Reconstruction of the chest wall.

Chest wall reconstructions can be a complex and challenging procedure and may require a multidisciplinary approach. The most common indications for chest wall reconstruction are repair of defects due to tumor resection, infection, radiation necrosis, congenital deformities or trauma. The repair of complex chest wall defects presents a challenging problem for the reconstructive surgeon. Although the majority of such defects can be repaired with the use of local and regional musculocutaneous flaps, more complicated cases require increasingly sophisticated reconstructive techniques. As defects increase in size, microsurgical techniques are necessary to augment blood flow to pedicled flaps or to provide free flap coverage from distant sites. A better understanding of the respiratory mechanics and local anatomy is crucial in managing these complex defects.

Intraoperative hyperthermia and chemoradiotherapy for inoperable pancreatic carcinoma.

The aim of this study was to evaluate the tolerability and the possible clinical benefit of intraoperative hyperthermia combined with multischedule chemotherapy and bypass surgery for the palliative treatment of inoperable pancreatic cancer. Ten patients with unresectable adenocarcinoma of the pancreas received preoperative chemotherapy [5-fluorouracil (5-FU)], bypass surgery and postoperative chemotherapy (5-FU, doxorubicin and cisplatin) plus sandostatin and radiotherapy (45 Gy, 25 fractions, 5 days a week). A single session of intraoperative hyperthermia was performed, by using a waveguide-type applicator (433 MHz). The tumour region was heated to 43-45 degrees C for up to 60 min, while 500 mg 5-FU was infused simultaneously through the gastroduodenal into the splenic artery. Postoperative recovery was uneventful for all patients. A brief instrument was developed for evaluating patients' quality of life. Chemotherapy-related toxicity included myelosuppression, vomiting, alopecia and increase in blood urea nitrogen (BUN), creatinine, SGOT and SGPT. Glucose and amylase determinations remained within normal limits throughout the whole treatment. There was a significant improvement before and 1 month after combined treatment in Eastern Cooperative Oncology Group (ECOG) status (1.8 +/- 0.4), Scott-Huskinsson pain scale (3.2 +/- 0.8) and quality of life score (30.5 +/- 6.7). No progressive disease was noticed and the median overall survival was 11 (SE = 2.4) months. There was also a significant (P = 0.002, Wilcoxon test) decrease in values of both serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9), from 7.6 +/- 1.3 ng/mL and 875.7 +/- 104.8 U/mL to 3.5 +/- 0.7 ng/mL and 65.3 +/- 14.1 U/mL respectively. The first clinical results suggest a potential advantage of using combined intraoperative hyperthermia, chemotherapy and postoperative radiotherapy in the palliative treatment of the adenocarcinoma of the pancreas. The whole procedure seems to be free of perioperative morbidity, while the chemotherapy toxicity was rather moderate. However, the preliminary nature limits the general applicability of our results.

Intraoperative hyperthermia in conjunction with multi-schedule chemotherapy (pre-, intra- and post-operative), by-pass surgery, and post-operative radiotherapy for the management of unresectable pancreatic adenocarcinoma.

The aim of this study was to evaluate the potential role of intraoperative hyperthermia (IOHT) in the management of stage IV pancreatic adenocarcinoma. Twenty-seven patients (group A) received pre-operative chemotherapy (5-FU), by-pass surgery with intraoperative bolus infusion of 5-FU and post-operatively multi-agent chemotherapy plus sandostatin and external beam irradiation (45Gy, 25 fractions, 5 days a week). In a non-randomized way, 10 patients (group B) received an additional single session of IOHT (43-45 degrees C, 1h) performed directly on the tumour using a waveguide applicator (433MHz) with interstitial measurements of temperature measured. A brief instrument was developed for evaluating patients' quality of life. No progressive disease (PD) was noticed in group B vs 11% (3/27) of PD in group A. There was also a significant increase of overall survival (OS) in group B vs A patients (p = 0.029, log-rank test). Moreover, there was a significant improvement for group B vs A patients regarding Karnofsky performance status (p < 0.001, Mann-Whitney test), pain score (p < 0.001, Mann-Whitney test) and quality of life score (p = 0.031, Mann-Whitney test). A significant correlation was noticed between OS and thermal parameters such as average T(min) (p = 0.043), average T(max) (p = 0.027) and cumulative minutes T(90) >or= 44 degrees C (p < 0.001). Combined IOHT with chemotherapy (pre-, intra- and post-operative) and external beam post-operative radiotherapy seem to have a potential benefit in the management of unresectable adenocarcinoma of the pancreas, concerning local response, OS and quality of life. Further clinical studies to evaluate the benefit of IOHT suggested in this study are warranted.

A phase II study of 9-nitrocamptothecin in patients with advanced pancreatic adenocarcinoma.

PURPOSE: Preclinical and phase I clinical data suggest that 9-nitrocamptothecin (9NC) is an agent with potential anticancer activity. A phase II study was undertaken in order to evaluate the potential benefit of oral 9NC administration in patients with advanced pancreatic cancer. This was the first clinical study of 9NC in Europe. METHODS: A total of 19 consecutive patients with locally advanced or metastatic adenocarcinoma were enrolled (8 males and 11 females, aged 37-73 years). The patients were given 9NC orally five times a week, once a day. The end-points of this study were toxicity, objective response rate, subjective response rate (i.e. pain control, performance status and body weight), and survival. RESULTS: An objective response was documented in 4 of the 14 evaluable patients (28.6%), while a subjective response was observed in 13 patients (92.9%). Overall median survival was 21 weeks (31 weeks in the group of 14 patients evaluable for response), and the 1-year survival was 16.7% and 23.1%, respectively. Toxicity leading to temporary discontinuation of 9NC was encountered in seven patients (36.8%), all related to a prior dose increase, while milder toxicity was observed in eight patients (42.1%). CONCLUSIONS: 9NC administered orally to patients with advanced pancreatic cancer gave promising results, while the toxicity of the therapy was mild and readily overcome. A larger scale clinical trial should be organized in order to establish the potential benefit of 9NC in patients with pancreatic adenocarcinoma.

Replacement of the pyloric sphincter with the ileocecal valve: an experimental study.

BACKGROUND: Several surgical methods have been devised and applied to overcome the complications associated with the loss of the pyloric sphincter after distal gastrectomy. However, none of these methods creates an efficient sphincteric mechanism at the anastomotic site. The purpose of this experimental study in dogs was to replace the pylorus with the ileocecal valve and determine whether its sphincteric function would be preserved in its new location without affecting gastrointestinal motility and the health of the animals. METHODS: Thirteen dogs underwent surgical removal of the pyloric sphincter and a partial distal gastrectomy. The ileocecal valve, with a short segment of ileum, was then relocated so that the ileal segment was anastomosed to the stomach while the cecal segment was anastomosed to the duodenum. Intestinal continuity was reestablished by anastomosing the distal ileum with the ascending colon. Intraileal and intracolic pressures were measured in all animals prior to and following transposition of the ileocecal valve. In 3 of these animals, pre-pyloric (intragastric) and post-pyloric (intraduodenal) pressures were also measured before the pylorus was removed. Pressure measurements on both sides of the transposed ileocecal valve were performed again 4-6 months later. All pressure measurements were made directly with a water manometer. Radiographic and fluoroscopic studies were carried out on all animals to assess gastrointestinal motility, gastric emptying times, and the sphincteric competence of the transposed ileocecal valve. Hematological and biochemical studies intended to assess the nutritional status of all animals were carried out. Also, postoperative measurements were made of gastric basic acid output. RESULTS: All animals were alive and well 4-6 months after the initial operative procedure. Hematological studies and biochemical tests and studies of liver function remained normal. There was a slight reduction in serum B12 levels and, as expected, a significant postoperative reduction in gastric basic acid output. The intraluminal pressure measurements and the radiographic and fluoroscopic studies all showed that the sphincteric mechanism of the ileocecal valve was preserved in its new location, that gastrointestinal motility was not impaired, and that the healthy condition of the animals was maintained. Gross and histological examination of the transposed segments of the intestinal tract did not reveal any abnormalities. CONCLUSION: Because the anatomy and physiology of the human alimentary tract are similar to those of the dog, this technique may be applicable clinically, when indicated, to avoid and/or relieve complications resulting from gastrectomy, when those complications do not respond or have not responded to conservative management.

Expression of receptors for estrogen and progesterone in malignant colonic mucosa as a prognostic factor for patient survival.

BACKGROUND AND OBJECTIVES: Estrogen receptors (ER) and progesterone receptors (PR) have been detected in both normal and malignant colonic mucosa, but the prognostic value of this observation is unknown. We aimed to define the prognostic significance of the presence of ER and PR in malignant cells from colorectal adenocarcinoma specimens. METHODS: An immunohistochemical assay for ER and PR was performed on paraffinized sections from 65 colorectal adenocarcinoma specimens. Survival curves were analyzed to define the prognostic implications of ER and PR. RESULTS: Twenty nine (45%) tumors tested receptor positive (32% for ER and 23% for PR). Tumors of advanced stage were more likely to express receptors than early stage tumors (56% vs. 32%; P = 0.01). Median survival of patients with neoplasms expressing PR was 30 months. For patients whose tumors did not express any receptors, median survival had not been reached at the time of follow-up (P = 0.04). Similarly, patients with tumors expressing both receptors had significantly reduced survival (median survival = 20 months; P = 0.003). CONCLUSIONS: Expression of receptors for sex steroids correlates with advanced stage disease. Expression of PR by the tumor cells is associated with a shorter patient survival. The results suggest that sex steroids may play a role in carcinogenesis and tumor progression.

Human leukocyte antigens as genetic markers in colorectal carcinoma.

PURPOSE: Similar to findings obtained for most carcinomas, the pathogenesis of colorectal cancer is considered to be multifactorial. There is strong evidence for an inherited, genetic predisposition to disease in patients with familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer. There is still debate, however, about the contribution of genetic factors to the pathogenesis of sporadic colorectal cancer. The present study was undertaken to search for human leukocyte antigen associations in a group of patients with colorectal cancer and to correlate the findings with both the histology of the disease and family history. SUBJECTS AND METHODS: The allele frequencies of serologically defined human leukocyte antigen class I and II antigens were studied in 101 patients with a recent, histologically confirmed diagnosis of colorectal cancer. All individuals in this study were unrelated to each other. After surgical treatment, all patients were grouped according to the stage (Dukes Stages A, B, C, and D), differentiation (Grades 1, 2, and 3), and the site of the tumor. Patients were also classified with regard to family history for colorectal cancer. The results obtained for human leukocyte antigen frequencies were compared with those of 105 healthy control subjects (control group). RESULTS: An increased frequency of human leukocyte antigen-B18 (27.72 vs. 14.28 percent; P < 0.025; odds ratio = 2.3) and of human leukocyte antigen-DQ5 (43.56 vs. 22.5 percent; P < 0.01; odds ratio = 2.65) was observed for patients with colorectal cancer vs. control subjects, respectively. In addition, human leukocyte antigen-B18 was present with increased frequency (30.76 percent; P < 0.05; odds ratio = 2.66; and 26.67 percent; P < 0.05; odds ratio = 2.18) among patients with rectal and colon carcinoma, respectively. A higher frequency of human leukocyte antigen-DQ5 (45.33 percent; P < 0.01; odds ratio = 2.84) was observed among patients with colon carcinoma. Remarkably, human leukocyte antigen-DQ5 (50 vs. 22.5 percent; P < 0.05; odds ratio = 3.43) and human leukocyte antigen-A1 (41.66 vs. 12.38 percent; P < 0.01; odds ratio = 5.05) were found to be strongly associated with a family history of colorectal cancer. CONCLUSION: The observation of specific human leukocyte antigen associations with particular subsets of colorectal cancer strongly suggests that genetic susceptibility for the development of colorectal cancer exists. Although the multifactorial pathogenesis of colorectal cancer must be considered, human leukocyte antigens may have useful predictive and diagnostic value.

Low T3 syndrome with asynchronous changes of TT3 and rT3 values in laparoscopic cholecystectomy.

Non-thyroidal illnesses, such as surgical stress, are associated with abnormal metabolism of thyroid hormones. However, the potential impact of variable surgical procedures remain to be elucidated. In order to evaluate the effect of mild surgical stress upon thyroid function, TT4, TT3, rT3 and TSH were measured in twenty-two patients undergoing laparoscopic cholecystectomy before (Stage 1), during (Stages 2-5), at the recovery room (Stage 6) and 24h postoperatively (Stage 7). The values of TSH remained within the normal limits with transient changes during the study period. Similarly, TT4 values displayed normal variations within the normal range without reaching a statistically significant difference during the study period. A decrease of TT3 values was detected early at stage 2 during induction of anaesthesia. TT3 remained at low levels during the perioperative period, and a further decrease was observed 24 h postoperatively. The above profile of thyroid hormone metabolism, reflects a low-T3 syndrome in patients undergoing laparoscopic cholecystectomy. Interestingly, there was a tendency for rT3 to increase and it reach its highest value 24h postoperatively with the difference being statistically significant (p<0.05). The asynchronous distribution of rT3 and TT3 might be attributed to multifactorial influences.

Beta human chorionic gonadotropin concentrations in serum of patients with pancreatic adenocarcinoma.

BACKGROUND: Human chorionic gonadotropin (hCG) is normally produced and secreted by trophoblastic cells during pregnancy and from gestational trophoblastic neoplasms. It is also detected in ovarian, stomach, and colon adenocarcinomas, as well as in squamous cell carcinoma of the oesophagus. Recently, interest in its role in the pathogenesis of tumours has been enlivened after the presence of beta hCG in the cell membrane of several malignant cells was shown in vitro. AIMS: To investigate the circulating concentrations of beta hCG in patients with exocrine pancreatic adenocarcinoma and to examine its potential prognostic value. PATIENTS: Thirty six patients with exocrine pancreatic adenocarcinoma, 12 patients with chronic pancreatitis, and 21 healthy volunteers were studied. METHODS: beta hCG serum concentrations were detected by the application of a radioimmunoassay technique. RESULTS: Fifteen of 36 patients with pancreatic adenocarcinoma and only one patient with chronic pancreatitis had detectable plasma concentrations of beta hCG (p < 0.01). The patients with circulating serum titres of beta hCG had a worse outcome compared with the group of beta hCG negative patients: the difference was statistically significant (p = 0.01). CONCLUSION: More than 40% of pancreatic exocrine tumours produce beta hCG and its production is correlated with an adverse effect on outcome.

Autoantibodies in the serum of patients with gastric cancer: their prognostic importance.

To evaluate the presence in serum and the clinical relevance of several antinuclear autoantibodies, we investigated 31 patients with initially diagnosed gastric cancer and 40 age-matched healthy controls. Autoantibodies against ssDNA, dsDNA, cardiolipin, actin, myosin, tropomyosin, GM1, GD1b and GT3 gangliosides, were detected with an enzyme-linked immunoassay (ELISA). Anti-ssDNA, anti-actin, anti-GM1 and anti-GD1b antibodies were detected in the serum of 11 (p = 0.001), 8 (p = 0.02), 11 (p = 0.001), and 9 (p = 0.008) patients with gastric cancer, respectively. There was no significant difference between patients with cancer and the control group, as far as the other autoantibodies were concerned. Most of the patients (90%) had autoantibodies against at least one of the antigens examined. Patients with anti-ssDNA, anti-actin, anti-GM1 and anti-GD1b antibodies were less likely to survive than the patients being negative to the above autoantibodies: the figures are 1 of 11 (9%) compared with 4 of 20 (20%); 1 of 8 (13%) compared with 5 of 23 (22%); 1 of 11 (9%) compared with 4 of 20 (20%); and 1 of 9 (11%) compared with 4 of 22 (18%), respectively. Our findings suggest that 4 of the 9 autoantibodies that we assayed are significantly more likely to be found in serum of patients with gastric cancer, indicating that the immune system has a role in the process of the malignant disease. If our results are confirmed by forthcoming studies, some of the immunological variables that we examined could be used as markers of prognostic value in patients with gastric cancer.

Evaluation of cathepsin D immunostaining in colorectal adenocarcinoma.

BACKGROUND AND OBJECTIVES: Cathepsin D (CD), an estrogen-regulated lysosomal protease, has been detected in a variety of tissues. CD expression has been correlated with the invasive potential of breast cancer, acting as an autocrine mitogen or as a protease that degrades the extracellular matrix. The role of CD expression in predicting prognosis or invasive potential in colorectal carcinomas is mostly unknown. METHODS: CD immunohistochemical expression was studied in 60 surgical specimens of colon adenocarcinomas. A three-step avidin biotinylated, horseradish immuno-peroxidase (ABC-HRP) staining technique was performed on 4 microm paraffin-embedded tissue sections with a polyclonal antibody to CD. RESULTS: Carcinoma cells showed positive CD immunostaining in 41.6% of adenocarcinomas (50%, 43.7%, 37.5%, and 25% of Dukes' Stage A, B, C, and D, respectively). Nonneoplastic stromal cells demonstrated positive staining in 68.3% of the adenocarcinoma specimens (37.5%, 62.5%, 91.6%, and 75% of Stage A, B, C, and D, respectively). Patients with colorectal carcinomas exhibiting simultaneously negative and positive CD expression in malignant and stromal cells, respectively, had a worse 5-year overall survival (P < 0.05). The mean 5-year survival of the 16 patients overexpressing CD in nonneoplastic stromal cells (>15% of stromal cells positive for CD) was significantly worse in comparison with the rest of the adenocarcinomas (n = 44) (27.6 +/- 4.6 vs. 46 +/- 2.7 months, respectively, P < 0.01). CONCLUSIONS: Expression of CD immunoreactivity by the stromal cells may be associated with a more invasive phenotype. Therefore, CD expression in tumor and stromal cells may serve as an important indicator of progression and guide postoperative treatment.

Sex hormone levels in the serum of patients with pancreatic adenocarcinoma.

The objective of this study was to evaluate the levels of several pituitary and gonadal hormones in pancreatic adenocarcinoma. We examined circulating levels of LH, FSH, Testosterone, Oestradiol, Progesterone and delta 4-Androstenedione in 36 patients with pancreatic adenocarcinoma, 12 patients with chronic pancreatitis and 87 age matched controls. According to our findings males with pancreatic cancer were found to have higher levels of FSH (p < 0.01). LH and oestradiol (p < 0.001) and lower levels of progesterone (p < 0.01) and testosterone (p < 0.05) than the controls. Female patients with pancreatic cancer were found to have higher levels of oestradiol (p < 0.001) and lower levels of LH, FSH and progesterone (p < 0.001), compared with group of healthy volunteers. Our data provide evidence of a generalised dysfunction of the hypothalamic-hypophysial-gonadal axis in pancreatic cancer patients.

Proliferating cell nuclear antigen and heat shock protein 70 immunolocalization in invasive ductal breast cancer not otherwise specified.

A series of 80 female patients undergoing surgery for primary breast ductal infiltrating carcinoma not otherwise specified (NOS) was immunohistochemically studied in order to verify any relationships between Proliferating Cell Nuclear Antigen (PCNA) immunostaining, Heat Shock Protein 70 (HSP70) immunoreactivity, and several clinicopathological predictors. Positive PCNA scores (> 20% of strongly immunopositive malignant nuclei) were observed in neoplastic cells' nuclei in 13 tumors (16.25%) and were intimately associated with axillary nodal involvement (p = 0.0131), relatively high tumor grades (p = 0.0016), increased tumor size (p = 0.0312), and low or negative levels of estrogen receptors (p = 0.0323). HSP70 positive immunoexpression in malignant cells' cytoplasm (percentage of HSP70 immunoreactive cells > 10%) was detected in 33 samples (41.25%). It correlated significantly with presence of axillary lymph nodal metastases (p = 0.0033) and rather poor tumor differentiation (p = 0.0014), whereas an association of borderline statistical significance emerged between HSP70 immunoreactivity and high progesterone receptor status (p = 0.0637). PCNA positive immunostaining demonstrates the tumors' proliferative fraction and might be used as an indicator of increased malignant potential in breast cancer since it was associated with four adverse prognosticators. HSP70 immunodetection is a probable marker of the biological stress experienced by breast cancer cells, since it was related to relatively high tumor grades. Since both proteins may potentially predict disease outcome, their prognostic significance must be validated by direct relation to survival. A multivariate statistical analysis including the variables with which both proteins were associated will reveal any possible independent prognostic value of PCNA and HSP70 immunostaining in local, ductal invasive breast cancer NOS.

Thyroid autoantibodies and thyroid function in patients with pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PA) patients often present high serum titres of several autoantibodies including autoantibodies against beta-islet cells and insulin. In the present study we examined with an hemagglutination method the sera of 33 patients with PA for the presence of both anti-mitochondrial and anti-thyroglobulin antithyroid autoantibodies (ATA). Twenty-six surgical patients with other non-malignant gastrointestinal tract (GI) disease (chronic pancreatitis or hernia) and 40 healthy volunteers were used as controls. Eight of the 33 PA patients were found to have ATA autoantibodies, whereas only one patient with chronic pancreatitis and 2 normal individuals had high serum ATA titres. The difference between the PA patients and either of the control groups was statistically significant (p < 0.05). The production of autoantibodies could be attributed to impaired immunoregulation caused by the malignant cells.

Increased estrogen receptor and epidermal growth factor receptor gene product co-expression in surgically resected gastric adenocarcinomas.

BACKGROUND: Evidence exists that estrogens influence the action of epidermal growth factor (EGF) and its receptor (EGF-R) at multiple levels. Estrogen and antiestrogen action on gastric and other gastrointestinal malignancies has been evaluated by several groups with conflicting results, and EGF-R has been implicated in the current growth factor-mediated models for gastric cancer progression. METHODS: ERs and EGF-Rs were detected immunohistochemically in a total of 53 advanced gastric carcinomas using monoclonal antibodies (mAbs) to human ERs and EGF-Rs. RESULTS: ERs were expressed in 30 (56%) and EGF-Rs in 20 (38%) of the gastric tumors. ER(+) gastric tumors were closely associated with the intestinal type (P < 0.01), whereas EGF-R(+) tumors were significantly correlated with poor differentiation status and ER(+) expression (P < 0.01). Of EGF-R(+) tumors, 85% were also ER(+). EGF-R and ER co-expression was demonstrated in 17 tumors (32% of the group). These cases were significantly corelated with poor differentiation and large tumor size upon resection (P < 0.05). CONCLUSIONS: ER and EGF-R co-expression indicates that a functional interaction between estrogens and EGF may exist in gastric cancer and that when such an interaction becomes operative, it may lead to dedifferentiation and increased tumor growth.

Autoantibodies against insulin and beta-islet cells in pancreatic adenocarcinoma: a possible explanation for diabetes mellitus.

To evaluate the prevalence of autoantibodies against the b-islet cells (ICA) and the molecule of insulin (IAA) in the serum of patients with pancreatic adenocarcinoma (PA), we examined the sera of 36 newly diagnosed pancreatic adenocarcinoma patients for the presence of these antibodies, using an enzyme-linked immuno-assay method. These results were correlated with survival. Ten patients with insulin-dependent diabetes mellitus (IDDM) and 21 healthy volunteers were evaluated as age-matched controls. Twenty out of 36 (57%) PA patients were found to have detectable ICA autoantibodies and 17 (48%) PA patients had detectable IAA antibodies. Five out of 10 (50%) and 3 out of 10 (30%) IDDM patients had ICA and IAA antibodies, respectively. None of the healthy volunteers was positive for either of the autoantibodies examined. The difference was statistically very significant and the presence of high serum titers of both autoantibodies was associated with a worse outcome for these patients than for those without such autoantibodies. Our data suggest that the high incidence of diabetes mellitus in patients with PA may be attributed to the presence of these autoantibodies. Further clinical studies are needed to establish the above autoantibodies as prognostic markers of pancreatic cancer.