Iain Martin

The Magenstrasse and Mill Operation for Morbid Obesity

Background: Our aim was to evolve a simpler, more physiological type of gastroplasty that would dispense with implanted foreign material such as bands and reservoirs. The Magenstrasse, or street of the stomach, is a long narrow tube fashioned from the lesser curvature, which conveys food from the esophagus to the antral Mill. Normal antral grinding of solid food and antro-pyloro-duodenal regulation of gastric emptying and secretion are preserved. Methods: 100 patients with morbid obesity (83M, 17F, mean age 40 years) were treated by the Magenstrasse and Mill procedure and followed-up for 1-5 years. Mean preoperative BMI was 46.3 kg/m2, and mean excess weight was 106%. Results: Operative mortality was 0. Major complications occurred in 4% of patients.There were few side-effects, although mild heartburn was fairly common. Mean weight loss was 38 kg (±14 kg), equivalent to 60% of excess weight, achieved within 1 year of operation, after which no further significant gain or loss of weight occurred. Conclusions:The Magenstrasse and Mill procedure is the simplest and most physiological gastroplasty yet described. Many of the drawbacks of vertical banded gastroplasty, adjustable banding and gastric bypass are avoided. It is safe, has few side-effects and leads to major and durable weight losses, similar to those produced by other types of gastroplasty.

Preservation of the spleen improves survival after radical surgery for gastric cancer.

One hundred and ninety five consecutive, potentially curative resections for adenocarcinoma of the stomach were performed in one surgical department between 1970 and 1989: 76 patients underwent gastrectomy with splenectomy and 119 gastrectomy without splenectomy. Operative mortality was 12% after gastrectomy with splenectomy, but only 2.5% after gastrectomy without splenectomy (p < 0.05). Postoperative complications were also significantly more common when splenectomy was combined with gastrectomy (41% v 14%, p < 0.01). Cumulative five year survival was 45% after gastrectomy with splenectomy, compared with 71% after gastrectomy alone (p < 0.01). When the results of the two groups of patients were compared, stage for pathological stage, no evidence was found that splenectomy improved survival. Application of Coxs proportional hazards model, which makes allowance for other variables such as the T and N stages, showed that splenectomy had an adverse influence on patients survival. Splenectomy does not benefit the patient and its routine use in the course of radical resections for carcinoma of the stomach should be abandoned.

Hereditary diffuse gastric cancer: predominance of multiple foci of signet ring cell carcinoma in distal stomach and transitional zone

Background and aims: Germline mutations in the CDH-1/E-cadherin gene are, to date, the only known cause of hereditary diffuse gastric cancer (HDGC). While two recent series of prophylactic gastrectomy described microscopic foci of signet ring cell carcinoma in sample sections from 10 macroscopically normal stomachs, whole stomach phenotype has not been mapped. We aimed to describe the size and distribution of foci in relation to mucosal zones and anatomical location. Methods: Six patients (from three HDGC kindred) were referred for total gastrectomy via three different referral pathways. Following fixation, five stomachs were completely blocked and one extensively sampled. Histopathology was mapped to a mucosal photograph of each stomach, enabling precise localisation of carcinoma foci, benign pathology, and mucosal zones. Results: There were 4–318 microscopic foci of intramucosal signet ring cell adenocarcinoma in the six macroscopically normal stomachs (foci size 0.1–10 mm in diameter). The distal third of the stomach contained 48% of total foci (range 29–75%). The body-antral transitional zone occupied 7.7% of mucosal area (range 3.6–11.8) but had 37% of foci (range 10%–75%). The largest foci were found in the transitional zone and foci density was five times greater in the transitional zone than in body or antral type mucosa. Conclusions: In germline CDH-1 mutation carriers, multiple microscopic foci of intramucosal signet ring cell carcinoma show a predilection for the distal stomach and the body-antral transitional zone. Targeting the transitional zone would maximise the likelihood of finding foci in macroscopically normal gastrectomies, and particular attention should be paid to this area during endoscopy.

Chromoendoscopic surveillance in hereditary diffuse gastric cancer: an alternative to prophylactic gastrectomy?

Background: Hereditary diffuse gastric cancer (HDGC) is defined by germline mutations in the E-cadherin gene, CDH-1. The first family in which CDH-1 mutations were identified was a large Maori kindred, where lifetime penetrance is 70%. Prophylactic gastrectomy is an unacceptable option for many mutation carriers. The results of annual chromoendoscopic surveillance using the methylene blue/congo red technique in 33 mutation carriers over a five year period are described. Patients and methods: Thirty three confirmed CDH-1 mutation carriers (18 males, 15 females), median age 32 years (range 14–69), were enrolled in 1999–2003. Medical records, endoscopy, and pathology were reviewed retrospectively. Results: Over five years, 99 surveillance endoscopies were performed, of which 93 were chromo-dye enhanced. Sixty nine chromoendoscopies were normal. In 24 procedures, 1–6 pale areas/stomach (size 2–10 mm) were detected post chromo-dye application (totalling 56 pale lesions). One biopsy was taken from each pale lesion: 23 lesions (41%) showed signet ring cell carcinoma (10 patients), 10 lesions (18%) gastritis (four patients), and 23 (41%) normal mucosa (10 patients). No chromo-dyes were used in six procedures with macroscopic lesions (two HDGC, four ulceration). Total gastrectomies from patients with carcinoma were macroscopically normal but pathological mapping showed multiple microscopic foci of early signet ring cell carcinoma. Correlation of chromoendoscopic and gastrectomy findings showed that congo red/methylene blue detected carcinoma foci 4–10 mm in size but not foci <4 mm. Conclusions: The use of chromoendoscopy following normal white light gastroscopy facilitated detection of early gastric carcinoma foci not visible with white light gastroscopy. If these findings are validated in other HDGC kindred, chromogastroscopy represents an improved surveillance technique that can be safely considered alongside prophylactic gastrectomy.

E-Cadherin Deficiency Initiates Gastric Signet-Ring Cell Carcinoma in Mice and Man

The importance of loss of the cell-cell adhesion molecule E-cadherin (encoded by CDH1) to tumor progression is well established. However, CDH1 germ-line mutations predispose to the cancer susceptibility syndrome hereditary diffuse gastric cancer (HDGC), suggesting a role for E-cadherin in tumor initiation. The earliest indications of cancer in the stomachs of CDH1 mutation carriers are microscopic foci of intramucosal signet-ring cell carcinoma (SRCC; designated eHDGC). Here, we used N-methyl-N-nitrosourea (MNU) to promote gastric carcinogenesis in wild-type (wt) and cdh1(+/-) mice. MNU induced a variety of gastric tumors; however, intramucosal SRCC developed with an 11 times higher incidence in cdh1(+/-) mice compared with wt mice. The murine SRCC resembled the human eHDGCs in that they were hypoproliferative, lacked nuclear beta-catenin accumulation, and had reduced membrane localization of E-cadherin and its interacting junctional proteins. The down-regulation of E-cadherin in the murine SRCCs confirmed the importance of the second CDH1 hit to the initiation of diffuse gastric cancer. CDH1 promoter hypermethylation has been proposed to be a major second hit in advanced HDGC; however, its contribution to eHDGC was unknown. We thus examined a series of human eHDGC and detected CDH1 promoter methylation in 50% of foci. Promoter methylation was accompanied by reduced wt CDH1 mRNA levels in the foci and had a monoclonal pattern, consistent with an epigenetic initiation of disease. Together, these findings provide compelling evidence for a deficiency in cell-to-cell adhesion being sufficient to initiate diffuse gastric cancer in the absence of hyperproliferation and beta-catenin activation.

Destabilized Adhesion in the Gastric Proliferative Zone and c-Src Kinase Activation Mark the Development of Early Diffuse Gastric Cancer

The initial development of diffuse gastric cancer (DGC) is poorly understood. The study of E-cadherin (CDH1) germ line mutation carriers predisposed to DGC provides a rare opportunity to elucidate the genetic and biological events surrounding disease initiation. Samples from various stages of hereditary and sporadic DGC were investigated to determine general mechanisms underlying early DGC development. Paraffin-embedded tissues from 13 CDH1 mutation carriers and from 10 sporadic early DGC cases were analyzed. Immunofluorescence and immunohistochemistry using differentiation, proliferation, and adhesion markers showed that DGC initiation seems to occur at the proliferative zone (the upper neck) of the gastric epithelium and correlates with absent or reduced expression of junctional proteins (beta-actin, p120, Lin-7). Slow proliferation of neoplastic cells at the upper gastric neck leads to the formation of intramucosal signet-ring cell carcinoma (SRCC) displaying differentiated features. As shown by immunolabeling, invasion from SRCC lesions beyond the gastric mucosa is associated with poor differentiation, increased proliferation, activation of the c-Src system, and an epithelial-mesenchymal transition. Our results provide a molecular description of the early development of DGC and explain the relationship between the two main DGC types, poorly differentiated carcinoma and SRCC: both share their origin, but SRCC develops following cancer cell differentiation and seems relatively indolent in its intramucosal stage.

Predictive validity and estimated cut score of an objective structured clinical examination (OSCE) used as an assessment of clinical skills at the end of the first clinical year

Assessment plays a key role in the learning process. The validity of any given assessment tool should ideally be established. If an assessment is to act as a guide to future teaching and learning then its predictive validity must be established.

Goseki histological grading of gastric cancer is an important predictor of outcome.

TNM (tumour, node, metastases) staging has thus far been the most important guide to prognosis in patients with gastric cancer. Histological grading, in contrast, has not provided any additional information. Recently a novel grading system based on tubular differentiation and mucus production has been proposed, which was correlated with patterns of tumour spread found at necropsy. This study set out to assess its value as a determinant of survival after gastric resection. In a consecutive series of 211 patients who had potentially curative resection for gastric cancer, five histological grading systems were assessed: the Lauren type, the WHO type, degree of differentiation, the type of tumour border, and the lymphocytic response to the tumour and compared with the Goseki grading (I-IV). When T and N stage were taken into account, using Coxs proportional hazards model, only the Goseki grading added further to the ability to predict survival. The proportional hazards ratios were: node negative v node positive 6.5 T1 v T3 2.45; Goseki I v Goseki IV 3.1. Five year survival of patients with mucus rich (Goseki II and IV) T3 tumours was significantly worse than that of patients with mucus poor (Goseki I and III) T3 tumours (18% v 53%, p < 0.003). Goseki grading identifies subgroups of patients with a poorer prognosis than is predicted by TNM staging alone. It could prove useful in the selection of patients for adjuvant therapy after potentially curative resection for gastric cancer.

Boerhaave's syndrome: 10 years experience and review of the literature

Background: u2003Spontaneous oesophageal rupture, also known as Boerhaaves syndrome, is a rare condition. It has a high mortality and its management is clouded with controversy.