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Three decades' experience in surgery of hepatocellular carcinoma.

In the author's institution, 2254 patients with hepatocellular carcinoma (HCC) have been treated during 1958-1994. The overall 5-year survival increased from 5.4% (1958-1970), to 11.9% (1971-1982), to 46.2% (1983-1984), which correlated well with the increasing proportion of small HCC in the series (2.6%, 12.1%, and 33.4%, respectively); with the increasing percentage of limited resection (3.1%, 32.2%, and 58.3%); with the increasing number of re-resections for recurrence (0, 27, and 114 patients); and with the increasing number of second stage resections (0, 5, and 67 patients). In our institution, surgical approaches that resulted in significantly prolonging survival included: small HCC resection, re-resection, and cytoreduction followed by sequential resection for initially unresectable HCC. Experience in these 3 aspects suggests: (a) Small HCCs are mainly found by screening using AFP and ultrasonography (US) in a high risk population, and limited resection is the best treatment in patients with compensated liver cirrhosis, the 5-year survival after resection being 62.9% (n = 549). (b) Postoperative monitoring using AFP/US every 2-3 months for 5-10 years after curative resection is needed to detect subclinical recurrence. Limited re-resection is indicated for liver recurrence less than 3 nodules, and lung lobectomy is of proven merit to prolong survival for solitary lung metastasis. Re-resection of subclinical recurrence has resulted in a 10-20% further increase in 5-year survival after curative resection. (c) Palliative surgery other than resection such as hepatic artery ligation (HAL) and cannulation with arterial infusion (HAI), cryosurgery, etc. are superior to palliative resection with residual cancer. (d) Cytoreduction and sequential resection have provided hope for localized unresectable HCC, particularly in the right cirrhotic liver. Multimodality combination treatments such as HAL+HAI+radioimmunotherapy/regional radiotherapy are acceptable cytoreductive therapies. Repeated transcatheter hepatic arterial chemoembolization (TACE) is an alternative nonsurgical approach. Sequential resection is important to eradicate residual cancer after cytoreduction. The 5-year survival of 72 patients with cytoreduction and sequential resection for initially unresectable HCC was 62.1% and resulted in improving 5-year survival in the entire series of unresectable HCC over the 3 periods from 0% to 7.4% to 25.7%, respectively. However, multicentric origin and tumor invasiveness are two major targets to be studied in the control of recurrence and metastasis.

Carcinoma, Hepatocellular↗

Risk factors for local recurrences after limb-salvage surgery for high-grade osteosarcoma of the extremities.

BACKGROUND: Improvements in preoperative staging as well as in chemotherapeutic regimens have made limb-salvage surgery a reliable modality of treatment for high-grade osteosarcomas of the extremities, with local recurrences in most series of less than 10% after this type of surgery. The quality of surgical margins and local response to preoperative chemotherapy are known to be the most significant factors in recurrence [1, 8-10, 12], and complications related to the biopsy procedure may also be a significant factor. The study reported here comprised a histopathological analysis of our recurrent cases as part of an effort to identify the impact of each of the factors cited above. MATERIALS AND METHODS: Five hundred fourteen cases of high-grade, non-multicentric osteosarcoma of the extremities were treated at the Istituto Ortopedico Rizzoli between March 1983 and August 1991. In this study we analyzed 23 cases of local recurrence in patients with classic osteosarcoma who underwent limb-salvage procedures. RESULTS: In 15 cases we found correlation between the site of local recurrence and the site where the margins were less than wide. In five cases the recurrence was secondary to complications of the biopsy procedure (hematoma, delayed healing). In one case we suspect a previously undetected skip lesion. In the remaining two cases no clear explanation was found for the recurrence. There was also a statistically significant difference in the time of appearance of recurrences related to the tumor response to chemotherapy. CONCLUSIONS: For only two cases of recurrence was there no clear explanation. In one we suspect an undetected skip metastasis, and in the other there were certain factors which may have increased its risk of recurrence (non diagnostic trochar biopsy followed by an incisional biopsy, fair tumor necrosis, recurrence in a 'problem' anatomical site, i.e., the popliteal space). In the remaining cases the following factors were found to be directly related to the development of a local recurrence: a) the quality of the surgical margins, b) site of the biopsy as well as complications related to the biopsy procedure, c) local response to preoperative chemotherapy.

Adolescent↗

[Recurrence of a stage I thymoma after resection].

A 61-year-old man had a non-invasive thymoma. The tumor recurred in the aortocaval groove 6 months after thymothymectomy. The second tumor was a non-invasive, lymphocytic thymoma with polygonal cells, and was similar to the first one. The tumor may have been a multicentric thymoma, with malignant cells remaining in thymic tissue behind the brachiocephalic veins. To resect thymomas, extended thymectomy should be done to prevent recurrence from the remaining thymic tissue. CT scans should be obtained for long-term follow up after surgery, to detect any recurrence in its early stage.

Follow-Up Studies↗

Methodologies for quantifying the results of intravesical chemotherapy of superficial tumors of the bladder.

Various evaluation methods exist to report results of installation therapy on superficial urinary bladder cancer. The following three, based on material previously gathered from 30 patients treated with adriamycin instillations, are analysed in this study: (1) The graphic expression method which covers the most necessary details, but demands space and does not permit adequate statistical analysis. (2) Evaluating the terms usually used in oncology, i.e. complete response (CR), partial response (PR), total response (TR), no change and progression. These are suitable for statistical analysis and are of crucial relevance in the study of carcinoma in situ TIS. In Ta-1 cancers however, these terms (CR, etc.) are not descriptive of time, and since their results depend completely on the choice of endpoints they do not permit realistic statistical analysis. (3) Determining indices (Ri/m, Ri/c) and recurrence rates (RR, MARR, MTBR) in Ta-1 cancers. These factors take into consideration both the time variable and multicentricity in space and time, making rigorous statistical analysis possible. In our opinion Ri/c states most accurately a patient's clinical course.

Administration, Topical↗

Pathologic spectrum and prognostic significance of underlying liver disease in hepatocellular carcinoma.

Although controversy persists about the influence of cirrhosis on the incidence of portal vein invasion and other prognostic indicators of recurrence and survival (e.g., histologic grade, mitotic activity, multiplicity), it is clear that the degree of cirrhosis is important for the long-term survival of patients with HCC. Multicentricity is especially important because it reflects the field carcinogenesis associated with viral hepatitis and particularly chronic HCV infection [59]. A better understanding of the different mechanisms linked to tumor recurrence will help select the best candidates for curative surgery and help tailor adjuvant therapy, such as interferon therapy, to each patient [60]. Finally, the importance of vascular invasion, number of tumors, and tumor size of HCCs in addition to the effect of fibrosis has led Vauthey et al [20] to propose a simplified staging of HCC with better prognostication of survival.

Carcinoma, Hepatocellular↗

[Castleman disease of the neck].

UNLABELLED: Castleman Disease is a rare disorder characterized by benign lymph node hyperplasia involving lymphatic tissue in the neck, mediastinum, abdomen, axilla. There are three types of Castleman Disease: hyalin-vascular type localized nodal involvement, asymptomatic form; plasma cell type and generalized and multicentric type. MATERIAL AND METHOD: Between 2000-2004, 5 cases with Castleman Disease hyalin-vascular type with cervical lymph node involvement were diagnosed and treated in E.N.T. Department of "St. Spiridon" Hospital Iaşi. 2 of these cases are presented: a 24 year old male and a 13 year old female were admitted with a asymptomatic neck mass with slow progressive growth. Paraclinical exams (radiology, cervical and abdominal echography, CT scanner) confirmed the lymphadenopathy and excluded another localization. Differential diagnosis included tuberculosis, metastatic lymphadenopathy, lymphoma, branchial cyst etc. RESULTS: The treatment of choice was surgical excision by cervicotomy in all cases, followed by vascular proliferation and hyalinization in affected lymph nodes. Postoperative controls no revealed recurrences. CONCLUSIONS: The prognosis of localized form of Castleman Disease hyalin-vascular tape is better than multicentric form surgical excision is both diagnostic and therapeutic.

Adolescent↗

Multicentre prospective audit of surgical outcomes and acute complications following short course pre-operative radiotherapy for resectable rectal cancer.

BACKGROUND: The addition of short course pre-operative radiotherapy to total mesorectal excision reduces local recurrence in resectable adenocarcinoma of the rectum. In a previous retrospective study potential factors associated with early complications following this combination were identified. The aim of this study was to examine these relationships in a prospective multicentre audit. METHODS: One hundred and seven patients who received short course pre-operative radiotherapy in four cancer centres between 1 October 2001 and 30 September 2002 were included. Data including patient age, radiotherapy field length, overall treatment time, operation type, surgical outcomes and complications occurring within 3 months of the 1st day of radiotherapy were collected. These were compared and combined with the previously studied cohort of 176 patients treated at one centre between 1st January 1998 and 31st December 1999. RESULTS: In the prospective cohort only patient age (P=0.001) was significantly associated with acute complications. However, both the overall treatment time (median 9.0 vs 11.0 days P <0.0001) and field length (median 16.6 vs 17.0 cm P=0.03) were significantly shorter in this cohort when compared to the previous retrospective study. In patients from both studies (n=283), increasing age (P=0.002) and field length (independent of operation type) (P=0.02) were independently associated with an increased risk of acute complications. CONCLUSIONS: This study suggests that meticulous selection of patients for short course pre-operative radiotherapy and smaller planning target volumes may be associated with a lower risk of acute complications. The use of MRI scanning to stage pelvic disease may reduce the number of patients with R1 resections receiving short course pre-operative radiotherapy.

Acute Disease↗

Influence of associated viral hepatitis status on recurrence of hepatocellular carcinoma after hepatectomy.

The purpose of this study was to investigate the relation between the recurrence of hepatocellular carcinoma (HCC) and the histologic status of underlying chronic liver disease from a viewpoint of multicentric hepatocarcinogenesis. Sixty-eight patients who underwent curative resection of HCC and have been followed for more than 2 years are reported. Based on the microscopic findings of the noncancerous part of the liver, the patients were divided into normal liver (N,n = 2), chronic persistent hepatitis (CPH,n = 6), chronic aggressive hepatitis (CAH,n = 31), and liver cirrhosis (LC,n = 29) according to a classification by the European Association for the Study of the Liver. Background data for the groups showed no significant differences. Recurrence was observed in none of the patients in the N and CPH groups, 26 (83.9%) of the patients in the CAH group, and 12 (41.4%) of the patients in the LC group. The cumulative disease-free survival rate of the CAH group was significantly lower than that of the CPH group (p < 0.05) and LC group (p < 0.01). This study revealed that the histologic status of the underlying chronic liver disease influenced the recurrence rate in patients with HCC. CAH was considered to be a risk factor for recurrence after resection of HCC.

Aged↗

Cognitive-behavioural therapy for severe and recurrent bipolar disorders: randomised controlled trial.

BACKGROUND: Efficacy trials suggest that structured psychological therapies may significantly reduce recurrence rates of major mood episodes in individuals with bipolar disorders. AIMS: To compare the effectiveness of treatment as usual with an additional 22 sessions of cognitive-behavioural therapy (CBT). METHOD: We undertook a multicentre, pragmatic, randomised controlled treatment trial (n=253). Patients were assessed every 8 weeks for 18 months. RESULTS: More than half of the patients had a recurrence by 18 months, with no significant differences between groups (hazard ratio=1.05; 95% CI 0.74-1.50). Post hoc analysis demonstrated a significant interaction (P=0.04) such that adjunctive CBT was significantly more effective than treatment as usual in those with fewer than 12 previous episodes, but less effective in those with more episodes. CONCLUSIONS: People with bipolar disorder and comparatively fewer previous mood episodes may benefit from CBT. However, such cases form the minority of those receiving mental healthcare.

Adult↗

Local Recurrence after Conservative Surgery for Breast Cancer.

The advent of limited operative therapy for breast cancer has produced both good cosmetic results and local recurrence. In our department we treated 38 cases with conservation surgery for early stage breast cancers between February 1988 and October 1994, and local recurrence occurred in 2. PATIENT 1. A 56-year-old-woman had a 1 x 0.8 cm tumor in the C region of the left breast. A quadrantectomy with axillary dissection (level 2) was performed as the margin of the nipple side was negative, followed by entire breast irradiation (50 Gy). Approximately four years after the first operation she developed a local recurrence in the CD region of the breast. A salvage mastectomy with subclavicular lymph node dissection was performed. After the second operation she appears to be healthy. PATINENT 2. A 54-year-old-woman noticed a 1 cm tumor located in the EAC region of the left breast. Excisional biopsy showed solid-tubular carcinoma. The distance between the nipple and the tumor was only 0.7 cm. A wide excision with axillary dissection (level 2) was performed as the margin of the nipple side was negative on the frozen section. Neither irradiation of the entire breast nor the adjuvant chemotherapy could be performed. After a three and a half year follow up local recurrence beneath the operative scar was recognized, and an additional wide excision was performed. A half year has passed since the second operation, there have been no signs of recurrence and she appears to be healthy. In conclusion, we experienced two local recurrences in 38 cases of breast conservation surgery for early breast cancers. One patient had multicentric cancers with histologically different types: mucinous and noninvasive ductal carcinoma, and another had a very short distance between the nipple and the tumor and did not undergo chemotherapy or radiotherapy.

Journal Article↗

Clinical spectrum and surgical approach of adult intussusceptions: a multicentric study.

BACKGROUND: The preoperative diagnosis of adult intussusceptions (AIs) remains difficult, and the assessment of the radiological methods has been evaluated very little in the literature. The aim of this study was to evaluate the interest of the different imaging modalities for the preoperative diagnosis of AI and describe causes of AI. PATIENTS AND METHODS: Consecutive patients of 15 years and older with the postoperative diagnosis of intussusception from 1979 to 2004 were reviewed retrospectively for this multicentric study. Data concerning clinical considerations, morphological examinations, surgical procedure, histological conclusions, mortality rate and recurrence were analysed. RESULTS: Forty-four patients with documented intussusception were included. The mean age was 51 years (15-93 years). The preoperative diagnosis of intussusception was made in 52% of the cases. The sensitivities of the different radiological methods were abdominal ultrasounds (35%), upper gastrointestinal barium study (33%), abdominal computed tomography (CT) (58%) and barium enema (73%). An organic lesion was identified in 95% of the cases. There was 29 enteric and 15 colonic (including appendicular) intussusceptions. Thirty-seven percent of the enteric lesions were malignant, and a bit less than 50% of them were metastatic melanomas. The benign enteric lesions were Meckel's diverticulum and Peutz-Jeghers syndrome in half of the cases. Fifty-eight percent of the pure colonic lesions (excluding appendix) were malignant, and 85% of them were primary adenocarcinomas. The benign colonic lesions were lipomas in 80% of the cases. All patients, except one, had a surgical treatment, and 13 of them had a complete reduction of the intussusception before resection. The mortality rate was 16% and recurrence occurred in three patients; two of them had a Peutz-Jeghers syndrome. CONCLUSION: Intussusception rarely occurs in adults, but nearly half of their causes are malignant. The CT scan is a helpful examination for enteric intussusceptions whether barium enema seems to be the most performing method for colonic lesions. Surgery is the recommended treatment, with or without a primary reduction of the intussusception. During the surgical procedure, this reduction can lead to a more limited bowel resection.

Adolescent↗

Metachronous mature cystic teratomas in the left ovary and bilateral diaphragm: Report of a case.

Mature cystic teratomas are found often in gonadal sites, but rarely in extragonadal sites, such as the retroperitoneum, mediastinum, central nerve system, lung, and liver. To our knowledge, only seven cases of pathologically benign mature cystic teratoma originating in the diaphragm have been reported. We report the case of a 45-year-old woman found to have a mature cystic teratoma below the left side of her diaphragm. She had undergone oophorectomy for a huge mature cystic teratoma in the left ovary 34 years earlier, followed 1 year later by excision of a tumor in the right side of the diaphragm. All sections of the pathological specimen showed evidence of a mature cystic teratoma and pathologically resembled the specimens obtained in the previous two operations. Although this tumor might have been a recurrence of the mature cystic teratoma in the left ovary, it is more likely that multicentric teratomatous foci metachronously developed in the gonadal and extragonadal sites.

Diagnosis, Differential↗

A phase II study of epirubicin in advanced transitional cell bladder cancer. The Yorkshire Urological Cancer Research Group.

A multicentre Phase II study of epirubicin has been performed in patients with measurable or evaluable recurrent or metastatic transitional cell bladder cancer. Epirubicin was given intravenously every 3 weeks at a dose of 100 mg/m2. An objective response rate of 28% was observed (one complete and nine partial remissions) in an evaluable group of 36 patients, (confidence interval 15%-45%). Subjective improvements in the condition of patients were seen in responding and 'no change' patients. An interesting observation was the good response seen in patients with recurrent bladder disease who had previously received radial radiotherapy. Toxicity was considered to be acceptable and manageable, the most frequent being alopecia, and nausea and vomiting. Haematological toxicity was slight. One patient developed skin pigmentation, a not previously recognized complication of epirubicin treatment. Three cases of possible cardiotoxicity were seen in the 43 patients evaluable for toxicity. Epirubicin in thus an active agent in transitional cell carcinoma of the bladder, with a role as a single agent for palliation. It may also be useful in combination regimens for more aggressive treatment.

Carcinoma, Transitional Cell↗

The diverse pathology of post-transplant lymphoproliferative disorders: the importance of a standardized approach.

Post-transplant lymphoproliferative disorders (PTLD) are a diverse group of abnormal lymphoid growths that include both hyperplasias and neoplasias. They have been divided into several general pathologic categories that have prognostic significance. These include early or hyperplastic PTLD, polymorphic PTLD, and lymphomatous or monomorphic PTLD. The majority of PTLDs are of B-cell origin and contain Epstein-Barr virus (EBV). However, PTLDs of T- or NK-cell origin have been described, and late-arising EBV-negative lymphoid tumors are becoming more frequently reported in this population. Other lymphoid neoplasms, such as those arising from mucosal-associated lymphoid tissue (MALTomas), have recently been recognized in transplant patients, and their relationship to PTLD is uncertain. Multicentric PTLD may represent either advanced-stage disease or multiple independent primary tumors. Likewise, recurrent PTLD may represent true recurrence or the emergence of a second primary tumor. Transplant patients are also at risk for other opportunistic neoplasms, including EBV-associated leiomyosarcomas that may be seen alone or in conjunction with PTLD. This underscores the necessity for pathologic diagnosis of mass lesions in this patient population. The pathologist should strive to categorize the form of post-transplant lymphoproliferation in accordance with currently accepted criteria. The diagnosis should incorporate the histopathologic appearance, cell phenotype, clonal status, and EB viral status. The pathologist may play a special role in guiding therapy by ascertaining the presence of such markers as CD20 on tumor cells. Specialized techniques, such as molecular analysis of oncogenes/tumor suppressor genes and evaluation of host:donor status of PTLD, may play important roles in diagnostic evaluation in the future.

Humans↗

[Special clinical and follow-up aspects of invasive lobular breast cancer].

We examined 121 invasive lobular breast carcinomas (ILCs) with regard to certain standardised prognosis parameters, such as tumour size, receptor status, histological grading, the presence of lymphangiosis carcinomatosa, and the histological nodal status of the axillae and correlated these findings with follow-up data obtained over a mean period of 65 months. The parameters, tumour size, presence of lymphangiosis carcinomatosa, and nodal status, were found to be correlated and to have a significant influence on the patients' overall survival time, but not on relapse-free survival. Receptor status appeared to have no significant influence on patient survival. However, the incidence of death, owing to tumour-related causes, was higher among patients with receptor-negative tumours than amongst those with receptor-positive carcinomas. In contrast, the histological grading of a tumour appeared to exercise no effect on tumour prognosis. At 30%, the rate of local tumour recurrence at the primary site was markedly higher than for other histological types of breast carcinoma. In nearly one-half (45%) of such relapses, however, further tumour progression did not occur. Most tumours, exhibiting only local recurrence were initially node-negative, whilst those that produced distant metastases later had usually exhibited axillary lymph node metastases at primary therapy. Bilateral carcinomas occurred more frequently (15.6%) than is the case amongst ductal carcinoma. The observed tendency amongst ILCs toward local recurrence and bilateral growth might be accounted for in terms of their high incidence of multicentral tumour growth and associated pre-invasive neoplastic alterations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Occlusal rehabilitation of a patient with hereditary multicentric osteolysis.

This article describes the fixed prosthodontic rehabilitation of a 53-year-old male patient with multicentric osteolysis. Before treatment, the patient exhibited signs and symptoms of temporomandibular disorder and had recurrent tension-type headaches and pain in the neck and shoulder area. One of his chief complaints was frequent fracture of restorations. After extensive occlusal rehabilitation, occurrence of headache and pain ceased, and other signs and symptoms of TMD diminished. The long-term prognosis depends on the stage of the genetic disorder, which cannot be determined.

Dental Care for Persons with Disabilities↗

The risks of antenatal subcutaneous heparin prophylaxis: a controlled trial.

The risks of long-term antenatal subcutaneous heparin therapy were assessed in a small controlled trial of prophylaxis of thromboembolism. Forty patients with a documented history of previous thromboembolism were randomly allocated either to receive heparin (10000 i.u. subcutaneously twice daily) throughout pregnancy and labour or to receive no treatment (control group). All patients were treated with heparin (8000 i.u. twice daily) for 6 weeks after delivery from the first postnatal day. There appeared to be no increased risk of antenatal or postnatal bleeding associated with subcutaneous heparin, but one patient in the control group developed a deep vein thrombosis and one in the treatment group developed severe debilitating osteopenia. The withholding of epidural analgesia may have contributed to both maternal and fetal morbidity in the treatment group. There was one abortion in each group but no other fetal or neonatal losses although more babies from the treated group entered the special care baby unit. Although the numbers are too small for statistical analysis, the findings indicate that the use of long-term low-dose subcutaneous heparin is not without complications and there is need for a larger, multicentre trial to allow precise quantification of fetal and maternal risks against the risk of recurrent thromboembolism.

Abortion, Spontaneous↗

Factors regulating the metastatic potential of benign giant cell tumour of bone--study of an unusual case with short review of literature.

Benign giant cell tumour of bone with metastases to other bones and lungs is extremely rare. Benign metastasising giant cell tumour is distinctly separate from multicentric giant cell tumour, primary and secondary malignant giant cell tumour. Factors regulating the local recurrence and metastatic potential of this benign tumour depend on its aggressiveness which can be better assessed by clinical and radiological parameters rather than the histopathological appearance. A benign giant cell tumour of ischium with metastasis to vertebra and lung over an eleven year period is discussed. Extreme paucity of literature prompted to publish the article. A short review of factors determining the recurrence and metastatic spread of benign giant cell tumour of bone is highlighted.

Adult↗