A systematic review of the perforated duodenal diverticula: lessons learned from the last decade.

BACKGROUND: The perforated duodenal diverticulum remains a rare clinical entity, the optimal management of which has not been well established. Historically, primary surgery has been the preferred treatment modality. This was called into question during the last decade, with the successful application of non-operative therapy in selected patients. The aim of this systematic review is to identify cases of perforated duodenal diverticula published over the past decade and to assess any subsequent evolution in treatment. METHODS: A systematic review of English and non-English articles reporting on perforated duodenal diverticula using MEDLINE (2008-2020) was performed. Only cases of perforated duodenal diverticula in adults (> 18 years) that reported on diagnosis and treatment were included. RESULTS: Some 328 studies were identified, of which 31 articles met the inclusion criteria. These studies included a total of 47 patients with perforated duodenal diverticula. This series suggests a trend towards conservative management with 34% (16/47) of patients managed non-operatively. In 31% (5/16) patients initially managed conservatively, a step-up approach to surgical intervention was required. CONCLUSION: Conservative treatment of perforated duodenal diverticula appears to be an acceptable and safe treatment strategy in stable patients without signs of peritonitis under careful observation. For patients who fail to respond to conservative treatment, a step-up approach to percutaneous drainage or surgery can be applied. If surgery is required, competence in techniques ranging from simple diverticulectomy to Roux-en-Y gastric diversion or even Whipple's procedure may be required depending on tissue friability and diverticular collar size.

Site of Recurrence and Survival After Surgery for Colorectal Peritoneal Metastasis.

BACKGROUND: Multimodal treatment, including systemic treatment and surgery, improved the prognosis of peritoneal metastasis (PM). Despite all efforts, recurrence rates remain high, and little data are available about clinical behavior or molecular patterns of PM in comparison to hematogenous metastasis. Here, we aimed to analyze recurrence patterns after multimodal treatment for PM from colorectal cancer. METHODS: Patients with colorectal PM undergoing multimodal treatment including systemic chemotherapy and cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) between 2005 and 2017 at 4 centers were analyzed retrospectively. RESULTS: A total of 505 patients undergoing CRS/HIPEC were analyzed. Of the patients, 82.1% received preoperative chemotherapy. Median peritoneal cancer index was 6 (interquartile range = 3-11). Median disease-free and overall survival was 12 (95% confidence interval [CI] = 11 to 14) months and 51 (95% CI = 43 to 62) months, respectively. Disease recurred in 361 (71.5%) patients, presenting as isolated peritoneal recurrence in 24.6%, isolated hematogenous recurrence in 28.3%, and mixed recurrence in 13.9% of patients. Recurrence to the peritoneum was associated with an impaired time from recurrence to death of 21 (95% CI = 18 to 31) months for isolated peritoneal and 22 (95% CI = 16 to 30) months for mixed recurrence, compared with 43 (95% CI = 31 to >121) months for hematogenous recurrence (hazard ratio [HR] = 1.79, 95% CI = 1.27 to 2.53; P = .001; and HR = 2.44, 95% CI = 1.61 to 3.79; P < .001). On multiple logistic regression analysis, RAS mutational status (odds ratio [OR] = 2.42, 95% CI = 1.11 to 5.47; P = .03) and positive nodal stage of the primary (OR = 3.88, 95% CI = 1.40 to 11.86; P = .01) were identified as predictive factors for peritoneal recurrence. CONCLUSIONS: This study highlights the heterogeneity of peritoneal metastasis in patients with colorectal cancer. Recurrent peritoneal metastasis after radical treatment represents a more aggressive subset of metastatic colorectal cancer.

Standard Operating Procedures for Anesthesia Management in Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Improve Patient Outcomes: A Patient Cohort Analysis.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) offer survival benefits in well-selected patients with peritoneal tumors. The complexity of CRS/HIPEC requires surgical specialization. In contrast, limited data are available regarding the impact of anesthesia management. We assessed the role of standard operating procedures (SOPs) for anesthesia on perioperative patient outcomes after CRS/HIPEC. METHODS: Between 2009 and 2015, 112 CRS/HIPEC were performed at the University Hospital of Zurich. Procedures were grouped in an "early or late" group before (n = 57) and after (n = 55) the introduction of SOPs, which defined management of fluids, serum albumin, hemostasis, and body temperature. RESULTS: Introduction of SOPs significantly changed patient management. Patients received in total less colloids (p = 0.03) and less diuretics (p = 0.007). We noticed an increased substitution of albumin (p = 0.001) and coagulation factors (p = 0.008). Body temperatures were higher at the end of the operation (p = 0.005), and more patients were extubated in the operating room (66% vs. 42%, p = 0.02). The rate of major complications (p = 0.003) and reoperations (p = 0.01) was reduced after the introduction of SOPs. On multivariate analysis, two independent prognostic factors were identified. The use of > 2000 mL of colloids [odds ratio (OR) 5.31 (1.06-26.56), p = 0.042] was associated with major morbidity. In contrast, substitution of albumin [OR 0.12 (0.01-0.96), p = 0.046] was associated with better outcomes. CONCLUSIONS: SOPs for perioperative anesthesia management have a major impact on outcomes of patients after CRS/HIPEC. Management of colloid administration was an independent prognostic factor for perioperative outcomes. This highlights the role of the anesthesiologist and the need for specialization beyond the surgical team.

Systemic inflammatory response after hyperthermic intraperitoneal chemotherapy (HIPEC): The perfusion protocol matters!

BACKGROUND: CRS/HIPEC gained acceptance as a treatment for selected patients with peritoneal metastasis. However, the pathophysiology behind HIPEC is poorly understood, and a variety of regimens are currently in use. In this study, we describe for the first-time changes in the postoperative systemic inflammatory reaction, highly different among HIPEC treatment protocols. METHODS: HIPEC was performed with three protocols, different with regard to perfusion times and drugs: (mitomycinC/doxorubicin, 90min), (cisplatin, 90min) (oxaliplatin, 30min). Serial blood samples were assessed for C-reactive protein (CRP), white blood cells (WBC), pancreatic stone protein (PSP) and bacterial component (16s rDNA). The study was approved by the local ethics committee and registered at clinicaltirals.gov (NCT02741167). RESULTS: Overall, 140 patients from two European centers were included. In patients without postoperative complications, a secondary peak of inflammatory parameters, CRP (p = 0.015) and PSP (p = 0.004) was observed after HIPEC for 90 min with mitomycinC/doxorubicin or cisplatin but not after 30 min oxaliplatin. In patients after 90 min HIPEC, postoperative serum bacterial 16srDNA level were 2.1 times higher (95% CI 0.646-3.032, p = 0.015) compared to 30 min oxaliplatin. DISCUSSION: In conclusion, we identified a secondary inflammatory reaction after 90 min HIPEC, either with mitomycinC/doxorubicin or cisplatin, not observed after short course HIPEC with oxaliplatin. This protocol dependent physiology of acute phase proteins should be known in the clinical management of patients after HIPEC.

Mutations of RAS/RAF Proto-oncogenes Impair Survival After Cytoreductive Surgery and HIPEC for Peritoneal Metastasis of Colorectal Origin.

BACKGROUND: Adequate selection of patients with peritoneal metastasis (PM) for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) remains critical for successful long-term outcomes. Factors reflecting tumor biology are currently poorly represented in the selection process. The prognostic relevance of RAS/RAF mutations in patients with PM remains unclear. METHODS: Survival data of patients with colorectal PM operated in 6 European tertiary centers were retrospectively collected and predictive factors for survival identified by Cox regression analyses. A simple point-based risk score was developed to allow patient selection and outcome prediction. RESULTS: Data of 524 patients with a median age of 59 years and a median peritoneal cancer index of 7 (interquartile range: 3-12) were collected. A complete resection was possible in 505 patients; overall morbidity and 90-day mortality were 50.9% and 2.1%, respectively. PCI [hazard ratio (HR): 1.08], N1 stage (HR: 2.15), N2 stage (HR: 2.57), G3 stage (HR: 1.80) as well as KRAS (HR: 1.46) and BRAF (HR: 3.97) mutations were found to significantly impair survival after CRS/HIPEC on multivariate analyses. Mutations of RAS/RAF impaired survival independently of targeted treatment against EGFR. Consequently, a simple point-based risk score termed BIOSCOPE (BIOlogical Score of COlorectal PEritoneal metastasis) based on PCI, N-, G-, and RAS/RAF status was developed, which showed good discrimination [development area under the curve (AUC) = 0.72, validation AUC = 0.70], calibration (P = 0.401) and allowed categorization of patients into 4 groups with strongly divergent survival outcomes. CONCLUSION: RAS/RAF mutations impair survival after CRS/HIPEC. The novel BIOSCOPE score reflects tumor biology, adequately stratifies long-term outcomes, and improves patient assessment and selection.

Where Oncologic and Surgical Complication Scoring Systems Collide: Time for a New Consensus for CRS/HIPEC.

INTRODUCTION: Morbidity and mortality rates after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are important quality parameters to compare peritoneal surface malignancy centers. A major problem to assess postoperative outcomes among centers is the inconsistent reporting due to two coexisting systems, the diagnose-based common terminology criteria for adverse events (CTCAE) classification and the therapy-oriented Clavien-Dindo classification. We therefore assessed and compared both reporting systems. PATIENTS AND METHODS: Complications after CRS/HIPEC were recorded in 147 consecutive patients and independently graded by an expert board using both systems. In a next step, a group of residents, experienced surgeons, and medical oncologists evaluated a set of twelve real complications, either with the Clavien-Dindo or CTCAE classification. RESULTS: The postoperative complication rate after CRS/HIPEC was 37 % (54/147), 6.8 % (10/147) were reoperated, and three (2 %) patients died. The most frequent complications were intestinal fistula or abscess, pulmonary complications, and ileus. Grading of complications with the CTCAE classification resulted in a significantly higher major morbidity rate compared to the Clavien-Dindo classification (25 vs. 8 %, p = 0.001). Evaluating a set of complications, residents, surgeons, and oncologists correctly assessed significantly more complications with the Clavien-Dindo compared to the CTCEA classification (p < 0.001). In addition, all participants evaluated the Clavien-Dindo classification as more simple. Residents (p < 0.001) and surgeons (p < 0.01) required less time with the Clavien-Dindo classification; there was no difference for oncologist. CONCLUSION: In conclusion, our data indicate that there is a different interpretation of severity grades of complications after CRS/HIPEC between the two classifications. There is a need for a common language in the field of CRS/HIPEC, which should be defined by a new consensus to compare surgical outcomes.

Portal Vein Embolization Followed by Liver Resection versus Liver Resection Alone: a Comparison of Liver Regeneration Dynamics.

BACKGROUND/AIMS: Portal vein embolization (PVE) is an accepted procedure, which, by redirecting portal vein flow toward specific hepatic segments, is able to pre-operatively increase the volume of the future liver remnant (FLR). The consequent reduction of liver dysfunction risk enables to extend the number of pa tients eligible for major hepatic resection. This study aims at comparing liver regeneration dynamics and long-term volumetric recovery after major hepatic re section preceded by PVE versus major hepatic resec tion not preceded by PVE. METHODOLOGY: Data from 24 consecutive patients who underwent PVE prior to major hepatic resection were collected and compared to 24 consecutive patients who underwent major hepatic resection, but on whom PVE was not performed. RESULTS: A significant growth of the FLR was observed after PVE. The liver remnant underwent a further regeneration burst after resection, with long-term volumetric recovery rates around 85% of the estimated total liver volume, similar to those observed for the control group and to those previously documented in the relevant literature. CONCLUSION: PVE gives a first impulse to liver regeneration before liver resection without compromising further regeneration after resection, resulting in long-term volumetric recovery rates similar to those known for regeneration after liver resection without prior PVE.

[Cytoreductive surgery and HIPEC: a curative strategy for primary and secondary peritoneal tumors]. / Radikale zytoreduktive Chirurgie mit hyperthermer intraperitonealer Chemotherapie (HIPEC) als kurativer Ansatz zur Behandlung primärer und sekundärer Peritonealtumore.

In patients with peritoneal carcinomatosis, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) offers a chance for long term survival in well selected patients. During cytoreductive surgery, all macroscopically visible tumors needs to be resected before HIPEC is performed in the same procedure. The aim of HIPEC is eradication of microscopic tumor cells after radical surgery. Perioperative morbidity and mortality are comparable with other major surgical procedures. Patients with peritoneal carcinomatosis from tumors of the appendix, the colon or primary peritoneal mesothelioma are currently recommended for evaluation of CRS/HIPEC in an interdisciplinary setting.

Chez les malades présentant une carcinomatose péritonéale, la chirurgie cytoréductive et la chimiothérapie intrapéritonéale hyperthermique offrent une chance de survie prolongée dans certains cas bien sélectionnés. Au cours de la chirurgie cytoreductive, toute la tumeur visible macroscopiquement doit être réséquée avant que ne soit effectuée, dans la même procédure, à la chimiothérapie intrapéritonéale hyperthermique. Le but de cette dernière est d'éradiquer toutes les cellules microscopiques de la tumeur après la chirurgie radicale. La morbidité et la mortalité périopératoires sont comparables à celles d'autres interventions chirurgicales majeures. La chirurgie cytoréductive et la chimiothérapie intrapéritonéale hyperthermique font partie de la stratégie de traitement multimodale chez les patients ayant des tumeurs limitées à la surface du péritoine. Il est recommandé aujourd'hui d'envisager un traitement par chirurgie cytoréductive et chimiothérapie intrapéritonéale hyperthermique chez les patients présentant une carcinomatose péritonéale avec pour origine l'appendice, le côlon ou le mésothéliome péritonéal primaire.

New insight into hyperthermic intraperitoneal chemotherapy: induction of oxidative stress dramatically enhanced tumor killing in in vitro and in vivo models.

BACKGROUND: The aim of hyperthermic intraperitoneal chemotherapy (HIPEC) is to eradicate microscopic residual tumor after radical surgical tumor excision in patients with peritoneal carcinomatosis. The common use of antineoplastic agents such as mitomycin C, doxorubicin, or oxaliplatin with hyperthermia fails to eradicate tumors in a significant subset of patients, and alternative approaches to target chemoresistant cells are needed. The induction of reactive oxygen species (ROS) by inhibiting the critical detoxification enzyme superoxide dismutase (SOD) during hyperthermia is an appealing approach to induce death of residual cancer cells. METHODS: Human and murine colon cancer cell lines were subjected to mild hyperthermia (40-42°C), and treated with chemotherapy, similar to clinical protocols. ROS were induced by the SOD inhibitor diethyldithiocarbamate (DDC), a metabolite of the drug disulfiram. In mice, peritoneal carcinomatosis use C57Bl/6 was induced in C57Bl/6 by intraperitoneal injection of syngenic tumor cells (MC38). RESULTS: Hyperthermia alone failed to kill cells but induced intracellular ROS and activated protective mechanisms. Chemotherapy conferred inconsistent cytotoxicity depending on the cell line and dose. In contrast, induction of ROS by DDC consistently activated apoptotic pathways, with increased cell death in combination with mild hyperthermia. In vivo, combined treatment with DDC and hyperthermia significantly delayed tumor progression in tumor-bearing mice. In addition, hyperthermic combined treatment with chemotherapy and DDC significantly improved animal survival compared with chemotherapy alone. CONCLUSIONS: Addition of DDC improves the efficacy of existing HIPEC protocols in a safe way and may open the door to a more effective, multimodal HIPEC.

Accessory spleen mimicking a pancreatic neuroendocrine tumor.

A 60-year-old man underwent computed tomography as part of colorectal cancer follow-up. A hypervascular nodule was found within the pancreatic tail and subsequently proved to be positive on [111In] DTPA-octreotide scan. A neuroendocrine tumor of the pancreas was supposed and a distal pancreatectomy performed. Heterotopic splenic tissue was finally proved by pathological examination. The present case suggests that intrapancreatic accessory spleen be considered in the differential diagnosis of pancreatic lesions positive on [111In] DTPA-octreotide scan.

Randomised comparison of complications from three different permanent central venous access systems.

PRINCIPLES: We present a prospective randomised trial comparing complications from three different permanent central venous access systems (PCVAS). METHODS: The PCVAS trial groups were I, polyurethane ChemoSite (AutoSuture); II, polyurethane Port-a-Cath (Pharmacia-Upjohn); and III, silicone Port-a-Cath. The PCVAS were inserted under local anaesthesia by direct puncture of the subclavian vein, using the Seldinger technique. Every complication and ist evolution was recorded and analysed. The follow-up period was closed five years after the last PCVAS was implanted, and interrupted when for any reason the device was removed. RESULTS: Over a period of 45 months, we included 228 patients (96 men, 132 women, average age 58 yr). Patients were followed from six days to 103 mo (median 14.7 mo). We observed 10 pneumothorax (4.3%), seven of them requiring drainage. Out of 10 infected ports (4.3%), eight were removed. We observed 46 complications (20.1%) related to the device (rupture, displacement, disconnection, and occlusion of the catheter). Most of the thirteen ruptures (5.7%) occurred in the space between the clavicle and the first rib. Catheters of group I ruptured more often than those of groups II and III (p <0.05). Polyurethane catheters ruptured more often than silicone catheters (p <0.01). CONCLUSION: The polyurethane catheters that ruptured more often had a larger diameter and a thicker wall than the other polyurethane catheters, and were probably subjected to greater shearing between the clavicle and the first rib. Silicone catheters, although thicker and of larger diameter than the two other catheters, seemed more resistant to shearing.

Localized hepatic ischemia after liver resection: a prospective evaluation.

OBJECTIVE: To prospectively assess the frequency, severity, and extension of localized ischemia in the remaining liver parenchyma after hepatectomy. BACKGROUND: Major blood loss and postoperative ischemia of the remnant liver are known factors contributing to morbidity after liver surgery. The segmental anatomy of the liver and the techniques of selective hilar or suprahilar clamping of the Glissonian sheaths permit identification of ischemia on the surface of the corresponding segments for precise section of the parenchyma. Incomplete resection of a segment, or compromised blood supply to the remaining liver, may result in ischemia of various extension and severity. METHODS: Patients undergoing hepatectomy received enhanced computerized tomodensitometry with study of the arterial and venous phases within 48 hours after resection. We defined hepatic ischemia as reduced or absent contrast enhancement during the venous phase. We classified the severity of ischemia as hypoperfusion, nonperfusion, or necrosis. The extension of ischemia was identified as marginal, partial, or segmental. Factors that may influence postoperative ischemia were analyzed by univariate and multivariate analyses. RESULTS: One hundred fifty consecutive patients (70 F, 80 M, mean age 62 +/- 12 years) underwent 64 major and 81 minor hepatectomies and 5 wedge resections. We observed radiologic signs of ischemia in 38 patients (25.3%): 33 hypoperfusions (17 marginal, 12 partial, and 4 segmental), 3 nonperfusions (1 marginal, 1 partial, and 1 segmental), and 2 necroses (1 partial, 1 segmental). One patient with a segmental necrosis underwent an early reoperation. In all other cases, the evolution was spontaneously favorable. Postoperative peak levels of serum aspartate aminotransferase and alanine aminotransferase were significantly higher in patients with ischemia. Patients with ischemia had a significantly higher risk of developing a biliary leak (18.4% vs. 2.6%, P < 0.001). There was no correlation between liver ischemia and mortality (2%). None of the following factors were associated with ischemia after univariate and multivariate analysis: age, preoperative bilirubin level, liver fibrosis, malignant tumor, type of hepatectomy, surface of transection, weight of resected liver, Pringle maneuver, blood loss, and number of transfusions. CONCLUSIONS: Some form of localized ischemia after hepatectomy was detected in 1 of 4 of our patients. Its clinical expression was discreet in the large majority of cases, even if it might have been one of the underlying causes of postoperative biliary fistulas. Clinical observation is sufficient to detect the rare patient with suspected postoperative liver ischemia that will require active treatment.

Preoperative concomitant hyperfractionated radiotherapy and gemcitabine for locally advanced rectal cancers: a phase I-II trial.

PURPOSE: The purpose of this study was to determine the maximum tolerated dose of gemcitabine when it was administered concomitantly with hyperfractionated radiotherapy before surgery in patients with locally advanced rectal cancers and to investigate the midterm efficacy of such a regimen. PATIENTS AND METHODS: Thirty-seven patients with stage II-III tumors as assessed by computed tomography/echoendoscopy were enrolled. Radiotherapy consisted of 50 Gy given in two daily fractions of 1.25 Gy over 4 weeks. The starting dose of gemcitabine was 10 mg/m(2)/day (in a 30-minute i.v. perfusion) twice weekly with planned escalation steps of 5 mg/m(2)/day. Surgery was planned at 6 weeks after the end of radiotherapy. Main end-points of the study were complete pathological tumor response, the rate of clear margin resection, and actuarial locoregional control and disease-free survival. The median follow-up for all patients was 32 months (range: 10-51 months). RESULTS: At the level of 45 mg/m(2), two of four patients presented with dose-limiting rectal toxicities (severe acute proctitis requiring hospitalization in the immediate postradiotherapy period). Thus, the gemcitabine biweekly dose of 40 mg/m(2) was considered to be the maximum tolerated dose. Among the 36 patients who underwent surgery, 17 (47%) had a marked pathological response, including six patients (17%) with a microscopically complete response and 11 (30%) with only microscopically residual carcinoma of less than 1 cm. All of them had clear surgical margins. At 3 years, actuarial overall survival rate was 85%, locoregional control was 94.5%, and disease-free survival was 67%. DISCUSSION: The present study determined the recommended dose of gemcitabine to be 40 mg/m(2) when administered concurrently twice a week with 50 Gy hyperfractionated radiotherapy for the preoperative treatment of locally advanced rectal cancers. The encouraging pathological response rate and the very low locoregional recurrence rate suggest that this innovative approach merits further investigation.

Assessment of quality of life in patients with rectal cancer treated by preoperative radiotherapy: a longitudinal prospective study.

PURPOSE: To assess prospectively the quality of life (QOL) of patients treated by preoperative radiotherapy (RT) and surgery for locally advanced rectal cancer. METHODS AND MATERIALS: We studied 53 patients treated with bi-fractionated RT (50 Gy in 40 fractions within 4 weeks) followed at a median interval of 45 days by abdominoperineal resection in 11 patients and low anterior resection in 42 patients. Their QOL was assessed using two self-rating questionnaires developed by the European Organization for Research and Treatment of Cancer (EORTC): one was cancer specific (EORTC QLQ-C30) and one was site specific (EORTC QLQ-C38). The questionnaires were completed before RT and 12-16 months after RT, at which time 17 patients had undergone colostomy. We hypothesized that at least some scores of the various scales would vary between the two analyses. RESULTS: Compared with the pre-RT scores, at 1 year, patients reported statistically significant improvement in their emotional state (median 75 vs. 100, p <0.0001), perspective of the future (67 vs. 100, p = 0.0004), and their global QOL (75 vs. 83, p = 0.0008), as well as a decrease in GI symptoms (13 vs. 0, p = 0.002). However, the sexual dysfunction score increased significantly, particularly in men (17 vs. 83, p = 0.0045), and a trend toward a lower body image score was observed (100 vs. 89, p = 0.068). At 1 year, patients with colostomies reported similar or significantly improved symptom scores for fatigue, pain, GI problems, and sleep disturbance, but no such improvements were observed in patients without stomas. CONCLUSION: One year after combined treatment for locally advanced rectal cancer, patients exhibited statistically significant improvement in some important QOL outcomes, including global QOL, despite a decrease in sexual function and body image. Any additional improvement in QOL outcome may require refinements in the RT and surgical techniques to reduce late sequelae, particularly sexual dysfunction. Our results suggest that QOL considerations do not justify sphincter-conserving approaches if locoregional tumor control would be compromised.

A historical perspective on colorectal liver metastases and peritoneal carcinomatosis: similar results, different treatments.

Similarities between peritoneal carcinomatosis and liver secondaries allow the oncologist to regard the peritoneum as an intraabdominal structure that can, like the liver, be resected with curative intent when disseminated disease has occurred. The possibility for cure of peritoneal carcinomatosis by cytoreductive surgery and IPHC must now be recognized. However, convincing data from controlled studies will be required for rapid general acceptance of this treatment, bringing, as a consequence, a chance of cure to a larger number of patients with a desperate prognosis. This fact, together with a scarcity of patients with peritoneal carcinomatosis eligible for definitive treatment, emphasizes the need for cooperative studies between centers of reference.

Preoperative hyperfractionated radiotherapy for locally advanced rectal cancers: a phase I-II trial.

PURPOSE: To assess the toxicity, pathologic response rates, type of surgery, and oncologic results in a prospective Phase I-II trial using pure hyperfractionated radiotherapy (RT) preoperatively in locally advanced rectal cancer. METHODS AND MATERIALS: Between September 1997 and April 2000, 50 patients with T3-T4 or N1 rectal cancers were treated preoperatively with 50 Gy (45 Gy to the pelvis and a 5-Gy tumor boost) in 40 fractions of 1.25 Gy during 4 weeks. The pretreatment tumor stage as determined by CT and endorectal ultrasonography (80% of patients) included 1 Stage T2 (2%), 45 T3 (90%), and 4 T4 (8%). Nodal involvement (N1) was documented in 26 patients (52%). Surgery was performed at a median interval of 45 days (range 26-114 days) after RT completion. Seventeen patients who presented with pT4 or pN1 and/or pM1 received 5-fluorouracil-based chemotherapy postoperatively. RESULTS: All patients completed the RT schedule as planned. Severe acute toxicities included two Grade 3 skin reactions (4%) that did not require a break. The other acute toxicities were Grade 2 or less (skin, diarrhea, urinary, rectal tenesmus, and fatigue). A complete pathologic response was observed in 7 patients (14%), and microscopic residual cancer was found in 10 (20%). Of the 20 patients presenting with tumor located < or = 6 cm from the anal verge, sphincter-saving surgery was performed in 14 (70%). At 3 years, the actuarial locoregional control rate was 90.5%, and the disease-free survival rate was 74.6%. At a median follow-up of 32 months, 4 patients (8%) presented with severe late complications (Grade 3-4) that might have been RT related (one rectovaginal fistula, two chronic perineal fistulas, and one bilateral ureteral stenosis). CONCLUSION: In locally advanced rectal cancer, preoperative hyperfractionated RT to a total dose of 50 Gy is feasible, with acceptable acute and late toxicity and an objective downstaging effect. In view of these results, this schedule might be used as a basis for additional investigation regarding RT dose escalation or the addition of concomitant chemotherapy.

Body surface area and body weight predict total liver volume in Western adults.

Computed tomography (CT) is used increasingly to measure liver volume in patients undergoing evaluation for transplantation or resection. This study is designed to determine a formula predicting total liver volume (TLV) based on body surface area (BSA) or body weight in Western adults. TLV was measured in 292 patients from four Western centers. Liver volumes were calculated from helical computed tomographic scans obtained for conditions unrelated to the hepatobiliary system. BSA was calculated based on height and weight. Each center used a different established method of three-dimensional volume reconstruction. Using regression analysis, measurements were compared, and formulas correlating BSA or body weight to TLV were established. A linear regression formula to estimate TLV based on BSA was obtained: TLV = -794.41 + 1,267.28 x BSA (square meters; r(2) = 0.46; P <.0001). A formula based on patient weight also was derived: TLV = 191.80 + 18.51 x weight (kilograms; r(2) = 0.49; P <.0001). The newly derived TLV formula based on BSA was compared with previously reported formulas. The application of a formula obtained from healthy Japanese individuals underestimated TLV. Two formulas derived from autopsy data for Western populations were similar to the newly derived BSA formula, with a slight overestimation of TLV. In conclusion, hepatic three-dimensional volume reconstruction based on helical CT predicts TLV based on BSA or body weight. The new formulas derived from this correlation should contribute to the estimation of TLV before liver transplantation or major hepatic resection.