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Analysis of recurrence following curative low anterior resection and stapled anastomoses for carcinoma of the middle third and lower rectum.

In a series of 93 patients with middle and lower rectal cancer, who underwent potentially curative surgery by low anterior resection (LAR) with EEA stapled anastomosis or by abdominoperineal excision (APE) between January 1977 and December 1981, the incidence of recurrence and survival rate was compared. LAR with stapler was performed in 61 patients: 55 (90.2 percent) with tumors of the middle third and six (9.8 percent) for tumors of the lower third of the rectum. APE was performed in 32 patients: 13 (40.6 percent) with cancer of the midrectum and 19 (59.4 percent) of the lower rectum. Tumor site, Dukes' distribution, grade of malignancy, and extent of local spread were recorded. The tumor stages for LAR with stapler and for APE, respectively, were Dukes' A 7/1; Dukes' B 27/10; Dukes' C 25/18; Dukes' D 2/3. In a follow-up period of four years (range, 6 to 52 months) the overall recurrence rates were 20.4 percent in the LAR with stapled anastomosis group and 21 percent in the APE group. Local recurrence percentages were 9.8 percent after LAR and 14 percent after APE (P = N.S.). Distant recurrences were 12 percent and 14 percent, respectively. The four-year overall survival rates were 76.7 percent after LAR and 65.5 percent after APE (P = N.S.) The clinical and pathologic factors correlated with recurrence in low rectal carcinoma were reanalyzed and the controversial points of the surgical management for and against LAR with stapled anastomosis and APE were discussed. It is concluded that LAR with the EEA stapler can be carried out in the middle and lower rectum with the prospect of ultimate cure, when performed with proper technical skills in selected patients.

Adult↗

Local recurrence following curative resection for carcinoma of the rectum.

One hundred ninety-three patients had curative resections for carcinoma of the rectum between January 1971 and December 1979. Nineteen patients developed local recurrence (9.8 per cent): 5/95 after abdominoperineal excision (5.2 per cent) and 14/98 after anterior resection (14.3 per cent). There was no difference in the overall survival rate between the two operations, but there was a trend toward decreased survival for patients who developed local recurrence. Metastatic spread to the lymph nodes increased the risk of local recurrence.

Adenocarcinoma↗

Prediction of recurrence after curative resection of gastric carcinoma invading the muscularis propria: a multivariate analysis.

BACKGROUND: In Japan, the incidence of gastric cancer invading the muscularis propria is about 10% of all patients with gastric cancer undergoing surgical resection. Although many prognostic factors for early gastric cancer and advanced gastric cancer have been identified, there are few reports concerning prognostic factors for gastric cancer invading the muscularis propria, and the characteristics of recurrence are not well understood.METHODS: We retrospectively analyzed data on 167 patients with gastric cancer that had invaded the muscularis propria. All patients had undergone curative resection.RESULTS: Recurrences were evident in 37 patients (22.2%). Based on our univariate analysis, the recurrence was associated with lymph node metastases. Multivariate analysis showed that independent risk factors for recurrence were lymph node metastases and location of tumor in the upper or lower one-third of the stomach. With respect to the pattern of recurrence, 17 (46.0%) were secondary to hematogenous recurrence, 8 (21.6%) to peritoneal dissemination, and 6 (16.2%) to a local recurrence in the remnant stomach and in regional lymph nodes. Most deaths occurred during the second year after surgery, and approximately two-thirds of all patients (64.8%) died within 3 years after surgery.CONCLUSION: In patients with the risk factors of lymph node metastases and tumor in the upper or lower one-third of the stomach, lymph node dissection and postoperative adjuvant therapy are vital to try to prevent recurrences, especially during the first 2 years after surgery.

Journal Article↗

Successful curative resection of gastric cancer with AIDS infection.

This report describes the case of a 47-year-old Japanese man with human immunodeficiency virus (HIV) infection with AIDS, who was successfully treated for gastric cancer. A review of gastric cancer associated with HIV is also presented. Prior to surgical treatment, azidothymidine (AZT), nerfinavir (NFV), and lamivudine (3TC) were administered to the patient in order to improve his blood CD4 count and reduce the viral burden. Consequently, distal gastrectomy was performed as a curative resection without any complications. The gastric cancer included a signet-ring cell carcinoma, as was noted in eight of the nine reported cases associated with HIV. This suggests that the HIV virus may play a role in causing signet-ring cell carcinoma, especially in the stomach.

Journal Article↗

Type-oriented intraoperative and adjuvant chemotherapy and survival after curative resection of advanced gastric cancer.

Recent observations and our experience that histologic types of gastric cancer related significantly to patterns of recurrence prompted us to develop intraoperative and postoperative chemotherapy based on the preoperatively diagnosed histologic types of cancer and to evaluate its effectiveness by a prospective randomized trial. This chemotherapy regimen consisted of the intraoperative administration of mitomycin C (MMC) and postoperative administration of cisplatin (80 mg/patient, day 14), and tegaful and uracil (UFT) (300-600 mg/day for 2 years). Patients with a diffuse type of cancer were randomly assigned to one of three treatment groups: no intraoperative chemotherapy and UFT 300 mg/day (P0 group, n = 16); intraoperative chemotherapy and UFT 300 mg/day (P1 group, n = 13); or UFT 600 mg/day (P2 group, n = 17). Patients with an intestinal type of cancer were randomly assigned to one of three treatment groups: H0 (n = 17), H1 (n = 12), and H2 (n = 12); each group was subjected to the same protocols as the P0, P1, and P2 groups, respectively, except for the MMC administration route. MMC (10 mg/patient) was administered intraoperatively into the intraperitoneal cavity (P1 and P2 groups) or the portal vein (H1 and H2 groups). All patients underwent curative resection. Background factors did not differ significantly among the treatment groups. The overall survival rates were progressively worsened in the order of P2, P1, and P0 or H2, H1, and H0, respectively. The survival rate of the P2 group was statistically higher than that of the P0 group (p < 0.05). The intermediate-term survival rate of the P2 group or H2 group was significantly higher than that of the P0 group (p < 0.05) or H0 group (p < 0.05), respectively. These results suggest the effectiveness of this therapy and the possible eradication of potential micrometastatic foci outside the surgical field by the direct administration of chemotherapeutic agents to the predicted recurrence site.

Aged↗

Management of anemia in patients undergoing curative radiotherapy. Erythropoietin, transfusions, or better nothing?

BACKGROUND AND RESULTS: Anemia is a well-known risk factor for decreased local control and survival in patients undergoing curative radiotherapy. There is clear evidence from recent clinical investigations that anemia is an independent risk factor and hemoglobin (Hb) levels during radiotherapy are important (and not pretreatment Hb levels). The most likely explanation for the prognostic impact is the association with tumor hypoxia. An "optimal" Hb range with regard to tumor oxygenation seems to exist, and Hb levels < 11 g/dl and > approximately 15 g/dl impair tumor oxygenation but have (over a broader range) no significant impact on normal tissue oxygenation. There is some evidence from retrospective and prospective studies that the response to radiotherapy and the prognosis, especially in cervical cancers, might be improved if the Hb levels during radiotherapy can be maintained in the optimal range, either by transfusions or by erythropoietin. The effect of any antianemic therapy should be analyzed according to whether or not treatment was successful with regard to achieving optimal Hb levels during irrradiation. Erythropoietin is probably more effective in steadily increasing and stabilizing Hb levels, but bears the risk of overcorrection of Hb levels. The clinical relevance of erythropoietin receptors on tumor cells remains questionable. CONCLUSIONS: Treatment of anemia with the objective of improving local control and survival in radiotherapy patients is probably more difficult and sophisticated than coping with symptoms of anemia or improving quality of life. Nevertheless, the potential of antianemic treatment is high on the basis of experimental and clinical data, and further clinical trials are warranted.

Anemia↗

[Curative vs palliative strategies in locoregional recurrence of gastrointestinal malignancies].

Locoregional recurrence is a relevant problem in surgical oncology. Intraluminal local relapse only occurs when the primary resection is carried through with inappropriate safety margins. If possible, a second surgical resection with wider margins is the treatment of choice. When the primary resection was appropriately done, extraluminal relapse in the original tumor bed indicates the primary tumor was already in an advanced stage. The indication for a second resection must be considered carefully. A realistic prospect of long-term tumor control exists only when the second resection yields tumor-free margins and is combined with chemo- and radiotherapy. There is usually no curative treatment option for recurrences in the draining lymph node region, the so-called fourth dimension.

Combined Modality Therapy↗

[Angiogenesis and density of dendritic cells do not correlate with metachronous distant metastases after curative surgery of rectal carcinoma].

INTRODUCTION: Besides surgery, treatment of rectal cancer increasingly comprises (neo-)adjuvant strategies. To optimise the selection process for these therapy regimens especially in the field of cellular and molecular biology, new prognostic factors besides the established TNM system are being investigated. METHODS: Retrospectively, two groups of patients (n = 2 x 85) with rectal carcinoma curatively treated by surgery alone were studied (median follow-up: 6.1 years). The patients were selected to be free of local disease, in order to exclude surgical influence. Patient groups were matched for age, gender, UICC stage and year of operation (1982-1991) and differed only in subsequent metachronous distant metastatic spread, the criterion to be studied. The factors to be investigated in uni- and multivariate analysis were angiogenesis, density of dendritic cells, grading, venous and lymphatic invasion. RESULTS: Grading always proved to be the only significant prognostic factor (P < 0.0001). In univariate analysis, absent venous invasion also correlated significantly with increased disease-free survival (P = 0.0170). CONCLUSIONS: Angiogenesis and density of dendritic cells in rectal cancer are not prognostic factors for metachronous distant metastasis and, therefore, cannot serve as selection parameters for adjuvant therapy.

Analysis of Variance↗

[Curative radiotherapy of localized prostate cancer. Treatment methods and results].

Radiation oncology has undergone rapid technical development during the last few years. The further development of treatment planning systems and treatment machines had a major impact on the improvement of radiation therapy results in prostate cancer. This paper presents different treatment modalities and results. Currently available are three-dimensional conformal radiation, intensity modulated radiation therapy (IMRT), high dose rate brachytherapy, and low dose rate brachytherapy (seed implantation). All modalities offer the possibility for dose escalation, which is essential for curative treatment. Dose escalation using these techniques makes it possible to reduce the dose for the surrounding organs at risk. Three-dimensional conformal radiation therapy can be delivered with doses up to 78 Gy. The biochemical control rate is up to 90% depending on the risk factors T stage, initial PSA, and Gleason score. The incidence of late side effects is <10%. IMRT is a newer modality for percutaneous radiotherapy. By individual dose modification in the treatment fields, doses >80 Gy can be delivered in small treatment volumes. Treatment has to be highly precise to avoid dose peaks in the organs at risk, i.e., rectum and bladder. The preliminary data for remission and toxicity rates are promising, but it is too early for final conclusions. For cases with high-risk factors such as PSA >10 ng/ml, Gleason score >6, and stage T3, percutaneous radiation can be combined with neoadjuvant or adjuvant hormonal treatment. Randomized trials showed an improvement of the results in favor of combined treatment. HDR brachytherapy in combination with external radiation is a good option for dose escalation in patients with locally advanced tumors and/or other high-risk factors. The biochemical control rates are between 60 and 84%, late effects occur in less than 10%. Seed implantation (LDR brachytherapy) as sole treatment is indicated for prognostically favorable situations (PSA <10 ng/ml, Gleason score < or =6, and T1c or T2a tumors). The biochemical control rates are between 80 and 90%. Toxicity consists of urine retention and proctitis, occurring in 10-20% of the patients.

Brachytherapy↗

Dermabrasion: a curative treatment for melasma.

Melasma is fairly common in Asian patients with a dark skin tone. It has long been known for its recalcitrance to any form of treatment. The objective of this article is to propose mechanical dermabrasion as a curative treatment for this entity. Five hundred and thirty-three patients with melasma were treated by mechanical dermabrasion using a rotatory diamond fraise. Four hundred and ten patients were available for long-term follow-up (mean follow-up time 5 years, range 1-9 years). Out of 410 patients, 398 (97%) achieved persistent clearance of melasma; in the remaining cases, there was partial recurrence after initial clearance. The common temporary sequelae were postoperative erythema or hyperpigmentation, pruritus, and milia formation. Two patients developed hypertrophic scars, one on the upper lip and one on the jawline, and one patient had permanent hypopigmentation on the forehead. In conclusion, mechanical dermabrasion is a relatively safe and highly effective means for curing melasma.

Adult↗

Clinicopathologic features of hepatocellular carcinoma patients with compensated cirrhosis surviving more than 10 years after curative hepatectomy.

BACKGROUND: The aim of this study was to clarify the clinicopathologic features of hepatocellular carcinoma (HCC) patients with compensated cirrhosis surviving more than 10 years after initial hepatectomy. STUDY DESIGN: Among 250 patients who underwent hepatectomy for HCC between 1987 and 1994 at our institute, 145 patients who had Child-Pugh class A liver function and who underwent curative resection were included in this study. Clinicopathologic factors in 10-year survivors and patients who died within 10 years (nonsurvivors) were compared, and the prognostic factors affecting survival were identified. RESULTS: There were 29 patients who survived for more than 10 years after initial hepatectomy, and 9 of those patients survived without cancer recurrence. The 3-, 5-, and 10-year survival rates were 76.2%, 53.0%, and 26.9% respectively. The corresponding disease-free survival rates were 43.1%, 25.7%, and 9.9% respectively. In multivariate analysis, liver fibrosis grade F0-2, female gender, ICG-R15 value of less than 15%, and absence of microscopic vascular invasion were favorable independent factors associated with 10-year survival. Disease-free interval after initial hepatectomy in 10-year survivors with recurrence was significantly longer than that in nonsurvivors with recurrence, 5.1 and 1.9 years respectively (P = 0.0004). The number of intrahepatic recurrent nodules in 10-year survivors tended to be fewer than that in nonsurvivors. CONCLUSIONS: Based on the results of our study, liver fibrosis grade F0-2, female gender, ICG-R15 value of less than 15% and absence of microscopic vascular invasion at initial hepatectomy might be biologically favorable conditions for long-term survival. Close follow-up as well as multimodal treatment could contribute to prolongation of survival in such patients, even if HCC recurrence develops.

Adult↗

Curative resection of microgastrinomas based on the intraoperative secretin test.

The intravenous secretin injection test (secretin test) has been used for the differential diagnosis of gastrinoma. In this study we report that the intraoperative secretin test (IOS test) is also useful for determining the extent of curability in patients with Zollinger-Ellison syndrome (ZES). Twelve patients with ZES underwent surgical exploration and the IOS test. The results of the IOS test were obtained by rapid radioimmunoassay of the serum gastrin level (IRG) within 60 minutes. The test was diagnosed as negative when the maximum increase of serum IRG was less than 80 pg/ml and also less than 20% of the basal serum IRG level. Three of the twelve patients underwent pancreatoduodenectomy (PD), and two patients underwent distal pancreatectomy. Extirpation of duodenal tumors with dissection of regional lymph nodes was performed in seven patients. In two of the seven patients the IOS test remained positive after extirpation of the duodenal tumors and the dissection of regional lymph nodes. In one patient PD was performed on the basis of the positive results, and the IOS test became negative after PD. In the other patient, two tiny metastatic liver tumors were identified and were resected, but the IOS test did not become negative. We closed the abdomen in 11 patients when we obtained negative results from the IOS test. The results of the IOS test were almost identical to the data obtained by the standard assay postoperatively. The serum IRG levels of all but one patient fell to the normal level, and the secretin test became negative postoperatively. The IOS test is thus useful and indispensable for curative resection of microgastrinomas in patients with ZES.

Adult↗

Modern diagnostics in chronic myeloproliferative diseases (CMPDs).

According to the new WHO classification a group of chronic myeloproliferative diseases (CMPDs) were defined: chronic myeloid leukemia (CML), chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia and hypereosinophilic syndrome (CEL/HES), polycythemia vera (PV), chronic idiopathic myelofibrosis (with extramedullary hematopoiesis, CIMF), essential thrombocythemia (ET), and so called CMPD/unclassifiable. As clinical features and laboratory findings differ widely between these diseases several diagnostic approaches are mandatory at diagnosis for classification and are needed also for follow up studies, especially for the measurement of minimal residual disease (MRD). We here outline the laboratory set up at diagnosis and during follow up in CMPDs with specific focus on the respective therapeutical consequences. Only by using a comprehensive diagnostic panel including cytomorphology, cytogenetics, and molecular genetic methods establishing the correct diagnosis, optimizing treatment as well as evaluating treatment response is possible in CMPDs today.

Blood Cell Count↗

Adjuvant intra-arterial 5-fluoruracil, leucovorin, epirubicin and carboplatin with or without systemic gemcitabine after curative resection for pancreatic adenocarcinoma.

BACKGROUND: The role of adjuvant therapy in pancreatic cancer remains controversial. Gemcitabine given systemically seems to be effective; intra-arterial chemotherapy (IAC) has a deep rationale. PATIENTS AND METHODS: The goal was to evaluate the impact of postoperative IAC followed or not by systemic gemcitabine in patients after curative resection for pancreatic adenocarcinoma. 5-fluoruracil 750 mg sq m(-1), leucovorin 75 mg sq m(-1), epirubicin 45 mg sq m(-1), carboplatin 225 mg sq m(-1) were administered every 3 weeks into celiac axis for three cycles (FLEC regimen), then gemcitabine at the dosage of 1 g sq m(-1) on days 1, 8 and 15 every 4 weeks for 3 months (FLECG regimen). RESULTS: Forty-seven patients entered the study. The first 24 received only IAC (FLEC regimen), the other 23 received the same intra-arterial regimen followed by systemic gemcitabine (FLECG regimen). After a median follow-up of 16.9 months, 29 patients recurred (61.7%). Median disease free survival (DFS) was 18 months and median overall survival (OS) was 29.7 months. One-year DFS was 59.4% and 1-year OS was 75.5%. Main grade 3 toxicity related to IAC was only nausea/vomiting in 4%; regarding gemcitabine, grade 3 toxicities were anaemia 8%, leukopenia 8%, thrombocitopenia 17%, nausea/vomiting 4%. CONCLUSIONS: FLEC regimen with or without gemcitabine is active with a very mild toxicity and results are very encouraging in an adjuvant setting.

Adenocarcinoma↗

Angiogenesis and dendritic cell density are not correlated with metachronous distant metastasis in curatively operated rectal cancer.

BACKGROUND AND AIMS: Apart from surgery, treatment of rectal cancer increasingly involves the use of (neo-)adjuvant strategies. To optimize the selection process for these therapy regimens, especially in the field of cellular and molecular biology, new prognostic factors additional to the established TNM system are being investigated. PATIENTS AND METHODS: Two groups of patients ( n=2x85) with rectal carcinoma curatively treated by surgery alone were studied retrospectively (median follow-up 6.1 years). To exclude the effect of the surgeon only patients free of locally recurrent disease were selected. Patient groups were matched for age, gender, UICC stage, and year of operation (1982-1991) and differed only in subsequent metachronous distant metastatic spread, i.e., the criterion to be studied. The factors investigated in uni- and multivariate analysis were angiogenesis, density of dendritic cells, grading, venous invasion, and lymphatic invasion. RESULTS: Grading invariably proved to be the only significant prognostic factor. In univariate analysis the absence of venous invasion was also correlated significantly with increased disease-free survival. CONCLUSION: Angiogenesis and dendritic cell density are not prognostic factors for metachronous distant metastasis in rectal cancer and therefore cannot serve as selection parameters for adjuvant therapy.

Age Factors↗

Long-term effect of 5-fluorouracil enhanced by intermittent administration of polysaccharide K after curative resection of colon cancer. A randomized controlled trial for 7-year follow-up.

BACKGROUND AND AIMS: The efficacy of a biological response modifier polysaccharide K in adjuvant immunochemotherapy was evaluated in primary colon cancer patients with macroscopic Dukes' C after curative resection. PATIENTS AND METHODS: Employing the minimization method using three factors (lymph node metastases, preoperative serum CEA level, and institution), 446 patients were allocated into groups P and C. Group P received immunochemotherapy, oral PSK (3 g per day) followed by oral 5-FU (200 mg/body per day), while group C received only intermittent chemotherapy, oral 5-FU (200 mg per day) followed by 4-week rest. Both groups received ten courses. RESULTS: Survival for cancer death was significantly higher in group P than in group C, but there was no difference in 7-year disease-free survival or overall survival had. CONCLUSION: Repeated alternating administration with PSK followed by 5-FU can improve survival for cancer death.

Adenocarcinoma↗

Adjuvant chemotherapy with folinic acid and 5-fluorouracil in patients with locally advanced rectal cancer previously treated by preoperative radiochemotherapy and curative tumor resection.

BACKGROUND AND AIMS: The role of postoperative adjuvant chemotherapy in patients with rectal cancer pretreated by preoperative radiochemotherapy (RCT) and curative surgery is still poorly investigated. PATIENTS AND METHODS: We pooled data from both arms of a phase III trial in which patients with locally advanced (T3/4) rectal cancer were randomized to preoperative RCT alone or combined with pelvic radio-frequency hyperthermia. After surgery, R0-resected patients were scheduled to adjuvant chemotherapy with four monthly courses of 50 mg folinic acid (FA) and gradually escalated 5-fluorouracil (5-FU, 350-500 mg/m2, days 1-5). Reasons preventing initiation of chemotherapy and treatment-related toxicities were evaluated. Patients' characteristics and survival parameters were compared between the treated and untreated patient groups. RESULTS: Out of 93 patients, 73 (79%) started adjuvant chemotherapy, whereas 19 (21%) did not, mostly due to perioperative complications and refusal. Chemotherapy-related toxicities were mild to moderate in most cases, but--together with protracted postoperative complications--prevented the intended dose escalation of 5-FU in 71% of patients. Distant-failure-free (p=0.03) and overall survival (p=0.03) were improved in the chemotherapy group, although there was a negative selection of patients with unfavourable characteristics into the untreated patient group. INTERPRETATION/CONCLUSION: Adjuvant chemotherapy using FA and 5-FU can be safely applied to the majority of patients with rectal cancer pretreated by RCT and surgery. Survival data are not suitable to allow far-reaching conclusions, but are in line with suggestions of a favourable effect of adjuvant chemotherapy in these patients.

Adolescent↗