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An 88-year-old man was referred to our hospital for further examination of an asymptomatic liver tumor. MRI showed low-intensity regions on T1-weighted images, high-intensity regions on T2-weighted images, high-intensity regions on diffusion-weighted images, and low-intensity regions in the arterial, portal, and hepatocyte phases of Gd-EOB-DTPA. PET scan of the tumor was positive, while endoscopy exhibited no malignant findings. The CT and MRI findings showed that the tumor could be a metastatic liver tumor, cholangiocellular carcinoma, or hepatic inflammatory pseudotumor. Considering the possibility of a malignant tumor, laparoscopic partial hepatectomy was performed as a diagnostic treatment. The patient was discharged on the 8th postoperative day. The histopathological diagnosis was diffuse large B-cell lymphoma. Since the lesion was localized to the liver, a diagnosis of malignant lymphoma originating from the liver was made. Six courses of R-THP-COP therapy were administered. No indication of recurrence was noted 18 months after surgery. Although primary hepatic lymphoma is difficult to diagnose, laparoscopic hepatectomy allows for an accurate diagnosis and early postoperative recovery, enabling rapid administration of chemotherapy.

Phyllodes tumors are uncommon breast neoplasms that constitute 1-2% of breast malignancies. Invasive ductal carcinoma in the epithelial component of phyllodes tumor is very rare. When carcinoma is detected within the specimen, the management of treatment changes completely. We report a rare case of invasive ductal carcinoma arising in a giant borderline malignancy phyllodes tumor in a 51-year-old female patient. A painful 20 cm mass was found in her right breast, and a needle biopsy revealed fibroadenoma or benign phyllodes tumor, and a total mastectomy was performed. Pathological results showed that a borderline malignant phyllodes tumor coexisted with invasive ductal carcinoma. We explained that axillary surgery was necessary because invasive cancer was diagnosed after surgery, but the patient requested follow-up using images. Endocrine therapy was performed as postoperative adjuvant therapy, and the follow-up is underway without recurrence.

A questionnaire survey was conducted by 17 doctors from 14 hospitals regarding treating elderly breast cancer in Yamaguchi Prefecture. The survey items are the implementation status of the geriatric assessment(GA)for the elderly, the state at the start of treatment(fit/vulnerable/frail), and the setting of restrictions on the indication of surgery and drug treatment (endocrine therapy/chemotherapy/molecular targeted therapy). Only one institution(6%)was used for GA; the tools used were the G8 and Charlson comorbidity index. Regarding surgical treatment, most facilities did not set restrictions according to age or condition. Endocrine and molecular-targeted therapies(anti-HER drugs)are highly tolerated, and most facilities do not have age restrictions. On the other hand, 40% of the respondents set age restrictions on chemotherapy. Four(24%) therapists said they would limit their age to 70 to 75 if the patient had a frail condition. These results tended to be similar to the reports of NCD-registered elderly breast cancer treatment.

In recent years, breast reconstruction has been increasingly performed in breast cancer surgery with improving the appearance of the breast. We report a case of local breast cancer recurrence after artificial breast reconstruction. The patient was a 52-year-old woman. She had undergone total mastectomy for left breast cancer 11 years ago, and reconstruction with breast implant 3 years ago. She presented to our hospital with the chief complaint of skin redness and induration of the reconstructed breast. A core needle biopsy was performed, and its results showed in the invasive ductal carcinoma. She had an operation of resection of tumor and reconstruction implant. As a result of histopathological diagnosis, it was a local recurrence of breast cancer 11 years ago. After the surgery, she underwent endocrine therapy and there is no recurrence. As the increase in the number of cases of breast reconstruction, the number of recurrences in the reconstructed breast is expected to increase the future. The treatment strategy for cases of local recurrence after breast reconstruction is currently under review, the accumulation of evidence is necessary.

A 41-year-old man with upper abdominal and back pain was admitted to another hospital. He had a history of recurring acute pancreatitis and pseudocyst. Six months later, abdominal CT revealed a pancreatic head tumor arising from the pseudocyst, and adenocarcinoma was suspected based on endoscopic ultrasound fine needle aspiration(EUS-FNA)findings. We selected neoadjuvant chemotherapy because resection was difficult due to severe inflammation and edema around the tumor. Chemotherapy(FOLFIRINOX followed by gemcitabine plus nab-paclitaxel)was effective, and the tumor almost disappeared on CT. Subtotal stomach-preserving pancreatoduodenectomy(SSPPD)was performed 12 months after starting chemotherapy, and curative resection was successful. The final Stage was ⅡA(T3[CH1]N0M0). Histopathological examination revealed no viable tumor cells. S-1 adjuvant chemotherapy was administered for 6 months. He was still alive 22 months postoperation without any recurrence. Neoadjuvant chemotherapy is effective in cases involving pancreatic cancer with severe inflammation, because pre-operative chemotherapy can reduce tumor size and alleviate the inflammation caused by acute pancreatitis and pseudocysts.

A-67-year old man was diagnosed with gastric cancer and a liver tumor. Extended left hemihepatectomy combined with caudate lobectomy and distal gastrectomy with lymph node dissection were performed. Histological examination revealed synaptophysin and CD56positive tumor cells with a solid and rosette structure, which was diagnosed as endocrine carcinoma (EC). Additionally, a tubular adenocarcinoma was present in the stomach. The liver tumor presented as EC with tumor thrombus in the left portal vein. Finally, the patient was diagnosed with gastric EC(pT3[SS], pN0, P0, CY0, M1[HEP], Stage Ⅳ, R0). He received 6courses of the adjuvant chemotherapy with cisplatin(CDDP)plus irinotecan(CPT-11), and has been alive without recurrence for 21 months post-operation. Gastric EC is a rare subtype of gastric cancer. The resection of liver metastasis of gastric EC may improve patients' prognosis and QOL. CDDP-based chemotherapy is recommended, due to the regimen for small cell lung cancer.

We report a case of a 61-year-old man who underwent open total gastrectomy and D2 lymph node dissection for gastric cancer. The pathological findings were suggestive of pT2N3M0, fStage ⅢA. S -1 was administered for 1 year post-surgery. One year and 9 months after the operation, an epigastralgia was found, and the PET-CT showed an increase of SUVmax 3.80 around the celiac artery. S -1 plus CDDP therapy was initiated. However, due to the occurrence of neutropenia, the therapy was changed to ramucirumab plus paclitaxel. After 20 courses of the same regimen, no PET-CT uptake was observed. We thus considered it cCR and discontinued further chemotherapy. The patient has been alive for 15 months without recurrence. By performing effective chemotherapy at an early stage, cCR could be observed after a secondary treatment. Therefore, longterm survival could be expected for post-operative recurrence of gastric cancer.

Complete visceral inversion occurs in 1/5,000 individuals. In 64%of cases, complete visceral inversion is complicated by the malformation of other organs. Careful attention is required when performing surgeries. In recent years, with the development of laparoscopic surgery, some cases of laparoscopic surgery with complete visceral inversion have been reported. Herein, we report a case of safely performed laparoscopic surgery for sigmoid colon cancer with complete visceral inversion along with a relevant discussion.

We investigated whether primary tumor resection performed at our department for the purpose of local control affects the disease progression of Stage Ⅳ breast cancer. Fifteen patients who underwent primary tumor resection between 2009 and 2017 were investigated. The median age at the time of surgery was 63 years. There were two postoperative deaths(1 at<1 year postoperatively and 1 at<2 years postoperatively). The median postoperative stable disease(SD)period was 11 months overall and was 12 months or longer in 7 patients. SD was attained by all patients with the first drug treatment after primary tumor resection. Patients who tended to have a longer postoperative SD period did not receive preoperative drug treatment, were luminal HER2-positive, and had one metastatic organ. Regardless of surgery timing and reason, there were no cases of rapid postoperative disease progression. In all patients, postoperative local control was satisfactory, and continuation of medical treatment was feasible for distant metastatic tumors. These data signify that primary tumor resection can be considered to treat Stage Ⅳ breast cancer for the purpose of local control.

Introduction: Although chemotherapy is the main treatment for recurrent colorectal cancer, the utility of radiotherapy as a local treatment has been widely reported. We performed chemoradiotherapy with S-1 for cases with recurrence after surgery, and the outcomes are reported herein., Materials and Methods: Chemoradiotherapy with S-1 was performed in 4 cases. S-1 was administered for 2 weeks during the irradiation period, and the off period provided was 1 week., Results: X-ray irradiation was performed in 2 cases and proton beam irradiation in the other 2. The progression free periods of the 2 cases receiving proton beam irradiation were 31 months and 36 months. In contrast, the progression free periods of the 2 cases given X-ray irradiation were 24 months and 21 months., Discussion: It is known that S-1 not only achieves a high anticancer effect via dihydropyrimidine dehydrogenase(DPD)inhibition, which is a major metabolic pathway of 5-FU, but also increases the radiation susceptibility of malignancies. S-1 is regarded as an ideal anticancer agent when used in combination with radiation therapy. Since the local control achieved in our 4 cases was good, chemoradiotherapy with S-1 was considered to be a useful treatment.

This study assessed the effect of pegfilgrastim in patients with early stage breast cancer who were receiving docetaxel and cyclophosphamide(TC)therapy(75mg/m / 2 docetaxel plus 600 mg/m2 cyclophosphamide). In total, 17 patients who were to receive 4 planned cycles of TC therapy every 3 weeks were included in this study. Of the 17 patients, 10 who received pegfilgrastim after January 2016 formed the Peg-G group and 7 who did not receive pegfilgrastim until December 2015 formed the control group. We observed a high successful execution rate and relative dose intensity(RDI)with docetaxel in both groups. The successful execution rates were 100% in the Peg-G group and 42.8% in the control group. The RDI was 86.5%(65.4-100%)in the Peg-G group and 52.5%(48.0-58.0%)in the control group. This study showed that the use of pegfilgrastim results in a high successful execution rate and RDI in patients with early stage breast cancer undergoing TC therapy.

Everolimus and exemestane combination therapy represents a treatment option for estrogen receptor(ER)-positive metastatic breast cancer. We evaluated the efficacy and safety of everolimus and exemestane therapy, retrospectively. After a median follow-up of 10.5 months, the median progression-free survivalin patients was 4.7 months. The clinicalbenefit rate was 27%and the disease controlrate was 64%. The most common all-grade adverse events(AEs)were stomatitis(82%) and non-infectious lung disease(27%). The most commonB3 grade AEs were cellulitis(18%)and hyperglycemia(18%). The AEs reported were mostly grade 1 and 2, and manageable with appropriate intervention. Combination therapy with everolimus and exemestane appears to be a useful addition for ER-positive metastatic breast cancer, with carefulmanage- ment of specific AEs.

Objectives: Resection of liver metastasis from colorectal cancer is known to improve prognosis; therefore, surgical treatment is recommended for resectable metastases in the Japanese Society for Cancer of the Colon and Rectum Guidelines for the Treatment of Colorectal Cancer. In this study, we investigated factors that affect the prognosis of resection of such metastatic liver tumors., Results: Thirty-three cases of liver resection performed during the period from 1998 to 2017 were investigated. The 5-year overall survival rate after liver resection was 47.3%, and the 5-year recurrence-free survival rate after liver resection was 29.9%. Univariate analysis identified CA19-9(p=0.02)and operative procedure(p=0.0046)as prognostic factors, while multivariate analysis revealed operative procedure(p=0.03)to be a prognostic factor. When prognosis was examined in terms of operative procedure(ie, lobectomy, segmental resection, or partial resection), the prognosis of patients undergoing lobectomy was significantly poorer compared to those undergoing segmental resection(p=0.0092, RR=28.94)and partial resection(p=0.0092, RR=25.37)., Conclusion: In this study, operative procedure was identified as a poor prognostic factor. The prognosis of liver metastasis requiring lobectomy is considered to be poor. Further accumulation of cases is needed to investigate the effects of other factors in the choice of operative procedure.

We report a case of a patient treated with everolimus and exemestane combination therapy for bone metastasis after breast surgery.The patient, a 58-year-old woman, consulted our department for back pain in October 2014.S he was diagnosed with left breast cancer when she was 41 years old.She had received Bt+Ax for left breast cancer and administered tamoxifen for 5 years.We decided on everolimus and exemestane combination therapy after observing an abnormal uptake in the 7th to 8th thoracic vertebrae on a PET-CT scan.The pain was controlled using oxycodone and fentanyl orally disintegrating tablet with zoledronic acid.After receiving treatment, the patient experienced pruritus and a Grade 2 rash, but they were managed with antihistamine administration and the treatment was continued.Four months later, the abnormal uptake on the right thoracic vertebrae shrunk; the pain almost disappeared, and oxycodone and fentanyl orally disintegrating tablet were discontinued.Subsequently, exemestane was used alone.Six months later, the range of abnormal uptake on the thoracic vertebrae progressed, and the disease was evaluated as PD.Four months later, everolimus and exemestane combination therapy was resumed, and the abnormal uptake on the thoracic vertebrae almost disappeared as observed on a PET scan.The effectiveness of the treatment was evaluated as CR because other local recurrence and new metastases were not found. Everolimus might exhibit bone resorption inhibiting effects and bone protection effects, but the decision regarding the periods of suitable use and the effects of long-term continuation of treatment are controversial, and further discussion based on experience of increasing use is required.

We report the cases of 2 patients with clinical T4( cT4) esophageal cancer who achieved pathological complete response on treatment with neoadjuvant chemoradiation therapy. Case 1 involved a 68-year-old woman who was diagnosed as having cT4 advanced esophageal cancer( with involvement of the aorta and left pulmonary vein). Neoadjuvant chemoradiation therapy with 5-fluorouraci(l 5-FU)( 800 mg/m2, days 1-5 and days 29-33), cisplatin( CDDP 80 mg/m2, days 1 and 29), and radiation (39.6 Gy/22 Fr) was administered, and the tumor showed a partial response (PR). Case 2 involved a 69-year-old man who was diagnosed as having cT4 advanced esophageal cancer( with involvement of the main bronchus). Neoadjuvant chemoradiation therapy with 5-FU( 800 mg/m2, days 1-5 and days 29-33), CDDP( 80 mg/m2, days 1 and 29), and radiation( 39.6 Gy/22 Fr) was administered, and the tumor showed a clinical PR. After tumor response was noted, curative esophagectomy was performed in both cases, without any complications, and a pathological complete response was achieved in both patients.

Here, we report a case wherein bevacizumab/XELOX combination therapy was remarkably effective for the treatment of a patient with unresectable advanced cecum cancer and carcinomatous peritonitis. A 52-year-old man was diagnosed with cecum cancer with extensive carcinomatous dissemination. He underwent open laparotomy, and the findings indicated a unresectable cecal tumor attached to the retroperitoneum; therefore, ileo-transverse colostomy was performed. After 6 courses of bevacizumab and XELOX therapy, the primary tumor as well as ascites and carcinomatous dissemination had disappeared, and a marked decrease in the serum carcinoembryonic antigen(CEA)level was noted. However, subsequently, positive emission tomography/computed tomography(PET/CT)indicated a recurrence of the primary tumor. Therefore, ileocecalectomy and D2 lymph node dissection were performed. Thus, we believe that bevacizumab/XELOX therapy may be useful as neoadjuvant chemotherapy for the treatment of advanced colon cancer with peritonitis carcinomatosa.

We report here the long-term survival case of advanced esophageal cancer treated with definitive chemoradiotherapy (CRT). A 61-year-old woman visited our hospital because of a disturbance in her swallowing in September, 2003. She was diagnosed with a middle esophageal type 3 tumor, which was 9 cm in length by endoscopy. Squamous cell carcinoma was diagnosed by pre-operative endoscopic biopsy. CT revealed the tumor with direct invasion to the aorta, and multiple metastases of the lymph nodes(T4, N1, M0: Stage IVa). CRT(combination of 5-FU and nedaplatin with 40 Gy of radiation)was administered. After the completion of CRT, the tumor size was remarkably reduced, but stenosis of the lumen of the esophagus remained partially. Therefore, we performed sub-total esophagectomy in February, 2004. A pathological complete response was diagnosed with no carcinoma cells evident in the resected specimen. Pathological therapeutic evaluation of the esophageal cancer was grade 3. The patient had received no adjuvant chemotherapy, but she is alive and healthy now with no relapse of carcinoma for more than 8 years after operation.

A 35-year-old woman underwent hemicolectomy and RFA for ascending colon cancer with multiple liver metastases in February, 2005. She received postoperative hepaticarterial infusion chemotherapy with 5-FU, and systemic hemotherapy with UFT for 10 months after the operation. A local recurrence of the anastomosis was detected in March, 2006, and she underwent a resection for it. This was followed by 6 courses of adjuvant chemotherapy with modified FOLFOX6. Because multiple liver metastases and lymph node metastases were detected in March, 2007, she received RFA and 6 courses of adjuvant chemotherapy with modified FOLFOX6 again. Liver metastases disappeared but lymph node metastases still remained. Therefore, she received 4 courses of bevacizumab plus modified FOLFOX6. The metastatic lesions disappeared and were judged to be CR. Therefore, she was followed-up with the oral administration of UFT. Metastases of liver and lymph nodes of the mediastinum were detected in May, 2008, for which she received 4 courses of bevacizumab plus FOLFIRI2. Because the effects of the chemotherapy were judged to be CR, she continued with 4 courses of the same regimen. The regimen was discontinued due to diarrhea, and she therefore began to receive 4 courses of bevacizumab plus LV/5-FU regimens. CR has been maintained at present, over 7 years after the initial surgery.

A 61-year-old complaining of anorexia and general fatigue was admitted to our hospital for further examination. She was diagnosed as advanced sigmoid colon cancer with multiple metastases of lung, liver, and left hydronephrosis. Since curative surgery was not deemed possible, we started chemotherapy with bevacizumab/FOLFOX6 (bi-weekly drip infusion). After the 6th course, colonoscopy revealed a significant tumor reduction and changes to the scar tissues. CT did not reveal a complete disappearance, but found some reductions in metastases of lung and liver. Sigmoidectomy and lymph node resection (D1) were performed. We did not disappeared any dissemination and the histological diagnosis revealed a complete disappearance of cancer cells in the main tumor. She was discharged 13 days after surgery, following chemotherapy which included bevacizumab and XELOX. The chemotherapy using bevacizumab/FOLFOX6 is a candidate for the standard treatment strategy for inoperable advanced colon cancer. Herein we report this rare case with a review of the literature.

A 46-year-old woman with lower abdominal distension was diagnosed as gastric cancer in our hospital. She had multiple metastases of lungs, lymph nodes, bilateral ovaries, and uterus. After she underwent sub-total gastrectomy, bilateral oophorectomy, and total hysterectomy, she received adjuvant chemotherapy followed by docetaxel and S-1. After 6 courses of chemotherapy, PET/CT revealed no recurrences (complete response), and she was therefore administered S-1 for only 6 months. She has remained without recurrence 15 months after the operation.

A case was a 40-year-old woman. Her right breast was presented with massive bleeding ulcer and fixed with a pectoral muscle. Diagnosis of Stage IIIb breast cancer( T4b, N1, M0) showed a high inflammatory response and severe anemia. Palliative surgery was difficult because of hemostasis, and her general health also was in poor condition. The pathological diagnosis was squamous cell cancer. We underwent a total of 30 Gy radiation emergency hemostasisose. After radiation and chemotherapy, the lesion was undergone a radical surgery, and was reduced in size significantly. It was diagnosed as squamous cell cancer, which was more sensitive to general radiation so neoadjuvant chemoradiation therapy was effective.

We experienced a case of anthracycline- and taxane-resistant recurrent breast cancer with multiple liver metastases and multiple bone metastases showing marked improvement by S-1. A 52-year-old woman visited our hospital because of her liver dysfunction in May 2008. She underwent a partial mastectomy preserving chest muscles in another hospital in 2000, but further details were unknown. Radiographic imaging tests revealed multiple metastases to the liver and bones in May 2008, and she was referred to our hospital for management of metastatic lesions. Tumor of the liver was diagnosed as metastases from the breast carcinoma, ER+, PgR+, HER2 (0), and histopathologically by core needle biopsy under ultrasonography. She received 4 courses of EC after 4 courses of biweekly docetaxel treatment. She showed a partial response (PR), so she was treated by the same course of treatment again. But she was diagnosed with an enlargement of liver metastases and recurrence of bone metastases by PET examination. Then the oral treatment with S-1 was started, and at the end of the second course, a significant reduction of abnormal accumulation in PET was noted. She has been quite well without any adverse effects from S-1. S-1 monotherapy was thus considered to be an effective treatment for advanced or recurrent breast cancer resistant to anthracyclines and taxanes.

We report two cases of advanced gastric cancer successfully treated with combination S-1 and docetaxel (DOC) therapy. Case 1: A 43-year-old woman underwent radical total gastrectomy for advanced type 4 gastric cancer one and a half years ago. She was diagnosed as peritonitis carcinomatosa with much ascites, so the following combination chemotherapy was started. Case 2: A 53-year-old man underwent palliative gastrectomy for advanced type 3 gastric cancer with multiple lymph node metastases involving Virchow's metastases. After surgery, he received the following combination chemotherapy: DOC at the starting dose of 40 mg/m2 by iv infusion over 1 hour on day 1 and S-1 at the full dose of 80 mg/m2 daily for two weeks every three weeks. After administration of this combination therapy, the Case 1 gastric cancer with much ascites and the Case 2 gastric cancer with multiple lymph nodes metastases had entirely disappeared. Thereafter the 2 cases received therapy with S-1 alone. No recurrence in Case 1 has been seen with S-1 chemotherapy. Case 2 revealed a few lymph node swellings in the abdominal cavity, so he is undergoing combination therapy of DOC and S-1. The combination DOC and S-1 show a high degree of safety and can be a new tool for the management of advanced gastric cancer with peritoneal dissemination and Virchow's metastases.

A 61-year-old man underwent amputation of the rectum for advanced lower rectal cancer in April 2005. UFT-E granules were administered orally daily at 400 mg/body/day following surgery. He developed perineal pain and perineal discharges following an increase the CEA level in April 2006. PET revealed a tumor in the perineum and multiple lung metastases. Chemotherapy with mFOLFOX 6 for 8 courses and FOLFIRI 2 for 4 courses were administered since July in 2006. Although CT revealed a the reduction in multiple lung metastases, CEA was increased to over a maximum 109, high fever continued and the pinealtumor was enlarged in December 2006. The patient underwent resection of the perinealmass, but he developed perinealsevere pain and perinealdischarge. So radiotherapy of the pelvic region was given at a total dose of 40 Gy(given 2 Gy each fragment)followed by administration of FOLFIRI 2 for 12 courses. After chemoradiotherapy, the CEA level was remarkably decreased. PET could not detect any mass in lung fields and revealed a little accumulation in the pelvic region. Chemotherapy with FOLFIRI 2 is administered monthly now, and the CEA level has been within the normal range since July of 2007. The pineal pain and pineal discharge disappeared, so the quality of life has improved dramatically.

A 64-year-old woman was diagnosed with multiple hepatic metastases from sigmoid colon cancer. She underwent resection of the colon and catheter insertion into the hepatic artery for arterial infusion in August 2006. She was then treated with postoperative combination chemotherapy consisting of UFT and CPT-11, 5-FU, l-LV. UFT was administered orally at 400 mg/body/day every day and CPT-11 was injected at 100 mg/body/week, 5-FU at 750 mg/body/week, and l-LV at 300 mg/body/week for 8 continuous weeks. After 2 months of the chemotherapy, the metastatic liver tumors disappeared. So hepatic arterial infusion with the same regimens was injected once every month 4 more times. Oral UFT was administered every day. After 6 months of the combined chemotherapy above, we judged the effects of the chemotherapy to be a complete response. Then the chemotherapy was followed by oral UFT only. As severe nausea and vomiting were seen in this patient with an initial dose of 150 mg/body/week of CPT-11 at first, we reduced the dose of CPT-11 to 100 mg/body/week. From then, outpatient care was possible because no severe events were observed. Combined chemotherapy consisting of oral UFT and CPT-11, 5-FU and l-LV by hepatic arterial infusion is suggested to be a new and effective treatment for multiple liver metastases from colorectal cancer.

Neoadjuvant chemotherapy (NAC) represents a new approach based on sound theoretical, pharmacokinetic, and experimental principles. The purpose of NAC is to improve control of the primary site by downstaging and to improve control of micrometastatic disease. NAC has been standard therapy in the management of locally advanced breast cancer. Patients with earlier stage breast cancer may also benefit from treatment with NAC. Recently some investigators have mentioned that NAC can be used instead of adjuvant chemotherapy and would be most appropriate for patients who wish to preserve their breast but who have tumors too large for breast conserving surgery. In this article, we reviewed the present status of NAC (indication, clinical response, pathologic response, survival, possibility of breast conservation, prognostic/predictive factors, neoadjuvant endocrine therapy) and discussed several unanswered questions on NAC (survival benefit, optimal number of treatment cycles, optimal regimens) and future direction. Combined modality therapy including NAC appears to provide excellent local control, the possibility of breast conservation, and, probably, an increased survival rate, at least for some subsets of patients. Furthermore, through sequential sampling, NAC provides indeed the opportunity to identify molecular mechanisms associated with pathologic response and to study the possibility to guide the choice for induction treatment and patient populations submitted to neoadjuvant chemotherapy.

Cervical adenocarcinoma and adenosquamous cell carcinoma are low in radiation sensitivity, and the prognosis is said to be inferior to that of squamous cell carcinoma. Eleven facilities nationwide participated in the historical control study on the recurrence prevention effect of carmofur (HCFU) administered at 300 mg/day for more than two years postoperatively as an adjuvant chemotherapy to patients with cervical adenocarcinoma or adenosquamous cell carcinoma for which radical operation is possible. Registered for the study was a total of 252 patients: 77 patients for whom administration of carmofur was begun during the period from January 1987 and March 1989, 71 patients (control 1) who were treated for the cancer after January 1982 but did not receive adjuvant chemotherapy, and 104 patients who received adjuvant chemotherapies with other than carmofur (control 2). In analyses with the Kaplan-Meier method, the carmofur administration group demonstrated a better cumulative survival rate and disease free rate than control 1 (no adjuvant chemotherapy), suggesting carmofur was effective in preventing the recurrence of cervical adenocarcinoma and adenosquamous cell carcinoma.

Image analysis of the nuclear morphology was performed on propidium iodide-stained isolated cells from 9 adenomas and 9 cancers of the colorectum. We analyzed DNA content, seven nuclear geometric features and four shape factors of tumor cells using an image cytometry system that has been developed in our laboratory. Nuclear breadth and the degree of contour irregularity of cancer cells were found to be significantly different from those of adenoma cells. The coefficients of variation (CV) of some nuclear features and the degree of contour irregularity were increased in cancer cells, while CV of the degree of circularity was increased in adenoma cells. Moreover, nuclear in G2 phase were found to be larger and more round than those in G1 phase. These results suggest that cell-cycle-related analysis of nuclear features would be a valid means to assess the nuclear morphology of colorectal tumors.

To study the cell characteristics of relatively small pancreatoduodenal cancers (less than 4 cm in the greatest dimension in histopathological examination), we analyzed the relation between the cell kinetics, and histopathological and immunohistochemical findings. Tumors were classified into t1 (0-2 cm in its greatest dimension) and t2 (2-4 cm). We analyzed DNA contents of five tumors of t1 and twelve of t2 by cytofluorometry. Histopathological and immunohistochemical (CA19-9 and CEA) examinations were also carried out. Nuclear DNA content histograms of the tumors in the t1 group showed all diploid pattern, while those in the t2 group exhibited 4 diploid, 7 euploid polyploid and 1 aneuploid patterns. Invasions to the lymphatic (ly), vein (v) and nerve (pn) were found in five cases of diploid tumors (3 of t1 and 2 of t2) and all (8 in t2) of non-diploid tumors. A medullary pattern of tumor growth was only noted in three tumors of t1. This pattern was not found in t2 (4 diploid, 8 non-diploid). These results suggest that the cellular DNA content increased in association with the tumor growth in size. In the histopathological findings, both the invasions (ly, v, pn) and fibrosis of the stroma more often appeared as the tumor size and polyploid and aneuploid cells increased. However, other histopathological findings and the immunohistochemical examination for CA19-9 and CEA had no relation to the tumor growth and the DNA ploidy pattern.

Analysis of both cell proliferation kinetics and effects of cis-diamminedichloroplatinum (CDDP) on cell cycle in human gastric cancer cell line (HGC-Y2) by measuring the contents of nuclear DNA, RNA and the Ki-67 antigen using autostage cytofluorometry system was described. In HGC-Y2 cells, RNA content increased during the cell cycle and reached to the maximum at G2/M phase. The results of pulse treatment with CDDP on these cells demonstrated a prolongation of S phase and G2 arrest with increasing of RNA content of these cells. We classified the cells by intranuclear distribution pattern of Ki-67 antigen and thus could identified the cells at G0 and M phases from these classification. The content of Ki-67 antigen was moderate grade at G1 phase and it decreased in the early S phase, then increased gradually during S phase and at the late S phase. It increased rapidly, reaching to the maximum at G2/M phase. After CDDP treatment, the content of Ki-67 antigen increased in the cells in prolonged S phase and in the cells arrested at G2 phase. It was also found that the syntheses of both Ki-67 antigen and RNA were not inhibited by CDDP. These results suggest that the method using autostage cytofluorometry system was useful for the research, on the mechanism of cancer therapy because of making possible to analyze precisely the cell cycle and the influence of anticancer drugs.

Technetium 99m macroaggregated albumin (Tc-MAA) perfusion scintigraphy has been performed during hepatic arterial infusion chemotherapy using implantable reservoir. A total of 40 radionuclide (RI) studies were performed on 25 patients with liver metastasis of colorectal origin. Of 40 RI studies, 12 (30%) showed impaired liver perfusion. Three studies showed no perfusion of the liver, 3 increased radiotracer accumulations at liver hilus, 2 extrahepatic distributions, 2 catheter occlusions, 1 extravasation and 1 unilobar distribution. The accumulation of Tc-MAA in the tumor was graded from Grade I (tumor uptake decreased or similar relative to liver) to Grade III (tumor uptake remarkably increased). The response to chemotherapy was evaluable in 14 cases. A case with Grade I resulted in NC. Of 6 cases with Grade II, 1 resulted in MR, 3 in NC and 1 in PD. Of 8 cases with Grade III, 2 resulted in PR, 1 in MR and 5 in NC. Tumor response was observed in cases showing increased uptake of Tc-MAA. SPECT was performed in 7 cases, and revealed that hepatic tumors were hypervascular. We concluded that RI examination reveals not only hepatic perfusion, but also tumor microcirculation.

We studied prognostic factors of survival in 121 patients unresectable non-small cell lung cancer treated between March 1983 and November 1988 at forth department of internal medicine, Kinki university school of medicine, about histology, clinical stage, age, sex, performance status, Brinkman Index, hemoglobin, serum TP, serum Alb, serum LDH, pulmonary function and chemotherapy. The prognostic factors were studied using survival rate by Kaplan-Meier method, univariate analysis by Log-rank test and generalized Wilcoxon test and multivariate analysis by proportional hazard model of Cox. The prognostic factors of pretreatment were age, serum Alb, serum LDH, pulmonary dysfunction of mixed type and performance status. In the classified study according to histology, age and pulmonary dysfunction of mixed type were prognostic importance in patients with squamous cell lung cancer. Hemoglobin in patients with squamous cell lung cancer was important, too. The chemotherapy given good response improved patient's prognosis.

Daily and intermittent continuous intravenous infusions [by gravity drip, (IVG) or infusion pump, (IVP)] and intermittent short-time intravenous drip infusion of 5-FU were carried out on advanced cancer patients. The MTD and dose-limiting toxicity were investigated in relation to the plasma concentrations of 5-FU determined by HPLC. Responses in eleven patients receiving IVG administration daily at 8-21 mg/kg/day were NC, but those given 5-FU alone showed no adverse reactions. Plasma concentrations were too low to be determined. In 9 patients receiving IVG or IVP administration weekly at 60 mg/kg for 24 hr, 1 of the 5 evaluable patients showed reduced hepatic metastatic lesions. One of 4 patients receiving IVP administration weekly at 120 mg/kg for 48 hr showed a disappearance of metastatic lesions in the skeletal muscle, but bone marrow suppression was observed as dose-limiting toxicity. Pharmacokinetics were more stable in IVP than in IVG with less individual difference in the plasma concentrations. Among the outpatients receiving short-time iv, IVG administration once or twice a week, 2 patients given weekly administrations at 20 mg/kg for 60 min showed slight adverse reactions. In 6 patients given high-dose administrations, bone marrow suppression was observed. When pharmacokinetics in the patients given 5-FU for 60 min were compared between the IVG and IVP groups, there were individual differences in plasma concentrations, but the differences were not significant. It was concluded from above results that the following practical dose schedules would be recommendable: 60 mg/kg for 24hr/week by IVP for inpatients and 20 mg/kg for 60 min/week by IVG for outpatients.

Recombinant interferon alpha-2 (Sch 30500) was administered to 29 patients with advanced gynecological cancers (14 patients with cancer of the cervix, 8 with ovarian cancer, 4 with uterine sarcoma, 2 with endometrial cancer and 1 with unclassified cancer). No antitumor effects (CR and PR) were noted in 23 evaluable patients. Side effects observed were fever, tachycardia, diarrhea, chills, general fatigue, anorexia, nausea and vomiting. In some patients, leukopenia, decrease of hemoglobin and elevation of SGOT and SGPT were observed. No production of antibody for Sch 30500 was noted.