Approach to the Porta Hepatis During Cytoreductive Surgery: Technical Considerations.

Peritoneal carcinomatosis has until recently been considered uniformly fatal; it results in intestinal obstructions, eventually leading progression of disease and death. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have become important options for patients with peritoneal carcinomatosis. Completeness of cytoreduction is a major determinant of survival. Frequently, the porta hepatis and the lesser sac are massively involved by tumor. Encasement of portal triad, lesser omentum, retrohepatic vena cava, duodenum, and stomach is frequently seen. The proximity to major portal structures as well as the retrohepatic vena cava makes this dissection challenging. This is the area where meticulous surgical technique and expertise are necessary to obtain complete removal of tumor. Some specific technical considerations are important to assure that all tumor is safely removed.

Consensus guidelines from The American Society of Peritoneal Surface Malignancies on standardizing the delivery of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer patients in the United States.

BACKGROUND: The American Society of Peritoneal Surface Malignancies (ASPSM) is a consortium of cancer centers performing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). This is a position paper from the ASPSM on the standardization of the delivery of HIPEC. METHODS: A survey was conducted of all cancer centers performing HIPEC in the United States. We attempted to obtain consensus by the modified method of Delphi on seven key HIPEC parameters: (1) method, (2) inflow temperature, (3) perfusate volume, (4) drug, (5) dosage, (6) timing of drug delivery, and (7) total perfusion time. Statistical analysis was performed using nonparametric tests. RESULTS: Response rates for ASPSM members (n = 45) and non-ASPSM members (n = 24) were 89 and 33 %, respectively. Of the responders from ASPSM members, 95 % agreed with implementing the proposal. Majority of the surgical oncologists favored the closed method of delivery with a standardized dual dose of mitomycin for a 90-min chemoperfusion for patients undergoing cytoreductive surgery for peritoneal carcinomatosis of colorectal origin. CONCLUSIONS: This recommendation on a standardized delivery of HIPEC in patients with colorectal cancer represents an important first step in enhancing research in this field. Studies directed at maximizing the efficacy of each of the seven key elements will need to follow.

Multicentre study of the learning curve and surgical performance of cytoreductive surgery with intraperitoneal chemotherapy for pseudomyxoma peritonei.

BACKGROUND: The learning curves for cytoreductive surgery with intraperitoneal chemotherapy for treatment of pseudomyxoma peritonei (PMP) were explored between international centres/surgeons to identify institutional or other factors that might affect performance. METHODS: Data from patients with PMP treated with the combined procedure across 33 international centres between 1993 and 2012 were analysed retrospectively. A risk-adjusted sequential probability ratio test was conducted after defining the target outcome as early oncological failure (disease progression within 2 years of treatment), an acceptable risk for the target outcome (odds ratio) of 2, and type I/II error rates of 5 per cent. The risk prediction model was elaborated and patients were evaluated sequentially for each centre/surgeon. The learning curve was considered to be overcome and proficiency achieved when the odds ratio for early oncological failure became smaller than 2. RESULTS: Rates of optimal cytoreduction, severe postoperative morbidity and early oncological failure were 84·4, 25·7 and 29·0 per cent respectively. The median annual centre volume was 17 (range 6-66) peritoneal malignancies. Only eight of the 33 centres and six of 47 surgeons achieved proficiency after a median of 100 (range 78-284) and 96 (86-284) procedures respectively. The most important institutional factor affecting surgical performance was centre volume. CONCLUSION: The learning curve is extremely long, so centralization and/or networking of centres is necessary to assure quality of services. One centre for every 10-15 million inhabitants would be ideal.

Hydrocarbon biomarkers responses in the bivalve, Tivela mactroides, exposed to polluted sediments.

The objective of this work was to evaluate the potential use of the bivalve Tivela mactroides, as a Caribbean sentinel species. Organisms were collected from a relatively clean sandy beach, and were exposed to a gradient of petroleum hydrocarbon-polluted sediments for periods of 3, 4 and 6 days, after which their activity levels of biotransformation enzymes were measured. NADPH-cytochrome c reductase, glutathione transferase and cytochrome b5 activities increased according to total hydrocarbon concentration, whereas NADH-cytochrome ferricyanide reductase activity decreased. Catalase activity was constant while superoxide dismutase activity was inhibited. The results indicated that T. mactroides may serve as a sentinel species. However, further studies are recommended on the influence of biotic and abiotic variables on basal activities of enzymes, and their responses to other pollutants.

Accuracy and clinical relevance of computed tomography scan interpretation of peritoneal cancer index in colorectal cancer peritoneal carcinomatosis: a multi-institutional study.

BACKGROUND: Evaluation of peritoneal metastases by computed tomography (CT) scans is challenging and has been reported to be inaccurate. METHODS: A multi-institutional prospective observational registry study of patients with peritoneal carcinomatosis from colorectal cancer was conducted and a subset analysis was performed to examine peritoneal cancer index (PCI) based on CT and intraoperative exploration. RESULTS: Fifty-two patients (mean age 52.6 ± 12.4 years) from 16 institutions were included in this study. Inaccuracies of CT-based assessment of lesion sizes were observed in the RUQ (P = 0.004), LLQ (P < 0.0005), RLQ (P = 0.003), distal jejunum (P = 0.004), and distal ileum (P < 0.0005). When CT-PCI was classified based on the extent of carcinomatosis, 17 cases (33%) were underestimations, of which, 11 cases (21%) were upstaged from low to moderate, 4 cases (8%) were upstaged from low to severe, and 2 cases (4%) were upstaged from moderate to severe. Relevant clinical discordance where an upstage occurred to severe carcinomatosis constituted a true inaccuracy and was observed in six cases (12%). CONCLUSIONS: The actual clinical impact of inaccuracies of CT-PCI was modest. CT-PCI will remain as a mandatory imaging tool and may be supplemented with other tools including positron emission tomography scan or diagnostic laparoscopy, in the patient selection for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Sentinel lymph node biopsy for breast cancer: a suitable alternative to routine axillary dissection in multi-institutional practice when optimal technique is used.

PURPOSE: Previous studies have demonstrated the feasibility of sentinel lymph node (SLN) biopsy for nodal staging of patients with breast cancer. However, unacceptably high false-negative rates have been reported in several studies, raising doubt about the applicability of this technique in widespread surgical practice. Controversy persists regarding the optimal technique for correctly identifying the SLN. Some investigators advocate SLN biopsy using injection of a vital blue dye, others recommend radioactive colloid, and still others recommend the use of both agents together. PATIENTS AND METHODS: A total of 806 patients were enrolled by 99 surgeons. SLN biopsy was performed by single-agent (blue dye alone or radioactive colloid alone) or dual-agent injection at the discretion of the operating surgeon. All patients underwent attempted SLN biopsy followed by completion level I/II axillary lymph node dissection to determine the false-negative rate. RESULTS: There was no significant difference (86% v 90%) in the SLN identification rate among patients who underwent single- versus dual-agent injection. The false-negative rates were 11.8% and 5.8% for single- versus dual-agent injection, respectively (P <.05). Dual-agent injection resulted in a greater mean number of SLNs identified per patient (2. 1 v 1.5; P <.0001). The SLN identification rate was significantly less for patients older than 50 years as compared with that of younger patients (87.6% v 92.6%; P =.03). Upper-outer quadrant tumor location was associated with an increased likelihood of a false-negative result compared with all other locations (11.2% v 3. 9%; P <.05). CONCLUSION: In multi-institutional practice, SLN biopsy using dual-agent injection provides optimal sensitivity for detection of nodal metastases. The acceptable SLN identification and false-negative rates associated with the dual-agent injection technique indicate that this procedure is a suitable alternative to routine axillary dissection across a wide spectrum of surgical practice and hospital environments.

Lung cancer screening with low-dose spiral computed tomography.

Computed tomography (CT) has been compared to plain radiographs and bronchial washings as a screening tool for lung cancer. In comparison with other screening modalities, CT allows detection of lung lesions at an earlier cancer stage. Technologic improvements have decreased imaging costs, thus making chest CT a more feasible option as a screening tool in the community hospital. In this study, smokers over the age of 45 years with a greater than 20 pack-year smoking history were referred for screening chest CT. Noncalcified nodules larger than 10 mm underwent CT-guided biopsy, and smaller nodules underwent follow-up CT in 3 months. Currently, patients have been followed for 4 years. The prevalence, stage, and histology of lung cancer were compared to study results from academic centers. Eighty-seven patients underwent screening chest CT. The study population was 51 per cent male with a mean age of 64 +/- 9 years. Four (3 female and 1 male) patients were biopsied and found to have lung cancer giving a prevalence of 5 per cent. Stage IA disease was found in three patients and stage IIIA disease was found in one patient. Adenocarcinoma was present in two patients, adeno-squamous carcinoma in one patient, and squamous cell carcinoma in one patient. The stage and histology of lung carcinomas in this study were comparable to studies performed at larger institutions. However, the disease prevalence was almost double the highest prevalence found in other studies. This discrepancy could be related to study size, as the patient populations were similar. Clearly, screening chest CT in the community setting is equally efficacious in the diagnosis of lung cancer at earlier stages. Following these patients beyond the 5-year mark will give some insight on the effect of screening chest CT on the mortality of lung cancer.

Extensive surgical history prior to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is associated with poor survival outcomes in patients with peritoneal mucinous carcinomatosis of appendiceal origin.

BACKGROUND: Patients with PMCA commonly undergo surgery before CRS/HIPEC. We evaluated the role of extensive surgical treatment before CRS/HIPEC in terms of overall survival (OS). METHODS: 105 patients with PMCA who underwent a CRS/HIPEC procedure were identified from a prospective database. Patients were divided into two groups based on Prior Surgery Score (PSS): PSS ≤ 1 limited surgery group (LSG), PSS >1 extensive surgery group (ESG). Survival of lymph node (LN) negative and positive patients was analyzed separately. RESULTS: 40 patients were in LSG and 65 in ESG. Mean time from diagnosis to CRS/HIPEC was 6 and 17 months for LSG and ESG, respectively (p = 0.004). Groups were well balanced in peritoneal cancer index, complete cytoreduction rate, and LN status. One, 3, and 5-year OS among LN negative patients was 95, 83, and 75% for the LSG (n = 22) group and 87, 55, and 32% for the ESG (n = 35), group respectively (p = 0.026). One, 3, and 5-year OS among LN positive patients was 69, 50, and 17% for the LSG (n = 18) group and 80, 21, and 14% for the ESG (n = 30), group respectively (p = 0.613). For all patients 1, 3, and 5-year OS was 84, 65, and 54% for the LSG (n = 40) group and 86, 43, and 26% for the ESG (n = 65) group, respectively (p = 0.029). CONCLUSION: Extensive surgical treatment before CRS/HIPEC is associated with delay of CRS/HIPEC and poorer OS overall, especially among LN negative patients. We recommend early referral of PMCA patients to a peritoneal surface malignancy center.

Systemic chemotherapy (SC) before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in patients with peritoneal mucinous carcinomatosis of appendiceal origin (PMCA).

BACKGROUND: The role of SC before CRS/HIPEC for patients with PMCA is unclear. This study explores the effect of SC prior to CRS/HIPEC on overall survival (OS) in patients with PMCA. METHODS: 72 patients with recently diagnosed PMCA who underwent CRS/HIPEC were identified from a prospective database. Thirty patients had SC before CRS/HIPEC (Group 1) and 42 did not (Group 2). Patients who were referred to our center after multiple lines of SC were excluded from this analysis. OS was estimated. RESULTS: Median follow-up was 3.2 years. Groups were similar regarding lymph node positivity, postoperative SC and rate of complete cytoreduction. Twenty-four (80%) patients in Group 1 and 21 (50%) in Group 2 had high grade histology (HG) (p = 0.01). OS from CRS/HIPEC at 1, 2, and 3 years was 93, 68, 51% in Group 1 and 82, 64, 60% in Group 2, respectively (p = 0.74). Among HG patients 3-year survival was 36% in the SC group vs. 35% in the group without SC (p = 0.67). The 3-year OS for patients with low grade (LG) tumors was 100% in the SC group vs. 79% in the group with no prior SC (p = 0.26). Among patients with signet ring cell (SRC) histology, 1, 2 and 3-year survival was 94, 67 and 22% in the SC group vs. 43, 14, 14% in the group with no SC, respectively (p = 0.028). There were only 6 patients with LG PMCA who received prior SC. CONCLUSIONS: Preoperative SC could improve the prognosis of patients with high-grade PMCA with SRC histology.

Practical guidelines for optimal gamma probe detection of sentinel lymph nodes in breast cancer: results of a multi-institutional study. For the University of Louisville Breast Cancer Study Group.

INTRODUCTION: Multiple radioactive lymph nodes are often removed during the course of sentinel lymph node (SLN) biopsy for breast cancer when both blue dye and radioactive colloid injection are used. Some of the less radioactive lymph nodes are second echelon nodes, not true SLNs. The purpose of this analysis was to determine whether harvesting these less radioactive nodes, in addition to the "hottest" SLNs, reduces the false-negative rate. METHODS: Patients were enrolled in this multicenter (121 surgeons) prospective, institutional review board-approved study after informed consent was obtained. Patients with clinical stage T1-2, N0, M0 invasive breast cancer were eligible. This analysis includes all patients who underwent axillary SLN biopsy with the use of an injection of both isosulfan blue dye and radioactive colloid. The protocol specified that all blue nodes and all nodes with 10% or more of the ex vivo count of the hottest node should be removed and designated SLNs. All patients underwent completion level I/II axillary dissection. RESULTS: SLNs were identified in 672 of 758 patients (89%). Of the patients with SLNs identified, 403 patients (60%) had more than 1 SLN removed (mean, 1.96 SLN/patient) and 207 patients (31%) had nodal metastases. The use of filtered or unfiltered technetium sulfur colloid had no impact on the number of SLNs identified. Overall, 33% of histologically positive SLNs had no evidence of blue dye staining. Of those patients with multiple SLNs removed, histologically positive SLNs were found in 130 patients. In 15 of these 130 patients (11.5%), the hottest SLN was negative when a less radioactive node was positive for tumor. If only the hottest node had been removed, the false-negative rate would have been 13.0% versus 5.8% when all nodes with 10% or more of the ex vivo count of the hottest node were removed (P =.01). CONCLUSIONS: These data support the policy that all blue nodes and all nodes with 10% or more of the ex vivo count of the hottest SLN should be harvested for optimal nodal staging.

Insulinoma and gastrinoma in Wermer's disease (MEN I).

The association of gastrin- and insulin-producing tumors of the pancreas is rare. In the 30 years' experience of Zollinger and others, of 40 patients with gastrinoma none had insulin-producing tumors. In contrast to patients with Zollinger-Ellison syndrome, of whom 15% to 26% are classified as having multiple endocrine neoplasias type I (MEN I), only 3% to 4% of patients with insulinomas have other endocrine neoplasms. Insulinomas in patients with MEN I are usually single tumors that usually can be cured with enucleation of the tumor. In contradistinction, gastrinomas in patients with MEN I are diffuse in nature and resection only rarely can be accomplished. Long-term management of gastric hypersecretion is best accomplished by H2-receptor antagonists. If the patient does not respond to H2-receptor antagonists or is unwilling to take the drug indefinitely, he or she will be a candidate for total gastrectomy.

Intra-abdominal recurrence of colorectal cancer detected by radioimmunoguided surgery (RIGS system).

Since 1986, 32 patients with metastatic colorectal cancer have undergone second-look radioimmunoguided surgery (RIGS system). The primary tumor was located in the right and transverse colon in 11 patients, left and sigmoid colon in 16, and rectum in five. The carcinoembryonic antigen level was elevated in 30 patients (94%); all patients underwent a computed tomographic scan of the abdomen and pelvis. The overall sensitivity of the computed tomographic scan was 41% (abdomen other than liver, 27%; liver, 58%; and pelvis, 22%). The RIGS system identified recurrent tumor in 81% of the patients. The most common site of metastasis was the liver (41%), independent of the primary location. Local/regional recurrences alone accounted for 40% of all recurrences. In six patients (18%), recurrent tumor was found only with the RIGS system. The RIGS system is more dependable in localizing clinically obscure metastases than other methods, and carcinoembryonic antigen testing remains the most accurate preoperative method to indicate suspected recurrences.

Radioimmunoguided surgery using iodine 125 B72.3 in patients with colorectal cancer.

Preliminary data using B72.3 murine monoclonal antibody labeled with iodine 125 suggested that both clinically apparent as well as occult sites of colorectal cancer could be identified intraoperatively using a hand-held gamma detecting probe. We report the preliminary data of a multicenter trial of this approach in patients with primary or recurrent colorectal cancer. One hundred four patients with primary, suspected, or known recurrent colorectal cancer received an intravenous infusion of 1 mg of B72.3 monoclonal antibody radiolabeled with 7.4 x 10 Bq of iodine 125. Twenty-six patients with primary colorectal cancer and 72 patients with recurrent colorectal cancer were examined. Using the gamma detecting probe, 78% of the patients had localization of the antibody in their tumor; this included 75% of primary tumor sites and 63% of all recurrent tumor sites; 9.2% of all tumor sites identified represented occult sites detected only with the gamma detecting probe. The overall sensitivity was 77% and a predictive value of a positive detection was 78%. A total of 30 occult sites in 26 patients were identified. In patients with recurrent cancer, the antibody study provided unique data that precluded resection in 10 patients, and in another eight patients it extended the potentially curative procedure.

Results of surgical excision of one to 13 hepatic metastases in 98 consecutive patients.

Metastatic carcinoma to the liver is generally considered to be associated with a poor prognosis, with five-year survival of only 20% to 30% after resection of solitary lesions. Ninety-eight consecutive patients underwent the surgical removal of one to 13 metastatic lesions from the liver. A rising carcinoembryonic antigen level was considered an indication for reexploration. All gross tumor was removed in every patient; 66 had more than one metastasis. Survival was unexpectedly high: 91 of 98 were alive at 12 months, 50 (70%) of 71 at 13 to 24 months, 23 (66%) of 36 at 25 to 36 months, 14 (74%) of 19 at 37 to 48 months, six (60%) of ten at 49 to 60 months, four (80%) of five at 61 to 72 months, and two (50%) of four 73 to 84 months after resection of multiple liver metastases. The procedure appears to be a safe and, in some patients, beneficial surgical technique for the removal of multiple hepatic metastases.

Hepatic resection at a community hospital.

Hepatic resection remains the "gold standard" in the primary management of primary and metastatic tumors to the liver. Advanced surgical techniques along with more modern and sophisticated equipment have led to an increasing number of hepatic resections being performed with a concomitant decrease in morbidity and mortality. We followed prospectively 18 consecutive hepatic resections performed over a period of approximately 2.5 years. The setting was a community teaching hospital with a low volume of referrals for hepatic resection. Sixteen (88%) had metastatic disease and two had primary liver disease. There were four trisegmentectomies, four lobectomies, four segmentectomies, and six large wedge re-sections. Average estimated blood loss was 608 ml. Seven patients required transfusions. Complications occurred in five patients (27%). In-hospital mortality was 0%. Our experience suggests that liver resections in a low-volume community hospital can be performed safely provided an experienced surgical team with familiarity of advanced surgical techniques and sophisticated equipment used in hepatic resection is readily available.

Management of primary and metastatic tumors to the liver.

Primary and metastatic liver tumors continue to be a significant health problem in the United States. Hepatic resection or, in selected cases, transplantation are the only curative therapies for patients with resectable disease confined to the liver. Careful preoperative selection is crucial to avoid unnecessary surgical explorations that considerably reduce the quality of the short remaining life of patients with unresectable tumors. The surgeon needs to understand the role of imaging techniques in the evaluation of hepatic tumors for better selection of the patients who are candidates for an aggressive surgical approach. Several other therapeutic options are available for patients with unresectable disease. Until further research delineates the specific interactions among environmental factors, hepatic injury, hepatic regeneration, host factors, and molecular mechanisms of malignant transformation that can lead to specific preventive and treatment interventions, control of this disease will continue to rely on modifications of currently available treatment modalities.

Laparoscopy-assisted small bowel resection.

The increased use of laparoscopy in the management of gastrointestinal problems continues to expand. Procedures such as jejunostomies, diagnosis of intestinal obstruction or ischemia, resection of the small bowel, and lysis of adhesions can be managed with this technique. We present our experience with four cases undergoing laparoscopic resection of the small bowel. The mean age of the three males and one female was 55 years. The operative procedure was performed under general anesthesia with complete laparoscopic exploration of the abdominal cavity. The type of pathology and extent of disease was defined: one had leiomyoma, two had unspecific ileitis, and one had metastatic breast cancer. This was followed by exteriorization and resection. Patients were allowed to have a liquid diet the day of surgery. The average hospital stay was 3 to 4 days. The mean intraoperative time was 124 minutes. No postoperative complications were observed. Laparoscopic small bowel resection can be performed expeditiously and with minimal morbidity, allowing accurate diagnosis and treatment of these conditions.

Bleeding hepatic adenoma: expectant treatment to limit the extent of liver resection.

Hepatic adenomas (HAs) are benign but can present as an acute surgical emergency. The relationship between HA and oral contraceptives (OCs) has been well documented and there have been several reports of tumor regression after the withdrawal of hormonal agents. However, not all HAs regress in this manner; have been reported to remain stable, increase in size, hemorrhage, or rarely, undergo malignant transformation. Given the unpredictable nature of these lesions they are generally treated surgically. In July 1995 a patient with a 6-year history of OC use was admitted with a history of sudden-onset right upper quadrant abdominal pain of 2 days' duration. The clinical picture and imaging studies led to the diagnosis of a bleeding hepatic adenoma without rupture. She was treated expectantly for a period of 14 months before surgery. This allowed the tumor to significantly decrease in size and thus limit the extent of resection. If the patient presented in this case had undergone surgery at the time of initial diagnosis a right hepatic lobectomy as opposed to a wedge resection would have been required. Treating this patient expectantly significantly decreased the potential morbidity associated with a larger resection.

Sarcoidosis of the breast: implications for the general surgeon.

Sarcoidosis is a multisystemic disease that may involve the breast parenchyma and can be confused with benign or malignant tumors. A recent case of sarcoidosis of the breast treated in our institution prompted us to review the world literature on the topic. From 1921 to 1997, 45 cases relating to sarcoidosis of the breast were reported; 10 of these cases were excluded from our review because of the lack of histological proof of sarcoidosis. The data were organized according to clinical presentation, diagnostic studies, treatment plan, and follow-up care. The mean age at presentation was 47 years (range 20-72 years) and all patients were female. Seven patients (20%) had a breast mass as primary presentation of sarcoidosis without any clinical evidence of systemic sarcoidosis. Thirty-one patients (89%) presented with a self-detected mass and three patients (8%) demonstrated skin dimpling and peau d'orange appearance mimicking cancer. The size of the breast lesions ranged from 0.25 to 5 cm in diameter. One patient presented with bilateral breast lesions and one with more than one lesion in the same affected breast. A single breast mass was found in the rest of the patients. Of the seven patients evaluated by mammography, only one revealed changes suspicious for malignancy. Fine-needle aspiration was used only in four cases; the results of two were compatible with sarcoidosis and two required an excisional biopsy as a result of inconclusive results. Seventeen cases reported excisional biopsy as the diagnostic procedure. In 11 patients the type of biopsy was not stated. In two cases of radical mastectomies for breast adenocarcinoma, sarcoidosis was an incidental finding, either in the remaining breast tissue or in the axillary nodes. One patient underwent a partial mastectomy revealing sarcoidosis as the definitive diagnosis. Ultrasound was used in two cases; one revealed a suspicious lesion and one was inconclusive. Although sarcoidosis of the breast constitutes a rare entity it should be considered in the differential diagnosis of breast cancer even in patients without clinical evidence of systemic sarcoidosis. These patients should undergo a biopsy to rule out malignancy because clinical findings, mammography, and ultrasound results can be misleading or inconclusive.