Toxicity and effects of adjuvant therapy in colon cancer: results of the german prospective, controlled randomized multicenter trial fogt-1

In this adjuvant three-arm multicenter trial, we studied whether modulating the standard 5-fluorouracil (S-FU) treatment with either folinic acid (FA) or interferon-alpha-2_a (IFN-α) was superior to the recommended standard of adjuvant treatment in RO resected colon cancer, 5-FU plus levamisole (LEV) for 12 months, in terms of toxicity and outcome. From July 1992 to October 1999, a total of 813 patients with resected colon cancer in stage II (T4N0M0; n = 63) or stage III (TxNl-3M0; n = 750) were randomized into three treatment groups and stratified according to N stage and participating centers (64 hospitals). The patients received a postoperative loading dose of S-FU (450 mg/m² on days 1 to 5 [arms A and C]) or S-FU (450 mg/m²) plus FA (Rescuvolin, Medac, Hamburg, Germany, 200 mg/m² on days 1 to 5 [arm BJ). After completion of the first chemotherapy cycle, LEV was administered orally at a dosage of 1.50 mg per day on days 1 to 3, once every 2 weeks. After a 4-week chemotherapy-free interval, the treatment was continued weekly for 52 weeks. Treatment in one arm A ("standard") (n = 279) consisted of 5-FU intravenously (450 mg/m² on day 1, once a week) plus LEV 5-FU plus LEV was modulated in arm B (n = 283) with FA (200 mg/m² on day 1, once a week) and in arm C (n = 251) with IFN-α at 6 million units three times a week repeated weekly. Treatment dosages were adjusted if toxic events above WHO grade 2 occurred. Patients were closely followed to determine recurrence and survival; the latter was calculated according to Kaplan-Meier analysis. Toxic events above WHO grade 2, mainly leukopenia, diarrhea, and nausea, occurred in 113 (14%) of 649 patients who had completed treatment in arms A (8.4%), B (13.5%), and C (31.7%). Discontinuance rates were as follows: 28% for all patients, 29% in arm A, 21% in arm B, and 34% in arm C. Overall relapse rates were 27% for all patients, 30% in arm A, 24% in arm B, and 28% in arm C. Relapses were local (8%) distant (78%), or combined (12%). Fouryear overall survival rates in arms A, B, and C were 66.1%, 77.5%, and 66.2%, respectively. The 4-year survival rate in arm B was significantly higher compared to arm A (P <0.02, log-rank test) with arm A being equal to arm C. Adjuvant therapy with 5-FU plus FA plus LEV for 12 months is superior to the recommended standard (5-FU + LEV for 12 months). IFN-α modulation of 5-FU (plus LEV) adds to the toxicity with no therapeutic benefit.     

Efficacy of a continuous venous infusion of fluorouracil and daily divided dose cisplatin as adjuvant therapy in resectable colorectal cancer: A prospective randomized trial

PURPOSE: Daily divided dose cisplatin (DDD-P) is used as an efficient modulator of fluorouracil (5-FU), as is leucovorin (LV). We performed a randomized trial to compare the efficacy 5-FU plus DDD-P (DDD-FP) therapy with 5-FU alone in resected colorectal cancer as the adjuvant therapy. METHODS: One hundred and eighty-eight stage II or III colorectal cancer patients were enrolled. Patients were randomly assigned to receive DDD-FP (5-FU, 320 mg/ m(2), daily for 21 days; CDDP, 3.5 mg/m(2) daily for 21 days) followed by oral 5-FU (200 mg/body daily for 2 years) (DDD-FP arm) or oral 5-FU therapy (200 mg/ body daily for 2 years) exclusively (oral 5-FU arm). RESULTS: The 5-year disease-free survival (DFS) rates and the overall survival (OS) rates indicated no significant difference between the two arms. By stratified analysis, in the colon cancer patients, the DFS and the OS for the DDD-FP arm were significantly increased: 93.5% and 95.7% in the DDD-FP arm as compared with 76.9% and 82.2% in the oral 5-FU arm (P = 0.024 and P = 0.038). Regarding adverse effects, grade 3-4 toxicities were not significant in two arms. CONCLUSIONS: DDD-FP followed by oral 5-FU therapy suggested a feasible regimen for patients with resected colon cancer as the adjuvant therapy.     

Effects of systemic and regional chemotherapy after hepatic resection for colorectal metastases

Background: Although the survival benefit of hepatic resection for colorectal metastasis has been established, some controversy remains regarding the significance of adjuvant chemotherapy after hepatic resection. Methods: One hundred thirty-two consecutive patients who had liver resection for colorectal metastasis at our hospital between 1980 and 1997 were studied. After curative hepatic resection, 37 patients underwent systemic chemotherapy, administered orally or intraportally. Forty patients had no adjuvant chemotherapy. The chemotherapeutic agents used for oral administration were uracil and Tegafur or Tegafur alone. Mitomycin C (MMC) or 5-FU was used for IV chemotherapy. Combinations of 5-FU/leucovorin or MMC/5-FU (doxorubicin) were used for regional chemotherapy. Univariate and multivariate analyses were applied to test the significance of adjuvant chemotherapy for patient survival or disease-free survival. Results: Overall 5-year survival was 42.2% (95% CL: 31.2%, 53.2%). Among the possible prognostic factors studied, univariate analysis showed a significant difference in survival based on the number of tumors and lymph node metastases in the hepatic hilum. There was a significant difference in disease-free survival based on adjuvant chemotherapy and lymph node metastasis. The multivariate analysis for patient survival selected four prognostic factors (P<.05), including adjuvant chemotherapy, lymph node metastasis, disease-free interval, and tumor size. The multivariate analysis for disease-free survival selected adjuvant chemotherapy, lymph node metastasis, and disease-free interval as significant factors. The most common recurrence site was remnant liver, regardless of adjuvant chemotherapy. Conclusions: Adjuvant chemotherapy significantly improved survival and disease-free survival after hepatic resection for colorectal metastases. It did not decrease recurrence rate in the remnant liver.Presented at the 51st Annual Cancer Symposium of The Society of Surgical Oncology, San Diego, California, March 26–28, 1998.     

Long-term outcomes of bilateral thoracoscopic T3 sympathectomy for primary focal hyperhidrosis in children

BackgroundThoracoscopic bilateral T3 sympathectomy for primary focal palmar hyperhidrosis in children has excellent short-term outcomes. However, data in the literature, on the long-term outcomes of the operation are scarce.MethodsWe conducted a retrospective institutional review of all children and adolescents undergoing T3 bilateral thoracoscopic sympathectomy for primary focal palmar hyperhidrosis between June 2013 and October 2020. We composed a quality of life (QoL) questionnaire evaluating the patient's perception of how much the hyperhidrosis affected their daily life in multiple domains. The questionnaire was completed before the operation and at every postoperative follow-up visit.ResultsWe operated on 58 patients with a median age of 15 (6–25) years. There were no intraoperative or postoperative complications, and all patients had immediate complete postoperative resolution of their palmar hyperhidrosis. Fifty-three patients (91.4%) had long-term follow-up data available with a median of 2.5 (range 0.1–7.5) years. Two patients (3.4%) experienced recurrence of their palmar hyperhidrosis. Nine patients (15.5%) experienced compensatory hyperhidrosis and required occasional medical management with oral anticholinergics. Two patients reported regretting having undergone the operation. Overall, the mean QoL score improved remarkably, from 42/100 before the operation to 92/100 at 1 month, 89/100 at six months to a year, 97/100 between two and four years, and 80/100 ≥ 5 years after the operation.ConclusionThoracoscopic bilateral T3 sympathectomy has a high success rate for primary palmar hyperhidrosis in children in the mid- to long-term. Compensatory sweating and recurrence can occur years after the operation, so long-term follow up is mandatory.Level of evidenceIV.     

Oncologic outcomes of patients with Merkel Cell Carcinoma (MCC): A multi-institutional cohort study

BackgroundMerkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine tumor that primarily affects elderly patients. Despite aggressive treatment, overall survival (OS) remains low.MethodsThis study is a multi-institutional, retrospective review of 102 patients with MCC. We evaluated OS, disease-specific survival (DSS), and risk factors for recurrence.ResultsMedian age of patients was 71.46% of patients recurred. Patients with stage I disease had median 5-year OS of 59.3%, compared to 68.1% DSS. For stage III, median 5-year OS was 46.0% vs 58.2% DSS. Disease stage and advanced age were risk factors for recurrence and decreased OS. Immunocompromised status and disease stage were the strongest predictors of DSS.ConclusionsDSS is significantly better than OS for patients with MCC. Many elderly patients with newly diagnosed MCC have low remaining life expectancy, regardless of their MCC diagnosis. Patient age and overall health status should be considered to personalize care plans for patients with MCC.     

Routine compared with nonscheduled follow-up of patients with “curative” surgery for colorectal cancer

Background: The main rationale for follow-up of colorectal cancer patients resected for “cure” is that early detection and treatment of recurrence and metachronous disease should result in improved survival. Our purpose was to assess in a prospective fashion the impact on survival of a follow-up program versus that of undergoing nonscheduled visits. Methods: Within the 14-year period from 1975 through 1988, a prospective study was carried out on 800 patients with colorectal adenocarcinoma radically resected with no evidence of synchronous cancers of the colon and rectum or in other organs, of whom 322 patients were to attend a 5-year follow-up, and 478 patients were free to make nonscheduled visits on account of symptoms. Results: Asymptomatic recurrence was found at follow-up in 92 (28%) of 322 patients, whereas 175 (36%) of 478 patients had a symptomatic recurrence detected at a nonscheduled visit. Diagnosis of resectable recurrence was established within a median time of 21.5 months. Surgical resection of recurrence was performed in 30 (32%) of 92 and in 13 (7%) of 175 patients (32 vs. 7%;p<0.001). Resection was curative in 13 (14%) of 92 and in two (1%) of 175. Five-year survival of resected recurrence was 10% in 30 of 92 patients and 0.8% in 13 of 175 (10 vs. 0.8%;p<0.01). Two patients are alive with no evidence of disease or two (2%) of 92. Metachronous colorectal lesions were treated for cure in 63 (19.5%) of 322 patients. The effectiveness of scheduled follow-up was 4% (13 of 322 patients). Conclusions: These results underline the rationale for a follow-up program in early detection and surgical treatment of recurrent disease in patients operated on for colorectal cancer.     

Long-Term Survival After Complete Resection and Repeat Resection in Patients With Adrenocortical Carcinoma

Background: One of the key issues in the treatment of adrenocortical carcinoma is the efficacy of repeat resection of local recurrence and metastatic disease in affected patients. Options in the treatment of locally recurrent or metastatic disease are limited because chemotherapy and radiotherapy generally do not provide any significant prolongation in survival in treated patients.Methods: A series of 113 patients who presented to Memorial Sloan-Kettering Cancer Center for treatment of adrenocortical carcinoma are presented.Results: The median overall survival for all 113 patients was 38 months (5-year survival, 37%). Patients presenting with early stage I or II disease (n = 57) had a median survival of 101 months (5-year survival, 60%), whereas those with late stage III or IV disease (n = 56) had a median survival of 15 months (5-year survival, 10%). Patients who had complete primary resection (n = 68) had a median survival of 74 months (5-year survival, 55%), whereas those with incomplete primary resection (n = 45) had a median survival of 12 months (5-year survival, 5%). Resection of locally recurrent or distant metastatic disease was performed in 47 of these patients. Patients who had a complete second resection had a median survival of 74 months (5-year survival, 57%), whereas those with incomplete second resection had a median survival of 16 months (5-year survival, 0%).Conclusions: Improved survival is seen in patients who present with early stage and have complete primary resection. Patients who undergo complete repeat resection of local recurrence or distant metastasis also have improved survival. Complete repeat resection was more readily accomplished in discrete distant metastatic lesions compared with bulky local recurrences.Presented at the 52nd Annual Meeting of the Society of Surgical Oncology, Orlando, Florida, March 4–7, 1999     

Five mm laparoscopic varicocelectomy versus conventional varicocele ligation in young men with symptomatic varicocele: A randomized clinical study

ObjectivesTo compare the therapeutic success, morbidity and the costs of 5 mm laparoscopic varicocele ligation (LV) compared to inguinal varicocelectomy (IV).Patients and methodsEighty patients with idiopathic symptomatic varicocele of grades I–III diagnosed by clinical examination and Doppler ultrasonography were randomly assigned to LV or IV (40 patients in each group). The mean patient age was 25.2 ± 1.4 (range 18–40) years. Of the 80 patients treated 21.3% had a left-sided varicocele, 70% had bilateral varicoceles and 8.8% a right-sided varicocele. Of 136 varicoceles, 37 (27.2%) were grade III, 51 (37.5%) grade II and 48 (35.3%) were grade I. The indications for varicocele ligation were: abnormal spermiogram in 47 patients (58.7%), scrotal pain in 19 (23.8%) and cosmetic impairment in 14 (17.5%). A total of 136 varicocele ligations were performed (67 IV and 69 LV). All patients were followed up for 4–8 months to assess early complications, testicular size, late complications and persistence or recurrence of the varicocele.ResultsLV was associated with shorter operative time, shorter hospital stay and lower cost compared to IV. The overall incidence of postoperative complications including hydrocele, epididymitis and local pain was significantly higher among patients undergoing IV compared with LV (17.5% vs 5%). The incidence of persistent varicoceles was not significantly different between the 2 groups, but the varicocele recurrence rate was significantly lower in the LV compared to the IV group (5% vs. 17.5%, p ≤ 0.02).ConclusionsLV is a less invasive treatment than IV for managing male varicoceles. It is also associated with lower costs and better outcomes and should therefore be the preferred method of treatment for male varicoceles.     

Modified Staging System for Extremity Soft Tissue Sarcomas

Background: The establishment of a universally acceptable staging system for soft tissue sarcomas has been hampered by the low incidence, various grading systems, and lack of consensus regarding the value of different prognostic factors. We aimed to evaluate prognostic factors in patients with extremity soft tissue sarcomas and to test the validity of the AJCC/UICC staging system.Methods: Prospectively collected data from 316 previously untreated patients with primary extremity soft tissue sarcomas treated at a single institution between 1989 and 1995 were studied. The influence of clinical and pathological factors on local recurrence, distant metastasis, and disease-specific survival was analyzed by univariate and multivariate techniques.Results: Large tumor size and high histological grade were independent adverse prognostic factors for distant metastasis. Large size, high grade, and positive microscopic surgical margins were independent adverse prognostic factors, and liposarcoma histology was an independent favorable prognostic factor for disease-specific survival. Within each histological grade, there was a progressive decline in survival with increasing tumor size, as reflected by an almost linear increase in hazard ratios. Similarly, there was a progressive fall in survival with increasing grade within each size group (<5 cm, 5 to 10 cm, 10 to 15 cm, and =15 cm). AJCC staging did not correlate well with prognosis. Survival for intermediate-grade tumors smaller than 5 cm (stage IIA) was better than that for low-grade tumors larger than 5 cm (stage IB) (86% vs. 73%). Survival for high-grade tumors smaller than 5 cm (stage IIIA) was better than that for intermediate-grade tumors larger than 5 cm (stage IIB) (72% vs. 57%). A modified staging system was formulated based on the additive influence of size and grade on the estimated hazard ratios for disease-specific survival, as follows: stage IA, G1T1; stage IB, G1T2 or G2T1; stage IIA, G1T3 or G2T2 or G3T1; stage IIB, G1T4 or G2T3 or G3T2; stage IIIA, G2T4 or G3T3; stage IIIB, G3T4; and stage IV, M1 (G1, G2, G3 = low, intermediate, and high grade; T1, T2, T3, T4 = tumor size < 5 cm, 5–10 cm, 10–15 cm, and >15 cm, respectively). The 5-year disease-specific survivals of stages IA, IB, IIA, IIB, IIIA, and IIIB were 100%, 83%, 74%, 61%, 39%, and 18%, respectively. The 5-year disease-specific survival for stages I, II, III, and IV were 90%, 67%, 31%, and 6% respectively. The survival difference between each stage was statistically significant (P < .001).Conclusion: Histological grade and tumor size are equally important determinants of distant metastases and survival. The AJCC/UICC staging system is based primarily on the grade of the tumor, with size used to subgroup each stage. A staging system for extremity soft tissue sarcomas with equal emphasis on grade and size is proposed that correlates extremely well with prognosis.     

Analysis for clinical feature and outcome of chondroblastoma after surgical treatment: A single center experience of 92 cases

BackgroundChondroblastoma is a rare, benign, cartilaginous bone tumor derived from epiphyseal chondrocytes. Although the clinical characteristics and experience of surgical treatment of the smaller number of patients has been reported in the literature, it is difficult to draw conclusions about the clinical and radiographic features and the outcome for surgical treatment of this disease due to the rarity of chondroblastoma. This study was aiming to review the epidemiologic characteristics and outcome of surgical management for patients with chondroblastoma.MethodsWe performed a retrospective analysis of 92 patients with chondroblastoma. Clinical data, radiographic images, surgical treatment and outcome were analyzed. Eighty-two patients received the extensive intralesional curettage and ten cases had the En-block resection.ResultsThe most common site of disease was proximal femur (20.7%, 19/92), followed by distal femur (18.5%, 17/92) and proximal tibia (16.3%, 15/92). The secondary aneurysmal bone cyst component was most common for chondroblastoma of the small irregular bones, such as patella and foot. Four (4.3%, 4/92) cases receiving the extensive intralesional curettage developed the local recurrence, respectively two at the proximal tibia, one at the pelvis and one at the calcaneus. Time to local recurrence were respectively 14.5, 8.8, 27.0 and 5.6 months, with the average 14 months. Kaplan–Meier estimated survivorship curve of local recurrence-free survival rates of one, two and five years were respectively 97.7%, 96.2% and 93.9%. The mean Musculoskeletal Tumor Society (MSTS) score was 29.4. At the last follow-up, no one had the pulmonary metastasis and death associated with the disease.ConclusionIntralesional curettage plus local adjuvants can obtain satisfactory outcome for chondroblastoma.Level of evidenceLevel IV.     

Risk factors for the recurrence of stage II perforated colorectal cancer: A retrospective observational study

BackgroundPatients with perforated colorectal cancer (PCRC) experience higher recurrence rates than those with non-perforated tissue. We identified the promoting factors of stage II PCRC recurrence after R0 surgery.MethodThis retrospective observational study included patients treated for colorectal cancer at a single facility between 2007 and 2016, and compared the clinicopathological features of patients with perforating versus non-perforating stage II tumors who underwent R0 resection, while focusing on recurrences.ResultsThirty-two and 112 patients (predominantly men) with perforating and non-perforating tumors, respectively, were included. The perforated group had significantly higher proportions of T4 tumors than the non-perforated group (44% vs. 15%). The perforated group had significantly lower numbers of resected lymph nodes than the non-perforated group (6 vs. 17). Seven of 17 patients with follow-up data in the perforated group experienced recurrence (41%), versus 19 of 104 in the non-perforated group (18%). In the non-perforated group, male sex (89% vs. 60%, p = 0.030), T4 stage (32% vs. 9%, p = 0.029), and fewer resected lymph nodes (12.5 vs. 18.6, p = 0.003) were significantly associated with recurrence; however, no such influences on recurrence were observed in the perforated group. The recurrence sites in the perforated group were mostly local (6 patients, 86%). Conversely, recurrences in the non-perforated group were mostly distant; 8 of 19 patients (42%) had liver metastasis and 1 (5%) had lung metastasis.ConclusionPatients with stage II PCRC experienced higher recurrence rates regardless of clinicopathological features and had high local recurrence rates indicating possible local tumor cell dispersal owing to perforation.     

Patient quality of life before and after ventral hernia repair

BackgroundRecurrence is often reported as the primary outcome among studies of patients with hernias; however, there is growing interest in patient quality of life. The relationship between quality of life and recurrence is poorly understood. This study evaluates this relationship.MethodsA secondary analysis of 3 prospective clinical trials was performed. The modified Activities Assessment Scale, a validated, abdominal wall–specific quality of life tool was used (1 = poor quality of life and 100 = perfect quality of life). Patients with and without a hernia recurrence were compared. Baseline quality of life, follow-up quality of life, and change in quality of life were measured. The relationship between quality of life and clinical outcomes was examined.ResultsA total of 238 patients were followed for median (range) 30 (14–44) months, of whom 31 (13.0%) had a clinical recurrence, whereas 207 (87.0%) had no clinical recurrence. Patients with recurrence were more likely to have a lower mean baseline quality of life (14 vs 26; P = .035), follow-up quality of life (42 vs 82; P < .001), and change in quality of life (19 vs 33; P < .018). The majority of patients with or without recurrence still experienced an improvement in quality of life (68% vs 79%; P = .142).ConclusionPatients with lower baseline quality of life are likely to experience a recurrence following repair; however, most still report substantial improvements in quality of life. Assessing follow-up quality of life without accounting for baseline quality of life is incomplete; follow-up quality of life should be assessed with appropriate adjustment for baseline quality of life.     

Loss of APKC expression independently predicts tumor recurrence in superficial bladder cancers

ObjectivesEpithelial-mesenchymal transition (EMT) is known to play an important role in the development of tumor invasion and progression in tumors of epithelial origin. Our aim was to investigate the role of tight junction proteins, Par3/Par6/atypical protein kinase C (APKC), Discs large (Dlg), and Scribble in human bladder pathogenesis.MethodsWe evaluated levels of APKC, Dlg, and Scribble in 92 superficial bladder tumors using tissue microarrays and immunohistochemistry, and correlated expression with pathologic variables and clinical outcomes.ResultsThere was a slight apparent enrichment in strong vs. weak staining for APKC (54.9% vs. 45.1%), Dlg (65.7% vs. 34.3%), and a marked enrichment for Scribble (75% vs. 25%) in the superficial bladder tumors. Univariate analysis determined that both tumor focality and APKC expression were significantly associated with tumor recurrence (P < 0.05). Multivariate analysis using the Cox's proportional hazards model revealed that only APKC (P = 0.025) as well as tumor focality (P = 0.018) were independent and significant prognostic factors for tumor recurrence in all patients. We found that no immunohistochemical staining of any of the cell polarity proteins significantly predicted for tumor progression on either univariate or multivariate analysis.ConclusionsLoss of APKC expression in superficial bladder tumors is a strong predictor of tumor recurrence.     

Prognostic value of recurrence pattern in locally advanced esophageal squamous cell carcinoma: Results from the phase III trial NEOCRTEC5010

ObjectivesThe prognosis of patients with locally advanced esophageal squamous cell carcinoma with different recurrence backgrounds is highly heterogeneous. This study aims to explore the effects of recurrence patterns on prognosis.MethodsThe phase III, multicenter, prospective NEOCRTEC5010 trial enrolled 451 patients with stage IIB-III esophageal squamous cell carcinoma randomly assigned to neoadjuvant chemoradiotherapy combined with surgery (NCRT group) or surgery alone (S group) and followed them long-term. We investigated the effects of recurrence patterns on survival in patients undergoing radical esophagectomy.ResultsIn total, 353 patients were included in the study. The 5-year overall survival of patients with different recurrence patterns was significantly different: recurrence versus recurrence-free (17.8% vs 89.2%; P < .001), early recurrence versus late recurrence (4.6% vs 51.2%; P < .001), and distant metastasis versus locoregional recurrence (17.0% vs 20.0%; P = .666). Patients with early recurrence had significantly shorter survival after recurrence than those with late recurrence (hazard ratio, 1.541; 95% confidence interval, 1.047-2.268, P = .028). There was no significant difference in postrecurrence survival between patients with distant metastasis and locoregional recurrence (hazard ratio, 1.181; 95% confidence interval, 0.804-1.734; P = .396). Multivariate logistic analysis showed that pN1 stage, lymph node dissection <20, and lack of response to NCRT were independent risk factors for postoperative early recurrence. Multivariate Cox regression suggested that NCRT, age ≥60 years, early recurrence, and the pN1 stage were independent risk factors for shortened survival after recurrence.ConclusionsPrerecurrence primary tumor stage is inaccurate in predicting postrecurrence survival. In contrast, recurrence patterns can guide follow-up while also predicting postrecurrence survival. NCRT prolongs disease-free survival but is associated with a worse prognosis in patients with recurrence, especially early recurrence.     

Risk Stratification of Patients with Stage I Cutaneous Melanoma Using 31-Gene Expression Profiling

BackgroundWhile patients with localized cutaneous melanoma (CM) generally have good five-year melanoma-specific survival rates, identifying patients with localized disease at a high risk of recurrence could allow them access to additional follow-up or surveillance.ObjectiveWe sought to examine the prognostic value of the 31-gene expression profile (31-GEP) test for the risk of recurrence in stage I CM patients according to 31-GEP main class (low risk: Class 1 vs. high-risk: Class 2) and the lowest and highest risk 31-GEP subclasses (Class 1A vs. Class 2B).MethodsData from a previously described meta-analysis detailing the 31-GEP results for patients with stage I CM (N = 623) were re-analyzed to determine 31-GEP accuracy.ResultsPatients with stage I CM and a Class 1 31-GEP result were less likely to have a recurrence (15/556; 2.7% vs. 6/67; 9.0%; p=0.018) than patients with a Class 2 result and had a higher five-year recurrence-free survival (RFS) (96% vs. 85%). Patients with a Class 2 result were 2.8 times as likely to experience a recurrence (positive likelihood ratio: 2.82; 95% confidence interval: 1.38–5.77). In a subset of patients with stage I CM stratified further into 31-GEP subclasses (n = 206), patients with a Class 1A result had a higher five-year RFS than those with a Class 2B result (98% vs. 73%). Patients with a Class 2B result were also 6.5 times as likely to experience a recurrence (positive likelihood ratio: 6.45; 95% confidence interval: 2.44–17.00) than those with a Class 1A result, and the 31-GEP had a negative predictive value of 96.3% (95% confidence interval: 92.3%–98.4%).ConclusionThe 31-GEP test significantly differentiates between low and high recurrence risk in patients with stage I CM.     

Factores de riesgo de mortalidad postoperatoria en el cáncer colorrectal: seguimiento de una cohorte en una unidad especializada

IntroductionThe treatment of colorectal cancer (CRC) is usually surgical and involves morbidity-mortality. The aim of this study is to quantify the postoperative mortality in our hospital and to determine their risk factors.Materials and methodsProspective observational study from 1996 to 2007 included 1017 patients who underwent surgery for CRC in our hospital. Identification of independent risk factors for postoperative mortality by multivariate analysis.ResultsThe mean age was 67.8 years. The surgery was elective in 879 (86.5%) and was considered curative in 878 (86.1%). The postoperative mortality was 3.6% (37 patients), 2.5% in the elective surgery and 10.9% in the urgent.The independent risk factors identified were: type of surgery (odds ratio for urgent vs. elective=2.8), American Society of Anesthesiologists (ASA) grade (odds ratio for ASA III–IV vs. I–II=2.4), age (odds ratio for age ≥ 85 vs. ≤ 74=7.6 and age 75–84 vs. ≤ 74=2.4).ConclusionsWe found a low postoperative mortality, which was mainly associated with age over 75 years, ASA III or IV stages and urgent surgery.     

Fluorouracil-based Chemoradiation with Either Gemcitabine or Fluorouracil Chemotherapy after Resection of Pancreatic Adenocarcinoma: 5-Year Analysis of the U.S. Intergroup/RTOG 9704 Phase III Trial

Background

The impact of the addition of gemcitabine to 5-fluorouracil (5-FU) chemoradiation (CRT) on 5-year overall survival (OS) in resected pancreatic adenocarcinoma are presented with updated results of a phase III trial.

Methods

After resection of pancreatic adenocarcinoma, patients were randomized to pre- and post-CRT 5-FU versus pre- and post-CRT gemcitabine. 5-FU was provided continuously at 250 mg/m²/day, and gemcitabine was provided at 1000 mg/m² weekly. Both were provided over 3 weeks before and 12 weeks after CRT. CRT was provided at 50.4 Gy with continuously provided 5-FU. The primary end point was survival for all patients and for patients with tumor of the pancreatic head.

Results

Four hundred fifty-one patients were eligible. Univariate analysis showed no difference in OS. Pancreatic head tumor patients (n = 388) had a median survival and 5-year OS of 20.5 months and 22% with gemcitabine versus 17.1 months and 18% with 5-FU. On multivariate analysis, patients on the gemcitabine arm with pancreatic head tumors experienced a trend toward improved OS (P = 0.08). First site of relapse local recurrence in 28% of patients versus distant relapse in 73%.

Conclusions

The sequencing of 5-FU CRT with gemcitabine as done in this trial is not associated with a statistically significant improvement in OS. Despite local recurrence being approximately half of that reported in previous adjuvant trials, distant disease relapse still occurs in ≥70% of patients. These findings serve as the basis for the recently activated EORTC/U.S. Intergroup RTOG 0848 phase III adjuvant trial evaluating the impact of CRT after completion of a full course of gemcitabine.     

Aplicabilidad y resultados del trasplante hepático combinado con quimiorradioterapia neoadyuvante en el tratamiento del colangiocarcinoma perihiliar irresecable

BackgroundIn 2007, a multicenter protocol was developed in Catalonia, Spain, combining neoadjuvant chemoradiotherapy and liver transplantation (LT) for those patients with unresectable hilar cholangiocarcinoma (hCCA).AimTo analyse the effectiveness of the neoadjuvant chemoradiotherapy and LT for those patients enrolled in the protocol based on intention-to-treat.MethodsObservational multicenter study which includes patients ≤ 68 years-old diagnosed with unresectable, solitary tumors ≤ 3 cm in radial diameter, without evidence of lymph node metastases. The protocol was based on a strategy of neoadjuvant therapy with high-dose radiation (45 Gy in total) plus intravenous fluorouracil (5-FU) given as a daily bolus for the first 3 days of radiation follow by oral capecitabine until transplantation. The patient was included in waiting list for LT if no evidence of disseminated disease was found.ResultsBetween 2007 and 2018, 13 patients were enrolled in the transplant protocol. Of those, 61% (8/13) of the patients were transplanted. The average time spent on the waiting list was 122 days (range 5-192). Intent-to-treat survival was 69% and 39% at one and 5 years. Post-transplantation overall survival was 87% and 62% and 29% recurrence rate at 5 years.ConclusionThe suitability of the neoadjuvant chemoradiotherapy and LT protocol was 61% in our series with long-term overall survival and should be considered as an alternative to resection for patients with localized node-negative hCCA.     

Thin #1 mm Level III and IV Melanomas Are Higher Risk Lesions For Regional Failure and Warrant Sentinel Lymph Node Biopsy

Background: Thin melanomas have become increasingly prevalent, and lesions 1 mm or less in thickness are frequently diagnosed. They are considered highly curable when treated with wide local excision alone with reported 5-year disease free survivals of 95% to 98%. However, thin Clark level III and IV melanomas may have an increased potential for metastasizing and late recurrence because of dermal lymphatics located at the interface of the papillary and reticular dermis. We have addressed this controversial area by reviewing the outcomes of patients with invasive thin (# 1.0 mm thick) melanomas.Methods: We reviewed 415 invasive melanomas from 1983–1995 in the Rhode Island tumor registries which kept records of both tumor thickness and Clark levels. Sixty-eight (16.4%) of the 415 invasive melanomas were thin (# 1.0 mm in thickness) and were treated by wide local excision only. In situ lesions were excluded. Thirty-eight (56%) of the 68 thin melanomas were either Clark level III or IV.Results: Seven (18.4%) of the 38 level III and IV thin melanomas had a recurrence at a minimum follow-up of 36 months. Median time to recurrence was 52 months, and the average measured depth of tumor thickness was 0.84 mm. Only one (3.3%) of 30 level II melanomas recurred (P < .05).Conclusions: Thin level III and IV melanomas are at increased risk for late recurrence when compared with all thin melanomas. Because there is effective adjuvant therapy with alpha interferon for patients with stage III melanoma to treat regional and systemic disease, and because sentinel lymph node biopsy (SLNB) offers minimal morbidity, we suggest using SLNB to accurately stage and treat all patients with thin melanoma that are high Clark levels that are at increased risk for metastases.