Significance of FDG-PET in Identification of Diseases of the Appendix – Based on Experience of Two Cases Falsely Positive for FDG Accumulation

A discussion of the significance of F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the identification of diseases of the appendix is presented based on two cases falsely positive for FDG accumulation. Both cases were palpable for a tumor in the lower right abdominal region and a prominently enlarged appendix was depicted by CT. Although the patients underwent ileocecal resection based on a strong suspicion of appendiceal cancer rather than appendicitis since abnormal accumulation exhibiting maximum standard uptake values (SUVs) of 7.27 and 17.11, respectively, was observed at the same site in FDG-PET examination and since there no malignant findings observed histologically, the patients were diagnosed with appendicitis. Although FDG specifically accumulates not only in malignant tumors, but also in diseases such as acute or chronic inflammation, abscesses and lymphadenitis, and identification based on SUVs has been reported to be used as a method of identification, the two cases reported here were both false-positive cases exhibiting high maximum SUVs. At the present time, although the significance of FDG-PET in the identification of diseases of the appendix is somewhat low and there are limitations on its application, various research is currently being conducted with the aim of improving diagnostic accuracy, and it is hoped that additional studies will be conducted in the future

Phase II trial of aflibercept with FOLFIRI as a second‐line treatment for Japanese patients with metastatic colorectal cancer

Aflibercept targets vascular endothelial growth factor. The present study involved assessing the efficacy, safety and pharmacokinetics of aflibercept plus 5‐fluorouracil/levofolinate/irinotecan (FOLFIRI) as a second‐line treatment for metastatic colorectal cancer (mCRC) in Japanese patients. Aflibercept (4 mg/kg) plus FOLFIRI was administered every 2 weeks in 62 patients with mCRC until disease progression, unacceptable toxicity or patient withdrawal. Tumors were imaged every 6 weeks. The primary endpoint was objective response rate (ORR); secondary endpoints were progression‐free survival, overall survival, safety, and pharmacokinetics of aflibercept, irinotecan and 5‐fluorouracil. A total of 60 patients were evaluated for ORR; 50 had received prior bevacizumab. The ORR was 8.3% (95% confidence interval [CI]: 1.3%‐15.3%), and the disease control rate (DCR) was 80.0% (69.9%‐90.1%). The median progression‐free survival was 5.42 months (4.14‐6.70 months) and the median overall survival was 15.59 months (11.20‐19.81 months). No treatment‐related deaths were observed, and no significant drug‐drug interactions were found. The most common treatment‐emergent adverse events were neutropenia and decreased appetite. Free aflibercept had a mean maximum concentration (coefficient of variation) of 73.2 μg/mL (15%), clearance of 0.805 L/d (22%) and volume of distribution of 6.2 L (18%); aflibercept bound with vascular endothelial growth factor had a clearance of 0.162 L/d (9%) (N = 62). Aflibercept did not significantly affect the pharmacokinetics of irinotecan or 5‐fluorouracil: The clearance was 11.1 L/h/m2 (28%) for irinotecan and, at steady state, 72.6 L/h/m2 (56%) for 5‐fluorouracil (N = 10). Adding aflibercept to FOLFIRI was shown to be beneficial and well‐tolerated in Japanese patients with mCRC. ClinicalTrials.gov Identifier: NCT01882868

直腸癌転移陽性リンパ節における癌細胞占拠比率の臨床的意義

直腸癌の転移陽性リンパ節における癌細胞の占拠の程度を分析し,癌のリンパ節浸潤の程度および微小転移の臨床的意義を明らかにすることを目的とした.対象は1994年1月から1997年12月までの4年間で,当科における直腸癌手術例のうち検索可能であった119例で,リンパ節転移陽性例は69例,転移陽性リンパ節294個であった.方法:転移陽性リンパ節の最大割面の病理組織標本を観察し,癌細胞の浸潤面積から(1)転移陰性(grade 0),(2)全体の1/4以下の転移(grade 1),(3)1/4～1/2以下の転移(grade 2),(4)1/2～わずかに正常リンパ組織が残存(grade 3-(1)),(5)完全に癌細胞で置き換わっている(grade 3-(2)),(6)分類不可能(grade 3-(3))に分類した.特にgrade 1に着目し,癌浸潤面積と臨床病理学的因子との関連を検討した.結果:1,931個のリンパ節のうち転移陰性1,637個(84.8%)に対し転移陽性は294個(15.2%)であった.臨床病理学的因子との関連は,原発巣の壁深達度がSS(A)以下の症例に有意にgrade 1が多かった.その他の臨床病理学的因子では相関関係は認めなかった.しかしながらリンパ節転移grade別にみるとN1にgrade 1が多かった(p=0.008).臨床病期別に検討を加えると1/4以下のリンパ節転移は転移総数が3個までのリンパ節転移,つまりStage IIIaに多かった(p=0.0011).これはリンパ節への癌の転移,浸潤過程の初期の状態を観察していると考えられる.grade 1を含みリンパ節個数の少ない症例の5年生存率は,単独転移が87.5%,転移リンパ節総数が2個までで70.0%,3個までで63.6%であった.症例が少なく推測にすぎないが,生存率は転移巣の占有比率の低い症例では,リンパ節転移があっても転移個数の少ない症例の方が予後が比較的良好である傾向であった.リンパ節転移の有無は予後を左右する重要な因子である.リンパ節転移の形態を検討し,それを明らかにすることが,微小転移の診断およびその臨床的意義の解明に寄与するものと考えられた.We conducted a retrospective analysis of lymph nodes with the histological evidence of metastasis in patients with rectal cancer. By studying the extent of cancer cell invasion of the lymph nodes, we tried to clarify the degree of cancer cell invasion in lymph nodes and the clinical significance of micrometastasis. We studied 119 rectal cancer patients who underwent surgery at our department from January 1994 to December 1997. Grade 1 lymph nodes (metastatic cells occupying 1/4 or less of the entire lymph node area) accounted for 11.9% of all cases with lymph node metastasis, and were also significantly more frequently encountered in stage Ilia cases. Our study implicated that at the early stage, the frequency of micrometastasis correlates with the depth of the tumor. Among the patients in whom the percentage area occupied by metastatic lesions in micrometastases was low, the outcome reflected by the 5-year survival rate was more favorable in patients with a smaller number of lymph node metastases. It is considered that assessment and elucidation of the morphology of lymph node metastases might contribute to making the diagnosis of micrometastases and to elucidation of their clinical significance

直腸癌転移陽性リンパ節における癌細胞占拠比率の臨床的意義

直腸癌の転移陽性リンパ節における癌細胞の占拠の程度を分析し,癌のリンパ節浸潤の程度および微小転移の臨床的意義を明らかにすることを目的とした.対象は1994年1月から1997年12月までの4年間で,当科における直腸癌手術例のうち検索可能であった119例で,リンパ節転移陽性例は69例,転移陽性リンパ節294個であった.方法:転移陽性リンパ節の最大割面の病理組織標本を観察し,癌細胞の浸潤面積から(1)転移陰性(grade 0),(2)全体の1/4以下の転移(grade 1),(3)1/4～1/2以下の転移(grade 2),(4)1/2～わずかに正常リンパ組織が残存(grade 3-(1)),(5)完全に癌細胞で置き換わっている(grade 3-(2)),(6)分類不可能(grade 3-(3))に分類した.特にgrade 1に着目し,癌浸潤面積と臨床病理学的因子との関連を検討した.結果:1,931個のリンパ節のうち転移陰性1,637個(84.8%)に対し転移陽性は294個(15.2%)であった.臨床病理学的因子との関連は,原発巣の壁深達度がSS(A)以下の症例に有意にgrade 1が多かった.その他の臨床病理学的因子では相関関係は認めなかった.しかしながらリンパ節転移grade別にみるとN1にgrade 1が多かった(p=0.008).臨床病期別に検討を加えると1/4以下のリンパ節転移は転移総数が3個までのリンパ節転移,つまりStage IIIaに多かった(p=0.0011).これはリンパ節への癌の転移,浸潤過程の初期の状態を観察していると考えられる.grade 1を含みリンパ節個数の少ない症例の5年生存率は,単独転移が87.5%,転移リンパ節総数が2個までで70.0%,3個までで63.6%であった.症例が少なく推測にすぎないが,生存率は転移巣の占有比率の低い症例では,リンパ節転移があっても転移個数の少ない症例の方が予後が比較的良好である傾向であった.リンパ節転移の有無は予後を左右する重要な因子である.リンパ節転移の形態を検討し,それを明らかにすることが,微小転移の診断およびその臨床的意義の解明に寄与するものと考えられた.We conducted a retrospective analysis of lymph nodes with the histological evidence of metastasis in patients with rectal cancer. By studying the extent of cancer cell invasion of the lymph nodes, we tried to clarify the degree of cancer cell invasion in lymph nodes and the clinical significance of micrometastasis. We studied 119 rectal cancer patients who underwent surgery at our department from January 1994 to December 1997. Grade 1 lymph nodes (metastatic cells occupying 1/4 or less of the entire lymph node area) accounted for 11.9% of all cases with lymph node metastasis, and were also significantly more frequently encountered in stage Ilia cases. Our study implicated that at the early stage, the frequency of micrometastasis correlates with the depth of the tumor. Among the patients in whom the percentage area occupied by metastatic lesions in micrometastases was low, the outcome reflected by the 5-year survival rate was more favorable in patients with a smaller number of lymph node metastases. It is considered that assessment and elucidation of the morphology of lymph node metastases might contribute to making the diagnosis of micrometastases and to elucidation of their clinical significance