Recent arguments in advanced gastric cancer treatment]

In advanced inoperable gastric cancer patients, survival was significantly prolonged for the group receiving antineoplastic treatment against only the best supportive care group by some randomized controlled studies. Greater prolongation of survival is expected from surgery in CR and PR cases because of the change from inoperable to operable. One problem is that the evaluation of response to the primary site is different between Japan and other countries. Outside of Japan, it is considered that barium contrast studies and routine endoscopy are not sufficient for tumor response assessment at the primary site. I think this is not true evaluation of the response to gastric cancer chemotherapy to exclude primary site assessment. We must generalize the Japanese criteria of gastric cancer chemotherapy throughout the world.     

Microcephalic osteodysplastic primordial dwarfism Taybi-Linder type: report of four cases and review of the literature

Although lymph node metastasis is a major prognostic factor in gastric cancer, the optimal extent of lymph node dissection still remains a subject of debate. The influence of extended D2 lymphadenectomy on morbidity and long-term survival is controversial. Reports from many Japanese and some Western institutions show similar morbidity and mortality rates for both limited D1 and extended D2 resections. However, the four available randomised trials show a significant increase in operative morbidity and mortality after a D2 resection. The authors of these trials believe that distal pancreaticosplenectomy is responsible for this increased morbidity and mortality and not the lymphadenectomy itself. Retrospective and prospective non-randomised studies show superior stage (II/IIIA) specific survival rates after D2 resections. However, these studies did not eliminate stage migration and randomised trials failed to show any survival advantage in favour of the D2 resection. Current data suggest that D2 resection is beneficial to the subgroup of patients with N1 or N2 disease undergoing potentially curative resection. However, Western studies that support D2 resection, fail to show any survival advantage for D2 resection in N2 patients, reporting a benefit only to N0 or N1 patients. In contrast, Japanese series report a large number of N2 long-term survivors. The question as to the possible beneficial effect of extended lymphadenectomy in gastric cancer is difficult and complex. D2 resection increases the potentially curative resection rate, at least in N2 patients, achieves a better locoregional tumour control and provides the only chance for cure among N2 patients since adjuvant treatment in gastric carcinoma has not yet been proved effective. However, all randomised comparisons warn of an increased risk after D2 resection. By avoiding pancreaticosplenectomy, however, the morbidity can be within acceptable limits. D2 gastrectomy seems to be the most attractive procedure in the surgical management of gastric cancer.     

Strategies to decrease the incidence of intra-abdominal recurrence in resectable gastric cancer

Two main approaches are suggested to improve treatment results in resectable gastric cancer: extended lymphadenectomy and adjuvant antitumour therapy. Progress is to some extent stalled by the perception of gastric cancer as a pathophysiologically uniform disease; it has been demonstrated, however, that there are variants of gastric cancer associated with predominantly intra-abdominal spread or with haematogenous metastases. Recent clinicopathological studies have provided information about the mechanisms of this metastatic diversity. A review of clinical trials suggests that no single method of treatment can efficiently address all variants of gastric cancer spread, but new treatment strategies may be based on defining the pathophysiological variant of gastric cancer and selecting adjuvant therapy according to the most probable mode of tumour spread. Treatment should start with surgery which includes a 'reasonably' extended lymphadenectomy aimed at achieving an increased rate of curative resection and more accurate staging. Risk factors for peritoneal spread of tumour require the perioperative use of intraperitoneal chemotherapy. Subsequent adjuvant therapy may be indicated in patients at high risk of further cancer spread or occult metastases, as determined by pathological examination of the resected specimen.     

Ovarian steroids modulate responsiveness to dopamine and expression of G-proteins in lactotropes

Considerable controversy surrounds the management of gastric cancer and this has largely overshadowed recent progress in our understanding of the epidemiology and molecular pathogenesis of the disease, and improvements in diagnostic and staging techniques. Differences identifiable in the molecular pathogenesis of the 'intestinal' and 'diffuse' types of gastric cancer may help to unravel the biological behaviour of variants and ultimately influence therapeutic strategies. Endoscopic ultrasound is well established as being accurate for T staging and the introduction of laparoscopy, with or without ultrasound, is obviating unnecessary laparotomy in non-bleeding, non-obstructed patients. Controversies in surgery encompass the role of laparoscopic surgery in early gastric cancer, the extent of lymphadenectomy including para-aortic nodal dissection, resection of en bloc contiguous organ involvement, pancreatosplenectomy, left upper abdominal evisceration, and modes of reconstruction (pylorus-preserving gastrectomy, pouch formation) to enhance quality of life. Whereas adjuvant chemotherapy does not impact favourably on survival, emphasis has now shifted to neoadjuvant (induction) chemotherapy to downstage the disease. Preoperative regional chemotherapy and intra-operative hyperthermic chemotherapy or irradiation may prove to be of benefit in patients with resectable disease, but some scepticism still exists as to the usefulness of biological response modifiers (e.g. OK432, PSK) for adjuvant treatment. Ethical issues relating to cultural differences in Asia sometimes mitigate against adequate trial design (e.g. a surgery-alone control group or a no adjuvant therapy treatment group may be considered inappropriate) and this has understandably hindered acceptance in Western countries of the value of current management practices in Asia. These issues and the need for ongoing well-conducted randomized trials with prospective subset analysis are now being addressed.     

Stomach cancer. A 10-year material with emphasis on early cancer

Between 1982 and 1991, 112 patients were treated for gastric cancer at Harstad Hospital in Northern Norway. Early gastric cancer accounted for 20% of all the adenocarcinomas (110), which is high compared with figures from other western studies. The role of endoscopy for detecting early gastric cancer is discussed. The five year survival rate after radical surgery was found to be significantly higher for patients with early gastric cancer than for patients who underwent curative surgery for either infiltrative or regional cancer. For patients with a tumour that had invaded the regional lymph nodes the five year survival rate was only 10%. This result can be improved by more extended lymph node dissection. The perioperative mortality rate (8%) was usually a result of severe cancer cachexia or underlying cardial disease, and not anastomotic leakage. The results as regards the cure of early gastric cancer are comparable with those described in other studies.     

Our experience with lymphadenectomy in gastric cancer surgery

The Authors in this work study a comparison between 27 patients who underwent total gastrectomy with "regional" lymphadenectomy for gastric cancer during the period 1986-1991 (Group A), and 27 patients who underwent total or sub-total gastrectomy associated to D2 or D3 lymphadenectomy (Group B) according to the rules of the Japanese School (localization of the neoplasia and node involvement). No statistically relevant differences were shown in the overall long term survival, although in the group B there were both an high number of patients with stage III neoplasia and more invasive carcinomas. Extended lymphadenectomies, regional and D2 or D3, gave good results as far as long term survival was concerned in early stage cancers, but the same success was not achieved in advanced cancers especially in stage III. In order to improve the survival in advanced neoplasias since one year a D4 lymphadenectomy is performed in T2 or T3 and/or N2+ cases.     

Surgical treatment of stomach cancer: analysis of our personal experience

The "curative" treatment of gastric carcinoma includes the complete removal of the tumour and of the nodes involved without any macroscopic residual of disease (RO). Out of 326 patients with gastric cancer observed, a series of 114 consecutive patients underwent surgical resection (total gastrectomy or subtotal distal gastrectomy) with D2 or D3 lymphadenectomy. Overall operative mortality was 5.3%. Since 1988 no postoperative death occurred. Overall morbidity was 15.8%, specific morbidity 10.5%, reduced after 1988 to 6.6%. No significant differences in operative mortality and need of blood transfusions were recorded between D2 and D3 lymphadenectomy. Overall 5-year survival was 32%. Univariate and multivariate analysis showed that only T and N stages are significant prognostic factors, whereas tumour location, total or subtotal gastrectomy in antral cancers, extent of lymphadenectomy (D2 vs D3) and histology were not significantly related to survival. Since most studies have clearly shown that T and N stages are the most important prognostic factors in gastric cancer, the present aim should be to plan the extent of surgical resection according to the T and N stages characteristics of the neoplasm.     

Surgical treatment of gastric adenocarcinoma: the role of lymph node dissection

In this retrospective study, 652 patients who had curative resections for gastric cancer from 1977 to 1991 were reviewed to evaluate improvements in gastric cancer surgery and the influence of the extent of lymphadenectomy on survival. The patients were grouped into three time periods: 1977 to 1981, 1982 to 1986 and 1987 to 1991. The percentage of patients with early gastric cancer increased from 17.7% during 1977 to 1981, to 24.3% during 1987 to 1991. The average number of dissected lymph nodes was 7.5 +/- 8.1 during 1977 to 1981 and 16.4 +/- 10.3 during 1987 to 1991, when more radical lymphadenectomy was adopted. Total gastrectomies increased from 10.9% to 25.9% in the same time periods while combined visceral resections increased from 26.7% to 38.1%. Operative mortality decreased from 5.0% to 1.7%. The overall 5-year survival rate increased from 34.8% to 59.4%. In subgroup analysis, significant improvement of the 5-year survival rate was noted in the following groups: patients with stage I, II and III tumors but not stage IV; both proximal and distally located tumors; tumors with or without lymph node metastases; T1 and T2 but not in T3 and T4 (cancer invasion beyond the serosa). The decreased surgical mortality in recent years suggests that curative resection with extensive lymph node dissection can now be safely performed. Radical gastrectomy with extended lymphadenectomy may be adopted in gastric cancer resection for better control of regional disease.     

Cost effectiveness analysis of FDG-PET in the differential diagnosis and staging of lung cancer in Japan

Several studies have shown that FDG-PET is more accurate than CT for the differential diagnosis and for the staging of lung cancer. We have analyzed potential effect of FDG-PET on the medical cost for the management of patients suspected of lung cancer. In the differential diagnosis, chest CT plus FDG-PET protocol reduced the number of bronchofiberscope (BFS) and biopsy by one fourth of that in the conventional protocol using CT alone. PET protocol reduced unnecessary examinations for the patients of benign disease, however, it increased the total cost of examinations by 25% due to the higher cost of PET than that of BFS and biopsy in Japan. In the staging of lung cancer, PET protocol improved accuracy of staging, reduced unnecessary surgery by 67%, and showed a saving of the cost of examination by 5%, and the total medical cost by 2.5% compared to that in the conventional protocol using CT, brain MRI, and bone scan. Conclusion: Use of FDG-PET for the staging may contribute to the improvement of patient management of lung cancer patients also to the saving of the medical cost.     

Surgery for gynecologic cancer

Surgery is an integral part of staging procedures for ovarian, endometrial, and vulvar cancers, with a move toward surgicopathologic rather than clinical staging in cervical cancer. Morbidity can be reduced without compromising patient cure by individualizing surgery for patients with early vulvar cancer, and reproductive potential can be maintained in some women with early ovarian cancer. The place of prophylactic oophorectomy and primary and secondary surgery in ovarian cancer remain controversial and await prospective study. Recent developments in laparoscopic techniques have been applied to a number of problems in gynecologic cancer surgery, and the feasibility of laparoscopic lymphadenectomy and radical pelvic surgery has been demonstrated. Care must be taken, however, to ensure that the tenets of surgical oncology are not sacrificed in order to offer minimal-access surgery to women with gynecologic cancer.     

Variants of the 3' region of the cagA gene in Helicobacter pylori isolates from patients with different H. pylori-associated diseases

The CagA protein of Helicobacter pylori is an immunogenic antigen of variable size and unknown function that has been associated with increased virulence as well as two mutually exclusive diseases, duodenal ulcer and gastric carcinoma. The 3' region of the cagA gene contains repeated sequences. To determine whether there are structural changes in the 3' region of cagA that predict outcome of H. pylori infection, we examined 155 cagA gene-positive H. pylori isolates from Japanese patients including 50 patients with simple gastritis, 40 with gastric ulcer, 35 with duodenal ulcer, and 30 with gastric cancer. The 3' region of the cagA gene was amplified by PCR followed by sequencing. CagA proteins were detected by immunoblotting using a polyclonal antibody against recombinant CagA. One hundred forty-five strains yielded PCR products of 642 to 651 bp; 10 strains had products of 756 to 813 bp. The sequence of the 3' region of the cagA gene in Japan differs markedly from the primary sequence of cagA genes from Western isolates. Sequence analysis of the PCR products showed four types of primary gene structure (designated types A, B, C, and D) depending on the type and number of repeats. Six of the seven type C strains were found in patients with gastric cancer (P < 0.01 in comparison to noncancer patients). Comparison of type A and type C strains from patients with gastric cancer showed that type C was associated with higher levels of CagA antibody and more severe degrees of atrophy. Differences in cagA genotype may be useful for molecular epidemiology and may provide a marker for differences in virulence among cagA-positive H. pylori strains.     

Indications for laparoscopic surgery in cases of gynecological malignancies (endometrial cancer)

The role of surgery in the treatment of patients with invasive cervical cancer is undisputed, but how radical surgery should be is debatable. Every case requires detailed knowledge of the development and spread of cervical cancer. Tumor volume is the most important diagnostic factor in cervical cancer and also correlates with vascular invasion and lymph node involvement. As radical hysterectomy requires in cervical cancer besides the laparoscopically easy performable lymphadenectomy also the resection of parametria with sceletonisation of ureters we started to treat endometrial cancer with a combined laparoscopic and vaginal approach. In patients with the suspicion of stage I endometrial cancer prior to laparoscopic staging, the prerequisites of histological grading with ploidy and measurement of monoclonal antibodies were performed. All patients underwent a general check with radiography, computer tomography, liver scan, bone scan and lymphography. The performance of lymphadenectomy in cases of stage I endometrial cancer remains a controversial subject. We believe that laparoscopic assisted surgical staging of stage I endometrial cancer is an attractive alternative to the traditional laparotomy-surgical approach. The change from laparotomy to a laparoscopic assisted vaginal approach allows for a similar success rate with the less invasive approach. No complications occurred in this series and the results of our pilot study were satisfactory.     

Carcinoma of the esophagus and esophagogastric junction: sensitivity of radiographic diagnosis

OBJECTIVE: The purpose of this study was to determine the sensitivity of barium studies in revealing carcinoma of the esophagus and esophagogastric junction. MATERIALS AND METHODS: We retrospectively reviewed 50 cases of squamous cell carcinoma of the esophagus (n = 25) and adenocarcinoma of the esophagus (n = 14) or esophagogastric junction (n = 11) in which double-contrast (n = 46) or single-contrast (n = 4) barium studies had been done. The original radiology reports were reviewed to determine whether the lesions had been seen on barium studies and whether cancer had been diagnosed. Records were also reviewed to determine the number of patients who underwent esophageal endoscopy because of findings suggestive of cancer on barium studies at some point from January 1992 through December 1992. Pathology records were then reviewed to determine the number of true- and false-positive barium studies during this same period. RESULTS: Lesions were shown on barium studies in 49 (98%) of 50 patients, and carcinoma of the esophagus or esophagogastric junction was diagnosed or suspected in 48 patients (96%). In a separate part of the study, we found that endoscopy had been recommended to rule out malignant tumor in only 26 (1%) of 2484 patients who underwent barium studies at some point from January 1992 through December 1992. Endoscopy revealed cancer in 11 of those 26 patients; the remaining 15 were assumed to have false-positive radiologic examinations. Barium studies therefore had a positive predictive value of 42%. CONCLUSION: The double-contrast barium study is a sensitive technique for the diagnosis of carcinoma of the esophagus and esophagogastric junction. This high sensitivity can be achieved while recommending endoscopy in only about 1% of all patients who undergo barium studies.     

Lipoprotein levels in elderly patients with asthma. Cardiovascular Health Study Research Group

OBJECTIVE: Our objective was to determine the relative frequency of transpyloric tumor spread in gastric antral carcinoma and lymphoma. MATERIALS AND METHODS: We reviewed the medical records of 127 cases of pathologically proven gastric malignant tumors, including 102 carcinomas and 25 lymphomas, over a 10-year period. The antrum had carcinoma in 64 cases and lymphoma in 15. We reviewed upper gastrointestinal barium studies and correlated the findings of transpyloric tumor extension with the results of surgery, pathology, and endoscopy. RESULTS: Tumor extension into the duodenal bulb occurred in 16 (25%) of 64 patients with carcinoma and in six (40%) of 15 patients with lymphoma of the gastric antrum. Transpyloric spread of antral carcinoma as revealed by barium study was much more common in our series than has been stated in the literature. CONCLUSION: Duodenal invasion of an antral carcinoma is not rare. Because of the higher incidence of carcinoma, transpyloric spread of gastric tumor as revealed by barium studied should not by itself suggest the diagnosis of lymphoma.     

Multiple recurring gastric erosions/aphthous ulcers)

Five patients are described who had repeated endoscopy because of continuing dyspeptic symptoms associated with a negative barium meal. They were found to have multiple recurring gastric erosions (aphthous ulcers). No common aetiological factor could be found, although four of these patients did have a mild or moderatley active superficial chronic gastritis. Conventional peptic ulcer therapy failed to control either symptoms or ulceration. Two patients finally came to gastric surgery (highly selective vagotomy), which resulted in the relief of symptoms and healing of the gastric aphthous ulceration.     

The accuracy of staging: an important prognostic determinator in stage I ovarian carcinoma. A multivariate analysis

BACKGROUND: Several prognostic factors for stage I ovarian carcinoma have been analyzed. Some of them are biological and clinical in nature, but others such as the thoroughness of the staging procedure, the extent of the surgery and the philosophy of treatment, are defined by the human element. PATIENTS AND METHODS: We reviewed the records of 351 patients with Stage I ovarian cancer who had been treated from 1981 to 1991. For all patients the following information was available: age, size of the tumor, FIGO sub-stage, tumor grade, histologic type, rupture of the tumor, cytology, extent of the staging and of the surgery (hysterectomy and bilateral salpingo-oophorectomy vs. fertility-conserving surgery) and use of adjuvant treatments. The thoroughness of the staging was defined as: optimal staging: total abdominal hysterectomy and bilateral salpingo-oophorectomy or fertility-conserving surgery, peritoneal cytology or washing, omentectomy, multiple peritoneal biopsies, sampling of the retroperitoneal nodes or formal lymphadenectomy, peritoneal staging: all the criteria described above were met with the exception of retroperitoneal sampling, incomplete staging: lack of any of the previously-cited criteria. RESULTS: An optimal staging was performed in 100 patients, a peritoneal staging in 107 and an incomplete staging in 144. Radical surgery was performed in 295 women and fertility-conserving surgery in 56. With a median follow-up of 108 months (range 14-184) 64 patients had recurrence of the tumor. Fifty-three died of the disease, two are currently alive with disease and nine were salvaged by surgery and/or chemotherapy. In a multivariate analysis only the tumor grade and the type of staging were significant independent prognostic factors for both disease-free and overall survival. CONCLUSIONS: As described by other authors, we confirm that tumor grade is the single most important biological prognostic factor in early ovarian carcinoma. The thoroughness of the staging impacts significantly on survival, particularly in poorly differentiated carcinomas. Fertility-sparing surgery is not associated with a worse outcome than standard radical surgery.     

The rise and fall of the plantar response in infancy

Herniation of the stomach through the umbilicus is exceedingly rare with only one case reported in the international literature in the past 40 years. One case of a reducible gastric umbilical hernia, not diagnosed by endoscopy, is reported. Diagnosis was made by double-contrast barium examination after 5 years of symptoms and ineffective treatment. Herniation of the stomach is difficult to diagnose by endoscopy and radiological studies can be more sensitive and allow a more specific diagnosis.     

Prognostic significance of lymph node dissection in gastric cancer

The results for 162 patients who underwent curative gastrectomy for gastric cancer from January 1988 to June 1994 were analysed statistically with special reference to the effect of lymph node dissection. Median survival was 69.3 months and the overall cumulative 5-year survival rate was 50.2 (95 per cent confidence interval (c.i.) 41.6-58.1) per cent. By univariate analysis age, histology, depth of tumour invasion, node involvement, number of metastatic lymph nodes and type of lymphadenectomy were found to be significant factors related to survival time. Multivariate analysis with the Cox model and stratified for tumour node metastasis stage revealed that only the number of metastatic nodes (P = 0.04) and the extent of lymphadenectomy (P = 0.003) affected survival independently. With respect to D1 lymphadenectomy, the relative risk associated with D2 and D4 lymphadenectomy was respectively 0.61 (95 per cent c.i. 0.34-1.10) and 0.26 (95 per cent c.i. 0.12-0.60). The 5-year survival rate was 28 per cent for patients who had a D1 dissection, 63 per cent for those who had D2 and 68 per cent for those who had D4. These results suggest that extended lymphadenectomy (D2) and especially superextended lymphadenectomy (D4) can improve survival in patients with gastric cancer.     

Biodistribution studies on L-3-[fluorine-18]fluoro-alpha-methyl tyrosine: a potential tumor-detecting agent

OBJECTIVES: To prospectively evaluate a clinical algorithm that predicts nodal status in patients with prostate cancer and to assess the impact on the outcome. METHODS: Between September 1988 and December 1994, 192 patients with organ-confined prostate cancer and considered surgical candidates for radical perineal prostatectomy (RPP) were stratified using the algorithm: prostate-specific antigen (PSA) 20 ng/mL or less, Gleason score 7 or lower, and clinical Stage T2a or lower. Patients failing any of these criteria were placed in the high-risk group and underwent a pelvic lymphadenectomy. Patients who satisfied all the criteria were placed in the low-risk group and underwent RPP without evaluation of the pelvic lymph nodes. Another contemporaneous cohort of patients (n = 65) underwent pelvic lymphadenectomy and radical retropubic prostatectomy (RRP) without use of the algorithm and were used as a control group. Patients were monitored for at least 24 months. RESULTS: In the RPP group, 177 patients were considered low risk according to the algorithm and were not offered staging lymphadenectomy before surgery, whereas 15 patients were categorized as high risk for metastasis and underwent staging lymphadenectomy. In the RRP and lymphadenectomy group, 41 patients were considered at low risk and 24 at high risk of disease spread according to the algorithm. In the RPP group, low-risk patients (no lymphadenectomy) had a PSA recurrence rate (27%) similar to that of low-risk patients in the RRP group with negative lymph nodes (29%), P = 0.8. Similarly, high-risk patients with negative lymph nodes in both groups had a similar recurrence rate (53% for RPP and 50% for RRP). Univariate logistic regression analysis showed that PSA was the most significant predictor for disease recurrence (P = 0.0004) followed by preoperative Gleason scores (P = 0.02) and clinical stages (P = 0.03). Multivariate stepwise analysis demonstrated that Gleason score and clinical stage did not add to the prediction of recurrence over PSA alone. CONCLUSIONS: Staging lymphadenectomy can be omitted in low-risk patients without deleterious effects on the outcome as measured by PSA recurrence.     

The flavonols quercetin, rutin and morin in DNA solution: UV-vis dichroic (and mid-infrared) analysis explain the possible association between the biopolymer and a nucleophilic vegetable-dye

Multimodality therapy is used in patients with esophageal cancer because accurate tumor staging is essential to determine whether treatment should be directed toward cure or palliation. Imaging strategies must not only include tumor visualization but also incorporate pretreatment staging as the most important objective. This article reviews the use of CT scans, endoscopic ultrasound, and barium studies in the staging of esophageal cancer.