Identifying Clonal Origin of Multifocal Hepatocellular Carcinoma and Its Clinical Implications.

Hepatocellular carcinoma (HCC) is characterized by high prevalence of multifocality. Multifocal HCC can arise synchronously or metachronously either from intrahepatic metastasis (IM) or multicentric occurrence (MO). To date, there have been no established criteria to accurately distinguish whether multifocal HCC originates from IM or MO. Histopathological features remain the most convenient strategy but with subjectivity and limited accuracy. Various molecular biological techniques involving assessment of TP53 mutation status, hepatitis B virus integration sites, and chromosomal alterations have been applied to determine the clonal origin. The introduction of next-generation sequencing facilitates a more comprehensive annotation of intertumor heterogeneity, resulting in more sensitive and accurate clonal discrimination. Generally, MO-HCC has better overall survival than IM-HCC after curative resection. Adjuvant antiviral treatment has been proved to decrease post-treatment recurrence probably by reducing MO-HCC recurrence, whereas adjuvant sorafenib treatment targeting prior micrometastasis failed to reduce IM-HCC recurrence. Recent studies recommended transcatheter arterial chemoembolization (TACE) and traditional Chinese medicine Huaier granule as effective adjuvant treatments probably by preventing IM and both types of recurrences respectively. Immunotherapy that inhibits immune checkpoint interaction may be an optimal choice for both MO- and IM-HCC. In the future, effective personalized therapy against multifocal HCC may be achieved.

Impact of Synchronous Versus Metachronous Onset of Colorectal Peritoneal Metastases on Survival Outcomes After Cytoreductive Surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC): A Multicenter, Retrospective, Observational Study.

BACKGROUND: Careful selection of patients with colorectal peritoneal metastases (PM) for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is crucial. It remains unknown whether the time of onset of colorectal PM (synchronous vs metachronous) influences surgical morbidity and survival outcomes after CRS with HIPEC. METHODS: Patients with histologically proven colorectal PM who underwent CRS with HIPEC between February 2006 and December 2017 in two Dutch tertiary referral hospitals were retrospectively included from a prospectively maintained database. The onset of colorectal PM was classified as synchronous (PM diagnosed at the initiational presentation with colorectal cancer) or metachronous (PM diagnosed after initial curative colorectal resection). Major postoperative complications (Clavien-Dindo grade ≥ 3), overall survival (OS), and disease-free survival (DFS) were compared between patients with synchronous colorectal PM and those with metachronous colorectal PM using Kaplan-Meier analyses, proportional hazard analyses, and a multivariate Cox regression analysis. RESULTS: The study enrolled 433 patients, of whom 231 (53%) had synchronous colorectal PM and 202 (47%) had metachronous colorectal PM. The major postoperative complication rate and median OS were similar between the patients with synchronous colorectal PM and those with metachronous colorectal PM (26.8% vs 29.7%; p = 0.693 and 34 vs 33 months, respectively; p = 0.819). The median DFS was significantly decreased for the patients with metachronous colorectal PM and those with synchronous colorectal PM (11 vs 15 months; adjusted hazard ratio, 1.63; 95% confidence interval, 1.18-2.26). CONCLUSIONS: Metachronous onset of colorectal PM is associated with early recurrence after CRS with HIPEC compared with synchronous colorectal PM, without a difference in OS or major postoperative complications. Time to onset of colorectal PM should be taken into consideration to optimize patient selection for this major procedure.

More Synchronous Peritoneal Disease but Longer Survival in Younger Patients with Carcinomatosis from Colorectal Cancer Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Colonoscopy to detect colorectal cancer (CRC) is recommended starting at age 50 years; however, CRC rates are increasing in the prescreening population. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been proven effective in select patients with peritoneal carcinomatosis (PC) from CRC, although it has not been evaluated specifically in patients < 50 years. METHODS: CRC patients aged < 50 years at diagnosis undergoing CRS/HIPEC 2007-2017 were compared with those aged ≥ 50 years. Age distribution was analyzed in patients undergoing colectomy alone versus CRS/HIPEC for CRC 1993-2013. RESULTS: A total of 98 patients underwent CRS/HIPEC, of which 44% were < 50 years. Younger patients were more likely to present with synchronous peritoneal metastases (p = 0.050). Receipt of perioperative chemotherapy was comparable (p = not significant [NS]). Charlson Comorbidity Index and ECOG score were similar (p = NS). Tumor grade was similar (p = NS). Peritoneal Carcinomatosis Index, total organs resected, and anastomoses created were comparable (p = NS). Major Clavien-Dindo morbidity and LOS were similar (p = NS). Younger patients survived longer after CRS/HIPEC (p = 0.011). Demographic data from patients undergoing colectomy (n = 225) and CRS/HIPEC (n = 98) showed that age < 50 years was increasingly common with the more aggressive procedure (9% and 44% respectively, p < 0.001). CONCLUSIONS: Younger patients with PC from CRC presented more often with peritoneal metastases at the time of diagnosis. Yet despite similar perioperative features at CRS/HIPEC, they survived longer than older patients. Patients undergoing CRS/HIPEC are overall younger than those undergoing index colectomy.

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy with lobaplatin and docetaxel to treat synchronous peritoneal carcinomatosis from gastric cancer: Results from a Chinese center.

BACKGROUND: This work was to evaluate the efficacy and safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) with lobaplatin and docetaxel to treat peritoneal carcinomatosis (PC) from gastric cancer (GC). METHODS: A total of 50 consecutive GC PC patients treated by 52 CRS+HIPEC procedures with lobaplatin 50 mg/m(2) and docetaxel 60 mg/m(2) in 6000 mL of normal saline at (43 ± 0.5) °C for 60 min. The primary endpoint was overall survival (OS), and the secondary endpoints were perioperative safety profiles. RESULTS: At the median follow-up of 22.5 (range, 5.1-50.7) months, the median OS was 14.3 (95% CI 7.6-21.0) months, and the 1-, 2-, and 3-year survival rates were 58%, 40%, and 32%, respectively. Mortality and serious adverse event (grade 3-5) morbidity rates in postoperative 30 days were 0.0% and 23.1%, respectively. Univariate analysis identified 4 parameters with significant effects on OS: completeness of cytoreduction (CC) 0-1, normal (N) the preoperative tumor markers level (TM), adjuvant chemotherapy ≥6 cycles, and peritoneal cancer index ≤20. However, multivariate analysis identified CC0-1, perioperative TM (N), adjuvant chemotherapy ≥6 cycles as the independent predictor for better survival. CONCLUSIONS: CRS+HIPEC with lobaplatin and docetaxel to treat selected GC PC could improve OS, with acceptable perioperative safety.

Treatment of retinoblastoma: The Institut Curie experience on a series of 730 patients (1995 to 2009).

INTRODUCTION: To describe the results of retinoblastoma treatment from 1995-2009 in a single institution. MATERIAL AND METHODS: Retrospective review of the charts of patients treated for retinoblastoma. Clinical characteristics at diagnosis, treatments and outcomes in terms of survival and ocular preservation are described. RESULTS: During the study period 826 children were referred for retinoblastoma and 730 were managed in our institution. Four hundred and eleven children presented with unilateral retinoblastoma and 319 with bilateral retinoblastoma. Median follow-up is of 93 months. Global survival is 98.5% of children, 10 children presented with second tumors, 11 children died (6 of tumor-related causes). Of the 411 children with unilateral retinoblastoma enucleation was needed at diagnosis for 324 (78.8%). Conservative treatments were attempted for 87 patients (21.2%) and ocular preservation obtained for 65 patients (74% of eyes). Three hundred and nineteen patients presented with bilateral retinoblastoma. Three hundred and ten could be treated conservatively for at least one eye. Initial intravenous chemotherapy was necessary for 75% of them. Ocular preservation without external beam radiation was possible for 221 patients (70%). The use of EBR decreased significantly after 2004 (9.1% of eyes vs 25.1%: P<0.001). DISCUSSION: Management and treatment of retinoblastoma are complex, adapted to the extent of the disease. Survival is good. Enucleation is still required for extensive ocular disease, especially for unilateral patients. Intravenous chemotherapy allows good tumor control and eye preservation and decrease the need of EBR. CONCLUSIONS: Retinoblastoma treatment with intravenous chemotherapy and ocular adjuvant therapies is very effective on the local tumor control and eye preservation.

Specifics of diagnosis and treatment in synchronous colorectal cancers (SCC).

INTRODUCTION: SCC have an incidence of 1,8% up to 12,4% and could have more simultaneous localizations. MATERIAL AND METHOD: Between January 2004 and January 2011, 214 patients with CRC have been operated on in our ward; from those, eight patients had multiple colorectal neoplasms. RESULTS: The majority of SCC (six cases) was hospitalized under emergency status, with incomplete or complete bowel obstruction through colonic obstructive tumour. The favourite localizations were on the sigmoid (six tumours) and the transverse colon (four tumours). The diagnosis was preoperatively assessed in three cases by colonoscopy and barium enema, intraoperative in four cases, postoperative in one case. Curative operations were performed in five cases and palliative operations in three. Immediate postsurgical evolution was good, long time evolution was marked by the complications of the primary disease. Out of five patients that were long term monitored, three have a five year survival, one has survived for three years and one deceased within a nine month period after surgery, with multiple metastases. CONCLUSIONS: Preoperative diagnosis of synchronous lesions can be difficult (emergency hospitalized patient, incomplete bowel preparation, bowel obstruction or intestinal bleeding) and the colonoscopy exam can be incomplete. Rigorous intraoperative colonic examination is necessary in order to diagnose synchronous lesions and avoid surgical reintervention.

Intraoperative radiotherapy and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. Five consecutive case reports of locally advanced rectal cancer with synchronous peritoneal carcinomatosis.

PURPOSE: Treatment of rectal cancer has markedly improved since the introduction of neoadjuvant strategies and better surgical techniques. However, treatment remains troublesome for patients with locally advanced rectal cancer (LARC) or with peritoneal carcinomatosis (PC). Patients presenting with LARC may now benefit from the integration of intra-operative radiotherapy (IORT) into multimodality treatment. Selected patients with PC now undergo cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) resulting in improved survival. Some patients present with locally advanced disease and synchronous peritoneal carcinomatosis and fulfill the eligibility criteria for both HIPEC and IORT, raising the question whether the combined application of both modalities within one operative procedure is feasible. CASE SERIES: This report includes five consecutive cases of rectal cancer patients presenting with LARC and synchronous PC who were treated with a multimodality treatment including IORT and HIPEC after cytoreductive surgery. Postoperative complications and survival are described. RESULTS: The combination of cytoreductive surgery with HIPEC and IORT appeared to be feasible and well tolerated. The observed complications did not differ from the morbidity associated with extensive pelvic surgery without HIPEC or IORT. No inhospital mortality occurred. One patient died after 11 months of recurrent disease. All other patients are currently alive with one patient already surviving 38 months. CONCLUSION: The current case series shows that a multimodality treatment containing IORT and HIPEC is feasible and safe with promising survival rates. This strategy may, therefore, be considered in selected rectal cancer patients presenting with both LARC and synchronous PC.

Modest advances in survival for patients with colorectal-associated peritoneal carcinomatosis in the era of modern chemotherapy.

BACKGROUND: The treatment of metastatic colorectal cancer (CRC) has evolved rapidly over the last decade, with combination chemotherapy and targeted biologic agents leading to significant improvements in survival. Despite these advances, little is known about their effectiveness in CRC-associated peritoneal carcinomatosis. The purpose of this study was to evaluate outcomes in patients with CRC-associated PC treated in the era of modern chemotherapy. METHODS: We retrospectively reviewed an institutional tumor database from 1996 to 2008. Survival data were evaluated for patients treated with PC before and after 2003. No patients before 2003 were treated with combination chemotherapy or biologic therapy. The modern chemotherapy group consisted of patients treated after 2003. Survival curves were estimated. RESULTS: Overall, 173 patients were identified. Median follow-up was 8.6 months. Median survival in the historic group (n = 91) was 8.9 months and 16.3 months in the modern chemotherapy group (n = 82) (P < 0.004). Age was the only significant covariate. The survival difference between the modern chemotherapy cohort and control cohort persisted after adjustment for age. In a subset of patients in the modern chemotherapy era group, for which treatment regimen could be definitively identified, survival was even greater-23.8 months. CONCLUSIONS: Patients with CRC-associated PC treated with modern combination chemotherapy and biologic therapy have a significantly longer median survival compared to our historical cohort. Despite these improvements, outcomes still remain poor. Therapeutic adjuncts such as surgical cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) in appropriately selected patients remain promising options to improve outcomes for patients with peritoneal-based disease.

[Peritoneal carcinomatosis of colorectal origin: results of cytoreductive surgery with peritonectomy and hyperthermic intraoperative chemotherapy]. / Peritonealkarzinose kolorektalen Ursprungs : Ergebnisse der zytoreduktiven Chirurgie mit Peritonektomie und hyperthermer intraoperativer Chemotherapie.

Until recently peritoneal carcinomatosis (PC) arising from colorectal cancer (CRC) was considered to be a terminal disease manifestation. Despite palliative systemic chemotherapy (CHT) the majority of patients died within a few months. Nowadays cytoreductive surgery (CRS) of the peritoneal cavity in combination with hyperthermic intraperitoneal CHT and perioperative systemic CHT may offer a chance for long-term survival in selected groups of patients. In this study we report the results obtained with this treatment strategy in 30 consecutive patients. Data were assessed prospectively. After a median follow-up of 16.9 months the median survival time in all 30 patients reached 24.3 months. Favorable prognostic factors are a low extent of intraperitoneal metastases as characterized by a low peritoneal cancer index (median survival PCI ≤ 10: 33.2 months vs. PCI 11-19: 12.1 months) and a complete or nearly complete CRS (median survival CCR 0/1: 33.1 months vs. CCR2/3: 12.1 months). The 2-year overall survival was 89% for patients with a PCI ≤ 10 and 65% for those with surgical CCR 0/1 cytoreduction. As not every patient with CRC and PC may profit from this relatively aggressive therapy an interdisciplinary patient selection (tumor board) and treatment in experienced surgical oncology centers is recommended.

Current concepts for diagnosis and treatment of retinoblastoma in Germany: aiming for safe tumor control and vision preservation.

Retinoblastoma affects approximately 40 children in Germany per year. Most children are diagnosed early with localized intraocular disease, and the overall survival rate exceeds 95%. However, the prognosis of metastasized retinoblastoma remains poor. In 40% of the patients, retinoblastoma occurs bilaterally and, especially for these children, the salvage of the eye and visual function is of major importance. The variety of conservative treatment options for localized retinoblastoma includes laser coagulation, thermotherapy, cryotherapy, brachytherapy and chemotherapy. While systemic chemotherapy has nearly completely replaced external beam radiotherapy in the primary treatment of intraocular retinoblastoma, intra-arterial, intravitreal and periocular application of chemotherapy was also shown to be effective in treating intraocular retinoblastoma in case series. Genetic testing is an integral part of the routine diagnostics of all patients. Available tumor material should be analyzed to detect mutational mosaicism, that affects >10% of children with unilateral retinoblastoma. Genetic testing also identifies children with heritable (50% of patients) retinoblastoma. These children have a genetic predisposition for second malignancies. For this reason, late effects are an increasing concern and the care of patients with retinoblastoma requires a multidisciplinary approach to tailor therapy and long-term follow-up. Multicenter clinical trials are being developed to evaluate evidence-based treatment concepts for localized and metastasized retinoblastoma to improve survival rates and quality of life of children with retinoblastoma.

Strategy for synchronous and multiple liver metastasis.

BACKGROUND/AIMS: Surgical indications for resection of synchronous metastasis from colorectal cancer (CRC) and the optimal timing of hepatectomy are still controversial and widely debated. METHODOLOGY: Synchronous and multiple metastatic liver tumors were detected in 57 patients since May 2005. Our treatment policy was to perform hepatectomy if the resection could be done with no limit on size and number of tumors. However, if curative resection could not be done, chemotherapy was begun and timing for the possibility of a radical operation was planned immediately. RESULTS: In 37 patients whose tumors were located only in the liver, primary tumor resection was performed in 16 patients and after tumor-decreasing by chemotherapy, in 7 patients. In 20 patients in whom chemotherapy was performed first, after controlling the distant metastasis, hepatectomy was performed in 3 patients and staged hepatectomy was performed in 10. Recurrence was detected after hepatectomy in 75.0% of simultaneous resection cases and in 70.0% of staged cases. In the recurrence cases, early detection after tumor resection occurred in 58.3% of the simultaneous and 14.2% of the staged. CONCLUSIONS: The present data show that neoadjuvant chemotherapy does not increase the risk of postoperative complications or the surgical difficulties of hepatectomy for colorectal metastases.

[Diagnosis and treatment of colorectal liver metastases - workflow]. / Diagnostik und Therapie von Lebermetastasen kolorektaler Karzinome - Workflow.

In this review, standards of diagnosis and treatment of colorectal liver metastases are described on the basis of a workshop discussion. Algorithms of care for patients with synchronous / metachronous colorectal liver metastases or locoregional recurrent tumour are presented. Surgical resection is the procedure of choice in the curative treatment of liver metastases. The decision about the resection of liver metastases should consider the following parameters: 1. General operability of the patient (comorbidity); 2. Achievability of an R 0 situation: i. if necessary, in combination with ablative methods, ii. if necessary, neoadjuvant chemotherapy, iii. the ability to eradicate extrahepatic tumour manifestations; 3. Sufficient volume of the liver remaining after resection ("future liver remnant = FLR): i. if necessary, in combination with portal vein embolisation or two-stage hepatectomy; 4. The feasibility to preserve two contiguous hepatic segments with adequate vascular inflow and outflow as well as biliary drainage; 5. Tumour biological aspects ("prognostic variables"); 6. Experience of the surgeon and centre! Extrahepatic disease does not contraindicate hepatectomy for colorectal liver metastases provided a complete resection of both intra- and extrahepatic disease is feasible. Even in bilobar colorectal metastases and 5 or more tumours in the liver, a complete tumour resection has been described. The type of resection (hepatic wedge resection or anatomic resection) does not influence the recurrence rate. Preoperative volumetry is indicated when major hepatic resection is planned. The FLR should be 25 % in patients with normal liver, 40 % in patients who have received intensive chemotherapy or in cases of fatty liver, liver fibrosis or diabetes, and 50-60 % in patients with cirrhosis. In patients with initially unresectable colorectal liver metastases, preoperative chemotherapy enables complete resection in 15-30 % of the cases, whereas the value of neoadjuvant chemotherapy in patients with resectable liver metastases has not been sufficiently supported. In situ ablative procedures (radiofrequency ablation = RFA and laser-induced interstitial thermotherapy = LITT) are local therapy options in selected patients who are not candidates for resection (central recurrent liver metastases, bilobar multiple metastases and high-risk resection or restricted patient operability). Patients with tumours larger than 3 cm have a high local recurrence rate after percutaneous RFA and are not optimal candidates for this procedure. The physician's experience influences the results significantly, both after hepatectomy and after in situ ablation. Therefore, patients with colorectal liver metastases should be treated in centres with experience in liver surgery.

[A 42-month disease free survival case of combined hepatocellular-cholangiocarcinoma with lymph node metastases treated with multimodal therapy].

Combined hepatocellular and cholangiocarcinoma (HCC-CC) is a rare type of liver cancer. We herein report a case of HCC-CC with lymph node metastases treated by multimodality therapy. The patient has been alive for more than 42 months. A 52-year-old man with a 9 cm diameter mass lesion in the liver was admitted to our hospital. The tumor was diagnosed as peripheral type of cholangiocarcinoma. Preoperative transhepatic arterial chemoenbolization (TACE) was performed. An accumulation pattern of lipiodol after TACE and an increase of serum alpha-fetoprotein led us to diagnosis of combined HCC-CC. A three segmentectomies of the liver and dissection of the local lymph nodes were performed. A histological examination of the resected specimen showed combined HCC-CC with lymph node metastases. Alpha fetoprotein, cytokeratins 7 and 19 were partially positive with immunohistochemical staining. The final diagnosis was a mixed type of combined HCC-CC. To improve a poor prognosis of combined HCC-CC, adjuvant chemotherapy with CDDP, 5 FU and radiation therapy were achieved. Fortunately, the patient is alive without any recurrence for 42 months after the operation.

[Adjuvant therapy of colon cancer stage C MAC. Adverse effects and efficacy in the Department of Oncology, Soroka Medical Center in the years 1991-1994].

The National Institutes of Health (NIH) held a consensus conference which recommended 5-FU and levamisole as adjuvant chemotherapy for colon cancer MAC (Modified Astler Coller) stage C. From 1991-1994, 37 such patients diagnosed here were treated with 5-FU (intravenous dose of 450/mg/m2/d for 5 days and from day 29, once a week for 48 weeks) and oral levamisole (50 mg 3 times/d. for 3 days, every 2 weeks for a year), as suggested by NIH guidelines. 16 patients were males and 21 were females, mean age was 62 years and median 64. Cancer locations were: right colon (in 16, 43%), left colon (19, 51%), multiple colon primaries (2, 1%). 25 (68%) had 1-3 positive lymph nodes and 12 (32%) had 4 or more positive lymph nodes. Only 20 (54%) finished treatment as prescribed. In the others, 1 or both drugs caused side-effects for which the drugs had to be stopped. 6 patients relapsed while on treatment. The most common side-effects were diarrhea, stomatitis and bone marrow suppression. 3 were hospitalized due to neutropenic fever. 5-year actuarial survival of all patients was 61%; 5-year relapse-free survival was 61%; 5-year relapse-free survival of right versus left colon was 41% and 82%, respectively (p < 0.01). There was no significant difference in 5-year survival of those with 1-3 positive lymph nodes as compared to those with 4 or more (62% and 56%, respectively). 5-year survival in those who finished or did not finish treatment (excluding those who stopped treatment because of progressive disease) was 83% and 70%, respectively (NS). The 5-year survival of our series was similar to that of patients treated similarly elsewhere. The 5-FU and levamisole treatment was not tolerated well by our study population. It has recently been replaced in our service by a 5-FU and leucovorin regimen given for 6 months.

Reduction of cancer mortality and incidence by selenium supplementation.

PATIENTS AND METHOD: In order to test the hypothesis that a dietary supplement of selenium (Se) may reduce cancer risk, 1312 patients with histories of basa/squamous cell carcinomas of the skin were assigned in random, double-blind fashion to daily oral supplements of either Se-enriched yeast (200 micrograms Se/day), or a low-Se yeast placebo. Patients were recruited in 1983 to 1990 and were followed with regular dermatologic examinations through, 1993 for a total of 8269 person-years of observation. Skin cancer diagnoses were confirmed histologically and plasma Se concentration was determined at 6 to 12 months intervals. All deaths and patient-reported illnesses were confirmed and documented by consultation with the patient medical care providers. RESULTS: Results showed that Se-supplementation did not significantly affect the incidences of recurrent basal/squamous cell carcinomas of the skin. However, Se-treatment was associated with reductions in total cancer mortality and in the incidences of lung, colorectal, prostate and total cancers. These effects were consistent over time and between study clinics. CONCLUSION: The results strongly suggest benefits of Se-supplementation for this cohort of patients and support the hypothesis that supplemental Se can reduce risks to at least some types of cancer.

[Synchronous and metachronous tumors of the colon and rectum]. / Tumores sincrônicos e metacrônicos de cólon e reto.

Three hundred and seventy-two patients with colorectal tumours treated by curative resection between January 1982 and January 1992 were reviewed in order to determine the role of colonoscopy and the outcome of patients with multiple tumours. Thirty (8.1%) of them with a mean age of 57 (35-79) years (20 males, 10 females) had synchronous (19 cases) or metachronous (11 cases) lesions. Rectum and sigmoid colon were the most frequent site of multiple lesions, accounting for 73% of all lesions. Accurate pre-operative diagnosis was performed in 14 of the 19 patients with synchronous lesions, and in the remaining 5 cases failure to perform an intra-operative colonoscopy was the cause of missing the lesions. Three of them had over-looked lesions on the previous barium enema. Synchronous lesions has the tendency to be less invasive as compared to metachronous ones. Five-year survival rates (Kaplan-Meier method) were 45% and 58% for patients with multiple and single lesions respectively (not significant). For patients with colorectal carcinoma a thorough examination of the whole colon by intra-operative colonoscopy should be accomplished in order to rule out the possibility of associated lesions as well as to decrease the incidence of "early" metachronous lesions.

[Clinical picture, diagnosis and treatment of multiple primary synchronous cancer of the large intestine]. / Klinika, diagnostika i lechenie pervichno-mnozhestvennogo sinkhronnogo raka tolstoi kishki.

Clinical course and procedures for diagnosis of primary multiple synchronous cancer of the colon are discussed on the basis of the data on 52 patients treated at the Institute's Clinic in 1962-1986. In 30.5%, these tumors were accompanied by single or multiple polyps of the colon. A significant role of endoscopy in the diagnosis was demonstrated. As a result of complex examination of the organ, a correct preoperative diagnosis of multifocal cancer was made in 48.1% of patients. Tumor multiplicity was established intraoperatively in 14 cases, at autopsy--in 2 (3.8%) and in the course of gross and histologic examination of the resected material--in 11 patients. Laparoscopy proved effective in 81.8%. Surgery is the major procedure for treatment of these tumors. Radical operation was carried out in 36 cases. The postoperative lethality rate was 13.9%. In the radical surgery group, 3-year survival was 61.7%.

[Effect of BCG vaccination on the incidence of the development of 90Sr-induced osteosarcomas in rats]. / Vliianie vaktsinatsii BTsZh na chastotu razvitiia u krys osteosarkom, indutsirovannykh 90Sr.

The frequency of 90Sr-induced osteosarcoma development was determined in the mongrel rats subjected to BCG vaccination. Injection of BCG (5 mg per animal) is shown to change the frequency of tumour development and their multiplicity only in male rats which were vaccinated 20 days before nuclide administration. An increase up to 10 mg per animal of BCG dose injected 10 days before 90Sr administration caused the carcinogenesis inhibition irrespective of the sex of the animals.