Nodal involvement in luminal complete response after neoadjuvant treatment for rectal cancer.

BACKGROUND: Pathological complete response (pCR) after neoadjuvant therapy in rectal cancer is correlated with improved survival. There is limited knowledge on the incidence of pCR at a national level with uniform guidelines. The aim of this prospective register-based study was to investigate the incidence and outcome of pCR in relation to neoadjuvant therapy in a national cohort. METHOD: All patients abdominally operated for rectal cancer between 2007 and 2012 (n = 7885) were selected from The Swedish Colo-rectal Cancer Register. Twenty-six per cent (n = 2063) had neoadjuvant therapy with either long or short course radiotherapy with >4 weeks delay with the potential to achieve pCR. The primary endpoints were pCR and survival in relation to neoadjuvant therapy. RESULTS: Complete eradication of the luminal tumor, ypT0 was found in 161 patients (8%). In 83% of the ypT0 the regional lymph nodes were tumor negative (ypT0N0), 12% had 1-3 positive lymph nodes (ypT0N1) and 4% had more than three positive lymph nodes (ypT0N2). There was significantly greater survival with ypT0 compared to ypT+ (hazard ratio 0.38 (C.I 0.25-0.58)) and survival was significantly greater in patients with ypT0N0 compared to ypT0N1-2 (hazard ratio 0.36 (C.I 0.15-0.86)). In ypT0, cT3-4 tumors had the greater risk of node-positivity. The added use of chemotherapy resulted in 10% ypT0 compared to 5.1% in the group without chemotherapy (p < 0.00004). CONCLUSION: Luminal pathological complete response occurred in 8%, 16% of them had tumor positive nodes. The survival benefit of luminal complete response is dependent upon nodal involvement status.

Clinical and biological significance of angiogenesis and lymphangiogenesis in colorectal cancer.

BACKGROUND: Angiogenesis and lymphangiogenesis are essential for tumour development and progression. However, in colorectal cancer (CRC), the relationship between angiogenesis and clinical outcome is controversial, and the prognostic significance of lymphangiogenesis is not well examined because of the lack of specific a marker for lymphatic vessels. AIMS: To evaluate blood microvessel density (MVD) following the proposed standard method for MVD assessment given by the first international consensus and lymphatic vessel density (LVD), and investigate their clinicopathologic and biologic significance in CRC. METHODS: MVD and LVD in primary tumours (n=210), along with their corresponding adjacent normal mucosa (n=105) and distant normal mucosa (n=27) specimens, were immunohistochemically examined by using CD31 and D2-40 antibodies. RESULTS: Both MVD and LVD were higher in tumour compared with the corresponding normal mucosa. In tumours, MVD was positively related to particular interesting new cysteine-histidine-rich protein (PINCH) expression (P=0.006), but not with clinicopathologic variables. LVD, in both intratumoural and peritumoural areas of tumours, was reversely related to Dukes' stage. There was no association between MVD or LVD and patients' survival (P>0.05). CONCLUSIONS: Angiogenesis and lymphangiogenesis occurred in CRC development, but were not related to CRC patient prognosis. PINCH may play a potential role in tumour angiogenesis.

Increase of serum C-reactive protein is an early indicator of subsequent symptomatic anastomotic leakage after anterior resection.

OBJECTIVE: This prospective study investigated the factors which might indicate anastomotic leakage after low anterior resection. METHOD: Thirty-three patients who underwent anterior resection for rectal carcinoma (n = 32) and severe dysplasia (n = 1), were monitored daily by serum C-reactive protein (CRP) and white blood cell count (WBC) estimations until discharge from hospital. Computed tomography (CT) scans were performed on postoperative days 2 and 7 and the amount of presacral fluid collection was assessed. All patients had a pelvic drain and the volume of drainage was measured daily. RESULTS: The level of the anastomosis was at a median 5 cm (3-12 cm) above the anal verge. There was no 30-day mortality. Nine (27.2%) of the 33 patients developed a symptomatic anastomotic leakage which was diagnosed at a median of 8 days (range 4-14) postoperatively. The serum CRP was increased in patients who leaked from postoperative day 2 onwards (P = 0.004 on day 2; P < 0.001 on day 3-8). The WBC was decreased in preoperatively irradiated patients on days 1-5 (P

Clinicopathological significance of microsatellite instability and mutated RIZ in colorectal cancer.

BACKGROUND: Several studies have shown that microsatellite instability (MSI) is related to favourable survival in colorectal cancer patients but there are controversial results. Tumour suppressor gene RIZ is a susceptible mutational target of MSI. However, its clinicopathological significance has not been investigated. We investigated the prognostic significance of MSI in Swedish colorectal cancer patients and the clinicopathological significance of RIZ mutations. PATIENTS AND METHODS: We analysed 438 colorectal adenocarcinomas for MSI by microsatellite analysis. Among them, 29 MSI and 28 microsatellite stable (MSS) tumours were examined for RIZ mutations by DNA sequencing. RESULTS: MSI (13% of 438 cases) was not associated with survival (rate ratio = 0.97, 95% confidence interval = 0.57-1.64, P = 0.90), although it was related to proximal tumour (P <0.001), poor differentiation and mucinous carcinomas (P <0.001), multiple tumours (P = 0.01) and negative/weak expression of hMLH1 (P = 0.03). RIZ mutations were detected in 31% of 29 MSI tumours but in none of the 28 MSS tumours. The mutations were related to female (P = 0.01), proximal tumour (P = 0.01), stage B (P = 0.01) and poor differentiation (P = 0.047). CONCLUSIONS: MSI was not a prognostic factor in the Swedish patients included in this study. Clinicopathological variables associated with RIZ mutations might be a consequence of the MSI characteristics.

Closed vs. open hemorrhoidectomy--is there any difference?

PURPOSE: The aim of this study was to compare closed (Ferguson) hemorrhoidectomy to open (Milligan-Morgan) hemorrhoidectomy regarding postoperative conditions, complications, and long-term results. METHOD: This was a randomized study of 77 patients with second-degree or third-degree hemorrhoids suitable for hemorrhoidectomy. In 39 patients the Milligan-Morgan procedure was used, and in 38 patients the Ferguson procedure was used. Details of operations, postoperative complications, and length of postoperative stay were recorded. Pain was assessed from a visual analog scale and by registration of postoperative analgesic medication. Follow-up was done at three weeks, six weeks, and by visit or telephone interview after at least a year. RESULTS: No statistically significant differences were found between the two methods regarding complications, pain, or postoperative stay. There were four reoperations for bleeding, all after Milligan-Morgan operations. At follow-up after three weeks 86 percent of the Ferguson patients had completely healed wounds, and none had signs of infection. Of the Milligan-Morgan patients, only 18 percent had completely healed wounds, and symptoms of delayed wound healing were significantly more frequent. One patient had a superficial wound infection. After one year more than 10 percent in each group had recurrent hemorrhoids with symptoms. CONCLUSION: Both methods are fairly efficient treatment for hemorrhoids, without serious drawbacks. The closed method has no advantage in postoperative pain reduction, but wounds heal faster, and the risk of wound dehiscence seems exaggerated.

Glutathione S-transferase T1 and M1 genotypes in normal mucosa, transitional mucosa and colorectal adenocarcinoma.

Gene codings for glutathione S-transferase T1 (GSTT1) and M1 (GSTM1) are polymorphic in humans with null genotypes present in approximately 20 and 50%, respectively. A significant excess of homozygous null GSTT1 and GSTM1 genotypes has been demonstrated among individuals with certain types of cancers. This finding suggests that GSTT1 and GSTM1 may play a role in tumour susceptibility. However, reports concerning colorectal cancer susceptibility are controversial. In the present study, we used a multiplex polymerase chain reaction (PCR) approach to identify and analyze simultaneously the genotypes of both the genes in 99 patients with colorectal cancer and 109 healthy controls. Compared with the control group, a significant excess of homozygous null genotypes for GSTT1 was found in normal mucosa among the cancer patients, but not for GSTM1. Both genes were more frequently deleted in tumours than in corresponding normal mucosa. Furthermore, GSTT1 null genotype in tumour tissue, was significantly related to old age and to poor differentiation of tumours. GSTM1 null genotype in tumour was more frequent in the rectal tumours compared with tumours of left colon and right colon. Our results suggest that individuals with GSTT1 null genotype may be genetically predisposed for an increased risk of developing colorectal cancer. Allele loss in tumour tissue, which reflects genetic instability, may be considered as a marker for evaluating clinico-pathological characteristics of the cancer patients.

A short diagnostic delay is more important for rectal cancer than for colonic cancer.

OBJECTIVE: To study the association between a short diagnostic delay and tumour stage in patients with colonic and rectal cancer. DESIGN: Prospective study. SETTING: Multicentre study, Sweden. PATIENTS: 336 patients with colonic, and 218 patients with rectal cancer. MAIN OUTCOME MEASURES: Incidence and duration of symptoms, delay in diagnosis, and stage at diagnosis. RESULTS: Patients with rectal cancer and a delay of less than a month between start of symptoms and diagnosis included a significantly larger proportion of Dukes' A tumours than patients with a longer delay (p = 0.004). Delay in patients with colonic cancer did not correlate with stage. CONCLUSION: A short delay in the diagnosis of rectal cancer was associated with better staging. This could not be shown for colonic cancer, which may be attributable to its initially vague symptoms and to a subgroup of highly malignant tumours with rapidly progressive symptoms.

Prognostic significance of p53 nuclear and cytoplasmic overexpression in right and left colorectal adenocarcinomas.

The prognostic significance of nuclear and cytoplasmic p53 protein, detected immunocytochemically using CM1 and PAb 1801 antibodies, was evaluated in right-sided and left-sided colorectal adenocarcinomas from 293 patients. CM1 nuclear and cytoplasmic p53 accumulation occurred in 38 and 25% of cases, respectively. PAb 1801 nuclear staining occurred in 18%, with no cytoplasmic staining. CM1 expression either in the nucleus or in the cytoplasm was positively related to PAb 1801 expression (P < 0.001 and P = 0.009, respectively). The incidence of CM1 nuclear and cytoplasmic expression was more frequent in right-sided tumours (P = 0.023 and P = 0.034, respectively), while PAb 1801 nuclear staining was more common in left-sided tumours (P = 0.011). In survival analyses, CM1 nuclear overexpression in the right-sided tumours (P = 0.016) and CM1 cytoplasmic overexpression in left-sided tumours (P = 0.04) were prognostic indicators, independent of Dukes' stage, DNA ploidy, PAb 1801 expression and each other. Further analysis showed that the prognostic value of CM1 nuclear expression was greater in right-sided tumours than in left-sided tumours (P = 0.018). The nuclear and cytoplasmic p53 protein detected with CM1 and PAb 1801 may play different roles in tumour progression and provide prognostic indicators for right- and left-sided colorectal tumours.

A pilot study on risk factors and p53 gene expression in colorectal cancer.

Of 311 colorectal cancers diagnosed in 1984-86 in the county of Ostergotland, Sweden, 179 were included in a case-control study, and, of these, 70 were investigated using immunohistochemical staining for p53 gene mutations. Alcohol use as well as medication with hydralazine-containing antihypertensive drugs, but not heredity were associated with p53 staining. The study is offered to illustrate the possible value of investigating molecularly defined tumour subtypes in relation to specific risk factors.

Local recurrence following total mesorectal excision for rectal cancer.

Early results after rectal cancer surgery in a defined population were compared before and after the introduction of total mesorectal excision. In the first period (1984-1986) 211 cases of rectal cancer were diagnosed and in the second (1990-1992) 230. Of these, 134 patients in the first period (group 1) had anterior resection or abdominoperineal excision which was considered curative. In the second period 128 curative anterior resections and abdominoperineal excisions were performed by a limited number of surgeons familiar with total mesorectal excision (group 2). No differences between the groups were found in stage distribution, rate of curative operations, postoperative complications or postoperative mortality. Local recurrence had developed in 19 patients in group 1 and in eight in group 2, 1 year after the end of the study periods (P = 0.03). Local radicality was in doubt in 13 patients in group 1 and in eight in group 2. In the remaining 121 and 120 patients, 13 and four local recurrences respectively were present (P = 0.03). Actuarial analysis showed a significant reduction in local recurrence rate (P = 0.03) and an increase in crude survival (P = 0.03) at 4 years in group 2 compared with group 1. Total mesorectal excision reduces the local recurrence rate after excision of rectal cancer.

Outcome of surgery for colorectal cancer in a defined population in Sweden from 1984 to 1986.

PURPOSE: This study was designed to investigate incidence, treatment, and outcome for patients with colorectal cancer. METHODS: From 1984 to 1986 in Ostergötland, a county in Sweden with a defined population, a prospective registration using a computerized protocol was undertaken. RESULTS: In the surgical departments 596 cases were diagnosed and 31 more cases were diagnosed in other departments, bringing the incidence to 53 cases per 100,000 inhabitants per year. Of the cases, 14 percent presented as emergencies. The resectability rate was 90 percent, and the rate of curative operations was 74 percent. Postoperative mortality within 30 days was 2.9 percent. Crude five-year survival for all patients was 40 percent, and the corrected survival rate was 53 percent. After curative resection the crude five-year survival rate was 53 percent, and the corrected survival rate was 70 percent. Prognosis was better for colon than for rectal cancer, 76 percent vs. 59 percent corrected five-year survival rate. For rectal cancer the local recurrence rate was 20 percent after curative resection. CONCLUSIONS: The prognosis was improved compared with a previous study from the same area because of decreased postoperative mortality, increased rate of operations for cure, and an increased five-year corrected survival rate. Local recurrence after rectal cancer was still high but may be reduced with improved surgical technique.

Do occupational factors influence the risk of colon and rectal cancer in different ways?

BACKGROUND: Occupational exposures and physical activity have been considered as risk factors for the development of colorectal cancer. METHODS: A case-control study on working conditions and the risk of colon and rectal cancer was performed in southeastern Sweden during 1984-86. Involved were 177 patients, 98 with colon cancer and 79 with rectal cancer, and two groups of control subjects, 371 hospital control subjects and 430 population control subjects. RESULTS: A significantly decreased risk of left-sided colon cancer was observed in persons involved in more than 20 years of physically active work and a significantly decreased risk of rectal cancer in persons involved in more than 20 years of sedentary work. A tendency toward increased risk was seen for colon cancer in male railroad workers and in male gas station workers. A reduced risk of rectal cancer was found for drivers, textile workers, and administration workers, whereas an increased risk of rectal cancer appeared among paper workers and assistant nurses. A low risk of both colon and rectal cancer was found among construction workers and forestry workers. Exposure to asbestos carried a slightly increased risk of colon cancer, whereas exposure to solvents slightly decreased the risk of rectal cancer. CONCLUSION: This study confirms earlier findings that physical activity decreases the risk for left-sided colon cancer, but also suggests that occupational factors influence the risk of colon and rectal cancer in different ways.

Cereal fiber, calcium, and colorectal cancer.

Food intake during the preceding 15 years was evaluated in detail in 41 patients treated for colorectal cancer and an equal number of matched control subjects by means of a dietary history technique that permitted quantitation of nutrients. Dietary habits of the control group could be compared against two larger groups of 371 hospital control and 430 population control subjects. Patients with cancer, who were interviewed after complete recovery from surgery, consumed more fat, protein, and carbohydrates, and thus more energy, than control subjects although these differences were not statistically significant. Per unit energy, the habitual diet of patients with cancer contained less cereal fiber (P less than 0.001), less riboflavin (P less than 0.05), less calcium (P less than 0.05), and less phosphorus (P less than 0.05) than the diet of the control subjects. A high intake of either cereal fiber, total fiber, calcium, and phosphorus in relation to energy intake was found to be associated with a reduced risk ratio of colorectal cancer. For colon cancer separately, a high intake of calcium and cereal fiber was associated with a reduced risk ratio. For rectal cancer, a high intake of total fiber and cereal fiber was associated with a reduced risk ratio. High alcohol consumption correlated with an increased risk ratio. These data are compatible with previous Scandinavian studies relating food consumption to the incidence and mortality of colorectal cancer.

Strangulated obturator hernia. A simple method for closure.

Three cases of strangulated obturator hernia are presented, two of them treated with a new method in which the urinary bladder wall was used to cover the hernial orifice. The literature is reviewed and the importance of early diagnosis and operation is stressed. The symptoms often are nonspecific, and if surgery is delayed the mortality is high.