Oesophageal cancer treatment: studies, strategies and facts

Esophageal cancer is among the ten most frequent cancers in the world. Once diagnosis is established prognosis is poor with five-year survival rates below 10%. Over the last few years, the evidence--base for treatment of oesophageal cancer has changed with the publication of several important articles in this field. This article reviews these and other relevant publications with focus on current evidence which holds potential for an improvement in survival in oesophageal cancer patients. Prevention and early detection represent the mainstay in the ongoing struggle to improve prognosis, which is most stringently linked to tumor stage. Other efforts have been dedicated to optimise surgical treatment, radiotherapy and chemotherapy and to discover the most efficient combinations of these treatment modalities. Strong but not unanimous evidence in favour of a multimodality approach with chemoradiotherapy followed by surgery has accumulated in recent years, and confirmatory trials are presently ongoing. A pathological complete response to chemoradiotherapy has been identified to significantly enhance survival. Among the strategies to achieve higher response rates, variations in the administration of the most commonly used drugs rather than higher drug and radiation dosages seem promising. Occult lymphatic spread has been recognized as a major source of recurrence and has been successfully targeted by three field surgical dissection and extended field radiotherapy. In search of the optimal treatment for patients with oesophageal cancer, a variety of different tracks are being pursued. This review outlines and analyses current treatment approaches and investigates how recent advances may impact on patient management.     

Unresectable pancreatic cancer: is a multi-modality approach a promising therapeutical alternative?

BACKGROUND/AIMS: The aim of this study was to evaluate the combination of immunochemotherapy and stop-flow upper abdominal chemotherapy in the prolongation of survival in patients with unresectable pancreatic cancer. METHODOLOGY: Thirty unresectable pancreatic cancer patients were treated with immuno-chemotherapy in combination with stop-flow upper abdominal chemotherapy, in an attempt to improve survival time. RESULTS: The results obtained in this study indicate that this kind of treatment is feasible, safe and effective for patients suffering from Stage III and IV pancreatic duct carcinoma. Twenty per cent of the patients within this group were able to undergo radical resection and remain alive and free of disease, with a mean survival rate of 16 months. CONCLUSION: The multi-modality approach used in this study achieved promising results for pancreatic cancer patients and is recommended as a promising therapeutic alternative.     

Experimental milk formulae with reduced protein content and desialylated milk proteins: influence on the faecal flora and the growth of term newborn infants

Diagnosing and monitoring pancreatic cancer is an ongoing challenge. Conventional markers such as tumor-associated antigens might be supplemented by molecular markers such as gene mutations and growth factor/growth factor receptor alterations in the future. Tumor-associated antigens can easily be measured by different EIA/ELISA systems, but the analysis of gene mutations, growth factors and their receptors requires advanced molecular techniques. CA 19-9 is the most widely used conventional marker for pancreatic cancer and is a useful tool in the diagnosis and follow-up of patients after tumor resection. Nonetheless, its role in detecting early pancreatic cancer is limited. The detection of K-ras and p53 mutations, which occur in about 90 and 50% of pancreatic cancers, respectively, in blood, stool, or bile samples, seems to be a promising approach in the diagnosis. Growth factor and growth factor receptor alterations are often associated with increased tumor aggressiveness and shorter survival following tumor resection. To date the analysis of growth factors/growth factor receptors in pancreatic cancer has not entered clinical use, but further molecular characterization of pancreatic cancer is necessary for earlier and more accurate diagnosis and it may result in new treatment options.     

Locally advanced adenocarcinoma of the pancreas: current therapeutic modalities

Pancreatic cancer still have bad prognosis. At the time of diagnosis, less than 10% of patients can undergo surgery with an overall 5-year survival rate of less than 2%. For patients with localized pancreatic adenocarcinoma, the combination of radiation therapy and chemotherapy has been shown to control symptoms and to enhance patient survival. This treatment should be proposed to all the patients with good performance status and without icterus. Pain management should be optimized and often need morphinic and co-antalgic (anticonvulsivants, steroids) consumption. The celiac plexus block with alcohol gives an excellent pain relief and should be more frequently used.     

What do we really know about Helicobacter pylori in gastric ulcer disease?

Advances in diagnostic and therapeutic technology have not appreciably changed the outlook of patients with pancreatic cancer. While those patients presenting with localized resectable disease have the best prognosis, local control and intra-abdominal metastases remain significant obstacles to survival. Localized chemoradiation has modestly improved median survival in localized and locally advanced disease. Patients presenting with locally advanced disease at diagnosis benefit from surgical palliation which includes biliary and gastric bypass. Intraoperative interstitial brachytherapy has been effective when utilized at laparotomy to improve local control in locally advanced disease. Advances in laparoscopic techniques have provided the ability to more accurately stage patients prior to laparotomy and perform palliative procedures without the need for laparotomy. The utilization of high-dose-rate brachytherapy has proven effective in palliating obstructive symptoms with minimal morbidity on an outpatient basis. Recent efforts have focused on preoperative chemoradiation to improve resectability in selected patients and prophylactic hepatic irradiation to reduce metastases for patients with locally advanced disease.     

The prognostic factors of pancreatic cancer--adhesion molecule CD44

The prognosis for pancreatic cancer is extremely poor, because there are usually invasion of surrounding tissues and metastases to lymph nodes, liver or peritoneum at the time of diagnosis. Many studies from the molecular-biological stand point have demonstrated this poor prognosis. However, the mechanisms underlying these invasive and metastatic capabilities have not yet been clarified. We reviewed several reports for prognostic factors of pancreatic cancer in molecular-biological examinations, and introduced our recent study on the adhesion molecule CD44. The CD44 variant 6 (v6) molecule has been noted as a marker for tumor metastasis and prognosis in several tumors. We examined whether or not v6 is a useful marker for evaluating the prognosis of pancreatic cancer patients. In addition, we attempted to assess the clinicopathological implications for pancreatic cancer of the variant 2 (v2) isoform using a recently developed monoclonal antibody against a v2 epitope. The expression of CD44 v6 and v2 was observed only in tumor cells, if at all. The expression of CD44 v6 and v2 was correlated with decreased overall survival. A significant correlation was obtained between CD44 v2 and vessel invasion. These results suggest that CD44 v2 and CD44 v6 may be useful markers of a poor prognosis.     

Surgical and nonsurgical management of primary and metastatic liver tumors

The medical records of 267 patients who had liver tumors, primary and metastatic, from 1988 to 1995 were retrospectively reviewed. Two hundred thirteen patients (80%) had metastatic disease, and 54 patients (20%) had primary liver disease. Their clinical manifestations and laboratory values were evaluated as factors predictive of diagnosis and survival. There was a significant increase in the occurrence of upper abdominal pain, weight loss, extrahepatic symptoms due to the metastatic origin, and hepatomegaly. Metastases from colorectal primary lesions were synchronous in 34 patients and metachronous in 31 patients. Stomach, lung, and pancreatic primaries were more commonly synchronous. Breast metastases were more commonly metachronous. Elevated serum glutamic-oxaloecetic transaminase and alkaline phosphatase and decreased albumin were the most common liver test abnormalities at diagnosis. Carcinoembryonic antigen values were elevated in the majority of colon cancer patients. Eighty-one percent of patients with primary liver cancer had elevated levels of alpha-fetoprotein, 40 per cent were seropositive for hepatitis B, and 23 per cent were seropositive for hepatitis C. Seventy-nine patients (30%) underwent surgery for their cancer, 37 (47%) had resections, 38 (48%) were unresectable, and 4 (5%) underwent liver transplantation. The patients who underwent surgery had a 32 per cent 5-year survival rate compared to a 0 per cent 5-year survival in the patients who did not have surgery (p = 0.0001). The patients who had resections had a better survival rate than those deemed unresectable at surgery (62% versus 0% at 5-years with p = 0.0008). The perioperative morbidity rate was 16 per cent, with lobectomies having the best rate and trisegmentectomies having the worst. Perioperative mortality rate was zero for all liver resections. Hepatic resection and, in selected patients, liver transplantation are the only two available therapeutic modalities that produce long-term survival with a possible cure in patients with primary and metastatic liver tumor.     

Survival of women with breast cancer in Europe: variation with age, year of diagnosis and country. The EUROCARE Working Group

Breast cancer is the most frequent malignancy among women in developed countries. Prognosis is better than for other major cancers, and an improvement in survival has been reported for several populations in recent decades. Within the framework of EUROCARE, a population-based project concerned with the survival and care of cancer patients in Europe, we analysed data from 119,139 women diagnosed with breast cancer between 1978 and 1985 in 12 countries and followed for at least 6 years. Multiple regression models of relative survival, which take mortality from all other causes in each area into account, were used to estimate the effect of age, period of diagnosis and country on survival. For the comparison between countries, survival rates were age-standardised to the age structure of the entire study population. Women aged 40-49 years at diagnosis had the best prognosis in all countries and throughout the study period. Women younger than 30 years at diagnosis had a worse prognosis than those aged 30-39. The highest relative survival at 5 years was in Finland and Switzerland (about 74%), intermediate levels were found for Italy, France, The Netherlands, Denmark and Germany (about 70%) and the lowest rates were in Spain, the United Kingdom, Estonia and Poland (55-64%). During the 6 months following diagnosis, survival was highly dependent on age and was sharply lower in women older than 49 years. For women surviving more than 6 months after diagnosis, survival was similar for all ages, although women aged 40-49 still had the better prognosis. The average rate of death from breast cancer fell by about 2.5% for each year of diagnosis between 1978 and 1985. This improvement manifested mainly in younger and older women, for whom survival was initially less good. The largest improvement was seen in Poland (-15% death risk per year). We suggest that the better survival of women aged 40-49 at diagnosis is related to lower levels of circulating sex hormones, resulting in reduced stimulation of tumour cell growth. Early diagnosis may also be important in the peri-menopausal period due to increased diagnostic attention. Low survival in the United Kingdom may be due to inadequate adherence to consensus treatment guidelines and greater variation in treatment.     

Expression of CD44 variants and its association with survival in pancreatic cancer

Since the CD44 variant 6(v6) molecule has been noted as a marker for tumor metastasis and prognosis in several tumors, we examined whether or not v6 is a useful marker for evaluating the prognosis of pancreatic cancer patients. In addition, we attempted to assess the clinicopathological implications for pancreatic cancer of the variant 2 (v2) isoform using a recently developed monoclonal antibody against a v2 epitope. The expression of CD44 variants was evaluated immunohistochemically in paraffin-embedded pancreatic cancer tissues from 42 patients who were confirmed surgically and histologically to have received curative resection. An indirect immunoperoxidase method was used with monoclonal antibodies against epitopes of the standard (CD44s) portion, v6 and v2. Protein expression data were evaluated statistically for any correlations with the length of survival or with histological parameters. The expression of CD44v6 and v2 was observed only in tumor cells, if at all. On the other hand, expression of total CD44 (including CD44v, as well as CD44s) was observed in both tumors and adjacent normal sites. Tumor tissue from 21 (50%) and 16 (38%) patients showed positive immunoreactivity with mAb 2F10 (anti-CD44v6) and mAb M23.6.1 (anti-CD44v2), respectively. The expression of CD44v6 and v2 was correlated with decreased overall survival (P = 0.0160 and P = 0.0125, respectively). A significant correlation was obtained between CD44v2 peptide expression and vessel invasion (P = 0.026). These results suggest that CD44v2 and CD44v6 may be useful markers for poor prognosis in curatively resected primary pancreatic cancer.     

Back pain in patients with ductal pancreatic cancer. Its impact on resectability and prognosis after resection

BACKGROUND: Back pain is a frequent and often ominous clinical sign in patients with ductal pancreatic cancer. METHODS: From 1971 to 1993 a pancreatic carcinoma could be resected in 192 patients, whereas 261 patients underwent either probatory laparotomy alone or palliative bypass procedures. In a retrospective study including uni- and multi-variate survival analysis we have determined the impact of preoperative back pain on both resectability and long-term prognosis after resection. RESULTS: Among the presenting symptoms of patients with ductal pancreatic cancer back pain was a predictive sign of irresectability. In the presence of preoperative back pain the long-term prognosis after resection of the tumour was also significantly impaired. In a multivariate analysis it could be demonstrated that the prognostic impact of back pain was as strong as the influence of residual tumour, tumour grading, and tumour size. CONCLUSIONS: Back pain often indicates irresectability of ductal pancreatic carcinoma and also impairs the long-term prognosis even after curative resection.     

The dental status of asthmatic British school children

Pancreatic cancer is a dismal disease. The 5-year overall survival ranges from 1% to 5%. Surgery is the only curative treatment available for this cancer, but it is indicated only in selected patients with a less than 4 cm tumor. In these patients, survival rate is about 30%. We have considered several aspects: the very difficult early diagnosis, the correct diagnostic flow chart, actual surgical procedures and new trends in biologic and genetic research. It is likely that better results can be achieved by defining an "early pancreatic cancer" and establishing how to detect it. This could be the wrigth one way is to significantly improve the survival of these patients.     

Long-term prognosis of breast cancer: an analysis of 462 patients in a general hospital in south east Netherlands

In this study the long-term prognosis was analysed of all 462 consecutive female breast cancer patients who were diagnosed and carefully staged between 1970 and 1980 in a 600-bed community hospital in Eindhoven, south east Netherlands. Follow-up of recurrence and causes of death was obtained until 1 January 1993. Observed survival rates at 5, 10 and 20 years were 66%, 45% and 32%, respectively, and the corresponding breast cancer-specific survival rates were 71%, 54% and 44%. The yearly risk for a recurrence of breast cancer after treatment steadily decreased from 10% the first year to 1% after 10 years. In a multivariate survival analysis both tumour size and nodal status appeared to be equally important prognostic factors in the first 5 years after diagnosis. After 5 years only tumour size had independent prognostic value, which was not significant any more after 10 years. In patients with a tumour size < or = 2 cm and without lymph node involvement at diagnosis, the risk for a recurrence was found to be negligible after 10 years. Those patients may be considered cured, although a search for early diagnosis of a second primary breast cancer in this group is still advisable.     

Unimanual performance as a measure of laterality

The diagnosis and treatment of colorectal cancer remains a formidable health care problem. Colorectal cancer is the second most frequently diagnosed cancer in both men and women in Western countries and accounts for over 55,000 deaths annually in the United States alone. Cancer of the colon and rectum is eminently curable by surgical resection if identified early; however, despite our best efforts, patient survival from this disease has changed little over the past 50 years. With the advent of molecular and genetic techniques, a number of novel discoveries have been made in the last decade which have greatly expanded our understanding of the etiology and cellular mechanisms contributing to the development and subsequent progression of colorectal cancer. This review summarizes the recent molecular advances in the understanding of both familial (HNPCC and FAP) and sporadic colorectal cancers. The numerous scientific advances described in this review offer the promise of the development of novel chemotherapeutic agents, more accurate prognostic indicators and better screening techniques.     

Colorectal cancer in the young patient

Although predominantly a disease of older adults, colorectal cancer affects the younger population with an incidence of two to six per cent. It is thought to carry a less favorable prognosis in the young than in the general population. This may be due to advanced stage of the tumor at diagnosis. This study is composed of 37 patients, aged 40 and younger, treated over a 20-year period for colorectal cancer at Louisiana State University Medical Center-Shreveport and E. A. Conway Hospital. It was performed to investigate the incidence, stage at diagnosis, and prognosis of colorectal cancer in these young patients. The location of the primary tumor was fairly evenly distributed throughout the colon and rectum in this population. Pain, weight loss, rectal bleeding, and nausea and vomiting were the most common presenting symptoms. A family history of colon cancer or premalignant lesions were not risk factors in this study. Seventy per cent of all patients were treated with curative intent, and 42 per cent of these patients developed recurrent disease. The patients in this review presented with a higher incidence of advanced disease. Thirty-seven per cent of the lesions were Duke's C and 22 per cent were Duke's D, with poor 5-year survival (11% and 0%, respectively) when compared with national studies. The absolute 5-year survival for all young patients with colorectal cancer was 26 per cent (5 of 19 patients). It is important for the surgeon to be aware of the potential for colorectal cancer in young patients and to take an aggressive approach to the diagnosis and early treatment of the disease.     

Phylloid pigmentary pattern with mosaic trisomy 13

PET is a diagnostic method that creates high resolution, 3 dimensional tomographic images of the distribution of positron emitting radionuclides in the human body. Recent technological developments allow the use of whole-body PET devices in clinical oncology. 18FDG is a glucose analog transported and competitively used with glucose reflecting the increased glucose metabolism into malignant cells. Differential diagnosis between chronic pancreatitis and pancreatic cancer is already a well-documented indication. For initial staging of gastro-esophageal and colorectal tumours, results are preliminary but the clinical impact seems to be rather limited. At present, the major indication of FDG-PET is the detection and staging of colorectal cancer recurrences. FDG-PET allows the differentiation between scared tissue and tumour when structural imaging is often confusing. In the same time, the whole-body imaging capability provides unique information that can modify loco-regional and liver staging. Overall, FDG-PET affects the clinical management of 30 to 40% of these patients. Quantitative assessment of therapeutic response to chemotherapy regimen appears to be one of the most promising applications of FDG-PET. Since the most effective therapy of colorectal cancer are often surgical, the role of chemotherapy in colorectal cancer remains limited to adjuvant therapy and in advanced disease. However, FDG-PET could be of great value in assessing the response of oesophageal carcinomas to chemo-radio therapy, before surgery. In our experience, FDG-PET appears to be the first line diagnostic method in the detection and staging of colorectal recurrence and differential diagnosis of pancreatic tumour versus chronic pancreatitis.     

Penile cancer in Taiwan--20 years' experience at National Taiwan University Hospital

To analyze the characteristics and prognostic factors of penile cancer in Taiwanese, we retrospectively reviewed the clinical data of patients with a diagnosis of penile cancer treated during a 20-year period (1977-1996) at National Taiwan University Hospital (NTUH). Of 71 patients treated for penile cancer during the study period, 17 were referred from other hospitals or clinics. Our analyses focused on the 54 previously untreated patients. Growth on the penis was the main symptom in all cases. Palpable inguinal lymph nodes were found only in 14 patients. All 54 patients with primary tumors were treated surgically. Pathologic examination showed squamous cell carcinoma (SCC) in 43 cases, extra-mammary Paget's disease in three, verrucous carcinoma in three, Bowen's disease in two, cutaneous lymphoma in two and basal cell carcinoma in one. Twenty-six (48%) patients had stage I penile cancer, 13 (24%) had stage II, seven (13%) had stage III, and eight (15%) had stage IV cancer. The five-year survival rate was 78% among patients with SCC and 84% among those with nonsquamous malignancies (p = 0.80). The five-year cumulative survival rates according to Jackson's cancer stage were 100% for patients with stage I, 88.9% for those with stage II, 66.7% for those with stage III, and 0% for those with stage IV (p < 0.001). Tumor staging (p = 0.027) and adjuvant chemotherapy (p = 0.042) were found to be the most significant prognostic factors. Penile cancer accounted for 0.254% of all malignancies among male patients at the NTUH during the study period. Our findings indicate that penile cancer is uncommon in Taiwanese and its prognosis is closely related to tumor staging and management. Early diagnosis and appropriate treatment may lead to prolonged survival.     

Colorectal cancer in patients under forty: presentation and outcome

Colorectal cancer is the third most frequent malignancy in adults of both sexes in this country, with 90 per cent of patients diagnosed after age 50 years. This disease is unusual in patients under 40 years of age, and controversy persists as to prognosis in this subset of patients. Patients diagnosed with invasive adenocarcinoma of the colon and rectum from 1985 to 1997 were identified. They were then grouped according to age (< 40 or > or = 40). Charts were reviewed with respect to patient epidemiologic characteristics, clinical presentation, tumor staging, and survival. Twelve women and 24 men less than 40 years of age (median, 31 years/range, 13-39 years) were diagnosed with colorectal adenocarcinomas. This represented 8.6 per cent of the total patients diagnosed with colorectal cancers during this time. Thirty-five (97%) had symptoms (pain, blood per rectum, weight loss, or alteration in bowel habits) before diagnosis, and 23 (64%) had multiple symptoms. Younger patients had more poorly differentiated tumors (28%) and more mucinous adenocarcinomas (26%) than the older group. Younger patients were more likely to present with stage III or IV disease (78%) as well. Despite these findings, the median survival for younger patients was no different than the older patients when compared by stage. Colorectal cancer in young adults is rare, but should be considered in the differential diagnosis for all patients with gastrointestinal symptomatology. The presentation of these patients is not unlike that of older patients. Those patients with early-stage disease should be treated aggressively, as long-term survival may be anticipated, whereas the outcome for those with metastatic disease is poor.     

Factors affecting hemopoietic recovery after high-dose therapy and autologous peripheral blood progenitor cell transplantation: a single center experience

Major depression is one of the most common psychiatric problems complicating the treatment and prognosis of patients with active medical illness. Recognizing and treating major depressive conditions in this population can often be challenging, even for the most seasoned clinicians. This article reviews the medical and neurologic conditions that have been associated with the high prevalence rates of major depression. Highlights of the evaluation process that help confirm this suspected diagnosis are addressed, and management issues are discussed. Brief reviews of supportive psychotherapeutic tools that the clinician may find helpful are included, as well as current advances in pharmacologic interventions.