Enhanced recovery after surgery pathway in patients with soft tissue sarcoma.

BACKGROUND: Patients undergoing surgery for soft tissue sarcoma have high morbidity rates, particularly after preoperative radiation therapy (RT). An enhanced recovery after surgery (ERAS) programme may improve perioperative outcomes in abdominal surgery. This study reported outcomes of an ERAS programme tailored to patients with soft tissue sarcoma. METHODS: A prospective ERAS protocol was implemented in 2015 at a high-volume sarcoma centre. Patients treated within the ERAS programme from 2015 to 2018 were case-matched retrospectively with patients treated between 2012 and 2018 without use of the protocol, matched by surgical site, surgeon, sarcoma histology and preoperative RT treatment. Postoperative outcomes, specifically wound complications and duration of hospital stay, were reported. RESULTS: In total, 234 patients treated within the ERAS programme were matched with 237 who were not. The ERAS group had lower wound dehiscence rates overall (2 of 234 (0·9 per cent) versus 31 of 237 (13·1 per cent); P < 0·001), after preoperative RT (0 of 41 versus 11 of 51; P = 0·004) and after extremity sarcoma surgery (0 of 54 versus 6 of 56; P = 0·040) compared with the non-ERAS group. Rates of postoperative ileus or obstruction were lower in the ERAS group (21 of 234 (9·9 per cent) versus 40 of 237 (16·9 per cent); P = 0·016) and in those with retroperitoneal sarcoma (4 of 36 versus 15 of 36; P = 0·007). Duration of hospital stay was shorter in the ERAS group (median 5 (range 0-36) versus 6 (0-67) days; P = 0·003). CONCLUSION: Treatment within an ERAS protocol for patients with soft tissue sarcoma was associated with lower morbidity and shorter hospital stay.

ANTECEDENTES: Los pacientes sometidos a cirugía por sarcoma de tejido blando (soft tissue sarcoma, STS) tienen altas tasas de morbilidad, particularmente después de la radioterapia preoperatoria (RT). El programa de recuperación intensificada después de la cirugía (enhanced recovery after surgery, ERAS) puede mejorar los resultados perioperatorios en la cirugía abdominal. Este estudio analizó los resultados de un programa ERAS diseñado para pacientes con STS. MÉTODOS: Se implementó un protocolo prospectivo ERAS en el año 2015 en un centro de alto volumen de sarcomas. Los pacientes en ERAS desde 2015 hasta 2018 fueron emparejados retrospectivamente con pacientes sin ERAS desde 2012 hasta 2018, según la localización quirúrgica, el cirujano, la histología del sarcoma y el tratamiento con RT preoperatoria. Se analizaron los resultados postoperatorios, específicamente las complicaciones de la herida y la duración de la estancia hospitalaria (length of stay, LOS). RESULTADOS: En total, 234 pacientes tratados con ERAS se compararon con 237 pacientes no tratados con ERAS. Los pacientes con ERAS tuvieron tasas globales más bajas de dehiscencia de la herida (2 (0,9%) versus 31 (13,1%), P < 0,001)), después de la RT preoperatoria (0 versus 11 (21,6%), P = 0,004)), y después de la cirugía de STS de extremidades (0 versus 6 (0,7%), P = 0,04)) en comparación con los pacientes no ERAS. Las tasas de íleo u obstrucción postoperatorias fueron más bajas en el grupo ERAS (21 (9,9%) versus 40 (16,9%), P = 0,02)) y en aquellos pacientes con sarcoma retroperitoneal (4 (11,1%) versus 15 (41,7%), P = 0,007)). La mediana (rango) de la LOS fue más corta en los pacientes con ERAS que fue de 5 (0-36) días que en los pacientes sin ERAS que fue de 6 (0-67) días (P = 0,003). CONCLUSIÓN: ERAS para pacientes con STS se asoció con una menor morbilidad y una estancia hospitalaria más corta.

A prospective evaluation of hepatic resection for colorectal carcinoma metastases to the liver: Gastrointestinal Tumor Study Group Protocol 6584.

We report here the results of the first multiinstitutional prospective evaluation of patients considered to have potentially resectable hepatic metastases from colorectal carcinoma. One hundred fifty-six patients were enrolled from 15 institutions. Six patients were subsequently excluded. One hundred fifty patients underwent surgery and are evaluable for analysis (median follow-up time, 3.1 years; range, 4 months to 5.1 years). Curative resection could be performed on 46% of patients (69 of 150), noncurative resection on 12% (18 of 150), while 42% were found to be unresectable (63 of 150). Thirty-day surgical mortality and morbidity rates in patients with attempted resection were 2.7% and 13%, respectively. The curative resection group was observed to have an improved median survival (37.1 months) compared with the noncurative resection group (21.2 months) and the unresectable group (16.5 months) (P less than .01). Computed tomographic (CT) scan was a poor predictor for resectability, and age was not a contraindication to curative resection. Preoperative carcinoembryonic antigen (CEA) values were also a poor predictor for resectability. However, the median CEA value 61 to 180 days postsurgery was significantly higher in unresectable patients compared with median CEA levels in noncuratively and curatively resected groups (P less than .01). Our results imply that curative resection leads to an increase in median survival. Noncurative resection provides no benefit to asymptomatic patients, since unresectable and noncurative resection groups have similar life expectancies. Longer follow-up will be needed to demonstrate the ultimate impact of curative resection on survival.

Clinical and molecular prognostic factors in sphincter-preserving surgery for rectal cancer.

As many as a third of patients with rectal cancers may be candidates for sphincter preservation surgery. The goal of the conservative management of adenocarcinoma of the distal rectum is to preserve rectal sphincter function without sacrificing local tumor control. To achieve this goal, a combined modality approach is necessary because multimodality therapy for more advanced disease has improved both local control and survival. Candidates for local excision are those with adenocarcinomas with a maximal diameter of less than 4 cm, mobile, and not poorly differentiated or mucinous and within 10 cm of the anal verge--usually within 6 cm. These criteria should be defined objectively by biopsy combined with state-of-the-art endorectal imaging. Newer molecular markers that are associated with prognosis and response to therapy may also be important for assessing prognosis, probability of local recurrence, and whether conservative treatment is appropriate. Patients with T0-3 N0 lesions meeting these standard clinicopathologic criteria have been treated successfully with wide local excision combined with chemotherapy and radiotherapy. Patients with larger or more advanced lesions may undergo low anterior resection with coloanal anastomosis. After resection, radiotherapy to at least 45 to 50 Gy is delivered to the pelvis and tumor bed often with concomitant chemotherapy. The overall rate of local failure in prospective single-institution trials in which local excision is performed with postoperative chemoradiotherapy has been 5% for T1 lesions, 7% for T2 lesions and 24% for T3 lesions. Although single-institution studies have supported the concept of conservative therapy, the safety and efficacy of this approach must still be confirmed in a multicenter, prospective trial, such as that underway in several of the cooperative oncology groups, before it may be considered a standard of practice.

Locally advanced rectal carcinoma: pelvic control and morbidity following preoperative radiation therapy, resection, and intraoperative radiation therapy.

PURPOSE: To determine the impact of intraoperative radiation therapy (IORT) combined with preoperative external beam irradiation and surgical resection in patients with locally advanced, unresectable rectal carcinoma. METHODS AND MATERIALS: Between 1982 and 1993, 40 patients with locally advanced colorectal cancer unresectable at initial presentation were treated with preoperative external beam radiation therapy (median dose 50.4 Gy). Thirty patients received concurrent 5-fluorouracil. Twenty-seven patients had primary tumors and 13 had recurrent disease; 1 patient had a solitary hepatic metastasis at the time of surgery. Four to 6 weeks after radiation, surgical resection was undertaken, and if microscopic or gross residual disease was encountered, IORT was delivered to the tumor bed. Patients with an unevaluable or high-risk margin were also considered for IORT. IORT was delivered through a dedicated 300-kVp orthovoltage unit. The median dose of IORT was 12.5 Gy (range 8-20). The dose was typically prescribed to a depth of 1-2 cm. The median follow-up was 33 months (range 5-100). RESULTS: Thirty-three patients were able to undergo a curative resection (83%). Five patients had gross residual disease despite aggressive surgery. Seven patients did not receive IORT: six because of clear margins, and one with gross disease that could not be treated for technical reasons. The remainder of the patients (26) received IORT to the site of pelvic adherence. The crude local control rates for patients following complete resection with negative margins were 92% for patients treated with IORT and 33% for patients without IORT. IORT was ineffective for gross residual disease. Pelvic control was none of four in this setting. The crude local control rate of patients with primary cancer was 73% (16 of 22), as opposed to 27% (3 of 11) for these with recurrent cancer. The 5-year actuarial overall survival and local control rates for patients undergoing gross complete resection and IORT were 64% and 75%, respectively. Seventeen of the 26 patients (65%) who received IORT experienced pelvic complications, as opposed to two patients (28%) who did not receive IORT. The incidence of complications was similar in the patients with primary versus recurrent disease. All cases were successfully treated with the placement of a posterior thigh myocutaneous flap. Of note, no pelvic osteoradionecrosis was seen in this series. CONCLUSION: Patients with locally advanced carcinoma of the rectum were aggressively treated with combined modality therapy consisting of preoperative external beam radiotherapy, surgery, and IORT. The pelvic control rate was 82% for patients with minimal residual disease. IORT failed to control gross residual disease. The incidence of pelvic wound healing problems was 65% in this series; however, a reconstructive procedure which replaced irradiated tissue with a vascularized myocutaneous flap was successful in treating this complication. We believe that IORT has therapeutic merit in the treatment of locally advanced rectal cancer, particularly in the setting of minimal residual disease.

Protein differences in human pancreatic cancer cell lines with diverse metastatic potential.

High-resolution two-dimensional polyacrylamide gel electrophoresis was performed on the pancreatic cell lines SG, SG-R, FG, and L3.5, which when injected into the spleen of nude mice produced hepatic metastases in 0%, 20%, 64%, and 100% of the animals, respectively. A total of 981 proteins were quantitatively identified. In the highly metastatic lines, 13 proteins were present in statistically significant greater quantities, while 4 proteins were present in statistically significant greater quantities in the cell lines with a low metastatic potential. Two proteins were unique to the highly metastatic lines, while 16 proteins were unique to the lines with a low metastatic potential. These results suggest that there are considerable quantitative and qualitative differences in the cellular proteins of human pancreatic cancer cell lines with a varying metastatic potential and imply a biochemical basis to tumor heterogeneity and metastases.

Inhibition of rat colon tumor isograft growth with dequalinium chloride.

In searching for a new approach to the systemic treatment of colorectal carcinoma, we have observed that certain lipophilic cationic compounds are accumulated and retained for a significantly longer period in the mitochondria of living carcinoma cells than in normal cells or sarcoma cells. We report the in vivo therapeutic effect of one of these compounds, dequalinium chloride, on the W163 rat colon carcinoma isograft, which grows rapidly in Wistar/Furth rats after primary tumor implantation, and which recurs rapidly after primary tumor resection. In the primary transplant model, tumors were implanted, and daily dequalinium chloride treatments were begun the following day in doses ranging from 1 to 10 mg/kg. In the recurrence model, isografts were implanted, allowed to grow for one week, and then all gross tumor was resected. Dequalinium chloride was administered in varying daily doses starting the day after resection. In both models, tumor was removed on day 11 after implantation or resection. At sublethal doses, dequalinium chloride significantly inhibited primary tumor growth to 60% that of controls and recurrent tumor growth to 50% that of controls. We propose that this unique biologic approach of targeting carcinoma mitochondria with lipophilic cationic compounds may provide a major new opportunity for treating colorectal carcinoma.

Role of staging laparoscopy in the treatment of hepatic malignancy.

Despite current radiologic imaging capabilities, 40% to 70% of patients with primary or metastatic hepatic malignancies are found to have unresectable disease at the time of laparotomy. The present study evaluates the use of laparoscopy in the staging of hepatic malignancy. Twenty-nine patients underwent staging laparoscopy prior to a planned laparotomy for resection of a hepatic malignancy that was deemed resectable by computed axial tomographic scan and ultrasonography. Twelve patients had primary hepatic malignancies, and 17 had metastatic malignancies. Laparoscopy demonstrated evidence of unresectability in 48% (14 of 29) of patients studied. Four patients had unsuspected cirrhosis, and 10 had unresectable or extrahepatic metastatic disease. Patients who underwent laparoscopy alone had shorter mean hospital lengths of stay than historical controls who underwent laparotomy alone. We conclude that diagnostic laparoscopy should precede laparotomy for planned resection of hepatic malignancies.

Preservation of the anus in the therapy of distal rectal cancers.

Using the gold standard of APR as a measure of cancer control, sphincter-sparing procedures appear to provide similar rates of local control and survival. Specifically, for T1, T2, and T3 lesions, local excision alone, local excision plus adjuvant therapy, and low anterior resection with coloanal anastomoses, respectively, have proven to be acceptable forms of therapy. However, questions remain as to the significance of certain prognostic factors, such as lymphatic invasion with regard to the treatment plan for patients with low rectal cancers. Lastly, quantitative studies addressing the issue of the function of the spared anal sphincters after surgery with or without adjuvant therapy, and how this relates to the patient's quality of life, need to be performed.

Recent advances in surgery for colon and rectal cancer.

Surgery is the mainstay of therapy for colon and rectal cancer. Over the past several decades, there have been important advances both in the understanding of the biology of colon and rectal cancer and in the preoperative and operative techniques for treating this disease. Although it appears in some studies that we have made a difference in the survival rates in the treatment of colon and rectal cancer, in actual fact, this phenomenon may only be secondary to better staging and, therefore, a greater ability to prognosticate a particular patient's chance of cure. What has been learned in the past 20 to 30 years is that most colon and rectal carcinomas start as polyps of the colon and rectum. Most often, polyps are sporadic, but there are certain high-risk groups that produce polyps and, consequently, colon and rectal cancer at a much higher rate. The goal of a practicing physician is to identify these high-risk individuals and to recommend frequent screenings so as to intervene before a polyp has had a chance to become a deeply invasive cancer. These high-risk groups are best typified by familial adenomatous polyposis, which if left untreated will, in 100% of cases, lead to the death of a patient from colon or rectal cancer. Other diseases that lead to an increase in colon and rectal cancer but may not go through the usual adenoma-to-carcinoma sequence include inflammatory bowel disease such as Crohn's colitis and ulcerative colitis. Most patients with colorectal carcinoma are asymptomatic at the time of diagnosis. This phenomenon has led to efforts to screen the general population for polyps and for cancer. Screening techniques such as the detection of occult blood in the stool and endoscopic procedures are currently the most popular. It is unclear at this time exactly what the efficacy of these techniques is in improving the survival of the general population from colorectal carcinoma. The surgical techniques to remove colon and rectal carcinomas have recently expanded to include a more aggressive local excision policy for small tumors of the rectum and the application of laparoscopic techniques, new stapling techniques, and new anastomosing techniques for tumors of the colon and rectum. These techniques have become possible in part through advances in surgical instrumentation and also in part from our increasing understanding of the biology of the disease. Both have allowed for more creative approaches to diagnosing and treating colon and rectal cancer.(ABSTRACT TRUNCATED AT 400 WORDS)

Current protocols and outcomes of local therapy for rectal cancer.

Rectal cancer is a devastating disease, with patients fearing the disease and the potential treatments that may alter sexual function, genitourinary function, and overall body image. Defining the precise role for less morbid approaches to this disease, such as local excision, is of critical importance in providing optimal care in the future. This article discusses endocavitary radiation and fulguration, local excision, and prospective studies.

Biopsy of lesions of the colon, rectum, and anus.

Most lesions of the colon, rectum, and anus can be biopsied only by using an endoscopic device. Adequate patient and bowel preparation, close communication with the pathologist, and meticulous handling and documentation of the specimen are required to ensure an accurate histologic diagnosis. Although somewhat controversial, most investigators agree that all but the smallest neoplasms of the colon and rectum should be excisionally biopsied when possible, incisionally biopsied when excision is not feasible, and destroyed if they are multiple, small, and not suspected of malignancy. Future studies will focus on the cellular biologic characteristics of the biopsy specimen to define more accurately the appropriate treatment plan and prognosis for patients.

Local excision of rectal cancer.

The prospect of treating a rectal cancer often leads to significant fear among patients because of the possibility of a permanent colostomy. Although radical resection, in particular abdominoperineal resection, has been used effectively for rectal cancer treatment, other techniques such as local excision with or without adjuvant therapy have been used with significantly less morbidity than that of the abdominoperineal resection, with excellent cure rates. There are essentially three local excision techniques that can be used to remove a small rectal cancer completely. Selection criteria are critical for choosing the appropriate patient for these techniques. Tumors must be less than 4 cm in diameter and take up less than 40% of the rectal wall circumference. They also need to be relatively close to the dentate line and have no evidence of any invasion into the mesorectum or perirectal nodes. Preoperative staging with endorectal ultrasonography, computed tomography, and digital examination helps select appropriate patients. Retrospective series have shown significant success using local excision techniques, with local recurrence rates ranging from 0% to 11% for early-stage lesions. Prospective series have shown similar recurrence rates. Postoperative function with or without adjuvant therapy has not been adequately documented along with quality of life and must be part of any future reports on local excision techniques as well as all rectal cancer treatment studies. Local excision does, however, seem to provide adequate treatment in well selected patients and provides a less morbid alternative to the treatment of rectal cancer than radical resection, particularly abdominoperineal resection, which obligates the patient to a permanent colostomy.

Second-look surgery for recurrent colorectal carcinoma: is it worthwhile?

Second-look surgery for recurrent colorectal carcinoma has been advocated for over four decades. Routine follow-up procedures gave way to clinically directed or carcinoembryonic (CEA)-directed procedures in the mid-1970's. In this paper, we review the results of second-look surgery for recurrent colorectal carcinoma and ask the question, "Is it worthwhile?" Excluding surgery for symptomatic patients, we conclude that second-look surgery should only be performed for recurrent colorectal carcinoma with the intent of rendering the patient disease-free. Without effective systemic therapy, "palliative" or "debulking" procedures probably do not increase survival. The most likely candidates for such a curative approach with second-look surgery are those with isolated liver, pulmonary, and, less frequently, regional recurrences.

Conservative management of rectal carcinoma: the efficacy of a multimodality approach.

The goals of the conservative management of adenocarcinoma of the distal rectum are to preserve rectal sphincter function and achieve excellent local tumor control. Multimodality therapy for more advanced disease suggests that these goals will be met by conservative surgery combined with radiation therapy and chemotherapy. Over 100 patients with T0-3 N0-1 lesions have been treated in prospective single institution trials with either local excision or anterior resection with coloanal anastomosis, usually combined with chemotherapy and radiotherapy. The typical criteria for local excision have been for lesions to be 4.0 cm or less, mobile, and not poorly differentiated or mucinous. Patients with larger or more advanced lesions may undergo anterior resection with coloanal anastomosis. Following resection, radiotherapy is delivered to the pelvis and tumor bed often with concomitant chemotherapy. The overall rate of local failure in the trials in which local excision is performed with postoperative chemoradiotherapy is 3% for T1 lesions, 5% for T2 lesions, and 30% for T3 lesions with a median follow-up of at least 25 months. Local failure in patients with a coloanal anastomosis is 9% overall. Salvage was successful in about half of the patients who failed locally. Importantly, nearly all patients remained continent. These institutional studies show that sphincter preservation can be used in patients who are objectively selected for this procedure. However, before this multimodality approach may be considered standard therapy the rate of local control must be confirmed in a large, Phase II, multicenter, prospective trial such as that now underway in many of the cooperative groups.

Laparoscopy/thoracoscopy for staging: I. Staging endoscopy in surgical oncology.

The application of laparoscopy to the staging of solid abdominal tumors is reviewed. The current evidence support the use of laparoscopy particularly in hepatic tumors. There is evidence that the hospital length of stay for a patient with a nonresectable hepatic tumor can be reduced from 5.6 +/- 0.4 days with a laparotomy to 1.5 +/- 0.3 days with a laparoscopy. Where the palliative and bypass issues are not limiting, cases of pancreatic and gastric carcinoma also appear to benefit in having a staging laparoscopy before a formal laparotomy for resection. Current instrumentation does produce limits, but with future prospects of laparoscopic ultrasound, and tumor staining, staging laparoscopy will become an important diagnostic tool in surgical oncology.

Laparoscopic surgery for colon and rectal cancer.

Laparoscopic techniques are now being applied to increasing numbers of general surgical procedures. Technical feasibility, margins, number of lymph nodes, and recurrence rates need to be assessed with the application of this new technique to colon or rectal malignancies. Technically, the right colon, sigmoid, and proximal rectum appear to be the most amenable to laparoscopic assisted or complete laparoscopic resection. Early results from a registry of laparoscopic assisted colectomies shows that there is no significant difference in the number of lymph nodes in the lymphovascular bundle compared to conventional colon resections. Early retrospective reports indicate that there may be a significant decrease in post op length of stay. We conclude that the technique of laparoscopic assisted colectomy for colon or rectal cancer needs to follow the same oncologic principles as that of conventional surgery, and ultimately a trial will be needed to compare conventional and laparoscopic cancer resections of the large bowel.

Prospective evaluation of local excision for small rectal cancers.

OBJECTIVE: Most data on local excisions for rectal cancer are based on retrospective studies. We review the results of a prospective registry of patients eligible for local excision of rectal cancer using a transanal, transsphincteric, or transcoccygeal technique combined with multimodality therapy for lesions penetrating the muscularis propria (T2) or perirectal fat (T3). METHODS: Patients with lesions less than 4 cm in diameter and less than 10 cm from the dentate line, with no evidence of distant metastases or invasion into the perirectal fat, were eligible for local excision. Patients with invasion into the muscularis propria (T2) or greater (T3) received adjuvant chemoradiation therapy. RESULTS: Forty-eight patients have been followed prospectively. Average age is 63 years. Thirty-three patients underwent a transanal excision. Fifteen patients underwent either a transsphincteric or technique excision. There was no perioperative mortality. Pathology revealed 1 Tis, 21 T1, 21 T2, and 5 T3 cancers. Mean follow-up is 40.5 months. Cancer-related overall mortality was 4 percent. Overall local or distant recurrence rate was 8 percent (4/48). Recurrence appeared to be related to presence of a positive margin or aggressive histology (lymphatic invasion). Local recurrences were treated with salvage therapy. CONCLUSION: Local excision can be used selectively for small rectal cancers, with minimum morbidity. Recurrence rates are low (8 percent). Patients with either a positive margin or lymphatic invasion need to be considered for further therapy, including abdominoperineal resection, even with T1 lesions. Adjuvant chemoradiation appears to be a benefit for all T2 or T3 cancers.