A systematic review of gut microbiota composition in observational studies of major depressive disorder, bipolar disorder and schizophrenia.

The emerging understanding of gut microbiota as 'metabolic machinery' influencing many aspects of physiology has gained substantial attention in the field of psychiatry. This is largely due to the many overlapping pathophysiological mechanisms associated with both the potential functionality of the gut microbiota and the biological mechanisms thought to be underpinning mental disorders. In this systematic review, we synthesised the current literature investigating differences in gut microbiota composition in people with the major psychiatric disorders, major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ), compared to 'healthy' controls. We also explored gut microbiota composition across disorders in an attempt to elucidate potential commonalities in the microbial signatures associated with these mental disorders. Following the PRISMA guidelines, databases were searched from inception through to December 2021. We identified 44 studies (including a total of 2510 psychiatric cases and 2407 controls) that met inclusion criteria, of which 24 investigated gut microbiota composition in MDD, seven investigated gut microbiota composition in BD, and 15 investigated gut microbiota composition in SZ. Our syntheses provide no strong evidence for a difference in the number or distribution (α-diversity) of bacteria in those with a mental disorder compared to controls. However, studies were relatively consistent in reporting differences in overall community composition (ß-diversity) in people with and without mental disorders. Our syntheses also identified specific bacterial taxa commonly associated with mental disorders, including lower levels of bacterial genera that produce short-chain fatty acids (e.g. butyrate), higher levels of lactic acid-producing bacteria, and higher levels of bacteria associated with glutamate and GABA metabolism. We also observed substantial heterogeneity across studies with regards to methodologies and reporting. Further prospective and experimental research using new tools and robust guidelines hold promise for improving our understanding of the role of the gut microbiota in mental and brain health and the development of interventions based on modification of gut microbiota.

Who gets Hartmann's reversed in a regional centre?

BACKGROUND: Many patients who undergo a Hartmann's procedure do not have their stoma reversed. We analysed parameters and co-morbidity scales to assess their accuracy in predicting likelihood of undergoing reversal. MATERIAL AND METHODS: Retrospective analysis of 165 patients from a prospective colorectal database who were discharged home following a Hartmann's procedure at Barwon Health (Geelong, Australia), a regional centre, between 2002 and 2010. Parameters measured included age, sex, time to reversal, ICU admission and pathology results were recorded. Patients' ASA, POSSUM and Elixhauser co-morbidity scales were retrospectively analysed. RESULTS: Reversal of Hartmann's was performed in 74/165 (45%) patients after a median of 294 days (range 70-902). Age (mean 58.5 vs 72.9 years, p < 0.001), ICU stay (34/74 vs 66/91, p < 0.001), ASA (p < 0.002), Elixhauser co-morbidity count (mean 1.14 vs 1.92, p < 0.002) and a malignant diagnosis (9/74 vs 31/91, p < 0.002) were all associated with a decreased reversal rate on univariate analysis. Age was the only parameter found to be significant on multivariate analysis. The complication rate was 23/74, with 7/74 noted to have major complications (Clavian-Dindo III-IV). Reasons for not reversing patients included age and co-morbidities, patient refusal, and malignant disease progression. CONCLUSIONS: More than half the patients undergoing a Hartmann's procedure did not proceed to a closure of their stoma. Age was the only parameter significant in predicting those patients undergoing reversal.

Eating marshmallows reduces ileostomy output: a randomized crossover trial.

AIM: Anecdotally, many ostomates believe that eating marshmallows can reduce ileostomy effluent. There is a plausible mechanism for this, as the gelatine contained in marshmallows may thicken small bowel fluid, but there is currently no evidence that this is effective. METHOD: This was a randomized crossover trial. Adult patients with well-established ileostomies were included. Ileostomy output was measured for 1 week during which three marshmallows were consumed three times daily, and for one control week where marshmallows were not eaten. There was a 2-day washout period. Patients were randomly allocated to whether the control or intervention week occurred first. In addition, a questionnaire was administered regarding patient's subjective experience of their ileostomy function. RESULTS: Thirty-one participants were recruited; 28 completed the study. There was a median reduction in ileostomy output volume of 75 ml per day during the study period (P = 0.0054, 95% confidence interval 23.4-678.3) compared with the control week. Twenty of 28 subjects (71%) experienced a reduction in their ileostomy output, two had no change and six reported an increase. During the study period, participants reported fewer ileostomy bag changes (median five per day vs six in the control period, P = 0.0255). Twenty of 28 (71%) reported that the ileostomy effluent was thicker during the study week (P = 0.023). Overall 19 (68%) participants stated they would use marshmallows in the future if they wanted to reduce or thicken their ileostomy output. CONCLUSION: Eating marshmallows leads to a small but statistically significant reduction in ileostomy output.

Fertility after young-onset colorectal cancer: a study of subjects with Lynch syndrome.

AIM: Infertility is a concern for young survivors of colorectal cancer (CRC), but this risk is not well quantified. Carriers of mismatch repair (MMR) mutations are a useful cohort for studying fertility after CRC as they commonly develop CRC when young, and unaffected family members provide demographically similar controls. The aim of this study was to determine the effect of CRC on fertility in a large cohort of MMR mutation carriers. METHOD: Mismatch repair mutation carriers identified from the Australasian Colorectal Cancer Family Registry were included. For each year of life within the fertile age range (15-49), the number of living individuals and the number of children born to them were determined. Individuals were grouped by whether or not they had had a diagnosis of CRC by that age. Age-specific and total fertility rates were calculated. RESULTS: We identified 1068 subjects (611 women and 457 men), of whom 467 were diagnosed with CRC. There were 1192 births during 18 674 person-years of follow-up to the women and 814 births during 14 013 person-years of follow-up to the men. The total fertility rate was decreased in women after a diagnosis of CRC compared with those who did not have CRC (1.3 vs 2.2; P = 0.0011), but age-specific fertility was only reduced in the 20-24-year age group. In men the total fertility rate was similar for both groups (2.0 vs 1.8; P = 0.27). CONCLUSION: Age-specific fertility was decreased in female CRC survivors with Lynch syndrome aged 20-24, but not in older women or in men.

Stenting as first-line management for all patients with nonperforating left-sided obstructing colorectal cancer.

AIM: Since 2005, we have used self-expanding metal stents (SEMS) as primary treatment for all patients with left-sided obstructing colorectal cancer without evidence of perforation. The purpose of this study was to assess the safety and efficacy of this treatment. METHOD: This was a prospective study of consecutive patients with left-sided obstructing colorectal cancer without perforation or peritonitis treated between January 2005 and June 2009. SEMS placement was attempted in all cases. Emergency surgery was reserved for patients in whom a stent placement failed. After successful decompression, surgery was offered to patients with potentially curable disease. RESULTS: Seventy-seven patients were included, with successful SEMS placement in 60/77 (78%) patients, 25 as a bridge to surgery and 35 for palliation. Immediate complications occurred in two (3%) cases. There was no mortality. Of 35 patients in whom SEMS was for palliation, 32 (91%) avoided surgery altogether. A stoma was fashioned in 5 (8.3%) of the 60 patients who were successfully stented, and in 12 (71%) of the 17 patients in whom stenting failed (P = 0.0001). CONCLUSION: A SEMS-based management protocol for patients with large bowel obstruction due to colorectal cancer is safe and effective.

Mismatch repair deficiency in colorectal cancer patients in a low-incidence area.

BACKGROUND: In a previous study we identified 206 patients with colorectal adenocarcinoma in the Northern Cape province of South Africa, diagnosed between January 2002 and February 2009. The age-standardised incidence was 4.2/100 000 per year world standard population. This is 10% of the rate reported in First-World countries. In high-incidence areas, the rate of abnormal mismatch repair gene expression in colorectal cancers is 2 - 7%. OBJECTIVES: The aim of this study was to determine the prevalence of hMLH1- and hMSH2-deficient colorectal cancer in the Northern Cape. METHODS: Formalin-fixed paraffin wax-embedded tissue blocks from 87 colorectal adenocarcinomas identified in the previous study were retrieved. Standard immunohistochemical staining methods were used to detect the expression of hMLH1 and hMSH2 (i.e. products of the hMLH1 and hMSH2 genes) in the tumours using heat-induced antigen retrieval and diaminobenzidene as a chromogen. Results. In 8 blocks there was insufficient tumour tissue and in 1 case the immunohistochemical staining failed, probably owing to poor fixation, leaving 78 cases for analysis. In 11 cases hMLH1 was deficient and in 6 cases hMSH2 was deficient. Overall, 21.8% of cancers were deficient for hMLH1 or hMSH2. CONCLUSION: Presuming that 80% of all hMLH1 deficiencies are due to hypermethylation of the gene, we found 10.5% of colorectal cancers in an area with a low incidence of colorectal cancer to be deficient in the product of the mismatch repair gene/s. This is approximately three times the reported rate in high-incidence areas.

Surgery for colonic cancer in HNPCC: total vs segmental colectomy.

AIM: The high reported risk of metachronous colon cancer (MCC) in hereditary nonpolyposis colorectal cancer (HNPCC) has led some authors to recommend total colectomy (TC) as the preferred operation for primary colon cancer, but this remains controversial. No previous study has compared survival after TC with segmental colectomy (SC) in HNPCC. The aim of this study was to determine the risk of developing MCC in patients with genetically proven HNPCC after SC or TC for cancer, and to compare their long-term survival. METHOD: This is a prospective cohort study of all patients referred to our unit between 1995 and 2009 with a proven germline mismatch repair gene defect, who had undergone a resection for adenocarcinoma of the colon with curative intent. All patients were offered annual endoscopic surveillance. RESULTS: Of 60 patients in the study, 39 had TC as their initial surgery and 21 had SC. After 6 years follow up, MCC occurred in eight (21%) SC patients and in none of the TC patients (P = 0.048). The risk of developing MCC after SC was 20% at 5 years. Colorectal cancer-specific survival was better in TC patients (P = 0.048) but overall survival of the two groups was similar (P = 0.29). CONCLUSION: Patients with HNPCC have a significant risk of MCC after SC. This is eliminated by performing TC as the primary operation for colonic cancer.

Self-expanding metal stents as an alternative to surgical bypass for malignant gastric outlet obstruction.

BACKGROUND: Gastroduodenal obstruction due to malignancy can be difficult to palliate. Self-expanding metal stents (SEMS) are gaining acceptance as an effective alternative to surgical bypass. METHODS: Patients not suitable for surgical bypass, with complete gastric outlet obstruction as a result of malignancy, were offered palliation with SEMS from November 2004 to December 2008. The procedure was performed under fluoroscopic guidance and conscious sedation. Data were collected prospectively. RESULTS: Seventy patients underwent SEMS placement (hepatobiliary and pancreatic malignancy, 44; antral gastric carcinoma, 19; other, seven). Follow-up was complete in 69 patients (99 per cent). Technical and clinical success rates were 93 and 95 per cent respectively. Median hospital stay was 2 (range 1-18) days, median survival was 1.8 (0.1-19.0) months, and 87 per cent had improved intake after SEMS placement, as determined by Gastric Outlet Obstruction Severity Score before and after stenting (P < 0.001). Complications included two episodes of minor bleeding. CONCLUSION: The use of SEMS to alleviate complete malignant gastric outlet obstruction in patients with limited life expectancy is successful in re-establishing enteral intake in most patients, with minimal morbidity, no mortality and a short hospital stay.

Incidence and histological features of colorectal cancer in the Northern Cape Province, South Africa.

AIM: The purpose of this study was to determine the incidence of colorectal cancer (CRC) in the Northern Cape province of South Africa, and to identify patients with histological and demographic features suggestive of hereditary non-polyposis colon cancer (HNPCC). METHOD: This is a retrospective review of all cases of primary adenocarcinoma of the colon or rectum diagnosed by the two pathology laboratories operating in the Northern Cape between January 2002 and February 2009. Demographic data were collected, as well as pathological staging of the tumours and histological features suggestive of HNPCC (according to the revised Bethesda guidelines for microsatellite instability testing). Population census data for the Northern Cape were obtained from Statistics South Africa. RESULTS: The annual incidence of CRC in the Northern Cape was 3.7/100,000 population (3.5/100,000 for men and 3.9/100,000 for women). The median age at which colorectal cancer was diagnosed was 59 years (range 16-90 years). On pathological and demographic criteria, 75/206 (36%) of the patients met at least one of the criteria of the revised Bethesda guidelines for microsatellite instability testing. CONCLUSION: CRC is rare in the Northern Cape, and one-third of the patients had demographic or tumour histological features suggestive of HNPCC.

Surveillance colonoscopy improves survival in a cohort of subjects with a single mismatch repair gene mutation.

OBJECTIVE: Previous studies have shown a benefit for surveillance colonoscopy in heterogeneous groups of subjects with suspected or proven hereditary nonpolyposis colon cancer. The aim of this study was to investigate whether surveillance colonoscopy improves the survival in subjects who all carry a single mismatch repair gene defect. METHOD: This is a prospective cohort study of 178 subjects who carry a mutation of the MLH1 gene in exon 13 (C1528T). They were offered surveillance colonoscopy between 1988 and 2006, and were followed up until September 2007. RESULTS: One hundred and twenty-nine subjects underwent surveillance colonoscopy, and 49 declined. After a median follow up of 5 years, colorectal cancer was diagnosed in 14/129 (11%) subjects in the surveillance group and 13/49 (27%) in the nonsurveillance group (P = 0.019). Cancers in the surveillance group were at an earlier stage than in the nonsurveillance group (P = 0.032). Death from colorectal cancer occurred in three of 129 (2%) subjects in the surveillance group, and six of 49 (12%) in the nonsurveillance group (P = 0.021). The Kaplan-Meyer estimates for median survival from birth were 78 years in the surveillance group, and 55 years in the nonsurveillance group (P = 0.024). The Kaplan-Meyer estimates for median colorectal cancer-free survival from birth were 73 years in the surveillance group and 47 years in the nonsurveillance group (P = 0.0089). CONCLUSION: Surveillance colonoscopy was associated with improved overall and colorectal cancer-related survival in subjects carrying a single mismatch repair gene mutation.

Risk of blood splashes to the eye during surgery.

BACKGROUND: With the advent of a new infectious era involving the HIV and hepatitis B and C viruses, concern has arisen about transmission of these viruses through ocular blood splashes during surgery. The purpose of the study was to determine the risk of ocular blood splashes to surgeons and their assistants during surgery. METHOD: Surgeons and assistants in several surgical disciplines were requested to wear facemasks with a transparent plastic visor. The visors were collected postoperatively and inspected for macroscopic and microscopic blood splashes. RESULTS: Fifty-nine per cent of the surgeons and assistants refused to wear facemasks with a visor. The incidence of blood splashes in those who participated was 45%. There was a trend for blood splashes to be more common during major surgery and during elective surgery. Surgeons and assistants were subject to similar risk. CONCLUSION: This study confirms the significant risk of ocular blood splashes during surgery, while also suggesting that both surgeons and assistants lack appreciation of the risk.

Long-term results of palliative stenting or surgery for incurable obstructing colon cancer.

OBJECTIVE: Self-expanding metal stents are an effective means of relieving left-sided malignant colonic obstruction, and in the setting of incurable disease may provide palliation while allowing the patients to avoid surgery altogether. With modern chemotherapy regimes, patients may have a long-life expectancy, even in the presence of metastases. The purpose of this study was to investigate the long-term results of palliative stent placement, compared with patients undergoing palliative surgery. METHOD: This is a retrospective study of 55 consecutive patients who underwent colonic stenting or palliative surgery for incurable, obstructing adenocarcinoma of the left colon. RESULTS: Twenty-nine patients underwent colonic stenting, and 26 had surgery during the study period. Survival was similar in the two groups (14 months in the stent group, 11 months in the surgery group). Median hospital stay was shorter in the stent group (4 vs 13.5 days), and fewer patients in the stent group had complications (2 vs 14). Only four patients in the stent group went on to require later surgery. The median time to failure of the stents was 14 months. CONCLUSION: Colonic stenting provides effective and durable palliation for patients with incurable, obstructing adenocarcinomas of the left colon. It can be performed with less morbidity than palliative surgery, and offers similar long-term survival.

Gastrojejunostomy for gastric outlet obstruction in patients with gastric carcinoma.

OBJECTIVE: To investigate the utility of gastrojejunostomy for the palliation of gastric outlet obstruction in irresectable or incurable gastric carcinoma. METHODS: This is a retrospective review of 67 patients who underwent a gastrojejunostomy for gastric outlet obstruction caused by gastric carcinoma between 1 January 1996 and 31 May 2003. RESULTS: There were 19 complications after surgery, including 4 patients with unsatisfactory gastrojejunostomy drainage. Sixty patients were discharged from hospital having resumed normal eating. Their median survival after surgery was 9 months. CONCLUSION: Gastrojejunostomy offers worthwhile palliation and may prolong survival in a significant group of patients with irresectable gastric carcinoma and gastric outlet obstruction.

No evidence of genetic anticipation in a large family with Lynch syndrome.

Lynch syndrome is the commonest inherited cause of colorectal cancer (CRC). Genetic anticipation occurs when the age of onset of a disorder decreases in successive generations. It is controversial whether this occurs in Lynch syndrome. Previous studies have included heterogenous groups of subjects from multiple families, including subjects with a clinical diagnosis (based on family history) as well as those with proven germline mismatch repair gene mutations. The purpose of this study was to determine whether genetic anticipation occurs in mismatch repair gene carriers from a single Lynch syndrome family. This study includes members of a single family known to carry an MLH1 gene mutation who are proven germline mutation carriers or obligate carriers (based on their offspring's mutation status). Evidence of genetic anticipation (determined by age of onset of first CRC) was sought in two ways: Firstly, subjects were grouped as parent-child pairs and individuals were compared with their own offspring; secondly they were grouped by generation within the family tree. The Kaplan-Meier technique was used to adjust for variable follow up times. The family tree consisted of 714 subjects. Ninety-two subjects over five generations were included in the study. There was no evidence of genetic anticipation over the generations. (P = 0.37). Similarly, in the 75 parent-child pairs identified, age of onset of CRC was similar for parents and children (P = 0.51). We could not identify any evidence of genetic anticipation in mutation carriers from a single family with Lynch syndrome.

Cancer risk in a cohort of subjects carrying a single mismatch repair gene mutation.

Hereditary non-polyposis colon cancer (HNPCC) is an autosomal dominant condition, caused by germline mutations in the mismatch repair genes, that presents with colorectal cancers at a young age, as well as extracolonic tumours. One of the causative mutations is the C1528T (Exon 13) mutation of the MLH1 gene. The purpose of this study is to document the cancer risk for subjects who carry this mutation. This is a prospective cohort study of 200 subjects who carry this mutation. We calculated the risk of developing colorectal cancer only in those subjects who had not undergone surveillance colonoscopy. The incidence of extracolonic cancers (for which surveillance is not routinely offered) was determined for the entire cohort. The results of the study are among the 71 subjects who did not undergo surveillance colonoscopy, colorectal cancers occurred in 36 (51%). They occurred at a median age of 44 years (range 17-73). Using Kaplan-Meier estimates, the risk of developing a colorectal cancer by age 65 was 92%. Eighteen subjects in the cohort of 200 were diagnosed with extracolonic tumours. The most common extracolonic malignancies were breast (6/98 women) and endometrial (3/98 women). Thus this mutation has a high penetrance for colorectal cancer, but is not associated with a high risk of developing extracolonic malignancies.