J Surg Oncol

Surgical treatment for carcinoma of the thoracic esophagus with major involvement in the neck or upper mediastinum.

Matsubara T. Ueda M. Nagao N. Takahashi T. Nakajima T. Nishi M.
Department of Gastroenterological Surgery, Cancer Institute Hospital, Tokyo, Japan.
BACKGROUND AND OBJECTIVES: In carcinoma of the thoracic esophagus, most surgeons consider that esophagectomy is contraindicated in patients with clinical evidence of major extraesophageal involvement in the lower neck or peritracheal regions. However, metastases to these regions are commonly found even in early phases of carcinoma invasion. With recent progress in preoperative assessment, operative technique and adjuvant therapy, esophagectomy could possibly benefit appropriately selected patients. METHODS: We retrospectively analyzed results in 42 patients who had major involvement in the neck or upper mediastinum and who underwent esophagectomy with systematic lymph node dissection. We operated upon patients unless lesions were assessed as definitely unresectable. Preoperatively, 32 had enlarged peritracheal nodes greater than 15 mm in diameter on computed tomography, 18 had hard unmobile tumors in the lower neck, 9 had recurrent laryngeal nerve palsy, and 10 had findings suggestive of tracheal invasion. Preoperative radiotherapy and/or chemotherapy was given to 32 low-risk patients. RESULTS: The hospital mortality rate was 4%. Bowel reconstruction was completed in all cases. No macroscopically recognizable lesion remained after operation in 35 patients. Eight patients were alive 5 years after esophagectomy, including 2 who had had tracheal invasion and 1 with recurrent nerve palsy. The cumulative 5-year survival was 38%. CONCLUSIONS: Evidence of major involvement of the neck and/or upper mediastinum does not always contraindicate resection. Aggressive esophagectomy combined with perioperative adjuvant therapy yielded acceptable palliation and occasional cure in cases with technically resectable lesions.

Expression of interleukin (IL)-12 mRNA in gastric carcinoma specimens: cellular antitumor immune responses.

Katano M. Nakamura M. Kuwahara A. Fujimoto K. Matsunaga H. Miyazaki K. Morisaki T.
Department of Surgery, Saga Medical School, Japan. Katano@post.saga-med.ac.jp
BACKGROUND AND OBJECTIVES: Several tumor-related antigen peptides that are recognized by autologous cytolytic T cells (CTL) have been reported. However, most human solid tumors, including gastric carcinoma, are only weakly immunogenic. In this study, we focused on interleukin (IL)-12 and interferon-gamma (IFN-gamma) as key cytokines for estimating positive cellular immune responses. METHODS: To estimate the immunogenicity of gastric carcinomas, we examined IL-12 and IFN-gamma at mRNA levels by reverse transcription-polymerase chain reaction assay (RT-PCR) in tumor specimens and adjacent nontumor specimens from 36 gastric carcinoma patients. RESULTS: IL-12 expression was detected in 12 tumor specimens and in only two adjacent nontumor specimens (P = .003). The frequency of IFN-gamma gene expression was higher in the IL-12 mRNA-positive tumor specimens than in the IL-12 mRNA-negative tumor specimens (P = .015). In the IL-12 mRNA-positive tumors, IFN-gamma expression was higher in the tumor specimens than in the adjacent nontumor specimens (P = .007). Conversely, in the IL-12 mRNA-negative tumors, IFN-gamma expression was lower in the tumor specimens than in the nontumor specimens (P = .03). Many tumor-infiltrating mononuclear cells, predominantly T cells, were found in four of the 12 IL-12-mRNA-positive tumor specimens and in none of the 24 IL-12-mRNA-negative tumor specimens (P = .008). CONCLUSIONS: These data suggest that possible immune responses against a tumor may occur at the mRNA level in approximately one-third of gastric carcinomas.

Assessment of the proliferative activity of superficial esophageal carcinoma using MIB-1 immunostaining for the Ki-67 antigen.

Chino O. Makuuchi H. Shimada H. Machimura T. Mitomi T. Osamura RY.
Second Department of Surgery, Tokai University School of Medicine, Kanagawa, Japan.
BACKGROUND AND OBJECTIVES: Lymph node metastasis or vascular invasion may occur in superficial esophageal squamous cell carcinoma when it invades to or into the muscularis mucosae. Therefore, the correlation between histopathological characteristics and the proliferative activity of superficial esophageal carcinoma was investigated. METHODS: Thirty-eight cases of esophageal squamous cell carcinoma, including 14 cases of mucosal carcinoma and 24 cases of submucosal carcinoma, who underwent surgical resection without preoperative treatment, were studied using monoclonal antibody MIB-1 for the Ki-67 antigen immunohistochemically. The labeling index (LI) was calculated with a computed image analyzer. RESULTS: The LI of MIB-1 at the invasive tip of m3 carcinoma was significantly higher than that of m1 or m2 carcinoma (P < 0.01). The LI at the invasive tip was significantly higher than that at the core of sm2 (P < 0.05) and submucosal carcinoma overall (P < 0.01). The LI values at both the invasive tip and core of poorly differentiated carcinoma in submucosal carcinoma were higher than that of well or moderately differentiated carcinoma with a significant difference (P < 0.05). The LI at the invasive tip of submucosal carcinoma with lymph node metastasis or lymphatic invasion was significantly higher than that without them (P < 0.05). CONCLUSION: Proliferative activities of cancer cells in superficial esophageal squamous cell carcinoma, immunostaining with the MIB-1, were related to the depth of invasion, differentiation, lymph node metastasis, and lymphatic invasion with a significant difference.

Radiation-induced tumors in irradiated stage I testicular seminoma: results of a 25-year follow-up (1968-1993).

Stein ME. Leviov M. Drumea K. Moshkovitz B. Nativ O. Milstein D. Sabo E. Kuten A.
Northern Israel Oncology Center, Rambam Medical Center, Haifa, Israel. m_stein@rambam.health.gov.il
BACKGROUND AND OBJECTIVES: Testicular seminoma is a very radiosensitive and curable cancer, with survival rates following radiation therapy within the range of 90-98% without apparent severe side effects. However, long-term survival following exposure to moderate-dose radiation therapy can result in radiation-induced tumors. METHODS: The incidence of radiation-induced tumors was determined in 81 irradiated stage I testicular seminoma patients treated at the Northern Israel Oncology Center (NIOC) from 1968 through 1993. RESULTS: Three (4%) patients developed second cancers within the high-dose volume. Indeed, those patients received a higher than usual dose to the para-aortic and pelvic regions. One patient, who developed inoperable pancreatic carcinoma, was treated with "hockey stick" field and mediastinal irradiation, plus, as a result of relapses, multiple cisplatin and VP-16 based regimens. CONCLUSIONS: The elimination of causative factors through lower total doses and field size reduction may reduce the, albeit very low, incidence of radiation-induced cancer in cured testicular seminoma.

Involvement of adhesion molecules in metastasis of SW1990, human pancreatic cancer cells.

Hosono J. Narita T. Kimura N. Sato M. Nakashio T. Kasai Y. Nonami T. Nakao A. Takagi H. Kannagi R.
Department of Surgery II, Nagoya University School of Medicine, Japan.
BACKGROUND AND OBJECTIVE: Peritoneal dissemination and hepatic metastasis commonly occur after patients with pancreatic cancer have undergone surgery. It is thought that specific adhesion molecules play corresponding roles in cancer metastasis. STUDY DESIGN/MATERIALS AND METHODS: We conducted in vitro and in vivo studies to assess the role of adhesion molecules in these processes, using SW1990 cells derived from human pancreatic cancer. RESULTS: SW1990 cells pronouncedly expressed sialyl Lewis(a) (s-Le[a]) and sialyl Lewis(x) antigens (s-Le[x]), CD44H, and beta1 integrin. Also, SW1990 cells showed a strong binding activity to IL-1beta activated human umbilical vein endothelial cells, cultured murine endothelial cells (F-2 cells), and human peritoneal mesothelial cells. Invasive ability of SW1990 cells to F-2 cells was also observed. The adhesion leading to implantation of cancer cells to endothelial cells were inhibited by treatment with the antibodies against s-Le(a) and against beta1 integrin, respectively. Treatments with the antibodies against s-Le(a) and beta1 integrin each inhibited the development of liver metastasis in nude mice with SW1990 cells. The adhesion of SW1990 cells to peritoneal mesothelial cells was markedly inhibited by antibodies each against CD44 or beta1 integrin, but was completely blocked by using a combination of these two antibodies. These antibodies inhibited the dissemination of SW1990 cells in the peritoneal cavity of nude mice and prolonged their survival. CONCLUSION: These findings suggest that s-Le(a) and integrin mediate the process from adhesion to implantation of SW1990 cells to endothelial cells, and CD44 and integrin play important roles in the initial attachment of SW1990 cells to mesothelial cells. It is thus speculated that compounds that interfere with the function of cell adhesion molecules may decrease the incidence of pancreatic cancer metastasis.

Morphologic and mucin histochemical analysis of transitional zones in advanced ulcerated colorectal carcinomas: potential prognostic indicators.

Tamai O. Miyazato H. Shiraishi M. Kusano T. Muto Y.
First Department of Surgery, Ryukyu University School of Medicine, Okinawa, Japan. gajyu0@ryukyu.ne.jp
BACKGROUND AND OBJECTIVES: The transitional zone, which is normal-appearing mucosa that surrounds a primary colorectal carcinoma, has characteristic histologic features, and an increased amount of sialomucin in the transitional zone have been associated with a poorer prognosis. To clarify the prognostic effects of changes in the transitional zone we studied the transitional zone in cancers of the colon and rectum. METHODS: A total of 105 specimens resected for advanced colorectal carcinoma were studied to identify the effectiveness of evaluating morphologic types (polypoid or nonpolypoid growth type) and mucin expression (sulfomucin or sialomucin type) of the transitional zone as a prognostic indicator. RESULTS AND CONCLUSIONS: Nonpolypoid carcinomas were likely to have invaded the deeper layers and lymphatic vessels and go on to develop advanced disease. Sulfomucin-type tumors were predominantly found in the right side colon and followed a relatively favorable course. Our results indicate that the morphologic and mucin components of the transitional zone may be prognostic indicators for advanced colorectal carcinoma.

Effects of en bloc esophagectomy on nutritional and immune status in patients with esophageal carcinoma.

Wang LS. Lin HY. Chang CJ. Fahn HJ. Huang MH. Lin CF.
Department of Surgery, Veterans General Hospital and National Yang-Ming Medical University, Taipei, Taiwan, Republic of China.
BACKGROUND AND OBJECTIVES: En bloc esophagectomy has been established as the treatment of choice for patients with resectable esophageal carcinoma. However, an extensive surgical procedure may result in further impairment of the patient's nutritional status and immune system. Thus a prospective study was undertaken to evaluate the perioperative sequential changes in patients' nutritional and immune status and the timing to institute postoperative adjuvant therapy. METHODS: Thirty-seven patients (34 male, 3 female) who had undergone en bloc esophagectomy with gastric institution for epidermoid carcinoma of the esophagus were studied. The mean age was 62.3 years. The nutritional and immune assessments were performed preoperatively, on the third postoperative day, in the first week, second week, third week, and at the end of the first and third month. The biochemical studies for nutritional evaluation included serum albumin, cholesterol, iron, transferrin, magnesium, zinc, total iron binding capacity (TIBC), and nitrogen balance. Evaluation of the immune status consisted of: (1) total lymphocyte count, (2) lymphocyte subpopulation, (3) immunoglobulins, (4) complements (C3 and C4), (5) lymphocyte blastogenic responses, (6) tumor necrosis factor-alpha and interleukin-2 secretion activity from mononuclear cells, and (7) C-reactive protein (CRP) level. RESULTS: All the parameters in nutritional assessment declined profoundly by the third postoperative day (P < 0.05). The most severe deterioration was in serum iron, followed by transferrin, TIBC, cholesterol, and zinc. Most of them returned to the preoperative levels within 2-3 weeks after surgery. However, the serum levels of iron, transferrin, and TIBC required a longer period of time (> 1 month) to return to normal. A remarkable increase of serum CRP was detected in the first postoperative week (P < 0.05), but immunoglobulins and complements decreased significantly yet variably (P < 0.05) in the second or third postoperative week before gradually returning to preoperative levels. Moreover, during the first week after surgery, CD3 and CD8 diminished following esophageal surgery, whereas CD20, CD4/CD8 ratio, and lymphocyte blastogenic responses increased significantly (P < 0.05). CONCLUSIONS: Except for iron-related parameters, all the other nutritional parameters returned to the preoperative level by the third postoperative week. An adequate supplementation of iron and protein for 1-3 months after surgery is needed. En bloc esophagectomy might have only a mild and temporarily adverse effect on the host immune defense. Regarding the postoperative recovery of a patient's nutritional and immune status, postoperative chemo-radiotherapy is optimally instituted after the third postoperative week, instead of within 2 weeks of surgery.

Characteristics of rectal carcinomas that predict the presence of lymph node metastases: implications for patient selection for local therapy.

Zenni GC. Abraham K. Harford FJ. Potocki DM. Herman C. Dobrin PB.
Department of Surgery, Loyola University Medical Center, Maywood, Illinois 60153, USA.
BACKGROUND AND OBJECTIVES: It has been estimated that approximately 5% of middle and low rectal adenocarcinomas are amenable to local therapy. However, these treatment modalities are limited by their failure to identify and treat regional nodal metastases. METHODS: This study was undertaken to evaluate the role of tumor size, depth of penetration into the rectal wall, degree of histologic differentiation, DNA ploidy status, and their combination on the presence or absence of metastases in perirectal lymph nodes. Logistic regression was used to quantitatively predict the probability of positive lymph nodes. RESULTS: Tumor size did not correlate with the presence of nodal involvement; however, worsening degree of differentiation, increasing depth of wall penetration and aneuploidy did statistically correlate with the presence of nodal metastases. For any combination of tumor traits, aneuploidy markedly increased the probability of positive lymph nodes over that observed with diploid tumors. CONCLUSIONS: The combination of degree of differentiation, depth of penetration, and ploidy status may be used to identify patients whose tumors may be adequately treated with local measures. For any combination of tumor traits, aneuploidy markedly increased the probability of positive lymph nodes over that observed with diploid tumors.

Multiple bilobar liver metastases: cryotherapy for residual lesions after liver resection.

Hewitt PM. Dwerryhouse SJ. Zhao J. Morris DL.
Department of Surgery, University of New South Wales, St. George Hospital, Kogarah, Sydney, Australia.
BACKGROUND AND OBJECTIVES: Most patients with colorectal liver metastases are not eligible for resection because they have multiple lesions or because of anatomical constraints. We report the use of cryotherapy to destroy residual metastases following liver resection in patients with disease too widespread for treatment by resection alone. METHODS: Twenty patients with bilobar disease confined to the liver (median 3; range 2-8 lesions) were treated in this way. Seventeen patients also received regional chemotherapy postoperatively. RESULTS: Morbidity was high, but there were no procedure-related deaths and only one patient's hospital stay exceeded 24 days. Significant destruction of tumor, as evidenced by a decline in CEA levels, occurred within 3 months of surgery in all patients (P < 0.001). Median duration of follow-up was 15 (6-53) months. Survival rates at 1 and 2 years were 88% and 60%, respectively, and median survival was 32 months. Seven patients remain well and seven are alive with recurrent liver and/or other metastases. CONCLUSIONS: Although this is not a control study, it would appear that some patients with irresectable liver metastases benefit from this multimodality approach.

Hemobilia complicating hepatic cryosurgery.

Frank JL. Navab F. Ly K. Reed WP Jr.
Department of Surgery, Baystate Medical Center, Springfield, Massachusetts 01199, USA. frankjm@bmcnorth.bhs.org
We describe a 58-year-old man who developed hemobilia following hepatic cryotherapy. This was complicated by acute pancreatitis and recurrent cholangitis, which necessitated multiple endoscopic procedures (including biliary stenting) for successful management. As cryotherapy becomes more widely applied in the management of patients with liver tumors, it is essential that surgeons safeguard against the development of arteriobilious fistulae.

DNA content and other factors associated with ten-year survival after resection of pancreatic carcinoma.

Year 1998
Allison DC. Piantadosi S. Hruban RH. Dooley WC. Fishman EK. Yeo CJ. Lillemoe KD. Pitt HA. Lin P. Cameron JL.
Department of Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
BACKGROUND AND OBJECTIVES: The 5-year survival rates after resection of pancreatic carcinoma have recently increased and are predicted by tumor size, DNA content, and lymph node metastases at the time of resection. However, whether the 10-year survival rates have also increased and are similarly predicted by these factors is not known. METHODS: The influence of preoperative imaging tests, alcohol consumption, cigarette smoking, K-ras mutations, anatomic location, details of surgical resection, pathologic findings, and tumor DNA content on survival was tested for 96 patients after a successful resection of a pancreatic carcinoma with 17 patients being followed for more than 5 years. RESULTS: The 5- and 10-year patient survival rates were 18% and 3%, respectively. Univariate and multivariable analyses showed that tumor DNA content, pathologic tumor size, and lymph node metastases were the strongest prognostic indicators for long-term patient survival, although the importance of tumor size may diminish 2 or more years after resection. Surprisingly, the 11 patients with diploid carcinomas > or = 4 cm had an estimated 10-year survival rate of 36%. CONCLUSION: These results show that the 10-year survival rate for pancreatic carcinoma remains very low, although the subset of patients with biologically favorable tumors has a prolonged survival and possible cure after resection.

The number of lymph node metastases influences survival in esophageal cancer.

Year 1998
Kawahara K. Maekawa T. Okabayashi K. Shiraishi T. Yoshinaga Y. Yoneda S. Hideshima T. Shirakusa T.
Second Department of Surgery, Fukuoka University School of Medicine, Japan.
BACKGROUND AND OBJECTIVES: Lymph node involvement adversely affects the survival of patients with esophageal cancer. We retrospectively investigated whether the number of involved lymph nodes and the degree of lymph node dissection affect survival. PATIENTS AND METHODS: Eighty-eight patients underwent surgical resection and reconstruction for T -T3 thoracic esophageal squamous cell carcinoma. Patients were classified into three groups: group 1, 32 patients without lymph node involvement; group 2, 26 patients with 1 to 3 positive nodes; and group 3, 30 patients with > or = 4 involved lymph nodes. RESULTS: The 3-year and 5-year survival rates were 34.8% and 30.0% in group 1, 30.0% and 22.7% in group 2, and 14.8% and 0% in group 3, respectively. The mean survival time (MST) X +/- SD of the patients in group 3 (453.06+/-74.5 days) was significantly shorter than in group 1 (450.1+/-450.5, P = 0.0005) and group 2 (937.3+/-1317.9, P = 0.0295). For patients in groups 1 and 2, the MST for three-field lymph node dissection (1136.9+/-1476.4 days) was longer than for two-field lymph node dissection (1007.4+/-1476.4 days, P = 0.0355). However, in group 3, there was no survival advantage to three-field lymph node dissection. CONCLUSION: We conclude that the survival in patients with thoracic esophageal cancer involving four or more nodes, is poorer than in patients with lesser involvement. Three-field lymph node dissection does contribute to prolonged survival in patients with node-negative disease or fewer than four positive nodes.

Adenoma with clear cell change of the large intestine.

Year 1998
Suzuki H. Ohta S. Tokuchi S. Moriya J. Fujioka Y. Nagashima K.
Second Department of Pathology, Hokkaido University School of Medicine, Sapporo, Japan.
BACKGROUND AND OBJECTIVES: Clear cell change of the large intestinal neoplasm is rare, and its character remains unclear. We report a case of the large intestinal adenoma with clear cell change with immunohistochemical and molecular studies to investigate whether the clear cell change is associated with a malignant progression of the adenoma. METHODS: We studied the histochemical and immunohistochemical staining characteristics of the tumor by staining with hematoxylin-eosin, periodic acid-Schiff, alcian blue, and by immunostaining using antibodies against carcinoembryonic antigen, epithelial membrane antigen, p53, and Ki-67. The c-K-ras codon 12 point mutations were analyzed using a nonradioactive restriction fragment length polymorphism technique. RESULTS: The tumor was composed of a typical tubular adenoma and a tubular adenoma with clear cytoplasm. The clear cytoplasm was negative by mucin stains. Immunohistochemically p53 was negative in both the components. Labeling index of Ki-67 showed no significant difference between the two components. No codon 12 mutation of c-K-ras gene was observed in both the components. CONCLUSION: These findings suggest that the clear cell change of the tubular adenoma is not associated with a malignant progression in adenoma-carcinoma sequence involving c-K-ras and p53.

Micrometastasis in colorectal carcinoma: a review.

Year 1998
Calaluce R. Miedema BW. Yesus YW.
Department of Pathology and Anatomical Sciences, Ellis Fischel Cancer Center and Harry S. Truman Veterans Administration Hospital, University of Missouri, Columbia 65203, USA. robert_calaluce@muccmail.missouri.edu
Lymph node metastasis is the most important predictor of prognosis, after surgery, in colorectal carcinoma. The term "micrometastasis" has evolved from a morphological definition to one that is used with molecular-based techniques. We review the literature to evaluate the significance of detecting micrometastases in colorectal carcinoma, either by morphological or molecular techniques, and address technical difficulties encountered with both. Routine use of immunohistochemistry is not recommended as most studies show little change in staging or prognosis. Radioimmunoguided surgery may prove beneficial, but problems of false positives in benign diseases need to be addressed. Immunohistochemical detection of micrometastatic deposits in bone marrow aspirates holds the most promise for clinical practice. Molecular techniques are more sensitive than immunohistochemistry, but prognostic value needs to be determined. Molecular diagnostics can also determine genetic alterations and mutations that should improve our understanding of metastatic colon cancer and staging accuracy.

Biliary tree malignancies.

Year 1998
Erickson BA. Nag S.
Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee 53226, USA.
Radiation therapy is used as definitive treatment for unresectable bile duct tumors, or as adjuvant therapy after resection. External beam irradiation of 45-50 Gy is generally given whenever feasible. Intraluminal brachy-therapy is a useful technique to deliver higher doses of radiation to the tumor while respecting the tolerance of the surrounding normal tissues. Brachytherapy can be given at a high dose rate or low dose rate via an in-dwelling biliary drainage catheter to boost external beam doses. Brachytherapy alone is reserved for palliative therapy. Techniques should be implemented with care to make them not only effective but safe. The long-term efficacy and morbidity of this mode of radiation should be studied further. Only large prospective trials can lead to resolution of some of the questions yet unsolved in treatment of these challenging malignancies.

Submucosal gastric cancer with lymph node metastasis.

Year 1998
Morita M. Baba H. Fukuda T. Taketomi A. Kohnoe S. Seo Y. Saito T. Tomoda H. Sugimachi K.
Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
BACKGROUND AND OBJECTIVES: The intraoperative assessment of lymph node metastasis of gastric cancer remains difficult and the characteristics of recurrence after gastrectomy are not well known regarding submucosal cancer. METHODS: We examined 452 patients with submucosal gastric cancer and compared the clinicopathologic features as well as recurrence patterns between the 71 cases with lymph node metastasis (group I) and the 381 without it (group II). RESULTS: The mean tumor sizes were 44.8 and 33.5 mm, respectively (P < 0.01). The incidences of lymphatic invasion and vascular invasion were 91.5% (65/71) and 45.1% (32/71) in group I, which were significantly higher than those in group II (36.7 and 14.2%, 140/381 and 54/381, respectively, P < 0.01). A total of 21 patients (4.6%, 21/452) experienced recurrence after undergoing a gastrectomy and hematogenic recurrence was the most frequent type of recurrence (2.0%, 9/452). However, in group I, lymphatic recurrence was most frequently observed (7.0%, 5/71), and it was more frequent than in group II (0.3%, 1/381, P < 0.01). The median intervals between gastrectomy and recurrence were 34.5 and 64.0 months in groups I and II, respectively (P < 0.05). CONCLUSIONS: The submucosal cancer with larger size, lymphatic invasion, and vascular invasion has high risks for lymph node metastasis. Furthermore, a strict follow-up for lymphatic as well as hematogenic recurrence is important for the patients with node positive submucosal cancer, especially within 5 years after operation.

Spread of colorectal cancer micrometastases in regional lymph nodes by reverse transcriptase-polymerase chain reactions for carcinoembryonic antigen and cytokeratin 20.

Year 1998
Futamura M. Takagi Y. Koumura H. Kida H. Tanemura H. Shimokawa K. Saji S.
Second Department of Surgery, Gifu University School of Medicine, Japan. 2geka@cc.gifu-u.ac.jp
BACKGROUND AND OBJECTIVES: Lymph node metastasis is known as a significant predictor of prognosis in colorectal cancer patients. Recently, reverse transcriptase polymerase chain reaction (RT-PCR) has been applied to detecting micrometastasis. To assess the risk of recurrence and accurately determine the spread of tumor cells, we examined lymph node micrometastases in a series of colorectal cancer patients. METHODS: We examined 202 lymph nodes obtained from 13 colorectal cancer patients who underwent curative operation and were histologically diagnosed to be node-negative, using RT-PCR to amplify mRNAs for two epithelial markers, carcinoembryonic antigen (CEA) and cytokeratin 20 (CK-20). RESULTS: All the cases, including early stage patients, had micrometastases. A total of 102 among 202 lymph nodes (50.5%) were positive for either CEA or CK-20, or both (47.0, 40.1, and 36.6% respectively). Positive lymph nodes were spread along the courses of vascular trunks as well as being located in more distant regions. CONCLUSIONS: Even in histologically negative lymph nodes, there is a considerable possibility that micrometastases may exist. Their detection by RT-PCR may improve clinical staging and indications for cancer therapy. We should also take care in the choice of surgical approach.

Level of alpha-catenin expression in colorectal cancer correlates with invasiveness, metastatic potential, and survival.

Year 1998
Raftopoulos I. Davaris P. Karatzas G. Karayannacos P. Kouraklis G.
Second Department of Propedeutic Surgery, Laikon Hospital, Athens University Medical School, Greece.
BACKGROUND AND OBJECTIVES: Decreased expression of the E-cadherin/alpha-catenin cell-cell adhesion complex is considered to elicit detachment of tumor cells from primary lesions and development of metastases. The immunohistochemical profile of alpha-catenin in colorectal cancer, as well as its correlation with differentiation, lymph node/liver metastasis and patient survival is presented in this study. METHODS: Alpha-Catenin expression was investigated with immunohistochemistry technique, in 85 paraffin-embedded and 21 fresh frozen specimens, including 82 colon adenocarcinomas, 10 adenomas, 10 lymph nodes, and 3 liver metastases. Preserved alpha-catenin expression was considered for those tumors that demonstrated more than 90% alpha-catenin(+) cancer cells and reduced alpha-catenin expression for those tumors with less than 90% alpha-catenin(+) cancer cells. The chi2-test was used to calculate the statistical correlation of alpha-catenin expression with grade of differentiation and metastatic potential and the log-rank test for the correlation with survival rate. RESULTS: Normal mucosa, as well as 8/10 of the colon adenomas, showed strong membranous alpha-catenin expression. Reduced alpha-catenin expression was found in 32/82 (39%) colorectal cancers examined, which was associated with de-differentiation (P < 0.01), lymph node metastasis (P < 0.025), and poor clinical outcome (P < 0.012). Alpha-Catenin expression was preserved in 3 liver metastases and their corresponding primary tumors. By contrast, 6/10 of lymphogenous metastases showed decreased alpha-catenin expression. CONCLUSIONS: Our findings demonstrate a significant down-regulation of alpha-catenin expression in colorectal cancer which is associated with poor differentiation, higher metastatic potential and unfavorable prognosis. These preliminary results suggest that alpha-catenin may be a useful marker of invasiveness, metastatic potential, and survival in colorectal cancer patients.

Hepatic cryosurgery for recurrent hepatocellular carcinoma after hepatectomy: a preliminary report.

Year 1998
Lam CM. Yuen WK. Fan ST.
Department of Surgery, University of Hong Kong, Queen Mary Hospital, China.
BACKGROUND AND OBJECTIVES: The treatment of choice for recurrent hepatocellular carcinoma (HCC) is repeated resection. However, only a small percentage of patients are suitable for further hepatic resection. The aim of this study was to evaluate the surgical risk and operative outcome of hepatic cryosurgery in patients with recurrent HCC. METHODS: A retrospective analysis of patients with recurrent HCC after previous curative hepatectomy treated with cryosurgery. Four patients with recurrent HCC not suitable for further resection were enrolled for cryosurgery, their clinical parameters, the operative details and outcome were studied. RESULTS: No intraoperative or postoperative complications were noted. The duration of operation ranged from 3-5.2 hr and the operative blood loss from 173-1,300 ml. All patients are still alive with survival after cryosurgery ranging from 12-23 mo (25-63 mo after the hepatic resection). Three patients showed evidence of recurrent disease and one patient was disease free. CONCLUSIONS: Hepatic cryosurgery is a safe therapy for patients with unresectable recurrent HCC.

Characterization of signet ring cell carcinoma of the stomach.

Year 1998
Otsuji E. Yamaguchi T. Sawai K. Takahashi T.
First Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
BACKGROUND AND OBJECTIVES: As there is no consensus regarding the prognosis of patients with signet cell carcinoma of the stomach compared with other types of gastric cancer, we retrospectively studied the clinicopathologic features and prognosis of signet cell carcinoma in comparison with other types of gastric cancer. METHODS: Gastrectomies were performed because of gastric cancer in 1,498 patients between 1970 and 1994. Of the 154 patients diagnosed with signet ring cell carcinoma, 94 had early and 60 had advanced gastric carcinoma. The percentage of patients with an early carcinoma was significantly higher among those with signet ring cell carcinoma compared with those with other gastric carcinoma histologies. RESULTS: The survival of the total group of patients with signet ring cell carcinoma was significantly better than that of patients with other types of gastric carcinoma (P < 0.05). Survival of the subset of patients with early signet ring cell carcinoma was also improved compared with patients with other types of gastric carcinoma (P < 0.05). However, patients with advanced signet ring cell carcinoma had a poor prognosis similar to that of patients with other types of gastric carcinoma.