Clinical commentary: granulocytic fragments in sepsis.

Granulocytic fragments have been described in the peripheral blood of patients with sepsis and the systemic inflammatory response syndrome (SIRS). Although initially proposed as a morphologic clue for distinguishing the leukoerythroblastosis of sepsis from that of myelophthisis or marrow replacement by tumor, granulocyte-derived fragments may be part of a spectrum of cellular fragmentation associated with pathological inflammation and thrombosis, and thus play an important role in the pathophysiology of sepsis and SIRS. Pathologists, hematologists, and medical technologists should be aware of their existence, the morphologic features that distinguish them from macrothombocytes and schistocytes, and their potential significance.

Chemoprevention of breast cancer.

We critically examined the literature regarding tamoxifen and raloxifene for breast cancer chemoprevention, a controversial topic of interest to all providers of health care services for women. The National Surgical Adjuvant Breast and Bowel Project showed that tamoxifen decreased the incidence of breast cancer in women at increased risk. Two European studies did not confirm this benefit. Although well-tolerated, tamoxifen chemoprevention continues to be associated with an increased risk of endometrial cancer. Raloxifene is a promising agent that has not been established to reduce the incidence of breast cancer in women at increased risk and currently should not be considered an alternative to tamoxifen outside of clinical trials. Tamoxifen results in a decreased risk of causing breast cancer in women at increased risk for having the disease. Women at increased risk are encouraged to participate in the ongoing clinical trial comparing tamoxifen and raloxifene for breast cancer prevention.

Histological correlation of microcalcifications in breast biopsy specimens.

HYPOTHESIS: Nonpalpable malignant-appearing microcalcifications discovered by mammography geographically target the location of the most important abnormality within the breast. Core needle or open biopsy of these microcalcifications will sample or remove underlying proliferative or invasive disease. DESIGN: A prospective database of 403 consecutive patients undergoing breast biopsy for nonpalpable abnormalities from July 1, 1994, to December 31, 1996, was reviewed to identify biopsies done for indeterminate microcalcifications. Specimens showing atypical hyperplasia, carcinoma in situ, or invasive carcinoma were identified and reviewed by 1 pathologist. The position of microcalcifications larger than 100 microm were recorded in reference to the histological findings. SETTING: A 450-bed referral community teaching hospital in rural Wisconsin. PATIENTS: Indeterminant microcalcifications were identified on mammograms in 167 (41.4%) of 403 patients. Sixty-one (36.5%) of 167 biopsy specimens contained atypical hyperplasia, carcinoma in situ, or invasive carcinoma, and the slides of these 61 initial breast biopsy specimens were reviewed. MAIN OUTCOME MEASURES: Relationship of breast histopathological findings to microcalcifications. RESULTS: In these 61 specimens, 82 areas of atypical hyperplasia, carcinoma in situ, or invasive carcinoma were noted. The microcalcifications correlated with these areas in 43 (52%) of 82 areas on slide review and were present in the most important abnormality in 33 (54%) of 61 biopsy specimens. CONCLUSIONS: Indeterminant microcalcifications identified by mammography may not target the exact location of underlying breast disease. Careful evaluation of the entire biopsy specimen and close follow-up of patients with benign pathologic findings are recommended.

Image-guided or needle-localized open biopsy of mammographic malignant-appearing microcalcifications?

BACKGROUND: The evaluation and initial management of abnormalities detected on screening mammography have evolved substantially over the last decade. This study was designed to evaluate the most appropriate initial diagnostic biopsy technique for patients presenting with malignant-appearing microcalcifications on screening or diagnostic mammography. STUDY DESIGN: An institutional review of a prospective database was performed to compare initial image-guided breast biopsy (IGBB) and needle-localized open biopsy (NLOB) in patients presenting with malignant-appearing microcalcifications. Patients with atypical hyperplasia (AH) or carcinoma in situ (CIS) were identified and reviewed separately. Measures of outcomes included the total number of procedures, time from initial biopsy to definitive treatment, charges, and percentages of patients who required both procedures. RESULTS: A total of 17,121 patients underwent mammography from July 1994 to December 1996 at Gundersen Lutheran Medical Center. Indeterminate microcalcifications were found in 167 patients and were the reason for IGBB in 112 and NLOB in 55 patients. Histologic results included 81 patients (48%) with benign lesions, 25 (15%) with invasive cancers, and 61 (37%) having a proliferative finding including AH or CIS. Ductal CIS was present in 42 (72%) of the 61 proliferative lesions. Comparisons were made between the groups of patients with CIS or AH who underwent initial NLOB (n = 25) versus those having initial IGBB that was followed by a secondary NLOB (n = 25). The median elapsed time to definitive therapy was 20 days (range 0 to 336 days) for initial IGBB followed by NLOB and 7 days (range 0 to 79 days) for an initial NLOB performed for suspicious microcalcifications (p = 0.0367). The total number of procedures performed on each patient and total costs were also less for patients having an initial NLOB. CONCLUSIONS: The time to definitive local therapy, the number of procedures, and overall charges were less for patients with AH or CIS having initial NLOB as opposed to initial IGBB. Careful initial evaluation of microcalcifications may identify some patients for whom an initial NLOB remains the most appropriate procedure. Such patients desiring breast-conserving therapy may benefit in terms of time to definitive treatment, total number of procedures performed, and cost if a careful NLOB is the initial procedure performed as a formal lumpectomy.

Analysis of morbidity and mortality in 60 patients with peritoneal carcinomatosis treated by cytoreductive surgery and heated intraoperative intraperitoneal chemotherapy.

BACKGROUND: Peritoneal carcinoma has been regarded as a uniformly lethal clinical entity. A treatment plan combining cytoreductive surgery and heated intraoperative intraperitoneal chemotherapy (HIIC) was devised and tested to treat such patients. The purpose of this study was to evaluate the morbidity and mortality associated with this treatment approach. METHODS: Sixty patients with peritoneal carcinomatosis from adenocarcinoma of the colon or appendix were included in the study. Extensive cytoreductive surgery was combined with heated intraperitoneal mitomycin in an intraoperative lavage technique followed by one cycle of early postoperative intraperitoneal 5-fluorouracil. Eleven clinical variables were selected and statistically correlated with morbidity and mortality. RESULTS: Twenty-five complications occurred in 21 patients (morbidity = 35%). Morbidity related to gastrointestinal function included anastomotic leak (n=6), bowel perforations (n=5), bile leak (n=3), and pancreatitis (n=2). Four patients presented with severe hematologic toxicity (Grade 3 or 4). There were three cases of postoperative bleeding, one case of abdominal wound dehiscence, and one case of pulmonary embolism. Morbidity was significantly associated with three clinical factors: male sex, high intraabdominal temperature during HIIC, and duration of the surgical procedure. Enteral complications (bowel fistula and anastomotic leak) occurred in patients with a significantly higher number of peritonectomy procedures and a significantly longer operation. Three patients died within 8 weeks after the procedure (mortality = 5%). Mortality was significantly associated with age and intraabdominal temperature. CONCLUSIONS: Cytoreductive surgery combined with HIIC is associated with a 35% morbidity rate and a 5% mortality rate. Extensive surgery (duration and number of peritonectomy procedures) and high intraabdominal temperature represent the major risk factors for postoperative morbidity and mortality of patients treated with this new therapeutic approach.

Wound complications after resection and immediate postoperative brachytherapy in the management of soft-tissue sarcomas.

BACKGROUND: When used as the sole source of postoperative radiotherapy, brachyradiation therapy (BRT) (4,500-6,000 cGy) should be delayed beyond the fourth postoperative day to minimize wound complications. However, when 1,000-2,000 cGy BRT are given as a "boost" to the tumor bed, it is unclear if a similar treatment delay is necessary. The purpose of this review was to determine the incidence of wound complications when BRT (1,000-2,000 cGy) is administered < or = 48 h after soft-tissue resection. METHODS: The results of treatment in 21 patients with soft-tissue sarcomas of the extremity and superficial trunk treated with resection, immediate postoperative brachytherapy, and external beam radiation were reviewed. All patients were followed through the completion of radiation (median follow-up 30 months). A median of seven (range 3-24) after-loading catheters were placed at the time of resection and were loaded with iridium-192 a median of 2 days postoperative to deliver 1,000-2,000 cGy radiation. RESULTS: Eight patients (38%) experienced minor wound complications (seromas, wound separation, and flap edge necrosis) within 30 days of operation. There were no early complications that required reoperation or delayed further therapy. CONCLUSIONS: Brachytherapy (1,000-2,000 cGy) can be administered < or = 48 h postoperatively with a low risk of major wound complications. Minor wound complications are common but do not delay further treatment.

Rationale for the current surgical management of gastric adenocarcinoma.

Gastric resection remains the primary curative treatment for adenocarcinoma of the stomach. However, the majority of patients continue to present with advanced disease, for which curative resection is impossible. Even when curative resection is technically feasible, local and regional treatment failures are common. No successful adjuvant therapy for gastric adenocarcinoma has been developed to date. In an effort to improve the poor results of resection, "radical gastrectomy," as promoted by Japanese surgeons, has been adopted in some US centers as the primary curative operation for gastric cancer. Only a few controlled clinical trials have been conducted to evaluate the influence of the extent of resection on survival and local disease control. Until the results of current clinical trials are available, radical gastrectomy should be used selectively in the management of gastric cancer.

Short-term intrahepatic FUdR infusion combined with bolus mitomycin C: reduced risk for developing drug resistance.

This study evaluates tumor response, survival, and development of resistance to HAI chemotherapy, comparing a combination of bolus MMC and short duration FUdR to short duration FUdR alone or to long duration FUdR alone, using a rat hepatic metastases model. After intrasplenic injection of 10(7) K12/TRb colon cancer cells in BD-IX rats on day 0, hepatic metastases were evaluated and HA catheters were placed on day 14. The response was determined on day 28. Chemosensitivity of the hepatic metastases after HAI treatments was determined using the MTT assay. Bolus MMC with short duration FUdR as well as long-term FUdR alone provided better hepatic tumor response and survival than short-term FUdR alone. However, bolus MMC with short duration FUdR decreased the acquired resistance to FUdR, compared to long-term FUdR, without causing resistance to MMC. These results provide a rationale for using short duration of FUdR in combination with other drugs.

Surgical management of recurrent liver tumors.

Hepatic resection remains the only potentially curative treatment modality for patients with primary and secondary malignant hepatic tumors. Unfortunately, most patients undergoing resection will develop recurrent disease. Aggressive local treatment of recurrent disease should be considered for patients with recurrence limited to the liver after an initial "curative" hepatic resection. In these patients, repeat hepatic resection can be performed safely and may result in long-term DFS. The decision to perform a repeat hepatic resection must currently be based on the same guidelines as used in selecting a patient for an initial hepatic resection: a limited number of metastases, the technical ability to resect all gross disease, satisfactory general medical condition of the patient, and adequate functional hepatic reserve. Cryotherapy is presently the only alternative to resection that may offer patients with intrahepatic recurrence a chance for long-term disease control. Although many questions remain regarding the ultimate role of cryotherapy and because current technology limits the size of lesions that can be successfully treated, experience to date indicates that it may be comparable to resection for some patients. Combinations of resection, cryotherapy, and regional chemotherapy may expand the population of patients with recurrent hepatic disease that may be managed surgically. Further evaluation of these treatment modalities in clinical trials will establish their ultimate role in the management of recurrent primary and secondary hepatic malignancies.

The role of myoneural and luminal continuity in the coordination of canine gastroduodenal patterns of motility.

Our aim was to determine the role of intrinsic myoneural and enteric luminal continuity in the coordination of gastric and duodenal motility patterns. Three groups of dogs were prepared: five dogs with an intact gastrointestinal tract served as a Control group; four dogs had transection and reanastomosis of the duodenum 0.5 cm distal to the pylorus (Pyloric Transection group); and seven dogs had identical proximal duodenal transection, but with oversewing of duodenum and pylorojejunostomy to a Roux-en-Y limb (Roux-en-Y group). In the Control and Pyloric Transection groups, the gastric and intestinal MMCs were similar in appearance, the cycle durations (x +/- SEM) were not different (134 +/- 19 vs 111 +/- 26 min, respectively; P > 0.05), and the times between the start of gastric and duodenal Phase III (gastroduodenal latency) were similar (6 +/- 1 vs 10 +/- 3 min; P > 0.05). In the Roux-en-Y group, MMCs also occurred in six of seven dogs but tended to have a longer cycle duration (176 +/- 19 min) and a more variable gastroduodenal latency (23 +/- 15 min). Plasma motilin concentration, measured only in the Roux-en-Y group, was greater during Phase III in the stomach and duodenum than during Phases I or II (P < 0.05). Feeding inhibited the gastric and duodenal MMCs in all groups, but the duodenal MMC returned earlier in the Roux-en-Y group. The Roux-en-Y jejunal limb exhibited a postprandial pattern in only seven of 14 studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Vagus-dependent disruption of interdigestive canine motility by gastric distension.

The purpose of this study was to determine the effect of proximal gastric distension on interdigestive patterns of canine gastrointestinal motility and to examine the role of extrinsic nerves in regulating such an effect. Serosal electrodes were placed on the antrum, duodenum, and jejunum. Animals were studied before and after transthoracic vagotomy or after neural isolation of the entire jejunoileum (extrinsic denervation). Proximal gastric distension for 5 h was provided by inflating with air a thin complaint bag placed into the proximal stomach after the onset of phase III of the migrating motor complex (MMC). Four volumes (0, 1.5, 12.5, and 25 ml/kg) were each tested four times in each animal. In neurally intact animals, gastric distension with volumes of 12.5 and 25 ml/kg consistently abolished the MMC in the antrum (100%), duodenum (96%), and proximal jejunum (greater than or equal to 62%), but less often in distal jejunum (greater than or equal to 25%). After vagotomy, gastric distension did not inhibit cycling of the MMC in the antrum, duodenum, or proximal or distal jejunum. After extrinsic denervation of the jejunoileum, gastric distension inhibited the MMC in the antrum and the duodenum but had no effect in the proximal or distal jejunum. These findings suggest that nonnutrient proximal gastric distension may contribute to postprandial changes in patterns of myoelectric activity in the upper gastrointestinal tract and that this effect is mediated by the vagus nerves.

Carcinoma of the body and tail of the pancreas: is curative resection justified?

BACKGROUND: The role of resection in the treatment of carcinoma of the distal pancreas remains unclear. The less frequent occurrence of tumor in the distal gland, advanced tumor stage at diagnosis, and a lack of reported success have combined to produce therapeutic nihilism in the minds of many surgeons. The goal of this review was to assess long-term survival after distal pancreatectomy for carcinoma of the pancreas. METHODS: The records of all patients undergoing distal pancreatectomy at the Mayo Clinic for a primary pancreatic malignant tumor during the 25-year period from 1963 to 1987 were reviewed. Forty-four patients undergoing potentially curative distal pancreatectomies were identified: 26 patients for ductal adenocarcinoma, 12 patients for islet cell carcinoma, and six patients for cystadenocarcinoma. RESULTS: Major postoperative morbidity occurred in 9% of the patients and operative death in 2% of the patients. Patients with ductal adenocarcinoma frequently were admitted with advanced disease (stage II or III). The median overall survival for patients with ductal adenocarcinoma was 10 months. Fifteen percent of the patients survived 2 years after operation, and 8% of the patients survived 5 years. In contrast, the 5-year survival after resection of islet cell carcinomas and cystadenocarcinomas was excellent (83% and 100%, respectively). CONCLUSION: The prognosis for patients with ductal adenocarcinoma in the distal pancreas who were treated with potentially curative distal pancreatectomy is poor; however, the results are not substantially different from those reported after pancreaticoduodenectomy for malignant tumors of the proximal pancreas. Some patients with adenocarcinoma of the distal pancreas who were treated with resection may be long-term survivors. We recommend resection of carcinoma of the distal pancreas when the disease is limited to the gland and believe that all patients with ductal adenocarcinoma should be considered for postoperative adjuvant radiation and chemotherapy.

Cyclic interdigestive pancreatic exocrine secretion: is it mediated by neural or hormonal mechanisms?

Cyclic interdigestive exocrine pancreatic secretion and duodenal motility are closely linked. However, the mechanisms controlling this association are not well understood. The aim of this study was to determine whether a neural or hormonal mechanism controls the temporal association of interdigestive secretion and duodenal motility. In five dogs, the pancreas was autotransplanted to the pelvis with anastomosis of the pancreatic duct orifice to the bladder. Electrodes were positioned to monitor motility patterns of the in situ duodenum. After 10 days, dogs were studied on four occasions during fasting. Pancreatic output of amylase activity continued to cycle, but the periodicity of enzyme peaks (mean +/- SE) was different from the period of the duodenal migrating motor complex (MMC) (60 +/- 3 vs. 125 +/- 7 minutes; P less than 0.05). When grouped according to phase of duodenal MMC, amylase output per 10 minutes during phase I was significantly less than the outputs during phase II or III (135 +/- 52, 214 +/- 78, and 228 +/- 73 x 10(3) U; P less than 0.05). However, there was no temporal relationship of the cyclic output of amylase to duodenal phase III. No differences were found when amylase output was analyzed for the 30 minutes before phase III compared with the 30 minutes after phase III (687 +/- 253 vs. 378 +/- 110 x 10(3) U; P greater than 0.05). Plasma motilin concentrations varied with duodenal MMC, but no relationship existed between plasma motilin or plasma pancreatic polypeptide and peaks in amylase output. This study suggests that the close temporal coordination of interdigestive pancreatic exocrine secretion and duodenal motility is controlled primarily by a neural mechanism.

Extended lymph node dissection for gastric cancer. Is it of value?

The value of extended lymph node dissection for gastric cancer has not been clearly defined. The incidence, staging, and, possibly, the biology of gastric carcinoma in Japanese and Western confound the evaluations of radical lymph node dissection. Surgeons and pathologists must be familiar with the unified international gastric cancer staging system, and careful attention should be given to accurate identification and rigorous examination of regional lymph nodal groups.

Management of retroperitoneal sarcomas.

The records of 116 adult patients who underwent operative treatment for retroperitoneal sarcomas at the Mayo Clinic during the years 1963 to 1982 were reviewed. Clinical, pathologic, and treatment variables were analyzed for their influence on recurrence and death from disease. Leiomyosarcomas, liposarcomas, and malignant fibrous histiocytomas represented 93% of the tumors. The primary tumor was completely excised in 54% of patients. Recurrent tumor developed in 68% of patients (median time to recurrence, 1.3 years). Tumor fixation to adjacent structures (T3 tumor) or a high-grade tumor (G2-4) identified patients at increased risk for recurrent disease. Five-year and 10-year survival rates were 40% and 22%, respectively. Survival was significantly better for patients who had (1) complete surgical excision of their tumors, (2) low-grade tumors (G1), (3) tumors not fixed to adjacent retroperitoneal structures (T1 and T2 sarcomas), and (4) tumors without metastases when initially seen. Complete surgical excision offers patients with retroperitoneal sarcomas the best chance for long-term survival, but recurrent disease remains a vexing problem. The therapeutic challenges in the treatment of retroperitoneal sarcomas continue to be the development of therapy that will increase the rate of complete resection, decrease the rate of local recurrence, and enhance patient survival.