Pre-operative oral carbohydrate loading in colorectal surgery: a randomized controlled trial.

OBJECTIVE: Surgery induces a catabolic response with stress hormone release and insulin resistance. The aim of this study was to assess the effect of pre-operative carbohydrate administration on grip strength, gastrointestinal function and hospital stay following elective colorectal surgery. METHODS: Thirty-six patients undergoing elective colonic resection were randomized into one of three groups. Group 1 were fasted; Group 2 were given pre-operative oral water, Group 3 received equivalent volumes of a Maltodextrin drink. Time to first flatus, first bowel movement and hospital stay were recorded. Muscle strength was measured pre-operatively, and on alternate days thereafter until discharge using a grip strength dynamometer. RESULTS: Patients in the carbohydrate group had a median postoperative hospital stay of 7.5 days compared with 13 days in the water group (P > 0.01) and 10 days in the fasted group (P = 0.06). The median time postsurgery to first flatus was 3 days for both the fasted and water groups compared with 1.5 days in the carbohydrate group (P = 0.13). First bowel movement occurred on day 3 in the carbohydrate group, day 4 in the fasting group and day 5 in the water group. The fasted group showed a significant reduction in postoperative grip strength (P < 0.05) with a median drop of 10% at discharge. Neither the water nor the carbohydrate groups showed significant reductions in muscle strength. CONCLUSION: We found that pre-operative administration of oral carbohydrate leads to a significantly reduced postoperative hospital stay, and a trend towards earlier return of gut function when compared with fasting or supplementary water.

Selective omission of loop ileostomy in restorative proctocolectomy.

Omission of a temporary ileostomy in patients undergoing restorative proctocolectomy is controversial. Although fewer operations may be required and some complications avoided, the risks of anastomotic dehiscence and pelvic sepsis may be greater. Patients undergoing restorative proctocolectomy with no ileostomy (Group NI, n = 72) were compared retrospectively with patients given a conventional loop ileostomy (Group I, n = 30). Criteria for avoiding faecal diversion included: absence of severe acute colitis, good nutritional status and favourable surgery with creation of a sound, tension-free anastomosis. Steroid intake was not a contraindication to single-stage surgery. Delayed stomas were necessary in 8% of Group NI. For Groups NI and I, the rates of anastomotic leak (3% vs 3%), pelvic sepsis without demonstrable leak (3% vs 0%), pouch fistula (3% vs 10%) and intestinal obstruction (8% vs 3%) were similar. Closure of the temporary ileostomy in Group I was associated with a 10% complication rate. Cumulative post-operative hospital stay was significantly less in Group NI (median 11 vs 16 days). Functional results at 1 year were similar. A temporary loop ileostomy can be safely avoided in carefully selected patients undergoing restorative proctocolectomy.

Evaluation of a policy of total mesorectal excision for rectal and rectosigmoid cancers.

BACKGROUND: Total mesorectal excision (TME) is advocated for rectal cancer but the indications and extent of resection vary widely between surgeons. METHODS: Seventy-six consecutive patients (61 elective, 15 acute admission) with rectal or rectosigmoid cancer were admitted to a unit where TME was the preferred surgical option for potentially curative cancer at all levels of the rectum. RESULTS: Procedures undertaken were anterior resection (38 patients), abdominoperineal resection (18), Hartmann's procedure (ten) and transanal excision (one). Six patients had proximal faecal diversion alone and surgery was withheld in three. Anastomotic leaks occurred in six of 37 patients who had anterior resection with primary anastomosis, resulting in one early death. The presence of a proximal stoma did not influence the rate or seriousness of anastomotic dehiscence. After potentially curative TME in 45 patients, there have been eight local recurrences, four associated with systemic metastases and four which occurred in isolation (median follow-up 34 months). CONCLUSION: Curative TME was deemed appropriate in 59 per cent of unselected patients with rectal cancer. It was associated with few local recurrences but a morbidity rate that questions its role in treatment of upper third tumours.

Imaging of the common bile duct in patients undergoing laparoscopic cholecystectomy.

Options for managing the common bile duct during laparoscopic cholecystectomy include routine peroperative cholangiography and selected preoperative endoscopic retrograde cholangiopancreatography (ERCP). The use of these methods was reviewed in 350 patients with symptomatic gall stones referred for laparoscopic cholecystectomy. Unit A (n = 114) performed routine cystic duct cholangiography but undertook preoperative ERCP in patients at very high risk of duct stones only; unit B (n = 236) performed selected preoperative ERCP on the basis of known risk factors for duct stones. The detection rate for common bile duct stones was similar for units A and B (16% v 20%). In unit A, five of seven patients who had preoperative ERCP had duct stones. Operative cholangiography was technically successful in 90% of patients and duct stones were confidently identified in 13, one of whom went on to immediate open duct exploration. Postoperative ERCP identified duct stones in only four patients, indicating spontaneous passage in eight. In unit B, preoperative ERCP was undertaken in 76 of 236 (32%) patients and duct stones were identified in 47 (20%). Duct clearance was successful in 42 (18%) but failed in five (2%), necessitating elective open duct exploration. Both protocols for imaging the common bile duct worked well and yielded satisfactory short term results.

Detection and significance of occult metastases in node-negative breast cancer.

The clinical value of lymph node immunohistochemistry was assessed in 343 consecutive patients with apparently node-negative breast cancer using antimucin monoclonal antibodies BC2, BC3 and 3E1.2. Occult metastases were detected in 41 patients (12 per cent). Although most of these were micrometastatic (< 2 mm in diameter), larger or diffuse deposits were found in ten patients. Blind assessment of repeat haematoxylin and eosin stained sections detected metastases in ten of the 41 patients with occult metastases. After a median follow-up of 79 months, patients with occult metastases had a shorter time to disease recurrence (P < 0.05) but not to death. After adjustment for other prognostic factors, the presence of occult metastases in two or more nodes was the most significant predictor of both disease recurrence (P < 0.01) and death (P < 0.01). When the ten patients with positive haematoxylin and eosin sections were excluded from the analysis, the presence of occult metastases in two or more nodes was still associated with a reduced disease-free interval (P < 0.05) and survival (P < 0.05). Lymph node immunohistochemistry is a simple technique affording more accurate definition of nodal involvement than conventional methods.

Rearrangement of chromosome 1p in breast cancer correlates with poor prognostic features.

In a cytogenetic study of breast cancer biopsies, clonal abnormalities of chromosome 1p were identified in 56% (14) of 25 informative patients. Translocations predominated, involving 1p22 (n = 1), 1p35 (n = 1) or 1p36 (n = 10) breakpoints. Chromosome 1p abnormalities were associated with estrogen receptor (ER) negativity (P = 0.03, 2-tailed Fisher Exact Probability test), high histological grade (P = 0.02, 2-tailed Mann-Whitney U-test) and an unfavourable Melbourne Prognostic Score (NEPA P = 0.02, SEPA P = 0.04, 2-tailed Mann-Whitney U-tests). These findings are consistent with the possibility that a gene located on chromosome 1p is implicated in tumour progression.

Breast cancer in the elderly: treatment of operable disease.

Between 1976 and 1985 122 elderly patients aged 70 years and over, were treated for 'operable' invasive breast cancer (UICC stage I-IIB). A tendency towards less aggressive investigation and treatment was noted in the elderly. Of 117 patients undergoing surgery, 79 (68%) had 'full' conventional treatment, either mastectomy with axillary clearance, sampling or radiotherapy, or local excision with radiotherapy. In 38 patients (32%) management of the breast or axilla was considered to have been less complete than the usual practice for younger patients ('limited' treatment group), either local excision without radiotherapy or simple mastectomy alone. The 'limited' treatment group were significantly older than the 'full' treatment group but were comparable for tumour size, clinical nodal status and oestrogen and progesterone receptor levels. Although there was no survival difference between the groups, those in the 'limited' treatment group were more likely to develop locoregional recurrence (chi 1(2) = 9.2, P = 0.002, log rank test). In practice, management of the elderly often appears to be influenced by chronological age rather than clinical or biological factors. It is suggested that elderly patients sufficiently fit to undergo surgery should be treated along the lines applicable to younger patients.

Breast cancer in the elderly: pattern of disease.

The elderly (aged 70 years or more) constituted 201 (37%) of 548 first-time admissions to a single institution for breast cancer between 1976 and 1985. The pattern of disease was studied and contrasted with that seen in younger patients (less than 70 years old). Currently, 5000 new breast cancers are diagnosed in Australia each year. It is projected that the proportion of new breast cancer patients who are elderly will rise from 37 to 60% by the year 2031. In general, the disease was similar to that seen in younger patients. Minor histological differences occurred and there were tendencies towards late presentation and clinically less aggressive disease. Tumour size, the presence of metastases and UICC staging were useful predictors of outcome but nodal status and hormone receptor levels did not discriminate. An unexpected finding was the relative longevity of elderly patients with breast cancer. The stage-specific 5-year survival rates (UICC stages: I--73%; II--65%; III--42%; IV--10%;) did not differ significantly from those seen in younger patients.

Cytogenetic features of twenty-six primary breast cancers.

Tumor preparations from 26 primary breast cancers were studied cytogenetically with G-banding, using a direct technique, synchronized short-term culture, or both. Two tumors had normal karyotypes, and 24 (92%) had chromosomal abnormalities. Nineteen tumors had chromosome 1 rearrangements, with 10 cases (40%) displaying distal short arm translocations (1p36). Other frequent breakpoints occurred at 3p21, 6q22-27, 11q21-25, 16q22-24, 17p, and 19q13. To seek primary rather than secondary cytogenetic changes, attention was directed toward tumors with diploid-range karyotypes (32-57 chromosomes per cell). Of four such tumors, three exhibited nonrandom involvement of chromosome 16q22. This, together with previously reported data, suggests that deletion or rearrangement of chromosome 16q21-24 may be a primary or specific event in a subset of breast cancers.

Comparison of EGFR, c-erbB-2 product and ras p21 immunohistochemistry as prognostic markers in primary breast cancer.

In a prospective study of 75 breast carcinomas, monoclonal antibodies EGFR1, Anti-serum 21N (As21N) and RAP-5 were used to assess immunohistochemically expression of Epidermal Growth Factor Receptor (EGFR), c-erbB-2 oncoprotein and ras protein p21. A careful comparison was made of their relative prognostic significance. Positive staining was seen with EGFR1 in 12/71 cancers (17%) and with As21N in 16/75 cancers (21%). Positive staining with RAP-5 occurred in all cancers and benign breast tissue, but varied in intensity. EGFR expression correlated with the number of involved lymph nodes, histological grade, estrogen and progesterone receptor (ER, PR) levels and the Melbourne Prognostic Index. C-erbB-2 and ras expression both correlated with ER levels and EGFR, but not with the Prognostic Index. Based on an immunohistochemical technique, EGFR expression emerges as the parameter with strongest prognostic associations.

Breast cancer cytogenetics and beyond.

It is hypothesized that cancers arise as a result of genetic or chromosomal alteration. Evidence for this is provided by the leukaemias and lymphomas in which cytogenetic studies are of established value in diagnosis, classification and follow-up. In contrast, the cytogenetic study of all solid tumours, including breast carcinoma, is in its infancy. However, cytogenetic studies indicate that clonal structural alterations do occur, affecting several loci on a number of chromosomes. Molecular studies provide further evidence of recurring chromosomal breakpoints in breast cancer. This paper reviews the chromosomal rearrangements observed to date and discusses their relevance to the biology of breast cancer.