Validity of local treatment including intraarterial infusion chemotherapy and radiotherapy for fungating adenocarcinoma of the breast: case report of more than 8-year survival.

A 39-year-old woman came to us complaining of severe anemia (hemoglobin: 2.3 g/dl) and a painful right breast that was entirely occupied by an ulcerative, foul-smelling tumor approximately 20 cm in maximum dimension. The tumor, which was determined to be mucinous adenocarcinoma at biopsy, had invaded the chest wall with multiple lung metastases (T4cN2M1 stage IV). After a blood transfusion, the patient received the following multimodal treatment: concurrent chemoradiotherapy (50 Gy), intraarterial infusion chemotherapy consisting of doxorubicin 50 mg, mitomycin-C 10 mg, and cisplatin 50 mg, and skin graft surgery. After intraarterial infusion chemotherapy, the fungating tumor disappeared. The patient experienced a relapse of right pleural effusion 2 years later and received multimodal treatment. Now, March 30, 2000, the patient is doing well without local recurrence, 8 years after her first admission. The combination of intraarterial infusion chemotherapy and radiotherapy plays a role in successful treatment of extensive local disease of the breast.

Breast conservation for huge-sized locally advanced breast cancer: a case report.

A 35-year-old woman with locally advanced stage IIIB breast cancer (medullary carcinoma) 12 cm in diameter underwent neoadjuvant chemotherapy consisting of three courses of intraarterial infusion [adriamycin (ADR), mitomycin (MMC), cisplatin (CDDP), 5-fluorouracil (5FU)] and four cycles of systemic chemotherapy (ADR, epirubicin, cyclophosphamide, MMC, CDDP) for three months. The tumor markedly diminished after the first course of intraarterial infusion chemotherapy, with a 3-cm tumor remaining after the completion of preoperative administration. Pathologically complete response was noted in specimens resected following breast conservation surgery. Postoperative radiotherapy was added and adjuvant chemohormonal therapy was continued for two years. The patient is alive without recurrence and has been able to conserve the breast for the past eight years, neoadjuvant chemotherapy including intraarterial infusion enabled breast conservation treatment even for huge-sized locally advanced breast cancer.

Intraarterial infusion chemotherapy and radiotherapy with or without surgery for patients with locally advanced or recurrent breast cancer.

We analyzed response, side effects, and local control rates of a multimodal treatment consisting of intraarterial infusion chemotherapy (IAIC) and radiotherapy with or without surgery for patients with locally advanced or recurred breast cancer. Thirty-three patients, clinically diagnosed as stage IIB in 1, IIIA in 2, IIIB in 12, IV in 18, were treated from 1991 to 1998. Twenty-five were primary and eight were recurrent cases after surgery. IAIC started as initial treatment up to three times maximum. In most cases, doxorubicin 50 mg, cisplatin 50 mg, and mitomycin 10 mg were infused in the subclavian and/or internal mammary artery. After IAIC, patients in primary cases underwent radical mastectomy or breast conservation surgery, after radiotherapy at a total dose of 50 Gy/25 fractions/5 weeks with a boost of 10 Gy. In recurrent cases, a full dose of radiotherapy was delivered. Clinical objective and complete response rates were 78% and 9% after IAIC. Despite a high rate of residual positive margin (67%) or clinically residual carcinoma, local recurrence developed only in 2 patients (6%) and local control rates at 5 years were calculated as 89%. Bone marrow suppression was frequent, and skin vesiculation (15%) and ulceration (9%) were experienced after IAIC. Skin ulcer (6%), brachial plexus neuropathy (3%), and radiation pneumonitis (3%) occurred as late toxicity. IAIC was effective as an induction treatment and radiotherapy played a role of local control for patients with locally advanced or recurrent breast cancer.

Diffuse intrahepatic recurrence after resection of hepatocellular carcinoma.

BACKGROUND/AIMS: An early diffuse type in the pattern of the postoperative intrahepatic recurrence of hepatocellular carcinoma has been recognized. The purpose of this study was to elucidate risk factors for diffuse recurrence of hepatocellular carcinoma. METHODOLOGY: The subjects involved in the present study were 114 patients with hepatocellular carcinomas resected in Tenri Hospital during the past 12 years. Univariate analysis was used for retrospective determination of the factors related to diffuse recurrences after surgery in 10 cases among 114 patients. RESULTS: The risk factors linked to diffuse recurrence were microscopical portal infiltration (P < 0.01), elevated alpha-fetoprotein (more than 1000 ng/mL) (P < 0.05), the absence of preoperative transcatheter arterial embolization (P < 0.01), and two or more segmentectomies of the liver (P < 0.01). Six of 10 patients with microscopical portal infiltration and elevated alpha-fetoprotein (more than 1000 ng/mL) had diffuse recurrence (P < 0.01). Six of 8 patients with two or more segmentectomies without preoperative TAE had diffuse recurrence (P < 0.01). CONCLUSIONS: When patients with the diagnosis of operable hepatocellular carcinoma have portal infiltration and elevated alpha-fetoprotein (more than 1000 ng/mL), two or more segmentectomies of the liver without preoperative transcatheter arterial embolization should be avoided.

Mismatched clinicopathological response after concurrent chemoradiotherapy for thoracic esophageal cancer.

We have been treating patients with operable thoracic esophageal cancer according to our own protocol. It includes the initial concurrent chemoradiotherapy (CRT) followed by continuous CRT or surgery. Patients with good response to initial chemoradiotherapy were allowed to continue chemoradiotherapy, whereas the others were treated with surgery. However, there were two cases which showed discrepancies in the clinicopathological response. Both patients received initial chemoradiotherapy, including two courses of cisplatin (100-120 mg), 5-fluorouracil (750-1000 mg for 4 days) and radiation (44-50 Gy). On completion of the initial chemoradiotherapy, all diagnostic imaging modalities including barium swallow, esophagoscopy, endoscopic ultrasonography and thoracic computed tomography strongly implicated residual tumor with a reduction rate of 40-50%. The patients underwent radical esophagectomy 15-20 days after initial chemoradiotherapy. Pathological specimens only revealed thickening of the esophageal wall due to inflammatory change without residual carcinoma. These facts suggest the current limitations of diagnostic images in evaluating the response to chemoradiotherapy.

Treatment results of esophageal carcinoma of clinical T3, T4M0: historical comparison between neoadjuvant chemoradiotherapy followed by surgery or definitive radiotherapy and conventional surgery.

We investigated results for thoracic T3-T4 esophageal squamous cell carcinoma in two strategies. The protocol group (46 patients) consisted of neoadjuvant chemoradiotherapy (44 Gy, CDDP, 5-FU), followed by either definitive radiotherapy (total 70 Gy) for responders or surgery for non-responders. The surgery group (26 patients) underwent esophagectomy with regional lymph node dissection. Nineteen of them received postoperative radiotherapy. Surgical candidates in both groups received intraoperative radiotherapy for abdominal lymphatics since 1991. In the protocol group, 23 patients underwent radical surgery after neoadjuvant chemoradiotherapy and the remaining 23 underwent definitive radiotherapy. The rates of recurrence were 64% in the protocol group, and 62% in the surgery group. Overall 3- and 5-year survival rates were 48% and 31% in the protocol group compared to those of 30% and 30% in the surgery group. The rate of the was 39% in the protocol group. There was no mortality in either group. Our protocol had at least comparable prognostic values with historical conventional surgery, and was excellent in having feasibility for organ preservation.

Selenium kinetics and changes in glutathione peroxidase activities in patients receiving long-term parenteral nutrition and effects of supplementation with selenite.

Selenium (Se) is an essential trace element in humans. Patients receiving long-term parenteral nutrition (PN) are at risk for Se deficiency. We investigated changes in Se levels and glutathione peroxidase (GSH-Px) activity in serum and tissue (red blood cells, RBC) in addition to urinary excretion of Se in patients receiving long-term PN with and without Se supplementation. In patients without Se supplementation, both Se levels and GSH-Px activity in serum decreased with duration of PN. The serum Se levels were below the lower limits of the control values in 19 of 33 patients (58%) who received PN for less than 1 mo. Conversely, RBC GSH-Px activity remained at a sufficient level in 9 of 12 patients (75%) who received PN for 3-6 mo. The RBC Se levels in all of these patients were lower than the control levels. Urinary Se concentrations were significantly correlated with serum Se concentrations by linear regression analysis (r = 0.707, P < 0.05). In patients with Se supplementation, urinary Se concentrations increased exponentially with increases in serum Se levels. These findings indicate that a time lag precedes the decrease in levels of serum Se, RBC Se, serum GSH-Px, and RBC GSH-Px in patients without Se supplementation and the increase in excretion of urinary Se in patients with Se supplementation. The monitoring of not only serum Se levels but also RBC GSH-Px activity and urinary Se levels is required for optimal Se supplementation during long-term PN.

Comparison between chemoradiation protocol intended for organ preservation and conventional surgery for clinical T1-T2 esophageal carcinoma.

PURPOSE: This retrospective study was designed to compare treatment results of the chemoradiation protocol with conventional surgery for thoracic T1-T2 esophageal squamous cell carcinoma. METHODS AND MATERIALS: Sixty-six patients with esophageal carcinoma, clinically diagnosed as T1 (tumor invading lamina propria or submucosa) or T2 (tumor invading muscularis propria) were treated for 12 consecutive years, from July 1986 to January 1998. The conventional surgery group included 30 patients who underwent esophagectomy with regional lymph node dissection. Twenty-one of them received postoperative radiotherapy. Thirty-six patients were assigned to the chemoradiation protocol, consisting of neoadjuvant chemoradiotherapy (44 Gy; CDDP: 60 mg/m2, day 1, bolus; 5-FU: 400 mg/m2, day 1-4, continuous), followed by either definitive radiotherapy with high-dose-rate intraluminal brachytherapy (total 70 Gy) for responders or surgery for nonresponders as in the conventional surgery group. Surgical candidates in both groups received intraoperative radiotherapy for abdominal lymphatics since 1991. RESULTS: In the protocol group, 4 patients underwent radical surgery after neoadjuvant chemoradiotherapy, and the remaining 32 underwent definitive chemoradiotherapy. Local control rates at 1 and 3 years were 85% and 70% in the T1/protocol group versus 91% and 80% in the T1/surgery group, and 83% and 83% in the T2/protocol group versus 94% and 80% in the T2/surgery group, respectively. There was no statistical significance. Overall 1- and 3-year survival rates were 100% and 83% in the T1/protocol group versus 82% and 72% in the T1/surgery group (p = 0.36), and 100% and 51% in the T2/protocol group, versus 95% and 68% in the T2/surgery group p = 0.61), respectively. There was no treatment-related mortality in either group. The rates of esophageal conservation were 92% in the T1/protocol group and 58% in the T2/protocol group. CONCLUSION: The chemoradiation protocol can result in comparable survival with conventional surgery for patients with T1-T2 esophageal carcinoma. A randomized trial between definitive chemoradiotherapy and surgery is required.

Intraoperative radiotherapy for the abdominal lymphatic system in patients with esophageal carcinoma.

We applied intraoperative radiotherapy (IORT) to the esophageal carcinoma in an attempt to prevent abdominal lymph node recurrence, and retrospectively studied patterns of failure and controllability of abdominal lymph nodes in patients treated with or without IORT. Between July 1986 and October 1997, 81 patients with radically resected esophageal carcinoma, aged 42-76 years (mean 61), were divided into two groups, the IORT group (39 patients) and the non-IORT group (42 patients). All patients except two, who received transhiatal esophagectomy for superficial carcinoma, underwent subtotal esophagectomy with thoracic and abdominal with/without cervical lymphadenectomy. Fourteen patients underwent only surgical resection, and the remaining 67 patients received radiotherapy to the mediastinum post-operatively (40-50 Gy/20-25 Fr/4-5 W) in 37 and preoperatively (44 Gy/40 Fr/4 W) in 30 patients. Preoperative irradiation was performed as a neoadjuvant chemoradiotherapy consisting of two courses of cisplatin (each patient received 80-100 mg, mean 60 mg m(-2), day 1, bolus injection) and 5-fluorouracil (each patient received 500-1000 mg day(-1), mean 400 mg m(-2), days 1-4, continuous infusion). The target volume of IORT encompassed the upper abdominal lymph node area including lymph node groups of right/left cardia, left gastric artery, celiac artery and abdominal para-aorta. A single dose of high-energy electrons (9-12 MeV) of 20-23 Gy, prescribed to the 90% isodose curve, was delivered. Treatment for the abdominal lymphatic system was classified into four categories: surgery alone in 30 patients, surgery with chemotherapy in 12, surgery with IORT in 15, surgery with chemotherapy and IORT in 24. There were no complications related to IORT. Forty patients (49%) had recurring carcinoma: in the lymph nodes (36%), in distant organs (27%) and locally (6%). The incidence of lymph node metastasis was 29% in the neck, 32% in the mediastinum, and 27% in the abdomen. Abdominal lymph node recurrence in the IORT group was less frequent than in the non-IORT group (p=0.048). In particular, 24 patients treated with a combination of surgery, chemotherapy and IORT had no recurrence in the abdominal lymphatic system. The overall median survival was 46 months, the survival at 1, 3, and 5 years being 85%, 52%, and 44% respectively. However, there was no difference in survival between the IORT group and the non-IORT group. The IORT for the abdominal lymphatic system was feasible for reduction of the rate of abdominal lymphatic recurrence without survival benefit in this study. This retrospective finding should be confirmed by a prospective randomized study.

Case report of 14-year survival after radiotherapy for clinical T3 esophageal carcinoma, with local recurrence finally rescued by surgery.

A 51-year-old man with increasing dysphasia was admitted to our hospital on March 18, 1985. Several examinations revealed thoracic esophageal squamous cell carcinoma 11 cm in length staged T3N0M0 (stage IIA) by UICC 1987. As he rejected our proposal of surgery, definitive radiotherapy (60 Gy) was delivered, and complete response was obtained. The patient had been doing well for 5 years after radiotherapy until superficial local recurrence was discovered at a periodic endoscopic examination. High-dose-rate intraluminal brachytherapy (10 Gy/2 Fr) was administered. After a 3-year disease-free interval, superficial recurrence developed in the same location, and early gastric cancer was detected as a secondary cancer. Radical salvage surgery was performed. The patient was alive and disease free 5 years and 5 months after surgery. We present this rare case of a patient who survived 14 years after the initial radiotherapy. The present case demonstrated the importance of long-term follow-up after radiotherapy, long-term local controllability of relatively low doses of intraluminal brachytherapy after superficial recurrence, and the feasibility of salvage surgery as long as local recurrence is limited to within the mucosal layer.

A prospective analysis of the factors influencing pancreaticojejunostomy performed using a single method, in 100 consecutive pancreaticoduodenectomies.

The factors influencing the healing process of pancreaticojejunostomy (P-J) following pancreaticoduodenectomy (PD) are still ill defined, allowing the recommendation of various anastomotic methods. We conducted a prospective study to determine the risk factors influencing the protracted healing of P-J, examining 100 consecutive patients who underwent PD followed by P-J, performed as an end-to-side "mucosa-to-mucosa" anastomosis using vertical mattress sutures (VMS method). Protracted healing of P-J was classified as either peripancreatic sepsis (PPS), defined as prolonged suppurative discharge of less than 50 ml a day from the drain beneath the P-J for more than 1 week; or a pancreatic fistula (PF), defined as prolonged discharge of more than 50 ml a day with a high amylase content (> 1000 IU) for more than 1 week. There were 80 patients with a malignant neoplasm, and 20 with benign disease. The overall incidence of healing problems following P-J was 9%, which included 6 patients (6%) with PPS and 3 (3%) with PF. Apart from an advanced age of more than 70 years, none of the patients' characteristics or postoperative complications influenced the healing of P-J. The type of reconstruction, an anastomotic stent, the duct size, and a "soft" pancreas were not risk factors either. In conclusion, no factors, apart from the age or any special problem of an individual patient, influenced the dehiscence of P-J when the VMS method was used after PD.

Malignant thymoma with direct invasion into the peritoneal cavity: report of a case.

Extrathoracic invasions or metastases from thymomas are extremely rare. We describe herein the case of a patient with malignant thymoma which recurred three times during an 8-year period and invaded directly into the peritoneal cavity, involving the gastrointestinal tract. The huge thymoma was completely resected, along with the fornix of the stomach, the transverse colon, and the 8th, 9th, and 10th ribs. Careful observation and multidisciplinary treatment against recurrent thymoma will be requisite for this patient, even though the tumor has been completely resected.

Anomalous duplicated cystic duct as a surgical hazard: report of a case.

Anomalies of the biliary ductal system are not uncommon, and their clinical significance is variable. We present herein the case of a 70-year-old Japanese woman found to have an anomalous duplicated cystic duct, which is an extremely rare congenital anomaly. Intraoperative delineation of the anomaly by real-time cholangiograms assisted us in being able to subsequently perform a safe cholecystectomy. This case serves to demonstrate the importance of being aware of the possibility of potential biliary variations in order to avoid ductal injuries during biliary surgery.

Neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose radiotherapy or surgery for operable thoracic esophageal carcinoma.

PURPOSE: A prospective clinical trial was undertaken to investigate the feasibility of concurrent chemoradiotherapy for esophageal carcinomas. MATERIALS AND METHODS: Between June 1989 and May 1996, forty patients with operable squamous cell carcinoma of the thoracic esophagus (Stage 0 to III: UICC 1987), ages 45 to 78 years (mean: 64), were enrolled in a study of neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose radiotherapy (CRT group) or surgery (CRT-S group). Neoadjuvant chemoradiotherapy consisted of 44 Gy in 40 fractions for 4 weeks (2.2 Gy/2 Fr/day) through 10-MVX rays, with 2 courses of cisplatin (80-100 mg/body, mean: 60 mg/m2, Day 1, bolus injection) and 5-fluorouracil (500-1000 mg/body/day, mean: 400 mg/m2, Days 1-4, continuous infusion). After completion of neoadjuvant chemoradiotherapy, an intermediate clinical response was assessed by barium swallow, esophagoscopy with/without biopsy, EUS in most cases, thoracic and upper abdominal CT scan, and cervical US. Definitive chemoradiotherapy was performed in patients when regression of more than 75% was evident (CRT Group), and esophageal resection was indicated in those who remained at less than 75% (CRT-S Group). In CRT Group, a cumulative dose of 60-70 Gy for Tis, T1 and 65-75 Gy for T2-T4 tumor with high-dose-rate intraluminal brachytherapy and a total of 3 courses of chemotherapy were planned. In CRT-S Group, intraoperative radiotherapy for abdominal lymphatic system and postoperative supraclavicular irradiation were added. RESULTS: At the time of intermediate assessment, complete response (CR) was observed in 16 patients, a partial response (PR) in 22, and no change (NC) in 2. Thirty responding patients (CR, 16; PR, 14) entered the CRT Group, and 10 nonresponding patients (PR, 8; NC, 2) were followed by surgery (CRT-S Group). Radiotherapy was completed satisfactorily, but chemotherapy was suspended in 26 patients (65%) because of acute toxicity. Clinical CR rate at the completion of treatment showed 90% in CRT Group, and pathologic CR rate 10% in CRT-S Group. The overall median survival was 45 months, survival at 1, 2, and 3 years being 100%, 72%, and 56%, respectively. Local-regional failure was observed in 7 patients (all in CRT Group), distant failure in 6 (3 in CRT Group, 3 in CRT-S Group) and local-regional with distant failure in 1 (CRT Group). Four patients with local-regional recurrence in the CRT Group were salvaged by surgery. Overall survival at 2 and 3 years for CRT vs. CRT-S Group was 72%, 64% vs. 75%, 38%, respectively. No treatment-related mortality was observed. The rate of the 'esophagus conservation' was 65% (Stage 0: 1 of 1, 100%; Stage I: 11 of 12, 92%; Stage II: 8 of 17, 47%; Stage III: 6 of 10, 60%). CONCLUSION: Our results demonstrated that almost all early disease (Stage 0-I) and about half of advanced disease (Stage II-III) could be conserved, their esophagus treated by the multidisciplinary approach centering on high-dose radiotherapy and concurrent chemotherapy.

The effect of short-term continuous epidural morphine on postoperative pain after laparoscopic cholecystectomy.

This study was undertaken to determine whether short-term continuous epidural analgesia using morphine would relieve pain after laparoscopic cholecystectomy. The authors retrospectively reviewed the clinical data of 182 cases who had undergone a laparoscopic cholecystectomy. These cases were divided into four groups according to their anesthetic modes as follows: a control group with general anesthesia only (n = 37); group I, general anesthesia combined with one shot of epidural morphine (n = 78); and group II, general anesthesia combined with continuous epidural analgesia using morphine (IIa for 12 h (n = 33); IIb for 8 h (n = 34)). The pain score on a four-category verbal scale and the frequency of analgesic use were investigated. There were no differences in the background characteristics of the patients among the groups, except for the duration of surgery (I vs IIa; P = 0.006). The pain scores were significantly different between the control group and the other groups. The frequency of analgesic use in the control group was also significantly higher than in the other groups. A tendency toward a higher frequency of analgesic use in group I, compared with that in groups IIa and IIb, was observed. These findings thus suggest that short-term continuous epidural analgesia using morphine can effectively relieve postoperative pain after a laparoscopic cholecystectomy.