the incidence of gastric cancers in this "high risk" group and to examine the potential for their early diagnosis and treatment. PATIENTS: A total of 1753 patients attended open access endoscopy. From these, 166 patients with dysplasia, intestinal metaplasia, atrophic gastritis, foveolar hyperplasia, regenerative changes, polyps, or ulcers who agreed to undergo annual surveillance endoscopy were studied. METHODS: Patients were endoscoped annually. Additionally, patients with ulcers were re-examined at two monthly intervals until ulcer healing. Cancers detected were treated by gastrectomy. RESULTS: Twenty two of 1753 patients attending open access endoscopy had gastric cancer (1.3%). In the study population, 14 cancers were detected over 10 years (8.4 %). These were of an earlier stage than those detected at open access (stage I and II 67% v 23%; p<0.05) and five year survival was significantly higher (50% v 10%; p=0.006). In atrophic gastritis and intestinal metaplasia the risk of malignancy was 11%. CONCLUSIONS: In patients with atrophic gastritis or intestinal metaplasia, annual surveillance can detect most new tumours at an early stage with a major improvement in survival. Potential benefits of such a surveillance programme are large and warrant further investigation in a multicentre randomised controlled trial.

Prospective, double-blind, placebo-controlled randomized trial of cimetidine in gastric cancer. British Stomach Cancer Group.

Cimetidine is thought to inhibit suppressor T-lymphocyte function and preliminary evidence from a randomized trial indicated that it might prolong survival for patients with operable and inoperable gastric cancer. The British Stomach Cancer Group conducted a randomized, double-blind, placebo-controlled trial examining the effects of cimetidine (400 mg or 800 mg twice a day) on the survival of patients with early (stages I, II and III: n = 229) and advanced (stages IVa and IVb: n = 201) gastric cancer. The primary end point was death. A total of 442 patients were randomized by 59 consultants in 39 hospitals between February 1990 and March 1995. Log-rank survival analysis was used to assess differences between the groups. Three hundred and forty patients died during the study: 166 (49%) in the cimetidine treatment groups and 174 (51%) in the placebo groups. Median survival for patients receiving cimetidine was 13 months (95% confidence interval (CI) 9-16 months) and 11 months in the placebo arm (95% CI 9-14 months). There was no significant difference in survival between the two treatment groups (P = 0.42) or between different doses of cimetidine tablets (P = 0.46). Five-year survival of those patients randomized to cimetidine was 21% compared to 18% for those patients randomized to placebo. Cimetidine at a dose of 400 mg or 800 mg twice a day does not have a significant influence on the survival of patients with gastric cancer compared to placebo.

Redefining surgery for gastric cancer.

BACKGROUND: Despite encouraging retrospective and non-randomized trials, two large prospective, randomized trials of D1 vs D2 resections show double the mortality in the D2 group, with no increase in long-term survival. However, the D2 resection still offers the only hope of cure when N2 nodes are involved. We propose a reclassification of the International Union Against Cancer TNM "N" staging to a system with an anatomical basis that is useful in defining the surgery performed. Junctional nodes lying between the N1 and N2 tiers will act as a guide to surgery. Where these nodes are uninvolved, the probability of gastric bed (N2) involvement is low and the radical D2 dissection with its higher mortality and morbidity can be avoided.CONCLUSION: Such "stage-appropriate" surgery will reduce the number of D2 resections while ensuring that patients with N2 disease are not denied curative surgery. A prospective, randomized, controlled trial of targeted surgery is required.

Radical surgery for early gastric cancer.

The role of radical surgery for early gastric cancer has become a topic of considerable debate. Despite excellent results from Japan and several retrospective and uncontrolled trials, results from two large prospective randomized trials appear to demonstrate no benefit from D2 compared to the D1 resections. These trials have prompted a move away from radical lymph-node dissection. We argue that this reasoning is flawed and based not on the lack of efficacy of the D2 resection but in an attempt to reduce post-operative mortality and morbidity. Post-operative complications are largely a result of distal pancreatectomy and splenectomy and the relative inexperience of surgeons performing the operations. By preserving these organs and concentrating surgery to specialized centres the complication rate of radical surgery can be significantly reduced to approximate that of non-radical surgery. Lymph-node metastasis to the N2 nodes in early gastric cancer has been shown to be as high as 23%. Non-radical surgery poses significant risks of leaving residual disease. Radical surgery must remain the operation of choice if non-curative surgery for a curable condition is to be avoided.

Screening for gastric cancer by Helicobacter pylori serology: a retrospective study.

BACKGROUND: Screening by serology for Helicobacter pylori in young dyspeptic patients has been shown to be effective in reducing demand for endoscopy. H. pylori has been implicated in the causation of gastric cancer and the reported seropositivity rate in patients with gastric cancer ranges from 69 to 94 per cent. The aim of this study was to assess the potential value of Helicobacter antibodies as a method of selecting dyspeptic patients over the age of 45 years for endoscopy. METHODS: A retrospective comparison of the antibody status to H. pylori was made between 154 patients with gastric cancer and a sex- and date of birth-matched dyspeptic control group. Results from the former group were correlated with demographic data and tumour characteristics. RESULTS: Significantly more patients with gastric cancer were seropositive than controls (77 versus 66 per cent). H. pylori was not related to the Laurén classification of the tumour. Tumour site was significant: body and antrum tumours were associated with Helicobacter whereas cardial tumours appeared to be unrelated. CONCLUSION: Screening by antibody assays to H. pylori would miss more than 30 per cent of current gastric cancers. The increasing incidence of cardial cancer would cause this percentage to rise in the future.

Determination by western blot (immunoblot) of seroconversions to toxic shock syndrome (TSS) toxin 1 and enterotoxin A, B, or C during infection with TSS- and non-TSS-associated Staphylococcus aureus.

Serum antibody responses to toxic shock syndrome (TSS) toxin 1 (TSST-1) and staphylococcal enterotoxins A, B, and C were determined by western blot (immunoblot) analysis of acute- and convalescent-phase paired sera from 18 TSS- and 31 non-TSS-associated Staphylococcus aureus infections. Compared with non-TSS cases, seroconversion to TSST-1 was significantly more frequent among both menstrual (5 of 8 versus 1 of 31; P less than 0.001) and nonmenstrual (3 of 10; P less than 0.05) patients. Seroconversion to staphylococcal enterotoxin A was also more frequent among both menstrual (2 of 8 versus 0 of 31; P less than 0.05) and nonmenstrual (2 of 9; P less than 0.05) TSS patients. In general, patients with TSS associated with TSST-1-positive S. aureus were more likely to seroconvert exclusively to TSST-1 (4 of 12 versus 0 of 6; P = 0.16), whereas those associated with TSST-1-negative S. aureus were more likely to seroconvert exclusively to enterotoxins (3 of 6 versus 0 of 11; P less than 0.05). Concurrent seroconversions to multiple exoproteins were more frequent among both menstrual (3 of 8; P less than 0.05) and nonmenstrual (2 of 9; P less than 0.05) TSS patients compared with persons without TSS (0 of 31). These data suggest but do not prove that enterotoxins (especially staphylococcal enterotoxin A) in addition to TSST-1 may be involved in both menstrual and nonmenstrual TSS. Furthermore, since exposure to multiple exoproteins is more likely to occur during TSS-associated than non-TSS-associated S. aureus infections, the possibility of additive or synergistic effects of these putative toxins in the pathogenesis of TSS should be further explored.

Interactions of ciprofloxacin with clindamycin, metronidazole, cefoxitin, cefotaxime, and mezlocillin against gram-positive and gram-negative anaerobic bacteria.

A total of 598 clinical isolates of anaerobic bacteria were tested against ciprofloxacin by the agar dilution technique with 10(5) CFU on Wilkins-Chalgren medium. Selected strains representative of the six major genera of anaerobes relatively resistant to the quinolones were tested for interactions with ciprofloxacin in combination with clindamycin, metronidazole, cefoxitin, cefotaxime, or mezlocillin by using a checkerboard agar dilution technique. Cefotaxime-ciprofloxacin and clindamycin-ciprofloxacin were the most effective combinations, with 16% of all isolates and 44% of the Bacteroides fragilis group isolates responding synergistically to the former combination and 9% of all isolates and 37% of Peptostreptococcus isolates responding synergistically to the latter. Occasional synergy was seen with all other antibiotic combinations except for metronidazole-ciprofloxacin. Likewise, synergism was seen with all groups of anaerobes except for Fusobacterium species. Antagonistic interactions were observed only with a Peptostreptococcus intermedius strain tested against clindamycin-ciprofloxacin. These data suggest that combinations of ciprofloxacin with these agents may be useful for certain resistant anaerobic infections.