Ikuya Takeuchi

Pneumoperitoneum with carbon dioxide enhances liver metastases of cancer cells implanted into the portal vein in rabbits

AbstractBackground: Little is known about the role of the CO2 pneumoperitoneum on tumor cells that spread from the portal system into the liver during laparoscopic surgery for gastrointestinal malignancies. Therefore, we designed a study to investigate the effect of CO2 pneumoperitoneum on cancer cells implanted in the portal vein in a rabbit model. Methods: Immediately after intraportal inoculation of 2.5 × 105 cells of VX2 cancer, the rabbits received either CO2 pneumoperitoneum at a pressure of 10 mmHg for 30 min (pneumoperitoneum group, n= 14) or laparotomy alone for 30 min (laparotomy group, n= 14). Results: The number (p < 0.01) and area of cancer nodules (p= 0.045) on the liver surface on day 17 were greater in the pneumoperitoneum group than in the laparotomy group. The frequency of cancer nodules >3.0 mm in diameter was higher in the pneumoperitoneum group than in the laparotomy group (p < 0.001). Conclusions: Compared with laparotomy, CO2 pneumoperitoneum enhanced the development of liver metastases in this experimental model.

Expression of E-cadherin, α-catenin, and β-catenin in tubulolobular carcinoma of the breast

Tubulolobular carcinoma (TLC) of the breast is a rare subtype of breast carcinoma categorized by Fisher et al. (Hum Pathol 8:679–683, 1977) as a tubular variant of lobular carcinoma. E-cadherin is a transmembrane glycoprotein, and complete loss of E-cadherin expression has been observed in invasive lobular carcinoma. Ductal carcinoma retains at least some expression of E-cadherin. Moreover, the adhesive function of E-cadherin is dependent on the integrity of the catenin components, which link E-cadherin to the actin filaments. In order to achieve improved categorization of TLC, we decided to investigate both E-cadherin and the catenins in TLCs and invasive lobular carcinomas. We reviewed all 1,430 cases of primary breast carcinoma that were surgically resected at Saitama Medical Center, Saitama Medical School, and at Saitama Red Cross Hospital between 1990 and 2005. Among these, 16 cases of TLC were reported retrospectively. The results were compared with those of 20 cases of invasive lobular carcinomas that were included as controls. Tumor tissue was immunostained for E-cadherin, α-catenin, and β-catenin. The presence of immunoreactivity in the TLC was seen in 12 (75%) cases for E-cadherin, in 8 (50%) cases for α-catenin, and in 10 (62.5%) cases for β-catenin. However, plasma-membrane-associated staining for E-cadherin, α-catenin, and β-catenin was completely absent in invasive lobular carcinomas. These results suggest the possibility that TLCs are not a variant of lobular carcinoma, but rather ductal carcinomas with a lobular growth pattern.

Increased insufflation pressure enhances the development of liver metastasis in a mouse laparoscopy model

Background: The effect of different insufflation pressures and durations of CO2 pneumoperitoneum on the growth of liver metastasis was investigated in a mouse model. The possible mechanisms involved in the pressure-related enhancement of liver metastasis were also examined. Methods: Mice inoculated intraportally with colon 26 cells underwent CO2 pneumoperitoneum at different pressures (5,10, or 15 mmHg) for 30 or 60 min, or received no treatment other than tumor cell inoculation (control). The subsequent growth of liver mestastases was examined. Mice injected intraportally with 111In-oxine-labeled colon 26 cells underwent pneumoperitoneum at three different pressures or served as controls. The radioacitivity of the liver was determined to evaluate tumor accumulation in the liver. Mice received pneumoperitoneum at three different pressures or received trocar placement alone. Changes in plasma interleukin-6 levels were determined. Results: The growth of liver metastases on day 14 was influenced by increased insufflation pressures (p < 0.05) rather than the prolonged duration of pneumoperitoneum without significant interaction. The 15-mmHg pneumoperitoneum group showed a higher (p < 0.05) accumulation of radioactivity in the liver compared with the 5-mmHg pneumoperitoneum group and controls. Pneumoperitoneum groups with 5 and 10 mmHg showed higher (p < 0.05) peak levels of IL-6 compared with controls. Conclusions: An elevated insufflation pressure plays an important role in the enhancement of liver metastases, and this pressure-related adverse effect may be partly relevant to facilitating accumulation of tumor cells in the liver.

The influence of different insufflation pressures during carbon dioxide pneumoperitoneum on the development of pulmonary metastasis in a mouse model

AbstractBackground: The effects of different insufflation pressures on the development of pulmonary metastasis was investigated in a mouse laparoscopy model. Methods: BALB/C mice intravenously inoculated with colon 26 cells were randomized to one of five treatment groups (10 mice per group): pneumoperitoneum at different pressures of 5, 10 or 15 mmHg; full laparotomy for 60 min; or anesthesia control. Cancer nodules on the lung surface 19 days postoperatively were compared between groups. Results: (a) As compared with the control group, pneumoperitoneum at 10 and 15 mmHg and laparotomy enhanced the growth of pulmonary metastases (p < 0.01). (b) The growth of metastases also was greater in laparotomy group mice than in mice undergoing pneumoperitoneum at 5 and 10 mmHg (p < 0.05). Conclusions: These results suggest that the effects of different insufflation pressures on the growth of pulmonary metastases are not identical, and that pneumoperitoneum with high pressure may promote pulmonary metastases similar to those with laparotomy.

Comparison of the effects of gasless procedure, CO2-pneumoperitoneum, and laparotomy on splenic and hepatic natural killer activity in a rat model

Background: Natural killer (NK) activity plays an important role in the prevention of tumor metastasis. However, few studies compared changes in NK activities between gas(less) laparoscopy and open surgery. Materials and methods: Donryu rats were randomized to 4 groups (n = 6–9, for each lime point in each group): gasless group, pneumoperitoneum group, laparotomy group, and control group. The surgical treatment groups received additional cecal resection at the end of the procedures. Spleen cells and hepatic nonparenchymal cells were harvested at 6, 24, or 96 h, to determine the splenic and hepatic NK activities against YAC-1 cells. Results: Compared with the anesthesia control, laparotomy and pneumoperitoneum depressed splenic NK activity at 24 h (p < 0.01 for laparotomy and p < 0.05, for pneumoperitoneum) and 96 h (p < 0.05). Laparotomy also depressed hepatic NK activity at 24 h (p < 0.05). In contrast, the gasless procedure did not show any deterioration in the splenic and hepatic NK activities. Conclusion: These results suggest that gasless laparoscopic surgery would be a favorable approach in terms of the preservation of NK activities.

Liver metastases are less established after gasless laparoscopy than after carbon dioxide pneumoperitoneum and laparotomy in a mouse model

Background: Although the liver is the most frequent site of cancer recurrence after conventional open surgery for colorectal cancer, the effect of laparoscopic procedures with or without gas insufflation on the development of liver metastases is largely unknown. Methods: Male BALB/C mice inoculated intraportally with colon 26 cells were randomized to undergo carbon dioxide pneumoperitoneum (n = 14), abdominal wall lifting (n = 14), or full laparotomy (n = 12), or to serve as control subjects without any procedures other than tumor inoculation (n = 13). Results: The growth of liver metastases 14 days after surgery was enhanced after full laparotomy (p < 0.01) and pneumoperitoneum (p = 0.02), as compared with that in the control subjects, whereas there was no difference in the growth of liver metastases between abdominal wall lifting and the control condition (p = 0.99). Conclusions: These results suggest that the defense against liver metastasis is better preserved after the gasless procedure than after laparotomy and carbon dioxide pneumoperitoneum in the reported animal model.

APC gene mutations in a jejunal adenoma causing intussusception in a patient with familial adenomatous polyposis

Adenomatous polyps of the jejunum/ileum in patients with familial adenomatous polyposis (FAP) are usually small (<5 mm) and are considered to be of little clinical importance. Genetic alterations in these polyps have not previously been analyzed. We herein report an extremely rare case of FAP presenting with intussusception caused by jejunal adenomas. Both somatic and germline mutations of the APC gene were detected in one of the polyps. A 40-year-old man with FAP was admitted for closure of an ileostomy that had been created because of an anastomotic leak after subtotal proctocolectomy with ileo-anal-canal anastomosis. During the follow-up after that surgery, he had occasionally complained of colicky abdominal pain, but it had quickly subsided. At the second laparotomy, for closure of the ileostomy, jejuno-jejunal intussusception was incidentally found, and segmental resection of the jejunum, including the leading point of the intussusception, was performed. There were five polyps clustered in the resected jejunum. Histologically, the polyps, ranging from 5 to 26 mm in diameter, were adenomas with moderate to severe atypia. Genetic examinations of one of the largest polyps, using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and direct sequencing methods, revealed somatic (T insertion at codon 1557) and germline mutations (4 base-pair deletion at codons 181–182) of the APC gene. This is the first evidence that the coexistence of somatic and germline alterations in the APC gene is involved in the development of a jejunal adenoma causing small-bowel intussusception.

Clinical and Pathologic Features of Fibroadenoma of the Mastopathic Type

PurposeFibroadenoma with mastopathic change (FAM) is a relatively uncommon subtype of fibroadenoma of the breast, with a high incidence of pathological misdiagnosis. This histological subtype remains poorly understood because of its rarity. Many questions remain unanswered about its clinicopathological importance, especially in the differential diagnosis of breast cancers.MethodsAmong 218 breast fibroadenomas surgically resected as excisional biopsies at our institute between 1990 and 2004, 19 were pathologically diagnosed as FAM. We reviewed these 19 patients.ResultsThe ages of the patients ranged from 20 to 51 years (mean 36.8 years). The tumor sizes ranged from 0.8 to 7 cm (mean 2.1 cm). Six of the 19 patients underwent core needle biopsy, resulting in a diagnosis of fibroadenoma in four patients and atypical ductal hyperplasia in two patients. Ultrasonography showed findings suggestive of solid tubular carcinoma in seven patients, fibroadenoma in ten patients, and unspecific malignant tumors in two. They were not specified clinically.ConclusionRecognition of this distinctive variant of fibroadenoma is important because it resembles intraductal carcinoma and is increasing in incidence. It is crucial to distinguish FAM from intraductal carcinoma in biopsy specimens. Thus, not only pathologists but also clinicians must be able to recognize this type of fibroadenoma, and cooperate closely to establish an accurate diagnosis.

Distribution of intrasplenically injected colon cancer cells following pneumoperitoneum in mice

Background: Few studies have examined tumor cell distribution following laparoscopic surgery for colorectal cancer. We examined the effect of carbon dioxide pneumoperitoneum on the distribution of intrasplenically injected colon cancer cells in mice. Methods: Mice were intrasplenically injected with 2 × 104 colon 26 cells labeled with 111In-oxine and were randomized to undergo pneumoperitoneum at 10 mmHg for 30 min or to receive no treatment other than anesthesia. Radioactivity of the liver, lungs, and spleen was measured 30, 60, 90, or 150 min following tumor inoculation. Results: The dynamic changes in the hepatic radioactivity were not similar between groups. However, the values were not significantly different at any time point. The radioactivity of lungs was extremely low in both groups throughout the experimental period. Conclusions: Pneumoperitoneum does not appear to cause the accumulation of intraportally spreading tumor cells in the liver, but it may affect the dynamic changes of tumor cells. Also, tumor cell localization in the lungs is negligible in both pneumopentoneum and control groups.